section name header

Introduction ⬇

VA Class:AM116

AHFS Class:

Generic Name(s):

Chemical Name:

Molecular Formula:

Associated Monographs

Cefuroxime is a semisynthetic, second generation cephalosporin antibiotic.1,3

Uses ⬆ ⬇

[Section Outline]

Cefuroxime axetil is used orally for the treatment of mild to moderate respiratory tract infections (i.e., acute maxillary sinusitis, acute exacerbations of chronic bronchitis, secondary infections of acute bronchitis, community-acquired pneumonia†) caused by susceptible bacteria;51,79,82,92,93,101,103,124,145,153,164,166,215 acute bacterial otitis media;79,82,88,89,102,110,143,145,184,215 pharyngitis and tonsillitis caused by Streptococcus pyogenes (group A β-hemolytic streptococci);79,90,91,145,175,215 mild to moderate uncomplicated skin and skin structure infections caused by Staphylococcus aureus (including β-lactamase-producing strains) or S. pyogenes ;79,82,94,145,215 and uncomplicated urinary tract infections caused by Escherichia coli or Klebsiella pneumoniae .79,82,95,96,104,145,215 Cefuroxime axetil also is used orally for the treatment of Lyme disease50,62,79,143,145,147,181,182,183,208 and has been used for the treatment of uncomplicated gonorrhea.79,125,144,145,147,215 The manufacturers of cefuroxime axetil oral suspension state that safety and efficacy of the suspension have been established only for the treatment of pharyngitis and tonsillitis,79 acute otitis media,79 and impetigo79 caused by susceptible bacteria.79 and for the treatment of Lyme disease.50,62,79,143,145,147,181,182,183,208

Cefuroxime sodium is used parenterally in the treatment of lower respiratory tract infections (including pneumonia), serious skin and skin structure infections, genitourinary tract infections, bone and joint infections, septicemia, and meningitis caused by susceptible organisms.1,214 Cefuroxime sodium also has been used parenterally for perioperative prophylaxis.1,3,6,48,66,71,193,194,195,196,197,214

Because cefuroxime, like other second generation cephalosporins, generally is less active against susceptible gram-positive cocci than are first generation cephalosporins, most clinicians state that cefuroxime probably should not be used in the treatment of infections caused by gram-positive bacteria when a penicillin or a first generation cephalosporin could be used.3,18,45 In addition, because cefuroxime generally is less active in vitro against Enterobacteriaceae than third generation cephalosporins, some clinicians state that a third generation drug such as cefotaxime or ceftriaxone generally is preferred if a parenteral cephalosporin is indicated in the treatment of infections known or suspected to be caused by these gram-negative bacteria.18,45

Prior to initiation of cefuroxime therapy, appropriate specimens should be obtained for identification of the causative organism and in vitro susceptibility tests.1,79 If cefuroxime is started pending results of susceptibility tests, it should be discontinued if the causative organism is found to be resistant to the drug.1,79 In the treatment of known or suspected sepsis or the treatment of other serious infections when the causative organism is unknown, concomitant therapy with an aminoglycoside may be indicated pending results of in vitro susceptibility tests.1,214

Acute Otitis Media !!navigator!!

Cefuroxime axetil is used orally for the treatment of acute otitis media (AOM) caused by S. pneumoniae , H. influenzae (including β-lactamase-producing strains), M. catarrhalis (including β-lactamase-producing strains), or S. pyogenes .79,82,88,89,102,110,145,198,199,200,215

When anti-infective therapy is indicated for the treatment of AOM, the American Academy of Pediatrics (AAP) recommends high-dose amoxicillin and amoxicillin and clavulanate potassium as the drugs of first choice for initial treatment.184 These experts recommend certain cephalosporins (cefdinir, cefpodoxime, cefuroxime, ceftriaxone) as alternatives for initial treatment in penicillin-allergic patients who do not have a history of severe and/or recent penicillin-allergic reactions.184

Results of controlled clinical studies in children 3 months to 12 years of age with AOM indicate that a 10-day regimen of oral cefuroxime axetil is as effective or more effective than a 10-day regimen of oral cefaclor,203,204 oral amoxicillin,201 or oral amoxicillin and clavulanate potassium.199,204 In published studies, the overall clinical response rate to a 10-day regimen of oral cefuroxime axetil in pediatric patients with AOM has ranged from 62-94%.199,201,202,203,204

Cefuroxime axetil also has been effective for the treatment of AOM in pediatric patients when administered in a 5-day regimen†.198,200 In a randomized study in children 3 months to 12 years of age with AOM, a satisfactory bacteriologic response (cure or presumed cure) was obtained in 92% of those who received a 5-day regimen of cefuroxime axetil (30 mg/kg daily given in 2 divided doses), 84% of those who received a 10-day regimen or cefuroxime axetil (30 mg/kg daily given in 2 divided doses), or 95% of those who received a 10-day regimen of amoxicillin and clavulanate potassium (40 mg/kg daily given in 3 divided doses).198 There is evidence from a randomized study in children 6-36 months of age with AOM that a 5-day regimen of oral cefuroxime axetil is as effective as and may be better tolerated than an 8- or 10-day regimen of oral amoxicillin and clavulanate potassium.200 The AAP states that oral anti-infective regimens of less than 10 days' duration are not recommended for the treatment of AOM in children younger than 2 years of age or in patients with severe symptoms.184

For additional information regarding treatment of AOM, including information on diagnosis and management strategies, anti-infectives for initial treatment, duration of initial treatment, and anti-infectives after initial treatment failure, see Acute Otitis Media under Uses: Otitis Media, in the Cephalosporins General Statement 8:12.06.

Pharyngitis and Tonsillitis !!navigator!!

Cefuroxime axetil is used orally for the treatment of pharyngitis and tonsillitis caused by S. pyogenes (group A β-hemolytic streptococci).79,90,91,145,175,215 Although cefuroxime usually is effective in eradicating S. pyogenes from the nasopharynx, efficacy of the drug in the subsequent prevention of rheumatic fever remains to be established.79,215

Selection of an anti-infective for the treatment of S. pyogenes pharyngitis and tonsillitis should be based on the drug's spectrum of activity, bacteriologic and clinical efficacy, potential adverse effects, ease of administration, patient compliance, and cost.45,170,171,173,174 No regimen has been found to date that effectively eradicates group A β-hemolytic streptococci in 100% of patients.45

Because the drugs have a narrow spectrum of activity, are inexpensive, and generally are effective with a low frequency of adverse effects, the AAP,143 Infectious Diseases Society of America (IDSA),171 American Heart Association (AHA),45 and others58,173 recommend a penicillin regimen (i.e., 10 days of oral penicillin V or oral amoxicillin or a single dose of IM penicillin G benzathine) as the treatment of choice for S. pyogenes pharyngitis and tonsillitis and prevention of initial attacks (primary prevention) of rheumatic fever. Other anti-infectives (e.g., oral cephalosporins, oral macrolides, oral clindamycin) are recommended as alternatives in penicillin-allergic individuals.45,143,171

If an oral cephalosporin is used for the treatment of S. pyogenes pharyngitis and tonsillitis, a 10-day regimen of a first generation cephalosporin (cefadroxil, cephalexin) is preferred instead of other cephalosporins with broader spectrums of activity (e.g., cefaclor, cefdinir, cefixime, cefpodoxime, cefuroxime).45,143,171

Although there is some evidence that a shorter duration of therapy with certain oral cephalosporins (e.g., a 5-day regimen of cefadroxil, cefdinir, cefixime, or cefpodoxime proxetil or a 4- or 5-day regimen of cefuroxime axetil) achieves bacteriologic and clinical cure rates equal to or greater than those achieved with the traditional 10-day oral penicillin V regimen,45,169,170,173,174,175,176,177 the IDSA and AHA state that use of cephalosporin regimens administered for 5 days or less for the treatment of S. pyogenes pharyngitis and tonsillitis cannot be recommended at this time.45,171

A 10-day regimen of oral cefuroxime axetil is at least as effective as a 10-day regimen of oral penicillin V for the treatment of S. pyogenes pharyngitis and tonsillitis.90,91,145,175 In addition, results of a prospective, randomized study in children 2-15 years of age indicate that a 4-day regimen of oral cefuroxime axetil (20 mg/kg of cefuroxime in 2 divided doses daily) is as effective as a 10-day regimen of oral penicillin V (45 mg/kg daily in 3 divided doses).169 The clinical response rate was 94.8% in those who received the 4-day cefuroxime regimen and 96.1% in those who received the 10-day penicillin regimen; 30 days after treatment, the bacteriologic relapse rate was 2.8 and 2.3%, respectively.169

Respiratory Tract Infections !!navigator!!

Cefuroxime axetil is used orally for the treatment of mild to moderate respiratory tract infections, including acute maxillary sinusitis caused by susceptible Streptococcus pneumoniae or Haemophilus influenzae (non-β-lactamase-producing strains only)58,79,145,153,164,166,215 and acute exacerbations of chronic bronchitis and secondary infections of acute bronchitis caused by susceptible S. pneumoniae , H. influenzae (non-β-lactamase-producing strains only), or H. parainfluenzae (non-β-lactamase-producing strains only).79,82,92,93,103,124,163,215

Cefuroxime sodium is used parenterally for the treatment of lower respiratory tract infections, including pneumonia, caused by susceptible S. pneumoniae , Staphylococcus aureus (penicillinase- and nonpenicillinase-producing strains), S. pyogenes (group A β-hemolytic streptococci), H. influenzae (including ampicillin-resistant strains), Escherichia coli , and Klebsiella .1

Acute Sinusitis

Cefuroxime axetil is used orally for the treatment of acute maxillary sinusitis caused by susceptible S. pneumoniae or H. influenzae (non-β-lactamase-producing strains only).58,79,145,153,164,166,215 The manufacturers state that insufficient data exist to establish efficacy of cefuroxime axetil in the treatment of acute bacterial maxillary sinusitis that is known or suspected to be caused by β-lactamase-producing strains of H. influenzae or M. catarrhalis .79,215

When anti-infective therapy is indicated for the treatment of acute bacterial sinusitis, the IDSA recommends amoxicillin and clavulanate potassium and the AAP recommends either amoxicillin or amoxicillin and clavulanate potassium as the drug of choice for initial empiric treatment.219,220 Because of variable activity against S. pneumoniae and H. influenzae , the IDSA no longer recommends second or third generation oral cephalosporins for empiric monotherapy of sinusitis in adults or children.219 If an oral cephalosporin is used as an alternative for empiric treatment of acute bacterial sinusitis in children (e.g., in penicillin-allergic individuals), the IDSA and AAP recommend a combination regimen that includes a third generation cephalosporin (cefixime or cefpodoxime) and clindamycin (or linezolid).219,220

Community-Acquired Pneumonia

Oral cefuroxime axetil is used for the treatment of mild to moderate community-acquired pneumonia† (CAP).51 The American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA) recommended cefuroxime as an alternative for treatment of CAP caused by penicillin-susceptible S. pneumoniae and as an alternative in certain combination regimens used for empiric treatment of CAP.51

Initial treatment of CAP generally involves use of an empiric anti-infective regimen based on the most likely pathogens and local susceptibility patterns; therapy may then be changed (if possible) to provide a more specific regimen (pathogen-directed therapy) based on results of in vitro culture and susceptibility testing.51 The most appropriate empiric regimen varies depending on the severity of illness at the time of presentation and whether outpatient treatment or hospitalization in or out of an intensive care unit (ICU) is indicated and the presence or absence of cardiopulmonary disease and other modifying factors that increase the risk of certain pathogens (e.g., penicillin- or multidrug-resistant Streptococcus pneumoniae , enteric gram-negative bacilli, Pseudomonas aeruginosa ).51 Most experts recommend that an empiric regimen for the treatment of CAP include an anti-infective active against S. pneumoniae since this organism is the most commonly identified cause of bacterial pneumonia and causes more severe disease than many other common CAP pathogens.51

For empiric outpatient treatment of CAP when risk factors for drug-resistant S. pneumoniae are present (e.g., comorbidities such as chronic heart, lung, liver, or renal disease, diabetes, alcoholism, malignancies, asplenia, immunosuppression; use of anti-infectives within the last 3 months), ATS and IDSA recommend monotherapy with a fluoroquinolone active against S. pneumoniae (moxifloxacin, gemifloxacin, levofloxacin) or, alternatively, a combination regimen that includes a β-lactam active against S. pneumoniae (high-dose amoxicillin or fixed combination of amoxicillin and clavulanic acid or, alternatively, ceftriaxone, cefpodoxime, or cefuroxime) given in conjunction with a macrolide (azithromycin, clarithromycin, erythromycin) or doxycycline.51 Cefuroxime and cefpodoxime may be less active against S. pneumoniae than amoxicillin or ceftriaxone.51

A sequential regimen of parenteral cefuroxime sodium (given for 48-72 hours) followed by oral cefuroxime axetil (given for 7 days) has been used effectively for the treatment of CAP in adults.167 If a parenteral cephalosporin is used as an alternative to penicillin G or amoxicillin for treatment of CAP caused by penicillin-susceptible S. pneumoniae , ATS and IDSA recommend ceftriaxone, cefotaxime or cefuroxime; if an oral cephalosporin is used for treatment of these infections, ATS and IDSA recommend cefpodoxime, cefprozil, cefuroxime, cefdinir, or cefditoren.51

For additional information on treatment of CAP, see Community-Acquired Pneumonia under Uses: Respiratory Tract Infections, in the Cephalosporins General Statement 8:12.06.

Gonorrhea and Associated Infections !!navigator!!

IM cefuroxime sodium has been used in conjunction with oral probenecid for the treatment of uncomplicated gonorrhea and disseminated gonococcal infections caused by Neisseria gonorrhoeae , including penicillinase-producing strains (PPNG).1,9,20 Cefuroxime axetil has been used orally for the treatment of uncomplicated urethral and endocervical gonorrhea caused by N. gonorrhoeae and for the treatment of uncomplicated rectal gonorrhea in females caused by nonpenicillinase-producing strains of the organism.79,83,84,85,86,87,125,126,127,144,145,146,215 However, parenteral cefuroxime sodium and oral cefuroxime axetil are not included in current US Centers for Disease Control and Prevention (CDC) recommendations for the treatment of gonococcal infections.36,68,143

Because of concerns related to recent reports of N. gonorrhoeae with reduced susceptibility to cephalosporins, the CDC states that oral cephalosporins are no longer recommended as first-line treatment for uncomplicated gonorrhea.68 For the treatment of uncomplicated urogenital, anorectal, or pharyngeal gonorrhea, the CDC recommends a combination regimen that includes a single dose of IM ceftriaxone and either a single dose of oral azithromycin or a 7-day regimen of oral doxycycline.68

The CDC states that cefuroxime axetil at the dosage recommended by the manufacturers (single 1-g oral dose of cefuroxime) meets the minimum efficacy criteria for treatment of urogenital and rectal gonococcal infections, but the pharmacodynamics of this oral drug are less favorable than those of IM ceftriaxone, oral cefixime, or oral cefpodoxime.36 In addition, cefuroxime axetil has unsatisfactory efficacy in pharyngeal infections.36

For additional information on current recommendations for the treatment of gonorrhea and associated infections, see Uses: Gonorrhea and Associated Infections in Ceftriaxone 8:12.06.12.

Lyme Disease !!navigator!!

Oral cefuroxime axetil is used in adults and children for the treatment of early Lyme disease manifested as erythema migrans.50,58,62,79,143,145,147,181,182,183,208,209,210,215 When an oral regimen is indicated, oral cefuroxime axetil also is used in the treatment of early neurologic Lyme disease† in patients with cranial nerve palsy alone without evidence of meningitis, Lyme carditis†, borrelial lymphocytoma†, and uncomplicated Lyme arthritis† without clinical evidence of neurologic disease.143,208,209

Lyme disease is a tick-borne spirochetal disease.134,135,182,143,181,183 In the US, Lyme disease is caused by the spirochete Borrelia burgdorferi , which is transmitted by the bite of Ixodes scapularis or I. pacificus ticks.134,135,182,143,181,183 For additional information on Lyme disease, see Lyme Disease in Uses: Spirochetal Infections, in the Tetracyclines General Statement 8:12.24.

Early Lyme Disease

Erythema Migrans

Oral cefuroxime axetil is used for the treatment of early Lyme disease manifested as erythema migrans.50,58,62,79,143,145,147,181,182,183,208,209,210,215

The IDSA, AAP, and other clinicians recommend oral doxycycline, oral amoxicillin, or oral cefuroxime axetil as first-line therapy for the treatment of early localized or early disseminated Lyme disease associated with erythema migrans, in the absence of specific neurologic involvement or advanced atrioventricular (AV) heart block.58,143,182,208,209,210 The IDSA states that a 14-day regimen (range 14-21 days) of any of these oral anti-infectives (doxycycline, amoxicillin, cefuroxime axetil) may be used for initial treatment of early Lyme disease since all 3 drugs have been shown to be effective for the treatment of erythema migrans and associated symptoms in prospective clinical studies.208 Doxycycline offers the advantage of also being effective for the treatment of human granulocytic anaplasmosis (HGA, formerly known as human granulocytic ehrlichiosis), which may occur simultaneously with early Lyme disease.143,208

Efficacy of cefuroxime axetil for the treatment of early Lyme disease has been evaluated in studies that included adults and pediatric patients 12 years of age or older with physician-documented erythema migrans (with or without systemic manifestations of infection), and results of these studies indicate that the drug is as effective as oral doxycycline in producing resolution of erythema migrans and preventing the development of manifestations of late Lyme disease.50,62,79,145,147 The clinical diagnosis of early Lyme disease in study patients was validated objectively by a blinded expert who examined available photographs of skin lesions taken before therapy and/or by serologic evidence of antibodies specific to B. burgdorferi identified using enzyme-linked immunosorbent assay (ELISA) and Western immunoblot.79 Patients were randomized to receive oral cefuroxime axetil (500 mg of cefuroxime twice daily) or oral doxycycline (100 mg 3 times daily) for 20 days and evaluated during treatment (days 8-12) and posttreatment (days 1-5, 1 month, and then at 3-month intervals for up to 1 year).50,62,79,147 In patients who were evaluated at 1 month posttreatment, a satisfactory clinical response consisting of either clinical success (defined as resolution of erythema migrans and other manifestations of infection within 5 days posttreatment and maintained through follow-up at 1 month posttreatment) or clinical improvement (defined as resolution of erythema migrans within 5 days posttreatment with incomplete resolution of other manifestations of infection at that time but further improvement or complete resolution of manifestations by follow-up at 1 month posttreatment) was attained in 91 or 93% of patients who received cefuroxime axetil or doxycycline, respectively.50,62,79 Clinical success was attained in 72 or 73% of patients receiving cefuroxime axetil or doxycycline, respectively; clinical improvement was attained in 19% of patients receiving either drug.50,62,79 In patients evaluated at 1 year, a satisfactory clinical outcome consisting of success (defined as the absence of signs or symptoms of late Lyme disease throughout the 1-year follow-up) or clinical improvement (defined as the presence of some signs or symptoms consistent with late Lyme disease but no objective evidence of active disease throughout the 1-year follow-up) was attained in 84 or 87% of patients who received cefuroxime axetil or doxycycline, respectively.50,62,79 Success at 1 year was attained in 73% of patients receiving either drug; clinical improvement was attained in 10% of patients receiving cefuroxime axetil and 13% of patients receiving doxycycline.50,62,79

Early Neurologic Lyme Disease

Oral cefuroxime axetil is used in the treatment of early neurologic Lyme disease† in patients with cranial nerve palsy alone without evidence of meningitis.208 Parenteral anti-infectives (IV ceftriaxone, IV penicillin G sodium, IV cefotaxime) are recommended for the treatment of early Lyme disease when there are acute neurologic manifestations such as meningitis or radiculopathy.143,182,208,209 However, some clinicians suggest that a 14-day regimen (range: 14-21 days) of oral anti-infectives (amoxicillin, doxycycline, cefuroxime axetil) may be used in patients with cranial nerve palsy without clinical evidence of meningitis (i.e., those with normal CSF examinations or those for whom CSF examination is deemed unnecessary because there are no clinical signs of meningitis).143,208,209 Although there is some experience using oral anti-infectives in patients with seventh cranial nerve palsy, it is unclear whether an oral regimen would be as effective for patients with other cranial neuropathies.208 Although anti-infectives may not hasten resolution of seventh cranial nerve palsy associated with B. burgdorferi infection, anti-infectives should be given to prevent further sequelae.208

Lyme Carditis

Oral cefuroxime axetil is used in the treatment of Lyme carditis†.208 The IDSA states that patients with AV heart block and/or myopericarditis associated with early Lyme disease may be treated with a 14-day regimen (range: 14-21 days) of oral or parenteral anti-infectives.208 Although there is no evidence to date to suggest that a parenteral regimen is more effective than an oral regimen for the treatment of Lyme carditis, a parenteral regimen usually is recommended for initial treatment of hospitalized patients; an oral regimen can be used to complete therapy and for the treatment of outpatients.143,182,208,209 When a parenteral regimen is used, IV ceftriaxone or, alternatively, IV cefotaxime or IV penicillin G sodium is recommended.143,182,208,209 When an oral regimen is used, oral doxycycline, oral amoxicillin, or oral cefuroxime axetil is recommended.143,182,208,209

Borrelial Lymphocytoma

Although experience is limited, the IDSA states that available data indicate that borrelial lymphocytoma† may be treated with a 14-day regimen (range 14-21 days) of oral doxycycline, oral amoxicillin, or oral cefuroxime axetil in the dosages used for the treatment of erythema migrans.208

Late Lyme Disease

Lyme Arthritis

Patients with uncomplicated Lyme arthritis† without clinical evidence of neurologic disease generally can be treated with a 28-day regimen of oral doxycycline, oral amoxicillin, or oral cefuroxime axetil.143,208,209 Patients with Lyme arthritis and concomitant neurologic disease should receive a parenteral regimen of IV ceftriaxone or, alternatively, IV cefotaxime or IV penicillin G sodium.143,208 While oral regimens are easier to administer, associated with fewer serious adverse effects, and less expensive than IV regimens, some patients with Lyme arthritis treated with oral anti-infectives have subsequently developed overt neuroborreliosis, which may require IV therapy for successful resolution.208,209 Therefore, additional study is needed to fully evaluate the comparative safety and efficacy of oral versus IV anti-infectives for the treatment of Lyme arthritis.208

In patients who have persistent or recurrent joint swelling after a recommended oral regimen, the IDSA and other clinicians recommend retreatment with the oral regimen or a switch to a parenteral regimen.182,208,209 Some clinicians prefer retreatment with an oral regimen for patients whose arthritis substantively improved but did not completely resolve; these clinicians reserve parenteral regimens for those patients whose arthritis failed to improve or worsened.208 It has been suggested that clinicians should consider allowing several months for joint inflammation to resolve after initial treatment before an additional course of anti-infectives is given.208

Meningitis !!navigator!!

Parenteral cefuroxime has been used in neonates†, children, and adults for the treatment of meningitis caused by susceptible S. pneumoniae , H. influenzae (including ampicillin-resistant strains), N. meningitidis , or S. aureus (penicillinase- and nonpenicillinase-producing strains);7,25,26,43,44,64,159,161 however, cefuroxime is not considered a drug of choice for these infections.58,143,165,217 Treatment failures have been reported when cefuroxime was used in the treatment of meningitis, especially in meningitis caused by H. influenzae .160,162 In addition, while results of some studies in pediatric patients with meningitis indicate that the clinical cure rate with IV cefuroxime is similar to that reported for IV ceftriaxone, the bacteriologic response to cefuroxime appears to be slower, which may increase the risk for hearing loss and neurologic sequelae.159,161 In a study in children 44 days to 16 years of age with acute bacterial meningitis who were randomized to receive empiric therapy with IV ceftriaxone (100 mg/kg once daily) or IV cefuroxime (240 mg/kg daily in 4 doses), all patients in both groups were considered clinically cured; however, the rate of sterilization of CSF after the first 18-36 hours of therapy was higher in those who received ceftriaxone (98%) than in those who received cefuroxime (88%).159 When a cephalosporin is indicated for the treatment of bacterial meningitis, a parenteral third generation cephalosporin (usually ceftriaxone or cefotaxime) generally is recommended.58,143,157,158,165,217

Perioperative Prophylaxis !!navigator!!

IV cefuroxime sodium is used for perioperative prophylaxis in patients undergoing cardiac surgery1,66,193,195,196,197,213,214 and is considered a drug of choice for cardiac procedures (e.g., coronary artery bypass, pacemaker or other cardiac device insertion, ventricular assist devices).71,213 IV cefuroxime also is considered a drug of choice when used alone for perioperative prophylaxis in patients undergoing clean head and neck surgery involving placement of prosthesis (excluding tympanostomy) and when used in conjunction with metronidazole for perioperative prophylaxis in patients undergoing clean-contaminated cancer surgery of the head and neck or other clean-contaminated head and neck procedures (excluding tonsillectomy and functional endoscopic sinus procedures).213

IV cefuroxime also has been used for perioperative prophylaxis in patients undergoing noncardiac thoracic surgery,213 GI or biliary tract surgery,3,6,213 gynecologic or obstetric surgery (e.g., vaginal hysterectomy),1,3,6,213,214 orthopedic procedures,194,213 or heart transplantation.213 However, other anti-infectives (e.g., cefazolin) usually are recommended for perioperative prophylaxis in patients undergoing these procedures.71,213 (See Uses: Perioperative Prophylaxis, in the Cephalosporins General Statement 8:12.06.)

Dosage and Administration ⬆ ⬇

[Section Outline]

Reconstitution and Administration !!navigator!!

Cefuroxime axetil is administered orally.79,215 Cefuroxime sodium is administered by IV injection or infusion or by deep IM injection.1,214 The drug should be given IV rather than IM in patients with septicemia or other severe or life-threatening infections or in patients with lowered resistance, particularly if shock is present.1

Oral Administration

Cefuroxime axetil oral suspension must be administered with food.79 Although cefuroxime axetil film-coated tablets may be given orally without regard to meals,79,215 administration with food maximizes bioavailability of the drug.79,81,82,97,99 (See Pharmacokinetics: Absorption.)

In children aged 3 months to 12 years who are unable to swallow tablets, cefuroxime may be administered as the commercially available oral suspension.79 Although commercially available cefuroxime axetil tablets have been crushed and mixed with food (e.g., applesauce, ice cream),79,88,110 the crushed tablets have a strong, persistent taste and the manufacturers state that the drug should not be administered in this manner.79,215 (See Cautions: Pediatric Precautions.) Cefuroxime axetil tablets also have been allowed to disintegrate in a small amount (60-90 mL) of beverage (e.g., apple juice or milk) and the beverage stirred and ingested immediately followed by additional amounts of bevera disintegration of the tablets is optimal when the beverage is at room temperature.116

Limited data from a study conducted by the manufacturer suggest that cefuroxime axetil is stable for 2 hours at room temperature when added as single 125- or 250-mg tablets to 40 mL of Tropicana® orange juice, Welch's® grape juice, or Nestle's® chocolate milk.123 However, extemporaneous preparation of an oral suspension of the drug intended for multiple dosing currently is not recommended since stability information for more prolonged periods currently is not available116 and because the drug is commercially available as an oral suspension.79

The child's tolerance of the taste of cefuroxime axetil should be ascertained by the clinician and parent, preferably when prescription of the drug is being considered (e.g., while the child is still in the physician's office).79

Reconstitution

Cefuroxime axetil powder for oral suspension should be reconstituted at the time of dispensing by adding the amount of water specified on the bottle to provide a suspension containing 125 or 250 mg of cefuroxime (as cefuroxime axetil) per 5 mL of suspension.79 After tapping the bottle to thoroughly loosen the powder for oral suspension, the water should be added in one portion and the suspension agitated well.79

The suspension should be agitated well just prior to each use and the cap replaced securely after each opening.79

Intermittent IV Injection

For direct intermittent IV injection, vials labeled as containing 750 mg or 1.5 g of cefuroxime should be reconstituted with 8 or 16 mL, respectively, of sterile water for injection to provide solutions containing approximately 90 mg/mL; the entire contents of the vial should be withdrawn for each dose.1

The appropriate dose should then be injected directly into a vein over a 3- to 5-minute period or injected slowly into the tubing of a freely flowing compatible IV solution.1

Intermittent or Continuous IV Infusion

ADD-Vantage® (TwistVial®) vials labeled as containing 750 mg or 1.5 g of cefuroxime should be reconstituted with 50 or 100 mL of 5% dextrose injection, 0.9% sodium chloride injection, or 0.45% sodium chloride injection in a compatible flexible container according to the manufacturer's directions.1

Alternatively, the commercially available Duplex® drug delivery system containing 750 mg or 1.5 g of cefuroxime and 50 mL of dextrose 4.1 or 2.9% injection, respectively, in separate chambers should be reconstituted (activated) according to the manufacturer's directions and administered by IV infusion.214

The 7.5-g pharmacy bulk vial should be reconstituted according to the manufacturer's directions.1 The pharmacy bulk vial is not intended for direct IV infusion.1

Thawed solutions of the commercially available frozen premixed cefuroxime sodium injection should be administered only by intermittent or continuous IV infusion.1 The frozen injection should be thawed at room temperature (25°C) or under refrigeration (5°C); the injection should not be thawed by warming in a water bath or by exposure to microwave radiation.1 Precipitates that may have formed in the frozen injection usually will dissolve with little or no agitation when the injection reaches room temperature; potency is not affected.1 After thawing to room temperature, the injection should be agitated and the container checked for minute leaks by firmly squeezing the bag;1 the container may be fragile and should be handled with care.1 The injection should be discarded if container seals or outlet ports are not intact or leaks are found or if the solution is cloudy or contains an insoluble precipitate.1 Additives should not be introduced into the injection container.1 The injection should not be used in series connections with other plastic containers, since such use could result in air embolism from residual air being drawn from the primary container before administration of fluid from the secondary container is complete.1

Other IV solutions flowing through a common administration tubing or site should be discontinued while cefuroxime is being infused unless the solutions are known to be compatible and the flow rate is adequately controlled.1,214 If an aminoglycoside is administered concomitantly with cefuroxime, the drugs should be administered at separate sites.1,214

Rate of Administration

Intermittent IV infusions of cefuroxime generally are infused over 15-60 minutes.41,44

IM Injection

IM injections of Zinacef® are prepared by adding 3 mL of sterile water for injection to a vial labeled as containing 750 mg of cefuroxime to provide a suspension containing approximately 220 mg/mL.1 The suspension should be shaken gently prior to administration, and the entire contents of the vial should be withdrawn for each dose.1

IM injections should be made deeply into a large muscle mass such as the gluteus or lateral aspect of the thigh.1 The plunger of the syringe should be drawn back before IM injection to ensure that the needle is not in a blood vessel.1

Dosage !!navigator!!

Dosage of cefuroxime axetil is expressed in terms of cefuroxime.79 Cefuroxime axetil tablets and oral suspension are not bioequivalent and are not substitutable on a mg/mg basis.79,215 (See Pharmacokinetics: Absorption.)

Dosage of cefuroxime sodium also is expressed in terms of cefuroxime and is identical for IM or IV administration.1,214

Adult Dosage

General Oral Adult Dosage

For the treatment of uncomplicated skin and skin-structure infections in adults and adolescents 13 years of age or older, the usual oral dosage of cefuroxime given as cefuroxime axetil tablets is 250 or 500 mg twice daily for 10 days.79,215 For the treatment of uncomplicated urinary tract infections (UTIs), the usual oral dosage of cefuroxime given as cefuroxime axetil tablets is 125 or 250 mg twice daily for 7-10 days.79,215

The usual parenteral adult dosage of cefuroxime given as cefuroxime sodium is 750 mg to 1.5 g every 8 hours.1,214 Uncomplicated UTIs, skin and skin structure infections, and uncomplicated pneumonia in adults generally respond to a parenteral dosage of 750 mg every 8 hours.1,214 Severe or complicated infections or bone and joint infections in adults generally require 1.5 g every 8 hours and life-threatening infections or infections caused by less susceptible organisms may require 1.5 g every 6 hours.1,214 Dosage of parenteral cefuroxime for the treatment of bacterial meningitis in adults should not exceed 3 g every 8 hours.1,214

Pharyngitis and Tonsillitis

For the treatment of pharyngitis and tonsillitis caused by Streptococcus pyogenes (group A β-hemolytic streptococci) in adults and adolescents 13 years of age or older, the usual oral dosage of cefuroxime given as cefuroxime axetil tablets is 250 mg twice daily for 10 days.79,215

Respiratory Tract Infections

For the treatment of acute bacterial maxillary sinusitis in adults and adolescents 13 years of age or older, the usual oral dosage of cefuroxime given as cefuroxime axetil tablets is 250 mg twice daily for 10 days.79,215 For the treatment of acute bacterial exacerbations of chronic bronchitis and secondary bacterial infections of acute bronchitis in adults and adolescents 13 years of age or older, the usual oral dosage of cefuroxime given as cefuroxime axetil tablets is 250 or 500 mg twice daily.79,215 The manufacturers recommend that therapy be continued for 10 days for the treatment of acute bacterial exacerbations of chronic bronchitis or for 5-10 days for the treatment of secondary bacterial infections of acute bronchitis.79,215 While there is evidence that a 5-day regimen of cefuroxime axetil is as effective as a 10-day regimen of the drug for the treatment of secondary bacterial infections of acute bronchitis,79,124,215 efficacy of the shorter regimen for the treatment of acute exacerbations of chronic bronchitis has not been established.79,215

If cefuroxime axetil is used for the outpatient treatment of community-acquired pneumonia† (CAP) in adults, the American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA) recommend an oral dosage of 500 mg of cefuroxime twice daily.51 For empiric treatment of CAP, cefuroxime must be used in conjunction with other anti-infectives.51 (See Community-acquired Pneumonia under Uses: Respiratory Tract Infections.)

For the treatment of uncomplicated pneumonia in adults, the manufacturers recommend a parenteral cefuroxime dosage of 750 mg every 8 hours.1,214 In severe or complicated infections, a dosage of 1.5 g every 8 hours is recommended.1,214

Gonorrhea and Associated Infections

For the parenteral treatment of uncomplicated gonorrhea caused by Neisseria gonorrhoeae , including penicillinase-producing strains (PPNG), the manufacturer of Zinacef® recommends that adults receive a single 1.5-g IM dose of cefuroxime and 1 g of oral probenecid; the cefuroxime dose should be divided and given at 2 different sites.1 For the parenteral treatment of disseminated gonococcal infections, the manufacturers recommend that adults receive 750 mg of cefuroxime IM or IV every 8 hours.1,214

For the oral treatment of uncomplicated urethral or endocervical gonorrhea caused by N. gonorrhoeae or for the oral treatment of uncomplicated rectal gonorrhea in females caused by nonpenicillinase-producing strains of the organism, adults and adolescents 13 years of age or older have received a single 1-g dose of cefuroxime.79,125,144,215

The US Centers for Disease Control and Prevention (CDC) does not recommend oral or parenteral cefuroxime for the treatment of gonococcal infections.68 (See Uses: Gonorrhea and Associated Infections.)

Lyme Disease

For the treatment of early Lyme disease manifested as erythema migrans, the manufacturers recommend that adults and adolescents 13 years of age or older receive 500 mg of oral cefuroxime twice daily for 20 days.79,215

IDSA and other clinicians recommend that adults receive 500 mg of oral cefuroxime twice daily for 14 days (range: 14-21 days) for the treatment of early localized or early disseminated Lyme disease manifested as erythema migrans, in the absence of specific neurologic involvement or advanced atrioventricular (AV) heart block.182,208,209

If an oral regimen is used for the treatment of early neurologic Lyme disease† in patients with cranial nerve palsy alone without clinical evidence of meningitis (see Early Neurologic Lyme Disease under Uses: Lyme Disease), Lyme carditis†, or borrelial lymphocytoma†, the IDSA recommends that adults receive 500 mg of oral cefuroxime twice daily for 14 days (range: 14-21 days).208

If an oral regimen is used for the treatment of uncomplicated Lyme arthritis† in patients without clinical evidence of neurologic disease (see Late Lyme Disease under Uses: Lyme Disease), the IDSA recommends that adults receive 500 mg of oral cefuroxime twice daily for 28 days.208

Perioperative Prophylaxis

For perioperative prophylaxis in adults undergoing open-heart surgery, the manufacturers recommend that a single 1.5-g dose of cefuroxime be given IV at the time of induction of anesthesia and every 12 hours thereafter for a total dosage of 6 g (i.e., up to 48 hours).1,214 Some experts recommend that 1.5 g of cefuroxime be given within 1 hour prior to surgical incision and that additional 1.5-g doses be given every 4 hours during prolonged procedures (longer than 4 hours) or if major blood loss occurs.71,213 Various data support a duration of perioperative prophylaxis ranging from a single preoperative dose to continuation of prophylaxis for 24 hours postoperatively; there is no evidence of benefit beyond 48 hours71 and no evidence to support continuing prophylaxis until all drains and indwelling catheters are removed.71,213

If cefuroxime is used for perioperative prophylaxis in other clean-contaminated or potentially contaminated surgery (e.g., vaginal hysterectomy), the manufacturers recommend that adults receive 1.5 g of cefuroxime IV just prior to surgery (approximately 30-60 minutes before the initial incision) and, in lengthy operations, 750 mg of the drug IV or IM every 8 hours.1,214 For most procedures, postoperative doses are usually unnecessary and may increase the risk of bacterial resistance.71 If the procedure is prolonged (longer than 4 hours) or if major blood loss occurs, 1.5-g doses of cefuroxime may be given IV every 4 hours.71,213

Pediatric Dosage

Cefuroxime axetil film-coated tablets and oral suspension are not bioequivalent and are not substitutable on a mg/mg basis. 79,215(See Pharmacokinetics: Absorption.)

General Pediatric Dosage

For the treatment of most susceptible infections (except bone and joint infections or meningitis) in children 3 months of age or older, the manufacturers recommend a cefuroxime dosage of 50-100 mg/kg daily given IM or IV in equally divided doses every 6-8 hours; the manufacturer states that 100 mg/kg should be given IM or IV for more severe infections.1,214 The IM or IV dosage of cefuroxime recommended by the manufacturers for the treatment of bone and joint infections in children 3 months of age or older is 150 mg/kg daily in 3 divided doses every 8 hours.1,214

The American Academy of Pediatrics (AAP) recommends that neonates 7 days of age or younger receive IM or IV cefuroxime in a dosage of 50 mg/kg every 12 hours, regardless of weight.143 Neonates 8-28 days of age should receive a dosage of 50 mg/kg every 8-12 hours if they weigh 2 kg or less or 50 mg/kg every 8 hours if they weigh more than 2 kg.143

For pediatric patients beyond the neonatal period, the AAP recommends an IM or IV cefuroxime dosage of 75-100 mg/kg daily given in 3 equally divided doses for the treatment of mild to moderate infections or 100-200 mg/kg daily in 3 or 4 equally divided doses for the treatment of severe infections.143 These clinicians recommend that children beyond the neonatal period receive oral cefuroxime in a dosage of 20-30 mg/kg daily in 2 equally divided doses for the treatment of mild to moderate infections.143 The AAP states that oral cefuroxime is inappropriate for the treatment of severe infections.143

Acute Otitis Media

For the treatment of acute otitis media in children 3 months to 12 years of age who can swallow tablets whole, the usual oral dosage of cefuroxime as cefuroxime axetil film-coated tablets is 250 mg twice daily for 10 days.79,215 Alternatively, children 3 months to 12 years of age with acute otitis media can receive cefuroxime as cefuroxime axetil oral suspension in a dosage of 30 mg/kg daily (maximum 1 g daily) given in 2 divided doses for 10 days.79

Cefuroxime axetil has been administered in a 5-day regimen† for the treatment of acute otitis media in children 3 months to 12 years of age.198,200 The AAP states that oral anti-infective regimens of less than 10 days' duration are not recommended for the treatment of AOM in children younger than 2 years of age or in patients with severe symptoms.184

Pharyngitis and Tonsillitis

For the treatment of pharyngitis and tonsillitis caused by S. pyogenes (group A β-hemolytic streptococci) in children 3 months to 12 years of age who can swallow tablets whole, the usual oral dosage of cefuroxime as cefuroxime axetil film-coated tablets is 125 mg every 12 hours for 10 days.79 Alternatively, children 3 months to 12 years of age may receive cefuroxime as cefuroxime axetil oral suspension in a dosage of 20 mg/kg daily (maximum 500 mg daily) in 2 divided doses for 10 days.79

Acute Sinusitis

For the treatment of acute bacterial maxillary sinusitis in children 3 months to 12 years of age who can swallow tablets whole, the usual oral dosage of cefuroxime as cefuroxime axetil film-coated tablets is 250 mg twice daily for 10 days.79,215 Alternatively, children 3 months to 12 years of age may receive cefuroxime as cefuroxime axetil oral suspension in a dosage of 30 mg/kg daily (maximum 1 g daily) given in 2 divided doses for 10 days.79

Lyme Disease

For the treatment of early localized or early disseminated Lyme disease manifested as erythema migrans, in the absence of specific neurologic involvement or advanced AV heart block, the manufacturer, IDSA, AAP, and other clinicians recommend that children receive oral cefuroxime in a dosage of 30 mg/kg daily (up to 1 g daily) administered in 2 divided doses for 14 days (range 14-21 days).141,143,181,182,208,209

If an oral regimen is used for the treatment of early neurologic Lyme disease† in patients with cranial nerve palsy alone without clinical evidence of meningitis (see Early Neurologic Lyme Disease under Uses: Lyme Disease), Lyme carditis†, or borrelial lymphocytoma†, the IDSA recommends that children receive oral cefuroxime in a dosage of 30 mg/kg daily in 2 equally divided doses (up to 500 mg per dose) for 14 days (range 14-21 days).208

If an oral regimen is used for the treatment of uncomplicated Lyme arthritis† in patients without clinical evidence of neurologic disease (see Late Lyme Disease under Uses: Lyme Disease), the IDSA and AAP recommend that children receive oral cefuroxime in a dosage of 30 mg/kg daily in 2 equally divided doses (up to 500 mg per dose) for 28 days.143,208

Meningitis

For the treatment of bacterial meningitis in children 3 months of age or older, the usual dosage of IV cefuroxime is 200-240 mg/kg daily given in divided doses every 6-8 hours.1,19,49,214

Skin and Skin Structure Infections

For the treatment of impetigo in children 3 months to 12 years of age, the usual oral dosage of cefuroxime as cefuroxime axetil oral suspension is 30 mg/kg daily (maximum 1 g daily) in 2 divided doses for 10 days.79

Perioperative Prophylaxis

If cefuroxime is used for perioperative prophylaxis in children, some clinicians recommend that 50 mg/kg of cefuroxime be given within 1 hour prior to surgical incision.213 If the procedure is prolonged (longer than 4 hours) or if major blood loss occurs, additional 50-mg/kg doses may be given IV.213 Various data support a duration of perioperative prophylaxis ranging from a single preoperative dose to continuation of prophylaxis for 24 hours postoperatively; there is no evidence of benefit beyond 48 hours71 and no evidence to support continuing prophylaxis until all drains and indwelling catheters are removed.71,213

Duration of Therapy

The duration of cefuroxime therapy depends on the type of infection but should generally be continued for at least 48-72 hours after the patient becomes afebrile or evidence of eradication of the infection is obtained.1,214

For the treatment of uncomplicated UTIs, the manufacturers recommend that therapy with cefuroxime axetil tablets be continued for 7-10 days.79,215 For the treatment of uncomplicated skin and skin-structure infections, or acute otitis media caused by susceptible organisms, the manufacturers recommend that therapy with cefuroxime axetil tablets be continued for 10 days.79,215

Chronic urinary tract infections may require several weeks of cefuroxime therapy, and bacteriologic and clinical assessments should be made frequently during therapy and for several months after the drug is discontinued.1,214 When cefuroxime is used in the treatment of staphylococcal and other infections involving a collection of pus, surgical drainage should be performed when indicated.1,214

Dosage in Renal Impairment !!navigator!!

Modification of usual dosage of parenteral cefuroxime is unnecessary in patients with creatinine clearances greater than 20 mL/minute.1,18,214 However, in patients with creatinine clearances of 20 mL/minute or less, doses and/or frequency of administration of parenteral cefuroxime must be modified in response to the degree of renal impairment, severity of the infection, and susceptibility of the causative organism.1,112,113,114,115,214 The manufacturers and some clinicians recommend that adults with creatinine clearances of 10-20 mL/minute receive 750 mg IM or IV every 12 hours and that adults with creatinine clearances less than 10 mL/minute receive 750 mg IM or IV every 24 hours.1,112,113,114,214 In children with impaired renal function, the manufacturers recommend that the frequency of administration of parenteral cefuroxime be modified based on the recommendations for adults with impaired renal function.1,214

In patients undergoing hemodialysis, a supplemental dose of parenteral cefuroxime should be given after each dialysis period.1,3,30,214

Safety and efficacy of oral cefuroxime axetil in patients with renal impairment have not been established.79,215

Cautions ⬆ ⬇

[Section Outline]

Adverse effects reported with cefuroxime axetil and cefuroxime sodium are similar to those reported with other cephalosporins.3,10,79

Dermatologic and Sensitivity Reactions !!navigator!!

Hypersensitivity reactions have been reported in less than 1% of patients receiving cefuroxime axetil or cefuroxime sodium.1,79,87 These reactions include rash (e.g., morbilliform),1,6,7,9,30,79,82,94,96 fever,7 pruritus,1,6,79,104 erythema,79 urticaria,1,79 Stevens-Johnson syndrome,1,79 erythema multiforme,1,79 toxic epidermal necrolysis,1,79 serum sickness-like reactions,79 angioedema,79 and anaphylaxis.1,79 At least one case of severe bronchospasm has been reported in a patient who received cefuroxime axetil.79 Positive direct antiglobulin (Coombs') test results have also been reported in a few patients receiving oral or parenteral cefuroxime;1,79,103 however, it is not clear whether the mechanism of this reaction is immunologic in nature. If a severe hypersensitivity reaction occurs during cefuroxime therapy, the drug should be discontinued and the patient given appropriate therapy (e.g., epinephrine, corticosteroids, maintenance of an adequate airway, oxygen) as indicated.1,79

There is clinical and laboratory evidence of partial cross-allergenicity among cephalosporins and other β-lactam antibiotics including penicillins and cephamycins; however, the true incidence of cross-allergenicity among these anti-infectives has not been established.30,178 When cefuroxime axetil was used in patients with a history of delayed hypersensitivity reactions to penicillins and no history of hypersensitivity to cephalosporins, a delayed hypersensitivity reaction occurred in about 3% of these patients.79 The manufacturer states that when cefuroxime sodium was used in patients with a history of hypersensitivity to penicillin, rash reportedly occurred in 4.4-6.7% of these patients.30

Local Effects !!navigator!!

The most frequent adverse reactions to IM or IV cefuroxime sodium are local reactions at the injection site.1,3,6 Mild to moderate pain, which persists for less than 5 minutes, has been reported in up to 95% of patients following IM administration of cefuroxime.3,9,19,20,21,28,30 Severe pain has been reported occasionally.3,30 IM injections of cefuroxime reportedly are less painful when the drug is administered as a suspension rather than a solution and are also less painful when the injection is given into the buttock rather than the thigh.30

Thrombophlebitis reportedly occurs in approximately 2%1 of patients receiving cefuroxime IV.1,6,7

GI Effects !!navigator!!

Nausea and vomiting have been reported in 2.6-6.7%79 and diarrhea or loose stools have been reported in 3.7-10.6%79 of patients receiving oral cefuroxime axetil.79,82,84,85,87,88,89,91,93,94,95,96,102,103,104,105,108 A strong, persistent, bitter taste has been reported when cefuroxime axetil was administered as crushed tablets79 (see Pediatric Precautions). In addition, up to 5% of children receiving the commercially available oral suspension of cefuroxime axetil disliked the taste of the suspension; during clinical trials, discontinuance of therapy because of the taste of the suspension or other problems with administration occurred in 1.4% of patients.79

Gagging,88 epigastric burning,84 GI bleeding,92 abdominal pain,79 flatulence,79 GI infection,79 ptyalism,79 indigestion,79 mouth ulcers,79 swollen tongue,79 anorexia,79 thirst,79 dyspepsia,79 and stomach cramps79,95 also have been reported in patients receiving the drug orally.

The frequency of adverse GI effects (particularly diarrhea) may be greater with oral cefuroxime axetil than with oral cefaclor,88,94,95,99,102,103,116 and nausea appears to be more common when oral cefuroxime axetil is used concomitantly with oral probenecid than when the antibiotic is used alone.85 In addition, adverse GI effects were reported more frequently with previously available oral formulations of cefuroxime axetil,82,84,87,90,102,103,104,105,116 and, in part, prompted several reformulations of the product.82,90,105,116 Adverse GI effects including nausea1 and diarrhea1,7 have been reported in less than 1% of patients receiving IM or IV cefuroxime sodium.1

Clostridium difficile-associated Diarrhea and Colitis

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile .185,186,187

C. difficile infection (CDI) and C. difficile -associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) have been reported with nearly all anti-infectives, including cefuroxime, and may range in severity from mild diarrhea to fatal colitis.1,31,79,104,105,108,185,186,187,214,215C. difficile produces toxins A and B which contribute to the development of CDAD;1,79,185,214,215 hypertoxin-producing strains of C. difficile are associated with increased morbidity and mortality since they may be refractory to anti-infectives and colectomy may be required.1,79,214,215

CDAD should be considered in the differential diagnosis in patients who develop diarrhea during or after anti-infective therapy and managed accordingly.1,79,185,186,187,214,215 Careful medical history is necessary since CDAD has been reported to occur as late as 2 months or longer after anti-infective therapy is discontinued.1,79,185,214,215

If CDAD is suspected or confirmed, anti-infectives not directed against C. difficile should be discontinued whenever possible.1,79,185,214,215 Patients should be managed with appropriate supportive therapy (e.g., fluid and electrolyte management, protein supplementation), anti-infective therapy directed against C. difficile (e.g., metronidazole, vancomycin), and surgical evaluation as clinically indicated.1,79,185,186,187,214,215

Hematologic Effects !!navigator!!

Decreased hemoglobin concentration1,3,9,30 and decreased hematocrit1,9 have been reported in about 10% of patients receiving cefuroxime.1 Transient eosinophilia occurs less frequently,1,3,30,79,91,92,95,103,104 and transient neutropenia, pancytopenia,79 thrombocytopenia, and leukopenia occur rarely.1,79 Thrombocytosis,103,104 lymphocytosis,91,103 hemolytic anemia,79 and increased prothrombin time79 also have been reported.

CNS Effects !!navigator!!

Headache,79 dizziness,79 somnolence or sleepiness,79,168 hyperactivity,79 irritable behavior,79 seizures,1,79,168 myoclonic jerks,168 and generalized hyperexcitability168 have been reported rarely in patients receiving cefuroxime.79

A psychotic reaction, consisting of disorientation, fluctuating consciousness, and episodes of restlessness, agitation, and anxiety, occurred in a geriatric patient who received IV cefuroxime sodium; symptoms resolved within 24 hours after the drug was discontinued.155 Some patients who experienced adverse CNS effects while receiving cefuroxime had preexisting renal impairment.155,168

Hepatic Effects !!navigator!!

Transient increases in serum AST (SGOT), ALT (SGPT), alkaline phosphatase, LDH, and bilirubin concentrations have been reported in less than 5% of patients receiving oral or parenteral cefuroxime.1,3,9,28,30,79 Jaundice has been reported rarely.79

Renal and Genitourinary Effects !!navigator!!

Acute renal failure and interstitial nephritis have been reported rarely in patients receiving cefuroxime.1,154 Although a causal relationship has not been established, transient increases in BUN and/or serum creatinine concentrations and decreased creatinine clearance have been reported in a few patients receiving cefuroxime.1,79,104 Bilateral renal cortical necrosis that appeared to be a hypersensitivity reaction has been reported in at least one patient who received cefuroxime axetil.152

Urinary tract infection,79 kidney pain,79 urethral pain or bleeding,79 dysuria,79 vaginitis,79 vaginal candidiasis,79 vulvovaginal pruritus, and vaginal discharge or irritation79 have been reported in less than 1% of patients receiving oral cefuroxime axetil therapy.79

Other Adverse Effects !!navigator!!

Jarisch-Herxheimer reaction has occurred in 5.6% of patients receiving cefuroxime axetil for the treatment of Lyme disease.79,215 In a clinical study in patients with early Lyme disease, the Jarisch-Herxheimer reaction occurred in 11.8% of patients receiving cefuroxime axetil and 11.5% of patients receiving doxycycline.62 These transient reactions generally last only 1-2 days.62

Overgrowth with nonsusceptible organisms (e.g., perianal, oral, or vaginal candidiasis; pseudomembranous colitis; superinfection) has occurred in patients receiving cefuroxime sodium or cefuroxime axetil.1,31,79,92,95,99,101,103,104,105 (See Cautions: GI Effects and also see Precautions and Contraindications.)

Mild to severe hearing loss has been reported in a few pediatric patients receiving cefuroxime sodium for the treatment of meningitis.1 Persistence of positive CSF cultures at 18-36 hours has been observed with cefuroxime sodium injection; however, the clinical relevance of this finding is unknown.1

Muscle spasm of the neck, muscle cramps or stiffness,79 chest pain or tightness,79 shortness of breath,79 tachycardia,79 chills,79 lockjaw-type reaction,79 viral illness,79 upper respiratory infection,79 sinusitis,79 fever,79 cough,79 joint swelling,79 and arthralgia79 have been reported in less than 1% of patients receiving oral cefuroxime axetil therapy.79 Diaper rash has been reported in 3.4% of pediatric patients receiving cefuroxime axetil as the commercially available oral suspension.79

Precautions and Contraindications !!navigator!!

Prior to initiation of cefuroxime therapy, careful inquiry should be made concerning previous hypersensitivity reactions to cephalosporins, penicillins, or other drugs.1,79,215 Cefuroxime axetil and cefuroxime sodium are contraindicated in patients who are hypersensitive to cefuroxime or other cephalosporins and should be used with caution in patients with a history of hypersensitivity to penicillins.1,79,215 Use of cephalosporins should be avoided in patients who have had an immediate-type (anaphylactic) hypersensitivity reaction to penicillins.178,179,215 Although it has not been definitely proven that allergic reactions to antibiotics are more frequent in atopic individuals,38 the manufacturer states that parenteral cefuroxime should be used with caution in patients with a history of allergy, particularly to drugs.1

To reduce development of drug-resistant bacteria and maintain effectiveness of cefuroxime and other antibacterials, the drug should be used only for the treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.1,79,214,215 When selecting or modifying anti-infective therapy, results of culture and in vitro susceptibility testing should be used.1,79,214,215 In the absence of such data, local epidemiology and susceptibility patterns should be considered when selecting anti-infectives for empiric therapy.1,79,214,215

Patients should be advised that antibacterials (including cefuroxime) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).1,79,214,215 Patients also should be advised about the importance of completing the full course of therapy, even if feeling better after a few days, and that skipping doses or not completing therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with cefuroxime or other antibacterials in the future.1,79,214,215

As with other anti-infectives, prolonged use of cefuroxime axetil or cefuroxime sodium may result in overgrowth of nonsusceptible organisms.1,31,79,88,92,101,103,104,105,214 Careful observation of the patient during cefuroxime therapy is essential.1,79,214 If suprainfection or superinfection occurs, appropriate therapy should be instituted.1,79,214

Individuals with phenylketonuria (i.e., homozygous genetic deficiency of phenylalanine hydroxylase) and other individuals who must restrict their intake of phenylalanine should be warned that Ceftin® oral suspensions containing 125 or 250 mg of cefuroxime per 5 mL contains aspartame (NutraSweet®), which is metabolized in the GI tract to provide 11.8 or 25.2 mg of phenylalanine/5 mL, respectively.79

Like other dextrose-containing solutions, the commercially available Duplex® drug delivery system containing 750 mg or 1.5 g of cefuroxime and 50 mL of dextrose injection should be used with caution in patients with overt or known subclinical diabetes mellitus or in patients with carbohydrate intolerance for any reason.214

Because CDAD has been reported with the use of cefuroxime and other cephalosporins, it should be considered in the differential diagnosis of patients who develop diarrhea during or after cefuroxime therapy.1,79,185,186,187,214,215 (See Clostridium difficile-associated Diarrhea and Colitis under Cautions: GI Effects.) Patients should be advised that diarrhea is a common problem caused by anti-infectives and usually resolves when the drug is discontinued; however, they should contact a clinician if watery and bloody stools (with or without stomach cramps and fever) occur during or as late as 2 months or longer after the last dose.1,79,214,215 Cefuroxime should be used with caution in patients with a history of GI disease, particularly colitis.1,79,214,215 The safety and efficacy of cefuroxime axetil therapy in patients with GI malabsorption have not been established.79

Although cefuroxime sodium only rarely causes adverse renal effects, the manufacturers state that renal function should be monitored during therapy with the drug, especially when maximum dosage is used in seriously ill patients.1

Safety and efficacy of oral cefuroxime axetil in patients with renal impairment have not been established.79,215 Because serum concentrations of cefuroxime are higher and more prolonged in patients with renal impairment than in patients with normal renal function, dose and/or frequency of administration of parenteral cefuroxime sodium should be decreased in patients with transient or persistent renal impairment.1,214 (See Dosage in Renal Impairment in Dosage and Administration: Dosage.)

Several cephalosporins (including cefuroxime) have been associated with the development of seizures, particularly in patients with renal impairment, in whom dosage of the drug was not reduced.1,79,214 If seizures associated with cefuroxime develop, the drug should be discontinued and anticonvulsant therapy initiated as clinically indicated.1,79,214

Because some cephalosporins have been associated with a decrease in prothrombin activity, the manufacturers state that prothrombin time (PT) should be monitored when cefuroxime is used in patients with renal or hepatic impairment, in patients with poor nutritional status, in patients receiving a protracted course of anti-infective therapy, or in those previously stabilized on anticoagulant therapy.1,79,215 Vitamin K should be administered if indicated.1,79,215

Pediatric Precautions !!navigator!!

Safety and efficacy of oral cefuroxime axetil79,215 or parenteral cefuroxime sodium1,214 in children younger than 3 months of age have not been established.

In vitro studies indicate that cefuroxime does not appear to displace bilirubin appreciably from albumin binding sites in neonates†.111

Cefuroxime Axetil

The manufacturers state that safety and efficacy of cefuroxime axetil for the treatment of acute bacterial maxillary sinusitis in pediatric patients 3 months to 12 years of age have been established based on safety and efficacy of the drug in adults.79,215 In addition, use of cefuroxime axetil in pediatric patients is supported by pharmacokinetic and safety data in adult and pediatric patients, clinical and microbiologic data from adequate and well-controlled studies of the treatment of acute bacterial maxillary sinusitis in adults and acute otitis media with effusion in pediatric patients, and postmarketing surveillance of adverse effects.79,215

Cefuroxime axetil tablets and oral suspension generally are well tolerated in children aged 3 months to 12 years.79 Cefuroxime axetil has a strong, persistent, bitter taste and complaints caused by the taste were reported in up to 66% of children who received the drug as crushed tablets79,82,99,101 and vomiting was induced aversively in some of these children.101 This bitter taste and/or problems with administering the drug required discontinuance of such cefuroxime axetil therapy in 2-28% of children in clinical trials.79 Although discontinuance of therapy with the suspension because of its taste or other problems with administration occurred in 1.4% of children receiving the oral suspension, the commercially available oral suspension should be used in children who cannot swallow the tablets whole.79

Cefuroxime Sodium

To avoid overdosage, the commercially available Duplex® drug delivery system containing 750 mg or 1.5 g of cefuroxime should not be used in pediatric patients only if the entire 750-mg or 1.5-g dose in the container is required.214

Geriatric Precautions !!navigator!!

In clinical studies of cefuroxime axetil, 375 patients were 65 years of age or older and 151 were 75 years of age or older.79,215 There were no apparent differences in safety or effectiveness between these individuals and younger adults.79,215 Although the group of patients aged 65 years or older experienced a lower incidence of some adverse effects (e.g., vaginal candidiasis, GI effects) compared with patients 12-64 years of age, no clinically important differences were observed between geriatric and younger patients and there have been no reports of differences in response in either group.79,215

In clinical studies of cefuroxime sodium involving over 1900 patients, approximately 47% of the patients were 65 years of age or older and 22% were 75 years of age or older.1,214 Although no overall differences in efficacy or safety were observed between geriatric and younger patients, and other clinical experience revealed no evidence of age-related differences, the possibility that some geriatric patients may exhibit increased sensitivity to the drug cannot be ruled out.1,214

Cefuroxime is substantially excreted by the kidney, and renal elimination of the drug may be decreased79,214 and the risk of severe adverse reactions may be increased in patients with impaired renal function.1,214 Limited data indicate that mean serum elimination half-life of cefuroxime is prolonged in geriatric patients (mean age: 83.9 years) who have a mean creatinine clearance of approximately 35 mL/minute.79 Despite this prolonged elimination, the manufacturers state that age-based dosage adjustment does not appear to be necessary.79,215 However, because geriatric patients are more likely to have decreased renal function, dosage should be selected with caution in these patients and monitoring of renal function may be useful.1,214

Mutagenicity and Carcinogenicity !!navigator!!

No evidence of mutagenicity was observed with cefuroxime in various in vitro and in vivo test systems, including the mouse lymphoma assay, micronucleus test, and bacterial mutation tests.1,79 Cefuroxime produced positive results in the in vitro chromosome aberration assay.1,79 Studies have not been performed to date to evaluate the carcinogenic potential of cefuroxime.1,79

Pregnancy, Fertility, and Lactation !!navigator!!

Pregnancy

Reproduction studies in mice and rabbits using cefuroxime sodium in dosages up to 6 and 2 times the usual human dosage based on mg/m2, respectively, and reproduction studies in mice and rats using cefuroxime axetil in dosages up to 14 and 9 times, respectively, the usual human dosage based on mg/m2 have not revealed evidence of impaired fertility or harm to the fetus.1,79,215 There are no adequate and controlled studies to date using cefuroxime in pregnant women, and cefuroxime axetil and cefuroxime sodium should be used during pregnancy only when clearly needed.1,79,215 Cefuroxime axetil has not been studied for use during labor and delivery.79,215

Lactation

Because cefuroxime is distributed into milk, cefuroxime axetil and cefuroxime sodium should be used with caution in nursing women.1,79,214,215

Drug Interactions ⬆ ⬇

[Section Outline]

Aminoglycosides !!navigator!!

In vitro studies indicate that the antibacterial activity of cefuroxime and aminoglycosides may be additive or synergistic against some organisms including Enterobacter ,2,6 Escherichia coli ,2,6 Klebsiella ,2,6 Proteus mirabilis ,6 and Serratia marcescens .2,6

Concurrent use of aminoglycosides and certain cephalosporins reportedly may increase the risk of nephrotoxicity during therapy.1,16 Although this effect has not been reported to date with cefuroxime, the possibility that nephrotoxicity may be potentiated should be considered if the drug is used concomitantly with an aminoglycoside.1,16,30

Diuretics !!navigator!!

The manufacturers state that cefuroxime should be used with caution in patients receiving diuretics because concurrent use of these drugs may increase the risk of adverse renal effects.1

Estrogens or Progestins !!navigator!!

Cefuroxime axetil may affect gut flora, leading to decreased estrogen reabsorption and reduced efficacy of oral contraceptives containing estrogen and progestin.1,79,215

Probenecid !!navigator!!

Oral probenecid administered shortly before or concomitantly with cefuroxime usually slows the rate of tubular secretion of cefuroxime and produces higher and more prolonged serum concentrations of cefuroxime.1,2,21,30 This effect has been used to therapeutic advantage in the treatment of gonorrhea.1 Peak serum concentrations of cefuroxime and the half-life of the drug are reportedly increased by up to 30% when probenecid is administered concomitantly;1,2,21,30,79 the area under the concentration-time curve (AUC) of cefuroxime is increased by about 50%.79 Concomitant administration of probenecid also reportedly decreases the apparent volume of distribution of cefuroxime by about 20%.3

Other Information ⬆ ⬇

[Section Outline]

Laboratory Test Interferences

Immunohematology Tests !!navigator!!

Positive direct antiglobulin (Coombs') test results have been reported in a few patients receiving cefuroxime axetil or cefuroxime sodium.1,79,103 This reaction may interfere with hematologic studies or transfusion cross-matching procedures.

Tests for Glucose !!navigator!!

Like most other cephalosporins, cefuroxime reportedly causes false-positive results in urine glucose determinations using cupric sulfate solution (Benedict's reagent, Clinitest®); however, glucose oxidase tests (Clinistix®) are unaffected by the drug.1,79

Cefuroxime may cause false-negative results when ferricyanide methods are used to determine blood glucose concentrations.1,79

Tests for Creatinine !!navigator!!

Although some cephalosporins reportedly cause falsely elevated serum or urine creatinine values when the Jaffé reaction is used, cefuroxime does not appear to interfere with this laboratory test.1,79

Acute Toxicity

Limited information is available on the acute toxicity of cefuroxime in humans.1 Overdosage of cephalosporins can cause CNS irritation leading to seizures.1 If acute overdosage of cefuroxime occurs, hemodialysis and/or peritoneal dialysis can be used to enhance elimination of the drug from the body.1

Mechanism of Action

Cefuroxime is usually bactericidal in action.2 Like other cephalosporins, the antibacterial activity of the drug results from inhibition of mucopeptide synthesis in the bacterial cell wall.2 For information on the mechanism of action of cephalosporins, see Mechanism of Action in the Cephalosporins General Statement 8:12.06.

Spectrum

Based on its spectrum of activity, cefuroxime is classified as a second generation cephalosporin.3,6,10,18,48 For information on the classification of cephalosporins and closely related β-lactam antibiotics based on spectra of activity, see Spectrum in the Cephalosporins General Statement 8:12.06.

Like other currently available second generation cephalosporins (e.g., cefaclor, cefamandole, cefprozil), cefuroxime generally is more active in vitro against gram-negative bacteria than first generation cephalosporins but has a narrower spectrum of activity against gram-negative bacteria than third generation cephalosporins.4,10,18,30,48 The spectrum of activity of cefuroxime resembles that of cefamandole and, to a lesser extent, that of cefoxitin.13,14 Cefuroxime is more resistant to hydrolysis by β-lactamases than cefamandole and is active against some strains of gram-negative bacteria (e.g., Escherichia coli, Enterobacter, Klebsiella, Neisseria ) that are resistant to cefamandole.6,8,30 Cefoxitin is active against several organisms that generally are resistant to cefuroxime (e.g., Serratia marcescens, Proteus vulgaris, Bacteroides fragilis ).6,13,14

In Vitro Susceptibility Testing !!navigator!!

Results of in vitro cefuroxime susceptibility tests are not generally affected by inoculum size, culture media, presence of serum, or pH.4,6,30 However, results of susceptibility tests for some gram-negative bacilli (e.g., Morganella morganii , Bacteroides fragilis , Serratia ) may be affected by the size of the inoculum.13,15,30

Different interpretive criteria are used for defining in vitro susceptibility of certain organisms to cefuroxime axetil and cefuroxime sodium, and the appropriate zone diameter or MIC categories should be used when determining whether or not an isolate is susceptible to the parenteral or oral preparation of the drug.63

Strains of staphylococci resistant to penicillinase-resistant penicillins (oxacillin-resistant [methicillin-resistant] staphylococci) should be considered resistant to cefuroxime and cefuroxime axetil, although results of in vitro susceptibility tests may indicate that the organisms are susceptible to the drug.63 In addition, β-lactamase-negative, ampicillin-resistant (BLNAR) strains of H. influenzae should be considered resistant to cefuroxime and cefuroxime axetil despite the fact that results of in vitro susceptibility tests may indicate that the organisms are susceptible to the drug.63

For information on interpreting results of in vitro susceptibility testing (disk susceptibility tests, dilution susceptibility tests) when cefuroxime and cefuroxime axetil susceptibility testing is performed according to the standards of the Clinical and Laboratory Standards Institute (CLSI; formerly National Committee for Clinical Laboratory Standards [NCCLS]), see Spectrum: In Vitro Susceptibility Testing, in the Cephalosporins General Statement 8:12.06.

Gram-Positive Aerobic Bacteria !!navigator!!

In vitro, cefuroxime concentrations of 0.5-1 mcg/mL inhibit most strains of Staphylococcus aureus (including penicillinase-producing and nonpenicillinase-producing strains)3,4,6,30 and concentrations of 1-2 mcg/mL inhibit most strains of S. epidermidis .2,3,30 Most strains of staphylococci resistant to penicillinase-resistant penicillins also are resistant to cefuroxime.4,6

In vitro, α-hemolytic2,3,4,30 and β-hemolytic streptococci4,30 are usually inhibited by cefuroxime concentrations of 0.05-0.5 mcg/mL and Streptococcus pneumoniae is usually inhibited by concentrations of 0.01-0.13 mcg/mL.3,4,30 Most strains of enterococci, including E. faecalis (formerly S. faecalis ), are generally resistant to cefuroxime.1,2,4,6,30

Listeria monocytogenes generally is resistant to cefuroxime.1,2,6

Gram-Negative Aerobic Bacteria !!navigator!!

Cefuroxime is active in vitro against most gram-negative aerobic cocci and many gram-negative aerobic bacilli including Enterobacteriaceae.1,6,30 Pseudomonas aeruginosa is resistant to cefuroxime.1,6,10,13,14,30 Acinetobacter calcoaceticus is also usually resistant to the drug.1,2,3

Generally, cefuroxime is active in vitro against the following Enterobacteriaceae: Citrobacter diversus ,30 C. freundii ,3,6 Enterobacter aerogenes ,3,6,15,30 Escherichia coli ,2,3,6,15,30 Klebsiella pneumoniae ,2,3,6,14,30 Proteus mirabilis ,2,3,6,14,15,30 Providencia stuartii , Salmonella ,6,15,30 and Shigella .6,30 Although cefuroxime is active in vitro against some strains of Morganella morganii (formerly Proteus morganii ), Providencia rettgeri (formerly Proteus rettgeri ), and Proteus vulgaris , most strains of these organisms are resistant to the drug.2,4,6,15 In addition, Enterobacter cloacae , Legionella , Pseudomonas , Campylobacter spp., Providencia , and most strains of Serratia are usually resistant to cefuroxime.1 Most susceptible Enterobacteriaceae are inhibited in vitro by cefuroxime concentrations of 1-12.5 mcg/mL.2,3,4,14,15,30,40 In vitro on a weight basis, the activity of cefuroxime against susceptible Enterobacteriaceae is approximately equal to that of cefoxitin14,15 but less than that of cefotaxime.14,15,34,40 Cefuroxime may be active in vitro against some strains of E. aerogenes that are resistant to cefoxitin;15,30 however, cefotaxime and, to a lesser extent, cefoxitin may be active in vitro against some strains of P. vulgaris and Serratia resistant to cefuroxime.10,14,40

Cefuroxime is active in vitro against Haemophilus influenzae (including ampicillin-resistant strains)1,2,3,4,6,30 and H. parainfluenzae .1 Most susceptible strains of H. influenzae are inhibited in vitro by cefuroxime concentrations of 0.1-2 mcg/mL.2,3,4,6,28,30

Cefuroxime is active in vitro against Neisseria gonorrhoeae (including both penicillinase-producing and nonpenicillinase-producing strains) and N. meningitidis .1 The MIC90 (minimum inhibitory concentration of the drug at which 90% of strains tested are inhibited) of cefuroxime reported for N. gonorrhoeae (including both penicillinase-producing and nonpenicillinase-producing strains) is 0.1-0.5 mcg/mL.2,4,6,9,30

Anaerobic Bacteria !!navigator!!

Cefuroxime is active in vitro against some anaerobic bacteria including Actinomyces ,6 Eubacterium ,6 Fusobacterium ,1,30 Lactobacillus ,6 Peptococcus ,1,2,6,30 Peptostreptococcus ,1,2,6,30 Propionibacterium ,6 and Veillonella .6 Cefuroxime is active in vitro against some strains of Clostridium ;1,2,6,30 however, C. difficile is usually resistant to the drug.1,6

Most susceptible anaerobes are inhibited in vitro by cefuroxime concentrations of 0.5-16 mcg/mL.2,6 Although cefuroxime concentrations of 16 mcg/mL inhibit some strains of Bacteroides fragilis in vitro, most strains of the organism are resistant to the drug.2,4,6,30

Spirochetes !!navigator!!

Cefuroxime is active in vitro and in vivo against Borrelia burgdorferi , the causative organism of Lyme disease.129,132 In vitro, the MIC of cefuroxime for B. burgdorferi reportedly is 0.13 mcg/mL129 and the minimum bactericidal concentration (MBC) is 1 mcg/mL.132

Resistance

For information on possible mechanisms of bacterial resistance to cephalosporins, see Resistance in the Cephalosporins General Statement 8:12.06.

Because cefuroxime contains a methoxyimino group that protects the β-lactam ring from hydrolysis by many penicillinases and cephalosporinases, the drug is more resistant to hydrolysis by β-lactamases than are first generation cephalosporins13,30 or cefamandole.30 Cefuroxime is generally resistant to hydrolysis by β-lactamases classified as Richmond-Sykes types I, II, III, IV, and V2,6,13,23,30 and most β-lactamases produced by Neisseria gonorrhoeae ,2,6,30 Haemophilus influenzae ,2,6,30 and staphylococci.2,6,30 However, cefuroxime is hydrolyzed by β-lactamases produced by B. fragilis 13 and some type I β-lactamases produced by Serratia ,30 P. vulgaris ,12,13,14,15 and P. rettgeri .30 Results of one in vitro study indicate that cefuroxime is hydrolyzed more rapidly than cefotaxime by β-lactamases produced by P. vulgaris and B. fragilis .13 Although cefuroxime is resistant to hydrolysis by β-lactamases produced by Ps. aeruginosa, these organisms are resistant to cefuroxime because the drug cannot penetrate their cell wall.8

Pharmacokinetics

In all studies described in the Pharmacokinetics section, cefuroxime was administered orally as the 1-(acetyloxy)ethyl ester (i.e., cefuroxime axetil) and parenterally as the sodium salt; dosages and concentrations of the drug are expressed in terms of cefuroxime. Because cefuroxime axetil is hydrolyzed rapidly (t½: 3.5 minutes) in vitro in blood or serum,82,108 some clinicians recommend that acetonitrile be added immediately to blood or serum samples intended for pharmacokinetic determinations of the drug in order to prevent further hydrolysis and resultant falsely high concentrations of active drug.108

Absorption !!navigator!!

Cefuroxime Axetil

Following oral administration of cefuroxime axetil, the drug is absorbed as the 1-(acetyloxy)ethyl ester from the GI tract and rapidly hydrolyzed to cefuroxime by nonspecific esterases in the intestinal mucosa and blood.79,82,92,93,97,98,99,104,105,106,107,108 Cefuroxime1,2,6,21,30 remaining within the intestinal lumen following hydrolysis of the ester106,107,108 is not absorbed appreciably. The drug has little, if any, microbiologic activity until hydrolyzed in vivo to cefuroxime.82,116

Bioavailability following oral administration of cefuroxime axetil is variable and depends on the formulation used and presence of food in the GI tract.79,81,82,97,98,99,109 Many published studies on the pharmacokinetics of the drug used various formulations that provided poorer bioavailability than the currently available tablets and cannot be used to provide information on the currently available preparation.82,99

When tested in healthy adults, the bioavailability of cefuroxime axetil oral suspension was found not to be equivalent to that of cefuroxime axetil tablets.79,215 Mean area under the concentration-time curve (AUC) for the oral suspension was 91% of the AUC for the tablets, and the mean peak plasma concentration of cefuroxime following administration of the cefuroxime axetil oral suspension was 71% of that achieved following administration of cefuroxime axetil tablets.79 Therefore, cefuroxime axetil oral suspension and tablet formulations are not substitutable on a mg/mg basis.79,215 (See Dosage: Pediatric Dosage in Dosage and Administration.)

In adults, bioavailability of cefuroxime following oral administration of commercially available cefuroxime axetil tablets averages about 37% when given in the fasting state and 52% when given with or shortly after food.79,81 Absorption of the drug is increased when given with milk or infant formula.98 In one study, the extent but not the rate of absorption was substantially greater when the drug was administered concomitantly with milk compared with applesauce or fasting.98

Following oral administration in adults of a single 125-mg, 250-mg, 500-mg, or 1-g dose of commercially available cefuroxime axetil tablets immediately following a meal, peak serum cefuroxime concentrations are attained approximately 2-3 hours after the dose and average 2.1, 4.1, 7, or 13.6 mcg/mL, respectively; serum concentrations 6 hours after the dose average 0.3, 0.7, 2.2, or 3.4 mcg/mL, respectively.79,81 AUC of the drug in these individuals averaged 6.7, 12.9, 27.4, or 50 mcg-h/mL, respectively.79

Results of a study in healthy adults indicate that cefuroxime axetil oral suspensions containing 125 mg/5 mL or 250 mg/5 mL are bioequivalent.79 In healthy adults who received a 250-mg dose of cefuroxime axetil given as a suspension containing 125 mg/5 mL or 250 mg/5 mL with food, peak plasma concentrations of cefuroxime were 2.4 or 2.2 mcg/mL, respectively, and were attained 3 hours after the dose.79

In pharmacokinetic studies of cefuroxime axetil oral suspension in children, the drug was administered postprandially or with food; no data are available regarding absorption of the suspension in fasting children.79,148 Following oral administration to children 3 months to 12 years of age (mean age: 23 months) of a single 10-, 15-, or 20-mg/kg dose of commercially available cefuroxime axetil oral suspension concomitantly with milk or milk products, peak serum cefuroxime concentrations are attained approximately 3.6, 2.7, or 3.1 hours after the dose, respectively, and average 3.3, 5.1, or 7 mcg/mL, respectively.79,148

Cefuroxime Sodium

Cefuroxime sodium is not appreciably absorbed from the GI tract and must be given parenterally.1,2,6,21,30 Following IM administration of a single 500-mg, 750-mg, or 1-g dose of cefuroxime in healthy adults with normal renal function, peak serum concentrations of the drug are attained within 15-60 minutes and range from 20.8-25.7, 26-34.9, and 32-40 mcg/mL, respectively.1,2,3,6,21,30 In one study following IM administration of a single 750-mg dose of cefuroxime in healthy adults, serum concentrations of the drug averaged 32.8 mcg/mL 40 minutes after the dose, 19.1 mcg/mL 2 hours after the dose, 6.1 mcg/mL 4 hours after the dose, 1.5 mcg/mL 6 hours after the dose, and 0.7 mcg/mL 8 hours after the dose.21 IM injection of a single 1.5-g dose of the drug reportedly results in peak serum concentrations averaging 46 mcg/mL.30 Mean peak serum concentrations of cefuroxime and the areas under the concentration-time curve (AUC) are not substantially different after IM injection of cefuroxime as a suspension or as a solution.30 The AUC of cefuroxime is proportional to the dose administered and is similar following IM or IV administration of the drug.6,30 In one preliminary study in women, serum concentrations of cefuroxime were lower when IM injections of the drug were given into the gluteus maximus than when the same dose was given into the thigh.30

In one study in healthy adults with normal renal function, a single 500-mg or 1-g dose of cefuroxime given by IV injection over 3 minutes resulted in serum concentrations of cefuroxime that averaged 66.3 and 99.2 mcg/mL, respectively, immediately after the injection; serum concentrations of the drug averaged 2.1 and 3.6 mcg/mL, respectively, 4 hours after the injection.21 In another study in healthy adults with normal renal function, IV injection over 2-3 minutes of a single 750-mg dose of cefuroxime resulted in serum concentrations of cefuroxime that averaged 52.6 mcg/mL 15 minutes after the injection, 24 mcg/mL 1 hour after the injection, 9.7 mcg/mL 2 hours after the injection, 3.5 mcg/mL 4 hours after the injection, and 0.5 mcg/mL 8 hours after the injection.27

IV infusion over 30 minutes of a single 500- or 750-mg dose of cefuroxime reportedly results in peak serum concentrations of the drug averaging 37.8 and 51.1 mcg/mL, respectively.6,30 IV infusion over 1 hour of a single 750-mg or 1-g dose of cefuroxime reportedly results in peak serum concentrations of the drug averaging 38 and 64.4 mcg/mL, respectively.6

In one study in neonates, IM administration of a single cefuroxime dose of 25 mg/kg resulted in serum concentrations of the drug that averaged 45 mcg/mL 30 minutes after the injection, 35 mcg/mL 3 hours after the injection, and 10.5 mcg/mL 12 hours after the injection.25 IM administration of a single cefuroxime dose of 10 mg/kg in neonates younger than 3 weeks of age reportedly resulted in serum concentrations of the drug that ranged from 15-25 mcg/mL 30-60 minutes after injection.42

Distribution !!navigator!!

The apparent volume of distribution of cefuroxime in healthy adults ranges from 9.3-15.8 L/1.73 m2.3,6,21

Following IM or IV administration of usual dosages of cefuroxime, the drug is widely distributed into body tissues and fluids1 including the kidneys,2 heart,2 gallbladder,2,6 liver,2 prostatic adenoma tissue,2 uterine and ovarian tissue,2,3 aqueous humor,1,2,3,6,30 saliva,2,3,151 sputum,1,3,6,30,151 bronchial secretions,2,3,30 bone,1,2,3,6,30 bile,1,2,3,6,30 adipose tissue,3 wound exudates,3 peritoneal fluid,2,5 ascitic fluid,1,5 synovial fluid,1,2,6,30 pericardial fluid,6 and pleural fluid.1,2,3,5,6

Following oral administration of cefuroxime axetil in pediatric patients with acute otitis media with effusion or with chronic or recurrent otitis media with effusion, cefuroxime is distributed into middle ear effusions.149,150 In a study in pediatric patients 1-4 years of age with acute otitis media with effusion who received a single 15 mg/kg dose of cefuroxime as cefuroxime axetil oral suspension, cefuroxime concentrations in middle ear effusions 2-5 hours after a dose ranged from 0.2-3.6 mcg/mL; concurrent serum concentrations were 2.8-7.3 mcg/mL.150

Cefuroxime is 33-50% bound to serum proteins.1,2,6,21,30,79

Cefuroxime concentrations in CSF are low following IV administration of usual dosages of the drug in patients with uninflamed meninges;2,3,30,35,43 however, therapeutic concentrations of cefuroxime may be attained following IV administration of the drug in patients with inflamed meninges.2,3,7,18,22,26,29,30,43 In one study in adults receiving 1-2 g of cefuroxime IV every 8 hours, the maximum CSF concentration of cefuroxime in patients with uninflamed or inflamed meninges was 0.1 or 8.28 mcg/mL, respectively.35 In adults with meningitis receiving 1.5 g of cefuroxime every 6 or 8 hours, mean CSF concentrations of the drug attained within 8 hours after dosing are 6 mcg/mL (range: 1.5-13.5) or 5.2 mcg/mL (range: 2.7-8.9), respectively.1 In one study in children 1-4 years of age with meningitis receiving rapid IV injection of cefuroxime 50 mg/kg every 6 hours, CSF concentrations of the drug after at least 2 days of therapy ranged from 1.1-9.8 mcg/mL in CSF specimens obtained 2 hours after a dose.26 In pediatric patients 4 weeks to 6.5 years of age with meningitis receiving 50 mg/kg every 6 hours, mean CSF concentrations of cefuroxime were 6.6 mcg/mL (range: 0.9-17.3).1 In another study in pediatric patients 7 months to 9 years of age with meningitis receiving 67-77 mg/kg every 8 hours, mean CSF concentrations of cefuroxime were 8.3 mcg/mL (range: less than 2 up to 22.5).1

Cefuroxime readily crosses the placenta.1,2,24 Amniotic fluid concentrations of cefuroxime reportedly average 17-18.6 mcg/mL 3-5.5 hours after a single 750-mg IM dose of the drug.2,24,30 Cefuroxime is distributed into milk.1

Elimination !!navigator!!

In adults, the serum or plasma half-life of cefuroxime following oral administration of commercially available cefuroxime axetil tablets or oral suspension ranges from 1.2-1.6 hours.79,81,98 In adults with normal renal function, the serum half-life of cefuroxime following IM or IV administration reportedly ranges from 1-2 hours.1,3,18,21,27,30 In adults, approximately 50% of an administered dose of cefuroxime axetil is recovered in the urine within 12 hours.79

In patients with renal impairment, the serum half-life of the drug is prolonged2,3 and generally ranges from 1.9-16.1 hours depending on the degree of impairment.3,30 In one study, the serum half-life of cefuroxime was 1 hour in patients with creatinine clearances of 50-79 mL/minute, 2.55 hours in patients with creatinine clearances of 25-46 mL/minute, 5.1 hours in patients with creatinine clearances of 10-24 mL/minute, and 14.8 hours in patients with creatinine clearances less than 10 mL/minute.6 A serum half-life of 15-22 hours has been reported in anuric patients.18,30

In neonates and children, the serum half-life of cefuroxime is inversely proportional to age.6,25,30 Following oral administration of cefuroxime axetil oral suspension in children 3 months to 12 years of age, the serum half-life of cefuroxime averages 1.4-1.9 hours.148 The serum half-life of cefuroxime following IM or IV administration is reportedly 5.1-5.8 hours in neonates 3 days of age or younger,6,25,30 2-4.2 hours in neonates 6-14 days of age,6,25,30 and 1-1.5 hours in neonates 3-4 weeks of age.6,25 The manufacturers of cefuroxime axetil state that the urinary pharmacokinetics of cefuroxime axetil have not been determined in children and that the renal pharmacokinetics of oral cefuroxime axetil as established in the adult population should not be extrapolated to children.79,215

Following oral administration, cefuroxime axetil is rapidly hydrolyzed to cefuroxime by nonspecific esterases in the intestinal mucosa and blood;79,82,92,93,97,98,99,104,105,106,107,108 the axetil moiety is metabolized to acetaldehyde and acetic acid.79,105,106 Cefuroxime is not metabolized and is excreted unchanged principally in urine by both glomerular filtration and tubular secretion.2,6,21,27,30 In adults with normal renal function, 90-100% of a single IM or IV dose of cefuroxime is excreted unchanged in urine within 24 hours;3,21,27,30 most of the dose is excreted within the first 6 hours following administration.30 Following IM administration of a single 750-mg dose of cefuroxime, urinary concentrations of the drug average 1.3 mg/mL in urine collected during the first 8 hours after administration.1 Urinary concentrations of cefuroxime average 1.15 or 2.5 mg/mL in urine collected over the first 8 hours following IV administration of a single 750-mg or 1.5-g dose of the drug, respectively.1

Concomitant administration of probenecid competitively inhibits renal tubular secretion of cefuroxime and produces higher and more prolonged serum concentrations of the drug.3,79 (See Drug Interactions: Probenecid.)

Cefuroxime is removed by hemodialysis1,2,3,6,30 and by peritoneal dialysis.6,30

Chemistry and Stability

Chemistry !!navigator!!

Cefuroxime is a semisynthetic cephalosporin antibiotic.1,3 cefuroxime contains a methoxyimino group at position 7 on the β-lactam ring and also contains a carbamate group at position 3 on the ring.2,12 The methoxyimino group results in stability against hydrolysis by many β-lactamases and the carbamate group results in metabolic stability.2,28

Cefuroxime is commercially available for parenteral administration as the sodium salt.1 The drug is commercially available for oral administration as film-coated tablets or as a powder for suspension of cefuroxime axetil, the 1-(acetyloxy)ethyl ester of the drug.79,215 Potency of cefuroxime sodium and cefuroxime axetil is expressed in terms of cefuroxime.1,79,215

Cefuroxime Axetil

Cefuroxime axetil is a prodrug of cefuroxime106,107,108 and has little,116 if any,82 antibacterial activity until hydrolyzed in vivo to cefuroxime.82,116 Esterification of the carboxyl C-4 group of cefuroxime results in a more lipophilic and readily absorbable (from the GI tract) form of the drug.21,82,86,92,99,108,109 Cefuroxime axetil occurs as a white to cream-colored,116 amorphous79 powder.116

Cefuroxime Sodium

Cefuroxime sodium occurs as a white to off-white powder.1 The drug has solubilities of about 200 mg/mL in water39 and 1 mg/mL in alcohol.41 The drug has a pKa of 2.45.41 The sodium salt of cefuroxime contains 2.4 mEq of sodium per gram of cefuroxime.1

Following reconstitution, cefuroxime sodium solutions are light yellow to amber in color and have a pH of 6-8.5, depending on the concentration of the drug and the diluent used.1 Reconstitution of cefuroxime sodium sterile powder for injection to provide a final concentration of 208 mg/mL results in the formation of a suspension;1 dilution to at least 100 mg/mL effects complete dissolution of the drug.1

When the commercially available Duplex® delivery system containing 750 mg or 1.5 g of cefuroxime and 50 mL of dextrose injection in separate chambers is reconstituted (activated) according to the manufacturer's directions, the resultant solution is iso-osmotic and has an osmolality of approximately 290 mOsm/kg.214

The commercially available frozen premixed injection of cefuroxime sodium containing 1.5 g of cefuroxime is a sterile, nonpyrogenic, iso-osmotic solution of the drug provided in a plastic container fabricated from specially formulated multilayered plastic PL 2040.1 The 1.5-g frozen injection contains 600 mg of sodium citrate hydrous as a buffer and 222 mg (9.7 mEq) of sodium, and has an osmolality of approximately 300 mOsm/kg.1 After thawing, the injection has a pH to 5-7.5.1

Stability !!navigator!!

Cefuroxime Axetil

Cefuroxime axetil tablets should be stored in tight containers at 20-25°C or 15-30°C, depending on the manufacturer.79,215 When cefuroxime axetil tablets are allowed to disintegrate in apple juice, the drug is stable for 24 hours at room temperature.116,117

Commercially available cefuroxime axetil powder for oral suspension should be stored at 2-30°C.79 Following reconstitution, oral suspensions of cefuroxime axetil containing 125 mg/5 mL or 250 mg/5 mL should be stored immediately at 2-8°C in a refrigerator.79 Any unused oral suspension should be discarded after 10 days.79

Cefuroxime Sodium

Commercially available cefuroxime sodium sterile powder for injection should be stored at 15-30°C and protected from light.1

Following reconstitution of vials containing 750 mg or 1.5 g of cefuroxime or the pharmacy bulk vial containing 7.5 g of the drug with sterile water for injection according to the manufacturer's directions, solutions for IV administration are stable for 24 hours at room temperature or 48 hours (750-mg and 1.5-g vials) or 7 days (7.5-g pharmacy bulk vial) when refrigerated (5°C).1 More dilute solutions, such as 750 mg or 1.5 g in 100 mL of sterile water for injection, 5% dextrose injection, or 0.9% sodium chloride injection also are stable for 24 hours at room temperature or 7 days when refrigerated.1

Following reconstitution of 750-mg or 1.5-g ADD-Vantage® (TwistVial®) vials of cefuroxime with 5% dextrose injection, 0.9% sodium chloride injection, or 0.45% sodium chloride injection according to the manufacturer's directions, solutions are stable for 24 hours at room temperature or 7 days under refrigeration;1 joined vials that have not been activated (diluted) may be used within a 14-day period.1

IM injections containing 225 mg/mL of cefuroxime prepared using the 750-mg vial and sterile water for injection according to the manufacturer's directions are stable for 24 hours at room temperature or 48 hours when refrigerated (5°C).1

Cefuroxime sodium is chemically and physically compatible with the following IV solutions: 0.9% sodium chloride; Ringer's; lactated Ringer's; 5% dextrose; 5% dextrose and 0.2%, 0.45%, or 0.9% sodium chloride; 10% dextrose; 10% invert sugar; or (1/6) M sodium lactate.1 Reconstituted solutions of cefuroxime that have been further diluted to a concentration of 1-30 mg/mL with one of the above IV solutions are stable for 24 hours at room temperature or at least 7 days when refrigerated.1

The manufacturer of Zinacef® states that cefuroxime sodium solutions prepared using the 750-mg or 1.5-g vials or the 7.5-g pharmacy bulk vial may be frozen immediately after reconstitution and dilution;1 the entire contents from the reconstituted 750-mg or 1.5-g vial or 8 or 16 mL from the 7.5-g vial should be immediately withdrawn and added to a Viaflex® minibag containing 50 or 100 mL of 0.9% sodium chloride injection or 5% dextrose injection and frozen.1 These extemporaneously prepared solutions are stable for 6 months when frozen at -20°C.1 After thawing at room temperature, these solutions are stable for 24 hours at room temperature or 7 days when refrigerated;1 these solutions should not be refrozen.1

The commercially available Duplex® drug delivery system containing 750 mg or 1.5 g of cefuroxime and 50 mL of dextrose injection should be stored at 20-25°C, but may be exposed to 15-30°C.214 Following reconstitution (activation), these IV solutions must be used within 24 hours if stored at room temperature or within 7 days if stored in a refrigerator and should not be frozen.214

The commercially available frozen premixed cefuroxime sodium injection should be stored at -20°C or lower.1 The frozen injection should be thawed at room temperature (25°C) or under refrigeration (5°C) and, once thawed, should not be refrozen.1 Thawed solutions of the commercially available frozen injection are stable for 24 hours at room temperature (25°C) or 28 days under refrigeration (5°C).1 The commercially available frozen injection of the drug is provided in a plastic container fabricated from specially formulated multilayered plastic PL 2040 (Galaxy® containers).1 Solutions in contact with PL 2040 can leach out some of its chemical components in very small amounts within the expiration period of the injection; however, safety of the plastic has been confirmed in tests in animals according to USP biological tests for plastic containers as well as by tissue culture toxicity studies.1

Cefuroxime sodium sterile powder and solutions of the drug tend to darken, depending on storage conditions; however, this discoloration does not necessarily indicate a change in potency.1

Cefuroxime sodium is potentially physically and/or chemically incompatible with some drugs, including aminoglycosides,1 but the compatibility depends on several factors (e.g., concentrations of the drugs, specific diluents used, resulting pH, temperature).37 Specialized references should be consulted for specific compatibility information. Admixtures in 0.9% sodium chloride injection containing cefuroxime sodium and heparin (10 or 50 units/mL) or potassium chloride (10 or 40 mEq/L) are stable for 24 hours at room temperature.1 The manufacturer of Zinacef® states that cefuroxime sodium not be diluted with sodium bicarbonate injection.1 Because of the potential for incompatibility, the manufacturers state that cefuroxime sodium and aminoglycosides should not be admixed.1

Additional Information

For further information on chemistry, mechanism of action, spectrum, resistance, pharmacokinetics, uses, cautions, drug interactions, laboratory test interferences, and dosage and administration of cefuroxime, see the Cephalosporins General Statement 8:12.06.

Preparations ⬆ ⬇

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Cefuroxime Axetil

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

For Suspension

125 mg (of cefuroxime) per 5 mL*

Ceftin®

GlaxoSmithKline

Cefuroxime Axetil for Suspension

250 mg (of cefuroxime) per 5 mL*

Ceftin®

GlaxoSmithKline

Cefuroxime Axetil for Suspension

Tablets, film-coated

125 mg (of cefuroxime)*

Cefuroxime Axetil Tablets

250 mg (of cefuroxime)*

Ceftin®

GlaxoSmithKline

Cefuroxime Axetil Tablets

500 mg (of cefuroxime)*

Ceftin®

GlaxoSmithKline

Cefuroxime Axetil Tablets

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Cefuroxime Sodium

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection

750 mg (of cefuroxime)*

Cefuroxime Sodium for Injection

Zinacef®

Covis

1.5 g (of cefuroxime)*

Cefuroxime Sodium for Injection

Zinacef®

Covis

7.5 g (of cefuroxime) pharmacy bulk package*

Cefuroxime Sodium for Injection

Zinacef®

Covis

For injection, for IV infusion

750 mg (of cefuroxime)*

Cefuroxime Sodium for Injection (available in dual-chambered Duplex® drug delivery system with 4.1% dextrose injection)

B Braun

Zinacef® TwistVial®

Covis

1.5 g (of cefuroxime)*

Cefuroxime Sodium for Injection (available in dual-chambered Duplex® drug delivery system with 2.9% dextrose injection)

B Braun

Zinacef® TwistVial®

Covis

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Cefuroxime Sodium in Water

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection (frozen), for IV infusion

30 mg (of cefuroxime) per mL (1.5 g)

Zinacef® Iso-osmotic in Sterile Water Injection (Galaxy® [Baxter])

Covis

Copyright ⬆ ⬇

AHFS® Drug Information. © Copyright, 1959-2024, Selected Revisions October 11, 2013. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References ⬆

1. Covis Pharmaceutics Inc. Zinacef® (cefuroxime sodium) powder for injection and injection prescribing information. Cary, NC; 2013 Jun.

2. Glaxo Inc. Product information monograph on Zinacef®. Research Triangle Park, NC; 1983.

3. Gold B, Rodriquez WJ. Cefuroxime: mechanisms of action, antimicrobial activity, pharmacokinetics, clinical application, adverse reactions and therapeutic indications. Pharmacotherapy . 1983; 3:82-100. [PubMed 6344037]

4. Eykyn S, Jenkins C, King A et al. Antibacterial activity of cefuroxime, a new cephalosporin antibiotic, compared with that of cephaloridine, cephalothin, and cefamandole. Antimicrob Agents Chemother . 1976; 9:690-5. [PubMedCentral][PubMed 1267441]

5. Lechi A, Arosio E, Xerri L et al. The kinetics of cefuroxime in ascitic and pleural fluid. Int J Clin Pharmacol Ther Toxicol . 1982; 20:493-6. [PubMed 6815108]

6. Smith BR, LeFrock JL. Cefuroxime: antimicrobial activity, pharmacology, and clinical efficacy. Ther Drug Monit . 1983; 5:149-60. [PubMed 6349019]

7. Johansson O, Cronberg S, Hoffstedt B et al. Cefuroxime versus ampicillin and chloramphenicol for the treatment of bacterial meningitis—report from a Swedish study group. Lancet . 1982; 1:295-8. [PubMed 6120310]

8. Browning AK, House CA. Pharmacokinetics of cefuroxime compared to other cephalosporins. In: Cefuroxime update. Royal Society of Medicine International Congress and Symposium Series No. 38. London; 1981. 87-99.

9. Lossick JG, Thompson SE, Smeltzer MP. Comparison of cefuroxime and penicillin in the treatment of uncomplicated gonorrhea. Antimicrob Agents Chemother . 1982; 22:409-13. [PubMedCentral][PubMed 6814355]

10. Weinstein AJ. The cephalosporins: activity and clinical use. Drugs . 1980; 20:137-54. [PubMed 6995096]

11. De Carneri I. Single-drug therapy of gonorrhoea with the new cephalosporins. Lancet . 1983; 2:821.

12. O'Callaghan CH. Description and classification of the newer cephalosporins and their relationship with the established compounds. J . Antimicrob Chemother. 1979; 5:635-71.

13. King A, Warren C, Shannon K et al. The in vitro antibacterial activity of cefotaxime compared with that of cefuroxime and cefoxitin. J Antimicrob Chemother . 1980; 6:479-94. [PubMed 6253433]

14. Legakis NJ, Kafetzis DA, Papadatos CJ et al. Antibacterial activity of HR-756, cefoxitin and cefuroxime against multiple antibiotic-resistant strains of Enterobacteriaceae and Pseudomonas aeruginosa. Chemotherapy. 1980; 26:334-43.

15. Masuyoshi S, Arai S, Miyamoto M et al. In vitro antimicrobial activity of cefotaxime, a new cephalosporin. Antimicrob Agents Chemother . 1980; 18:1-8. [PubMedCentral][PubMed 6251749]

16. Mannion JC, Bloch R, Popovich NG. Cephalosporin-aminoglycoside synergistic nephrotoxicity: fact or fiction? Drug Intell Clin Pharm. 1981; 15:248-56.

17. Kasemko JA, Walker SR. Cefuroxime plasma and CSF levels in children with meningitis. Arch Dis Child . 1979; 54:235-6. [PubMedCentral][PubMed 434912]

18. Nelson JD. Cefuroxime: a cephalosporin with unique applicability to pediatric practice. Pediatr Infect Dis . 1983; 2:394-6. [PubMed 6356062]

19. Corbeel L. Cefuroxime for treatment of bacterial meningitis. Lancet . 1982; 1:750. [PubMed 6122048]

20. Price JD, Fluker JL. The efficacy of cefuroxime for the treatment of acute gonorrhoea in men. Br J Vener Dis . 1978; 54:165-7. [PubMedCentral][PubMed 656890]

21. Foord RD. Cefuroxime: human pharmacokinetics. Antimicrob Agents Chemother . 1976; 9:741-7. [PubMedCentral][PubMed 949172]

22. Muller C, Netland A, Dawson AF et al. The penetration of cefuroxime into the cerebrospinal fluid through inflamed and non-inflamed meninges. J Antimicrob Chemother . 1980; 6:279-83. [PubMed 7380771]

23. Mathew M. Plasmid-mediated β-lactamases of gram-negative bacteria: properties and distribution. J Antimicrob Chemother . 1979; 5:349-58. [PubMed 385575]

24. Philipson A, Stiernstedt G. Pharmacokinetics of cefuroxime in pregnancy. Am J Obstet Gynecol . 1982; 142:823-8. [PubMed 7065060]

25. De Louvois J, Mulhall A, Hurley R. Cefuroxime in the treatment of neonates. Arch Dis Child . 1982; 57:59-62. [PubMedCentral][PubMed 7065695]

26. Pfenninger J, Schaad UB, Lutschg J et al. Cefuroxime in bacterial meningitis. Arch Dis Child . 1982; 57:539-43. [PubMedCentral][PubMed 7103546]

27. Gower PE, Dash CH. The pharmacokinetics of cefuroxime after intravenous injection. Eur J Pharmacol . 1977; 12:221-7.

28. Ball AP, Brooks GR, Farrell ID et al. Studies with cefuroxime: a new beta-lactamase resistant cephalosporin. Chemotherapy . 1979; 25:214-21. [PubMed 110540]

29. Corbeel L, Van Acker G, Eeckels R et al. Cefuroxime plasma and CSF levels in children with meningitis. Arch Dis Child . 1979; 54:729-30. [PubMedCentral][PubMed 518117]

30. Brogden RN, Heel RC, Speight TM et al. Cefuroxime: a review of its antibacterial activity, pharmacological properties and therapeutic use. Drugs . 1979; 17:233-66. [PubMed 37064]

31. Keighley MR. Antibiotic-associated pseudomembranous colitis: pathogenesis and management. Drugs . 1980; 20:49-56. [PubMed 7398539]

32. Tupasi TE, Crisologo LB, Torres CA et al. Cefuroxime, thiamphenicol, spectinomycin, and penicillin G in uncomplicated infections due to penicillinase-producing strains of Neisseria gonorrhoeae. Br J Vener Dis. 1983; 59:172-5.

33. Richmond MH, Wooton S. Comparative study of seven cephalosporins: susceptibility to beta-lactamases and ability to penetrate the surface layers of Escherichia coli. Antimicrob Agents Chemother. 1976; 10:219-22.

34. Fu KP, Neu HC. Beta-lactamase stability of HR 756, a novel cephalosporin, compared to that of cefuroxime and cefoxitin. Antimicrob Agents Chemother . 1978; 14:322-6. [PubMedCentral][PubMed 101128]

35. Friedrich H, Haensel-Friedrich G. Langmaak H et al. Investigations of cefuroxime levels in the cerebrospinal fluid of patients with and without meningitis. Chemotherapy . 1980; 26:91-7. [PubMed 7363711]

36. Workowski KA, Berman S, Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep . 2010; 59(RR-12):1-110.

37. Newton DW. Introduction: physicochemical determinants of incompatibility and instability of drugs for injection and infusion. In: Trissel LA. Handbook on injectable drugs. 3rd ed. Bethesda, MD: American Society of Health-System Pharmacists, Inc., Inc; 1983:xi-xxi.

38. Ettlin R, Hoigne R, Bruppacher R et al. Atopy and adverse drug reactions. Int Arch Aller Appl Immunol . 1981; 66(Suppl 1):93-5.

39. Windholz M, ed. The Merck index. 10th ed. Rahway, NJ: Merck & Co, Inc; 1983:272.

40. Fu KP, Neu HC. Antibacterial activity of ceftizoxime, a β-lactamase-stable cephalosporin. Antimicrob Agents Chemother . 1980; 17:583-90. [PubMedCentral][PubMed 6967294]

41. Furniss LD (Glaxo Inc, Research Triangle Park, NC): Personal communication; 1984 Mar 7.

42. Renlund M, Pettay O, Kostiala AA et al. Pharmacokinetics and clinical efficacy of cefuroxime in the newborn period. Proc R Soc Med . 1977; 70(Suppl 9):179-82. [PubMedCentral][PubMed 20919401]

43. Sirinavin S, Chiemchanya S, Visudhipan P et al. Cefuroxime treatment of bacterial meningitis in infants and children. Antimicrob Agents Chemother . 1984; 25:273-5. [PubMedCentral][PubMed 6608921]

44. Reviewer's comments (personal observations); 1984 Feb 29.

45. Gerber MA, Baltimore RS, Eaton CB et al. Prevention of rheumatic fever and diagnosis and treatment of acute Streptococcal pharyngitis: a scientific statement from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young, the Interdisciplinary Council on Functional Genomics and Translational Biology, and the Interdisciplinary Council on Quality of Care and Outcomes Research: endorsed by the American Academy of Pediatrics. Circulation . 2009; 119:1541-51. [PubMed 19246689]

46. Cooper RJ, Hoffman JR, Bartlett JG et al. Principles of appropriate antibiotic use for acute pharyngitis in adults: background. Ann Intern Med . 2001; 134:509-17. [PubMed 11255530]

48. Tartaglione TA, Polk RE. Review of the new second generation cephalosporins: cefonicid, ceforanide, and cefuroxime. Drug Intell Clin Pharm . 1985; 19:188-98. [PubMed 3884304]

49. Eichenwald HF. Antimicrobial therapy in infants and children: update 1976-1985. Part 1. J Pediatr . 1985; 107:161-8. [PubMed 4020539]

50. Nadelman RB, Luger SW, Frank E et al. Comparison of cefuroxime axetil and doxycycline in the treatment of early Lyme disease. Ann Intern Med . 1992; 117:273-280. [PubMed 1637021]

51. Mandell LA, Wunderink RG, Anzueto A et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis . 2007; 44 Suppl 2:S27-72. [PubMed 17278083]

52. Heffelfinger JD, Dowell SF, Jorgensen JH et al. Management of community-acquired pneumonia in the era of pneumococcal resistance. A report from the drug-resistant Streptococcus pneumoniae therapeutic working group. Arch Intern Med . 2000; 160:1399-1408. [PubMed 10826451]

58. Anon. Drugs for bacterial infections. Med Lett Treat Guid . 2010; 8:43-52.

62. Luger SW, Paparone P, Wormser GP et al. Comparison of cefuroxime axetil and doxycycline in treatment of patients with early Lyme disease associated with erythema migrans. Antimicrob Agents Chemother . 1995; 39:661-7. [PubMedCentral][PubMed 7793869]

63. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing: Twenty-first informational supplement. CLSI document M100-S21. Wayne, PA; 2011.

64. Marks WA, Stutman HR, Marks MI et al. Cefuroxime versus ampicillin plus chloramphenicol in childhood bacterial meningitis: a multicenter randomized controlled trial. J Pediatr . 1986; 109:123-30. [PubMed 3522832]

66. Slama TG, Sklar SJ, Misinski J et al. Randomized comparison of cefamandole, cefazolin, and cefuroxime prophylaxis in open-heart surgery. Antimicrob Agents Chemother . 1986; 29:744-7. [PubMedCentral][PubMed 3524428]

68. Centers for Disease Control and Prevention (CDC). Update to CDC's Sexually transmitted diseases treatment guidelines, 2010: oral cephalosporins no longer a recommended treatment for gonococcal infections. MMWR Morb Mortal Wkly Rep . 2012; 61:590-4. [PubMed 22874837]

70. Kaiser AB. Antimicrobial prophylaxis in surgery. N Engl J Med . 1986; 315:1129-38. [PubMed 3531863]

71. . Antimicrobial prophylaxis for surgery. Treat Guidel Med Lett . 2012; 10:73-8; quiz 79-80. [PubMed 22996382]

79. GlaxoSmithKline. Ceftin® (cefuroxime axetil) powder for oral suspension and film-coated tablets prescribing information. Research Triangle Park, NC; 2010 Jan.

81. Finn A, Straughn A, Meyer M et al. Effect of dose and food on the bioavailability of cefuroxime axetil. Biopharm Drug Dispos . 1987; 8:519-26. [PubMed 3427209]

82. Marx MA, Fant WK. Cefuroxime axetil. Drug Intell Clin Pharm . 1988; 22:651-8. [PubMed 3063476]

83. Wanas TM, Williams PE. Oral cefuroxime axetil compared with oral ampicillin treating uncomplicated gonorrhoea. Genitourin Med . 1986; 62:221-3. [PubMedCentral][PubMed 3733084]

84. Fong IW, Linton W, Simbul M et al. Comparative clinical efficacy of single oral doses of cefuroxime axetil and amoxicillin in uncomplicated gonococcal infections. Antimicrob Agents Chemother . 1986; 30:321-2. [PubMedCentral][PubMed 3094443]

85. Reichman RC, Nolte FS, Wolinsky SM et al. Single-dose cefuroxime axetil in the treatment of uncomplicated gonorrhea: a controlled trial. Sex Transm Dis . 1985; 12:184-7. [PubMed 3936198]

86. Gottlieb A, Mills J. Cefuroxime axetil for treatment of uncomplicated gonorrhea. Antimicrob Agents Chemother . 1986; 30:333-4. [PubMedCentral][PubMed 3767347]

87. Schift R, Van Ulsen J, Ansink-Schipper MC et al. Comparison of oral treatment of uncomplicated urogenital and rectal gonorrhoea with cefuroxime axetil ester or clavulanic acid potentiated amoxycillin (Augmentin). Genitourin Med . 1986; 62:313-7. [PubMedCentral][PubMed 3533755]

88. McLinn SE, Werner K, Cocchetto DM. Clinical trial of cefuroxime axetil versus cefaclor for acute otitis media with effusion. Curr Ther Res . 1988; 43:1-11.

89. Hebblethwaite EM, Brown GW, Cox DM. A comparison of the efficacy and safety of cefuroxime axetil and augmentin in the treatment of upper respiratory tract infections. Drugs Exp Clin Res . 1987; 13:91-4. [PubMed 3582135]

90. Gooch WM, Higbee MD, Cocchetto DM et al. Cefuroxime axetil and penicillin V compared in the treatment of group A beta-hemolytic streptococcal pharyngitis. Clin Ther . 1987; 9:670-7. [PubMed 3125976]

91. Pichichero ME, Disney FA, Aronovitz GH et al. A multicenter, randomized, single-blind evaluation of cefuroxime axetil and phenoxymethyl penicillin in the treatment of streptococcal pharyngitis. Clin Pediatr . 1987; 26:453-8.

92. Cooper TJ, Ladusans E, Williams PE et al. A comparison of oral cefuroxime axetil and oral amoxycillin in lower respiratory tract infections. J Antimicrob Chemother . 1985; 16:373-8. [PubMed 4055545]

93. Spencer RC, Griggs JV, Brown GW. A dose-ranging study of cefuroxime axetil in the treatment of lower respiratory tract infections in general practice. Drugs Exp Clin Res . 1987; 13:101-3. [PubMed 3582133]

94. Parish LC, Cocchetto DM, Werner K et al. Cefuroxime axetil in the treatment of cutaneous infections. Int J Dermatol . 1987; 26:389-93. [PubMed 3305394]

95. Cox CE, Sherrill JM, Cocchetto DM. Evaluation of cefuroxime axetil, cefaclor, and cephalexin in the treatment of urinary tract infections in adults. Curr Ther Res . 1987; 42:124-37.

96. Williams KJ, Hebblethwaite EM, Brown GW et al. Cefuroxime axetil in the treatment of uncomplicated UTI: a comparison with cefaclor and Augmentin. Drugs Exp Clin Res . 1987; 13:95-9. [PubMed 3556123]

97. Williams PE, Harding SM. The absolute bioavailability of oral cefuroxime axetil in male and female volunteers after fasting and after food. J Antimicrob Chemother . 1984; 13:191-6. [PubMed 6706890]

98. Ginsburg CM, McCracken GH, Petruska M et al. Pharmacokinetics and bactericidal activity of cefuroxime axetil. Antimicrob Agents Chemother . 1985; 28:504-7. [PubMedCentral][PubMed 3878129]

99. Peterson SE (Glaxo, Research Triangle Park, NC): personal communications; 1988 Sep.

101. Carson JWK, Watters K, Taylor MRH et al. Clinical trial of cefuroxime axetil in children. J Antimicrob Chemother . 1987; 19:109-12. [PubMed 3494006]

102. Finn AL, Sherrill JM, Debussey SS. A comparative study of cefuroxime axetil and cefaclor in the treatment of otitis media with effusion. Proceedings of ICAAC Minneapolis 1985. 1985:202. Abstract No. 600.

103. Schleupner CJ, Anthony WC, Tan J et al. Blinded comparison of cefuroxime to cefaclor for lower respiratory tract infections. Arch Intern Med . 1988; 148:343-8. [PubMed 3277562]

104. Adams DH, Wood MJ, Farrell ID et al. Oral cefuroxime axetil: clinical pharmacology and comparative dose studies in urinary tract infection. J Antimicrob Chemother . 1985; 16:359-66. [PubMed 4055543]

105. Sommers D, Van Wyk M, Williams PEO et al. Pharmacokinetics and tolerance of cefuroxime axetil in volunteers during repeated dosing. Antimicrob Agents Chemother . 1984; 25:344-7. [PubMedCentral][PubMed 6721467]

106. Campbell CJ, Langley C. Measurement of rat-intestinal cefuroxime axetil esterase activity: comparison of an h.p.l.c. and coupled-enzyme assay. Xenobiotica . 1985; 15:1011-9. [PubMed 2936009]

107. Campbell CJ, Chantrell LJ, Eastmond R. Purification and partial characterization of rat intestinal cefuroxime axetil esterase. Biochem Pharmacol . 1987; 36:2317-24. [PubMed 3606643]

108. Harding SM, Williams PEO, Ayrton J. Pharmacology of cefuroxime as the 1-acetoxyethyl ester in volunteers. Antimicrob Agents Chemother . 1984; 25:78-82. [PubMedCentral][PubMed 6703686]

109. Sommers D, Van Wyk M, Moncrieff J. Influence of food and reduced gastric acidity on the bioavailability of bacampicillin and cefuroxime axetil. Br J Clin Pharmacol . 1984; 18:535-9. [PubMedCentral][PubMed 6091711]

110. Aronovitz GH. Treatment of otitis media with cefuroxime axetil. South Med J . 1988; 81:978-80. [PubMed 3043692]

111. Wadsworth SJ, Suh B. In vitro displacement of bilirubin by antibiotics and 2-hydroxybenzoylglycine in newborns. Antimicrob Agents Chemother . 1988; 32:1571-5. [PubMedCentral][PubMed 3190184]

112. Cantu TG, Fantozzi D. Cefuroxime dosage in renal failure. Ann Intern Med . 1988; 109:989-90. [PubMed 3195883]

113. Aronoff GR. Cefuroxime dosage in renal failure. Ann Intern Med . 1988; 109:990. [PubMed 3195884]

114. Walstad RA, Nilsen OG, Berg KJ. Pharmacokinetics and clinical effects of cefuroxime in patients with severe renal insufficiency. Eur J Clin Pharmacol . 1983; 24:391-8. [PubMed 6861853]

115. Chan MK, Browning AK, Poole CJM et al. Cefuroxime pharmacokinetics in continuous and intermittent peritoneal dialysis. Nephron . 1985; 41:161-5. [PubMed 4047273]

116. Fus AF (Glaxo Inc, Research Triangle Park, NC): Personal communication; 1989 Jan 30.

117. St Claire RL III, Wilbourne DK, Caudill WL. Stability of cefuroxime axetil in apple juice. Pediatr Infect Dis J . 1988; 7:744. [PubMed 3186346]

123. St. Claire III RL, Caudill WL. Stability of cefuroxine axetil in beverages. Am J Hosp Pharm . 1989; 46:256.

124. Henry D, Ruoff GE, Rhudy J et al. Effectiveness of short-course therapy (5 days) with cefuroxime axetil in treatment of secondary bacterial infections of acute bronchitis. Antimicrob Agents Chemother . 1995; 39:2528-34. [PubMedCentral][PubMed 8585739]

125. Baddour L, Gibbs RS, Mertz G et al. Clinical comparison of single-oral-dose cefuroxime axetil and amoxicillin with probenecid for uncomplicated gonococcal infections in women. Antimicrob Agents Chemother . 1989; 33:801-4. [PubMedCentral][PubMed 2764526]

126. Moran JS, Levine WC. Drugs of choice for the treatment of uncomplicated gonococcal infections. Clin Infect Dis . 1995; 20(Suppl):S47-65.

127. Kinghorn GR, Spencer RC, Smith TK et al. Comparative study of cefuroxime axetil and procaine penicillin in the treatment of uncomplicated gonorrhoea. Int J STD AIDS . 1990; 1:285-7. [PubMed 2128472]

129. Agger WA, Callister SM, Jobe DA. In vitro susceptibility of Borrelia burgdorferi to five oral cephalosporins and ceftriaxone. Antimicrob Agents Chemother . 1992; 36:1788-90. [PubMedCentral][PubMed 1416868]

130. Bartlett JG. Antibiotic-associated diarrhea. Clin Infect Dis . 1992; 573-81.

131. Kelly CP, Pothoulakis C, LaMont JT. Clostridium difficile colitis. N Engl J Med . 1994; 330:257-62. [PubMed 8043060]

132. Johnson RC, Kodner CB, Jurkovich PJ et al. Comparative in vitro and in vivo susceptibilities of the Lyme disease spirochete Borrelia burgdorferi to cefuroxime and other antimicrobial agents. Antimicrob Agents Chemother . 1990; 34:2133-6. [PubMedCentral][PubMed 2073103]

134. Luft BJ, Gorevic PD, Halperin JJ et al. A perspective on the treatment of Lyme borreliosis. Rev Infect Dis . 1989; 11(Suppl 6):S1518-25.

135. Eichenfield AH, Athreya BH. Lyme disease: of ticks and titers. J Pediatr . 1989; 114:328-33. [PubMed 2644410]

138. Nocton JJ, Steere AC. Lyme disease. Adv Intern Med . 1995; 40:69- 117. [PubMed 7747659]

139. Spach DH, Liles WC, Campbell GL et al. Tick-borne diseases in the United States. N Engl J Med . 1993; 329:936-47. [PubMed 8361509]

140. Jantausch BA. Lyme disease, Rocky Mountain spotted fever, ehrlichiosis: emerging and established challenges for the clinician. Ann Allergy . 1994; 73:4-11. [PubMed 8030801]

141. Nadelman RB, Wormser GP. Erythema migrans and early Lyme disease. Am J Med . 1995; 98(4A):15-23S.

142. Steere AC. Musculoskeletal manifestations of Lyme disease. Am J Med . 1995; 98(4A):44-48S.

143. American Academy of Pediatrics. Red Book: 2012 Report of the Committee on Infectious Diseases. 29th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2012.

144. Thorpe EM Jr, Schwebke JR, Hook EW III et al. Comparison of single-dose cefuroxime axetil with ciprofloxacin in treatment of uncomplicated gonorrhea caused by penicillinase-producing and non-penicillinase-producing Neisseria gonorrhoeae strains. Antimicrob Agents Chemother . 1996; 40:2775-80. [PubMedCentral][PubMed 9124839]

145. Perry CM, Brogden RN. Cefuroxime axetil: a review of its antibacterial activity, pharmacokinetic properties and therapeutic efficacy. Drugs . 1996; 52:125-58. [PubMed 8799689]

146. Glaxo Wellcome Inc. Ceftin® tablets: efficacy in uncomplicated gonorrhea. Research Triangle Park, NC.

147. Glaxo Wellcome Inc. Ceftin® tablets: use in Lyme disease. Research Triangle Park, NC.

148. Powell DA, James NC, Ossi MJ et al. Pharmacokinetics of cefuroxime axetil suspension in infants and children. Antimicrob Agents Chemother . 1991; 35:2042-5. [PubMedCentral][PubMed 1759825]

149. Haddad J, Isaacson G, Respler DS et al. Concentration of cefuroxime in serum and middle ear effusion after single dose treatment with cefuroxime axetil. Pediatr Infect Dis J . 1991; 10:294-8. [PubMed 2062625]

150. Thoroddsen E, Marr C, Efthymiopoulos C et al. Concentration of cefuroxime in middle ear effusion of children with acute otitis media. Pediatr Infect Dis J . 1997; 16:959-62. [PubMed 9380472]

151. Havard CWH, Bax RP, Samanta TC et al. Sputum and blood concentrations of cefuroxime in lower respiratory tract infection. Thorax . 1980; 35:379-83. [PubMedCentral][PubMed 7434289]

152. Manley HJ, Bailie GR, Eisele G. Bilateral renal cortical necrosis associated with cefuroxime axetil. Clin Nephrol . 1998; 49:268-70. [PubMed 9582561]

153. Camacho AE, Cobo R, Otte J et al. Clinical comparison of cefuroxime axetil and amoxicillin/clavulanate in the treatment of patients with acute bacterial maxillary sinusitis. Am J Med . 1992; 93:271-6. [PubMed 1524078]

154. Goddard JK, Janning SW, Gass JS et al. Cefuroxime-induced acute renal failure. Pharmacotherapy . 1994; 14:488-91. [PubMed 7937287]

155. Vincken W. Psychotic reaction to cefuroxime. Lancet . 1984; 1:965. [PubMed 6143902]

156. Taggart SCO, Pijnenburg AJ, Balistrini A et al. An unusual complication of cefuroxime treatment. Clin Drug Invest . 1997; 13:223-5.

157. Paris MM, Ramilo O, McCracken GH. Management of meningitis caused by penicillin-resistant Streptococcus pneumoniae . Antimicrob Agents Chemother . 1995; 39:2171-5. [PubMedCentral][PubMed 8619561]

158. American Academy of Pediatrics Committee on Infectious Disease. Therapy for children with invasive pneumococcal infections. Pediatrics . 1997; 99:289-99. [PubMed 9024464]

159. Schaad UB, Suter S, Gianella-Borradori A et al. A comparison of ceftriaxone and cefuroxime for the treatment of bacterial meningitis in children. N Engl J Med . 1990; 322:141-7. [PubMed 2403654]

160. Mendelman PM, Chaffin DO, Krilov LR et al. Cefuroxime treatment failure of nontypable Haemophilus influenzae . meningitis associated with alteration of penicillin-binding proteins. J Infect Dis . 1990; 162:1118-23. [PubMed 2230238]

161. Lebel MH, Hoyt MJ, McCracken GH. Comparative efficacy of ceftriaxone and cefuroxime for treatment of bacterial meningitis. J Pediatr . 1989; 114:1049-54. [PubMed 2656960]

162. Arditi M, Herold BC, Yogev R. Cefuroxime treatment failure and Haemophilus influenzae . meningitis: case report and review of literature. Pediatrics . 1989; 84:132-5. [PubMed 2662131]

163. Vogel F, Droszcz W, Vondra V et al. Sequential therapy with cefuroxime followed by cefuroxime axetil in acute exacerbations of chronic bronchitis. J Antimicrob Chemother . 1997; 40:863-71. [PubMed 9462439]

164. Klein GL, Whalen E, Echols RM et al. Ciprofloxacin versus cefuroxime axetil in the treatment of adult patients with acute bacterial sinusitis. J Otolaryngol . 1998; 27:10-6. [PubMed 9511113]

165. Quagliarello VJ, Scheld WM. Treatment of bacterial meningitis. N Engl J Med . 1997; 336:708-16. [PubMed 9041103]

166. Sydnor A, Gwaltney JM, Cocchetto DM et al. Comparative evaluation of cefuroxime axetil and cefaclor for treatment of acute bacterial maxillary sinusitis. Arch Otolaryngol Head Neck Surg . 1989; 115:1430-3. [PubMed 2510772]

167. Van den Brande P, Vondra V, Vogel F et al. Sequential therapy with cefuroxime followed by cefuroxime axetil in community-acquired pneumonia. Chest . 1997; 112:406-15. [PubMed 9266876]

168. Herishanu YO, Zlotnik M, Mostoslavsky M et al. Cefuroxime-induced encephalopathy. Neurology . 1998; 50:1873-5. [PubMed 9633748]

169. Aujard Y, Boucot I, Brahimi N et al. Comparative efficacy and safety of four-day cefuroxime axetil and ten-day penicillin treatment of group A beta-hemolytic streptococcal pharyngitis in children. Pediatr Infect Dis J . 1995; 14:295-300. [PubMed 7603811]

170. Mehra S, Van Moerkerke M, Welck J et al. Short course therapy with cefuroxime axetil for group A streptococcal tonsillopharyngitis in children. Pediatr Infect Dis J . 1998; 17:452-7. [PubMed 9655533]

171. Shulman ST, Bisno AL, Clegg HW et al. Clinical practice guideline for the diagnosis and management of group A streptococcal pharyngitis: 2012 update by the Infectious Diseases Society of America. Clin Infect Dis . 2012; 55:1279-82. [PubMed 23091044]

173. Pichichero ME, Cohen R. Shortened course of antibiotic therapy for acute otitis media, sinusitis and tonsillopharyngitis. Pediatr Infect Dis J . 1997; 16:680-95. [PubMed 9239773]

174. Tack KJ, Henry DC, Gooch WM et al et al. Five-day cefdinir treatment for streptococcal pharyngitis. Antimicrob Agents Chemother . 1998; 42:1073-5. [PubMedCentral][PubMed 9593129]

175. Pichichero ME. Cephalosporins are superior to penicillin for treatment of streptococcal tonsillopharyngitis: is the difference worth it? Pediatr Infect Dis . 1993; 12:268-74.

176. Milatovic D. Evaluation of cefadroxil, penicillin and erythromycin in the treatment of streptococcal tonsillopharyngitis. Pediatr Infect Dis J . 1991; 10:S61-3. [PubMed 1945599]

177. Adam D, Hostalek U, Troster K. 5-day cefixime therapy for bacterial pharyngitis and/or tonsillitis: comparison with 10-day penicillin V therapy. Infection . 1995; 23(Supp 2):S83-6. [PubMed 8537138]

178. Kishiyam JL, Adelman DC. The cross-reactivity and immunology of β-lactam antibiotics. Drug Saf . 1994; 10:318-27. [PubMed 8018304]

179. Thompson JW, Jacobs RF. Adverse effects of newer cephalosporins: an update. Drug Saf . 1993; 9:132-42. [PubMed 8397890]

181. Nadelman RB, Wormser GP. Lyme borreliosis. Lancet . 1998; 352:557-65. [PubMed 9716075]

182. Anon. Treatment of Lyme Disease. Med Lett Drugs Ther . 2000; 42:37-9. [PubMed 10825919]

183. Rahn DW, Felz MW. Lyme disease update. Current approach to early, disseminated, and late disease. Postgrad Med . 1998; 103:51-4, 57-9, 63-4. [PubMed 9590986]

184. Lieberthal AS, Carroll AE, Chonmaitree T et al. The diagnosis and management of acute otitis media. Pediatrics . 2013; 131:e964-99. [PubMed 23439909]

185. Cohen SH, Gerding DN, Johnson S et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol . 2010; 31:431-55. [PubMed 20307191]

186. Fekety R for the American College of Gastroenterology Practice Parameters Committee. Guidelines for the diagnosis and management of Clostridium difficile -associated diarrhea and colitis. Am J Gastroenterol . 1997; 92:739-50. [PubMed 9149180]

187. American Society of Health-System Pharmacists Commission on Therapeutics. ASHP therapeutic position statement on the preferential use of metronidazole for the treatment of Clostridium difficile -associated disease. Am J Health-Syst Pharm . 1998; 55:1407-11. [PubMed 9659970]

189. Da Costa A, Kirkorian G, Cucherat M et al. Antibiotic prophylaxis for permanent pacemaker implantation: a meta-analysis. Circulation . 1998; 97:1796-801. [PubMed 9603534]

190. Gonzalez RP, Holevar MR. Role of prophylactic antibiotics for tube thoracostomy in chest trauma. Am Surg . 1998; 64:617-20. [PubMed 9655270]

191. Aznar R, Mateu M, Miro JM et al. Antibiotic prophylaxis in non-cardiac thoracic surgery: cefazolin versus placebo. Eur J Cardiothorac Surg . 1991; 5:515-8. [PubMed 1756043]

192. Mangram AJ, Horan TC, Pearson ML et al. Guideline for prevention of surgical site infection, 1999. Infect Control Hosp Epidemiol . 1999; 20:250-78. [PubMed 10219875]

193. Nooyen SM, Overbeek BP, de la Riviere B et al. Prospective randomised comparison of single-dose versus multiple-dose cefuroxime for prophylaxis in coronary artery bypass grafting. Eur J Clin Microbiol Infect Dis . 1994; 1033-7.

194. Meyer JM. Comparative study of ceftriaxone and cefuroxime for perioperative prophylaxis in orthopedic surgery. Am J Surg . 1984; 148(Suppl 4A):27-9. [PubMed 6091477]

195. Wymenga A, van Horn J, Theeuwes A et al. Cefuroxime for prevention of postoperative cositis. One versus three doses tested in a randomized multicenter study of 2,651 arthroplasties. Acta Orthop Scand . 1992; 63:19-24. [PubMed 1738963]

196. Doebbeling BN, Pfaller MA, Kuhns KR et al. Cardiovascular surgery prophylaxis. A randomized, controlled comparison of cefazolin and cefuroxime. J Thorac Cardiovasc Surg . 1990; 99:981-9. [PubMed 2193200]

197. Vuorisalo S, Pokela R, Syrjala H. Comparison of vancomycin and cefuroxime for infection prophylaxis in coronary artery bypass surgery. Infect Control Hosp Epidemiol . 1998; 19:234-9. [PubMed 9605271]

198. Gooch WM, Blair E, Puopolo A et al. Effectiveness of five days of therapy with cefuroxime axetil suspension for treatment of acute otitis media. Pediatr Infect Dis J . 1996; 15:157-64. [PubMed 8822290]

199. McLinn SE, Moskal M, Goldfarb J et al. Comparison of cefuroxime axetil and amoxicillin-clavulanate suspensions in treatment of acute otitis media with effusion in children. Antimicrob Agents Chemother . 1994; 38:315-8. [PubMedCentral][PubMed 8192458]

200. Pessey JJ, Gehanno P, Thoroddsen E et al. Short course therapy with cefuroxime axetil for acute otitis media: results of a randomized multicenter comparison with amoxicillin/clavulanate. Pediatr Infect Dis J . 1999; 18:854-9. [PubMed 10530579]

201. Brodie DP, Griggs JV, Cunningham K. Comparative study of cefuroxime axetil suspension and amoxycillin syrup in the treatment of acute otitis media in general practice. J Int Med Res . 1990; 18:235-9. [PubMed 2113874]

202. Gooch WM 3rd, Blair E, Puopolo A et al. Clinical comparison of cefuroxime axetil suspension and amoxicillin/clavulanate suspension in the treatment of pediatric patients with acute otitis media with effusion. Clin Ther . 1995; 17:838-51. [PubMed 8595636]

203. Turik MA, Johns D Jr. Comparison of cefaclor and cefuroxime axetil in the treatment of acute otitis media with effusion in children who failed amoxicillin therapy. J Chemother . 1998; 10:306-12. [PubMed 9720470]

204. Pichichero M, Aronovitz GH, Gooch WM et al. Comparison of cefuroxime axetil, cefaclor, and amoxicillin-clavulanate potassium suspensions in acute otitis media in infants and children. South Med J . 1990; 83:1174-7. [PubMed 2218657]

205. Kozyrskyj AL, Hildes-Ripstein GE, Longstaffe SEA et al. Treatment of acute otitis media with a shortened course of antibiotics: a meta-analysis. JAMA . 1998; 279:1736-42. [PubMed 9624028]

206. Pichichero ME, Cohen R. Shortened course of antibiotic therapy for acute otitis media, sinusitis and tonsillopharyngitis. Pediatr Infect Dis J . 1997; 16:680-95. [PubMed 9239773]

207. Paradise JL. Short-course antimicrobial treatment for acute otitis media: not best for infants and young children. JAMA . 1997; 278:1640-2. [PubMed 9388072]

208. Wormser GP, Dattwyler RJ, Shapiro ED et al. The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis . 2006; 43:1089-134. [PubMed 17029130]

209. Steere AC. Lyme disease. N Engl J Med . 2001; 345:115-25. [PubMed 11450660]

210. Thompson C, Speilman A, Krause P. Coinfecting deer-associated zoonoses: Lyme disease, babesiosis, and ehrlichiosis. Clin Infect Dis . 2000; 33:676-85.

213. Bratzler DW, Dellinger EP, Olsen KM et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health Syst Pharm . 2013; 70:195-283. [PubMed 23327981]

214. B. Braun. Cefuroxime sodium and dextrose injection prescribing information. Irvine, CA; 2010 May.

215. Apotex. Cefuroxime axetil tablets film coated prescribing information. Westin, FL; 2007 Oct.

217. Tunkel AR, Hartman BJ, Kaplan SL et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis . 2004; 39:1267-84. [PubMed 15494903]

219. Chow AW, Benninger MS, Brook I et al. IDSA clinical practice guideline for acute bacterial rhinosinusitis in children and adults. Clin Infect Dis . 2012; 54:e72-e112. [PubMed 22438350]

220. Wald ER, Applegate KE, Bordley C et al. Clinical Practice Guideline for the Diagnosis and Management of Acute Bacterial Sinusitis in Children Aged 1 to 18 Years. Pediatrics . 2013; :. [PubMed 23796742]