Cefixime is a semisynthetic, third generation cephalosporin antibiotic.1, 3, 4, 6, 7, 13, 23, 57, 60, 75, 83
Cefixime is a cephalosporin antibiotic that is used orally for the treatment of various infections caused by susceptible bacteria.1 Because cefixime has a long serum half-life and can be administered once or twice daily, some clinicians suggest that the drug may be particularly useful when patient compliance is a concern (e.g., in the treatment of otitis media).3, 40, 43, 56, 62, 63, 64, 75 Although cefixime is an effective alternative to other anti-infective agents for the treatment of many infections, the drug offers no clear advantage (except for a convenient dosage regimen) over other equally effective, less expensive anti-infectives available for the treatment of uncomplicated urinary tract infections or upper and lower respiratory tract infections.3, 75, 102 In addition, use of cefixime as empiric therapy in some infections (e.g., urinary tract infections, respiratory tract infections, soft tissue infections) is limited by its spectrum of activity since the drug is inactive against staphylococci, enterococci, and Pseudomonas aeruginosa .1, 3, 8, 51, 60, 74, 75, 101 Because cefixime is inactive against most anaerobic bacteria, the drug is ineffective in and should not be used alone if a mixed aerobic-anaerobic bacterial infection is suspected.60
Prior to initiation of cefixime therapy, appropriate specimens should be obtained for identification of the causative organism(s) and in vitro susceptibility tests.1 Cefixime therapy may be started pending results of susceptibility tests, but should be discontinued and other appropriate anti-infective therapy substituted if the organism is found to be resistant to cefixime.1
Cefixime is used for the treatment of adults and pediatric patients ≥6 months of age with uncomplicated urinary tract infections (UTIs) caused by susceptible isolates of Proteus mirabilis 1, 40, 51, 64, 74, 75, 182 or E. coli 1, 2, 40, 51, 64, 74, 75, 182 The drug also has been effective when used in a limited number of adults or children for the treatment of uncomplicated UTIs caused by other gram-negative bacteria, including Citrobacter spp. †, 51, 64, 74 C. diversus †, 74 C. freundii †, 74 Enterobacter spp. †, 40, 51 E. aerogenes †, 2, 40, 74 E. agglomerans †, 64 Klebsiella spp. †, 40, 51, 182 K. pneumoniae †, 64, 74 Morganella morganii †, 2 Proteus spp. †, 51, 64 or Serratia †.51, 74 In controlled studies in men and women with uncomplicated UTIs caused by susceptible gram-negative bacteria, oral cefixime (400 mg once daily or 200 mg twice daily) was as effective as oral co-trimoxazole (160 mg of trimethoprim and 800 mg of sulfamethoxazole every 12 hours)23, 51, 74 or oral amoxicillin (250 mg 3 times daily).23, 40, 75 The once- and twice-daily cefixime regimens were equally effective51, 75 and resulted in a bacteriologic cure in about 90-100% of adults with uncomplicated UTIs.23, 40, 51, 74, 75 In a study in pediatric patients 1-24 months of age with UTIs, a 14-day regimen of oral cefixime (16 mg/kg on day 1 followed by 8 mg/kg once daily) was as effective as a 14-day regimen that included a parenteral drug (IV cefotaxime 200 mg/kg daily given in 4 divided doses for 3 days or until the child was afebrile for 24 hours) followed by oral cefixime (8 mg/kg once daily).182
Cefixime has been effective in a few adults for the treatment of uncomplicated UTIs caused by gram-positive bacteria, including Staphylococcus epidermidis †, 2 Staphylococcus spp. †, 2, 51 Streptococcus agalactiae †, 2, 40 nonhemolytic streptococci†, 2, 40, 51 or Enterococcus faecalis †.2, 40 However, treatment failures have occurred when cefixime was used in the treatment of UTIs caused by gram-positive bacteria,51 and some of these organisms (e.g., staphylococci, S. agalactiae , enterococci) have been isolated in urine either during or after therapy with the drug.2, 51, 74
Some clinicians suggest that cefixime offers no advantage over other equally effective, less expensive anti-infective agents (e.g., sulfisoxazole, amoxicillin, co-trimoxazole) for the treatment of uncomplicated UTIs.3, 75, 102 For empiric therapy of acute, uncomplicated UTIs, co-trimoxazole, a fluoroquinolone, fosfomycin, or nitrofurantoin usually is recommended.104 Because cefixime is inactive in vitro against enterococci and staphylococci, the drug probably should not be used for empiric therapy of nosocomial UTIs.75, 102 It has been suggested that cefixime be reserved for the treatment of UTIs caused by multidrug-resistant gram-negative bacteria (e.g., E. coli ) and used as an alternative to co-trimoxazole, amoxicillin and clavulanate potassium, norfloxacin, and ciprofloxacin for these infections.3, 9
Cefixime has been used with some success in a limited number of adults for the treatment of pyelonephritis and other complicated UTIs†2, 23, 40, 75 caused by susceptible Enterobacteriaceae , including E. coli .2, 23 Response rates in patients with complicated UTIs receiving cefixime are not as good as those reported in patients with uncomplicated UTIs;23, 40, 75 bacteriologic cure rates in adults with complicated UTIs have been reported to be 67-100%.2, 23, 40 Further study is needed to evaluate efficacy of cefixime in the treatment of complicated UTIs.23
Cefixime is used for the treatment of adults and pediatric patients ≥6 months of age with otitis media caused by susceptible isolates of Haemophilus influenzae , Moraxella catarrhalis , and Streptococcus pyogenes .1, 2, 3, 23, 43, 56, 61, 62, 63, 75, 138, 164, 165 Cefixime also has been used for the treatment of otitis media caused by Streptococcus pneumoniae ; however, overall response was approximately 10% lower for cefixime than for the comparator in clinical studies.1
In clinical studies in children 6 months to 16 years of age with otitis media, a 10-day regimen of oral cefixime produced a favorable clinical response (e.g., clinical cure or improvement with absence of fever, irritability, otalgia, and tympanic membrane erythema with or without middle ear effusion) in 83-100% and a presumptive bacteriologic cure in 60-97% of patients.2, 23, 43, 62, 63, 102, 150, 164 At 2-4 weeks after cefixime therapy, a clinical cure was still evident in 71-77% of children with H. influenzae infections, 84-100% of those with M. catarrhalis infections, and 69-82% of those with S. pneumoniae infections;1, 2 persistent effusions were present in 15% of patients and 17% were considered to be treatment failures.1 In studies in children with otitis media, oral cefixime (8 mg/kg once daily or 4 mg/kg twice daily) was as effective as oral amoxicillin (20 or 40 mg/kg daily given in 3 equally divided doses),43, 61, 63, 165 oral amoxicillin and clavulanate potassium (40 mg of amoxicillin per kg daily in 3 equally divided doses),138 oral cefpodoxime proxetil (10 mg/kg once daily),149 or oral cefaclor (40 mg/kg daily given in 3 equally divided doses)62, 150 for the treatment of infections caused by susceptible β-lactamase-producing M. catarrhalis or H. influenzae .2, 61, 165 Both the once- and twice-daily cefixime regimens appear to be equally effective in the treatment of otitis media caused by susceptible organisms.2, 56, 61, 75
There is some evidence that cefixime is less effective than some other anti-infective agents for the treatment of otitis media caused by S. pneumoniae .1, 2, 3, 23, 61, 162, 164, 165 In some studies where results were stratified according to causative organism, the bacteriologic response reported for cefixime in infections caused by S. pneumoniae was lower than that reported for amoxicillin.1, 2, 3, 23, 165 Because at least one case of pneumococcal bacteremia developed in a child who was receiving cefixime for the treatment of otitis media,170 some clinicians suggest that cefixime not be used for the treatment of otitis media known or suspected of being caused by S. pneumoniae .162 Although the clinical importance is unclear, staphylococci have been isolated from middle-ear fluid after treatment in a few patients receiving cefixime.61
When anti-infective therapy is indicated for the treatment of otitis media, the American Academy of Pediatrics (AAP) recommends high-dose amoxicillin or amoxicillin and clavulanate potassium as the drug of first choice for initial treatment.184, 750, 751 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, 750, 751
Cefixime is used in the treatment of adults and pediatric patients ≥6 months of age with pharyngitis and tonsillitis caused by susceptible isolates of Streptococcus pyogenes .1, 2, 3, 23, 44, 56, 64, 75 Although cefixime usually is effective in eradicating S. pyogenes from the nasopharynx,1, 169 efficacy of the drug for prevention of subsequent rheumatic fever has not been established.1
The American Academy of Pediatrics (AAP),82, 750 Infectious Diseases Society of America (IDSA),152 American Heart Association (AHA),86 and others104, 154, 156 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.5, 82, 86, 104, 152, 750
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).82, 86, 152, 750
Acute Exacerbations of Chronic Bronchitis
Cefixime is used for the treatment of adults and pediatric patients ≥6 months of age with acute exacerbations of chronic bronchitis caused by susceptible isolates of Streptococcus pneumoniae and Haemophilus influenzae .1, 2, 23, 72, 75, 103, 180
Cefixime also has been used for the treatment acute exacerbations of chronic bronchitis caused by M. catarrhalis †.2, 44, 70, 72, 103
There is some evidence that 5- or 10-day regimens of oral cefixime (400 mg once daily) are equally effective in patients with acute exacerbation of chronic bronchitis; in one study, the clinical and bacteriologic response rates reported with a 5-day regimen were 88-91 and 69-74%, respectively, and those reported with the 10-day regimen were 88-91 and 53-82%, respectively (intent-to-treat analysis).180 In one study in adults, cefixime (400 mg once daily) was as effective as oral amoxicillin (500 mg 3 times daily) for the treatment of lower respiratory tract infections caused by susceptible organisms.44 Other controlled studies in adults indicate that cefixime (200 mg twice daily or 400 mg once daily) was as effective as oral amoxicillin and clavulanate potassium (500 mg/125 mg 3 times daily), oral cefaclor (500 mg 3 times daily), or oral cephalexin (250 mg 4 times daily) for the treatment of these infections.2, 23, 70, 72, 103 However, the bacteriologic cure rate reported with cefixime in the treatment of lower respiratory tract infections has ranged from 54-100%,2, 23, 44, 70, 72, 75, 103 and some clinicians suggest that further study is needed to evaluate the drug's role in the treatment of these infections.75, 102
Cefixime is used for the treatment of adults and pediatric patients ≥6 months of age with uncomplicated gonorrhea (cervical/urethral).1, 48, 82, 106, 108, 109, 110, 111, 118, 119, 120, 130, 194, 197 However, because of concerns related to reports of Neisseria gonorrhoeae with reduced susceptibility to cephalosporins, the US Centers for Disease Control and Prevention (CDC) states that cefixime is no longer recommended as first-line treatment for uncomplicated gonorrhea.130, 197
Although cefixime has been effective when given as a single 400- or 800-mg oral dose for the treatment of acute uncomplicated endocervical gonorrhea in women and urethral gonorrhea in men caused by penicillinase- and nonpenicillinase-producing N. gonorrhoeae ,1, 2, 23, 48, 71, 106, 108, 109, 110, 111 N. gonorrhoeae with reduced susceptibility to cefixime, including some treatment failures, have been reported in the US and other countries with increasing frequency.130, 194, 195, 196, 197, 198 Because of the possibility of emergence of resistance and because bactericidal concentrations attained with the CDC-recommended 800-mg dose of oral cefixime are lower and not as sustained as those provided by a single 500-mg IM dose of ceftriaxone, cefixime should only be used for the treatment of urogenital or rectal† gonococcal infections when ceftriaxone is unavailable or cannot be used.130 In addition, cefixime is not recommended for the treatment of pharyngeal gonorrhea since it has only limited efficacy for the treatment of these infections.130, 195, 197
Currently, CDC, AAP, and other clinicians state that ceftriaxone (single IM dose of 500 mg in patients <150 kg and 1 g in patients ≥150 kg) is the drug of choice for gonococcal infections in the US.130, 746, 747, 748 Although dual therapy with ceftriaxone and azithromycin was recommended in previous treatment guidelines and may have mitigated the emergence of reduced susceptibility to ceftriaxone in N. gonorrhoeae , concerns regarding potential harm to the microbiome and effects on other pathogens have caused the CDC and AAP to no longer recommend dual therapy for gonococcal infections.130, 746, 747 In addition, CDC no longer recommends cefixime as a first-line agent for gonorrhea treatment in the US.130, 747
If chlamydia has not been excluded, CDC states that patients with gonorrhea also should be treated for chlamydia with doxycycline (100 mg twice daily for 7 days).130
In adults and adolescents with cephalosporin allergy, CDC states that a dual treatment regimen that includes a single dose of IM gentamicin (240 mg) and a single dose of oral azithromycin (2 g) could be considered for the treatment of uncomplicated urogenital gonorrhea; however, GI effects may limit use of this regimen.130, 747 If available, spectinomycin (no longer commercially available in the US) is an effective alternative for the treatment of urogenital and anorectal gonorrhea.130 Although monotherapy with a single 2-g dose of oral azithromycin was previously recommended for the treatment of uncomplicated urogenital gonorrhea in patients with cephalosporin allergy, CDC states that monotherapy is no longer recommended because of concerns related to development of resistance and because there have been documented treatment failures with azithromycin monotherapy.130
If necessary when ceftriaxone is not available or cannot be used, CDC states that adults and adolescents can receive a single 800-mg dose of oral cefixime for the treatment of uncomplicated urogenital or anorectal gonorrhea.130, 747
A test-of-cure follow-up (culture or NAAT) is not usually needed in patients with uncomplicated urogenital or rectal gonorrhea who receive a recommended or alternative treatment regimen.130, 746, 747
The CDC recommends that health-care providers treating gonorrhea remain vigilant for treatment failures (evidenced by persistent symptoms or a positive follow-up test despite treatment).130 If there is evidence of treatment failure, relevant clinical specimens should be cultured and in vitro susceptibility testing performed.130, 197 In addition, an infectious disease specialist, an STD/HIV Prevention Training Center ([Web]), or the CDC (800-232-4636) should be consulted for treatment advice and the case should be reported to the CDC through local or state health departments within 24 hours of diagnosis.130 A test-of-cure should be performed 7-14 days after retreatment.130 For all patients with gonorrhea, clinicians should ensure that the patient's sexual partners from the preceding 60 days are evaluated promptly and receive presumptive treatment.130
Oral cefixime has been effective when used in adults or children for the treatment of mild to moderate pneumonia, including community-acquired pneumonia†.137, 166 When used in the treatment of hospitalized patients with community-acquired pneumonia, therapy was initiated with a parenteral third generation cephalosporin (e.g., ceftriaxone, cefotaxime) and then changed to oral cefixime, as appropriate, allowing therapy to be completed on an outpatient basis.137, 166
Other cephalosporins (e.g., ceftriaxone, cefotaxime, ceftaroline, ceftazidime, cefpodoxime, cefuroxime) are recommended by the American Thoracic Society/Infectious Diseases Society of America and others when a cephalosporin is used in the treatment of community-acquired pneumonia.512, 750, 751
For additional information on management of community-acquired pneumonia, current clinical practice guidelines from IDSA available at [Web] should be consulted.512, 513
Oral cefixime has been used in a limited number of patients for the treatment of Lyme disease†.181 In an open-label, randomized study in patients with disseminated Lyme borreliosis, oral cefixime (200 mg daily with oral probenecid 500 mg 3 times daily) given for 100 days was as effective as a regimen of IV ceftriaxone (2 g daily given for 14 days) followed by oral amoxicillin (500 mg 3 times daily with oral probenecid 500 mg 3 times daily) given for 100 days.181 However, other cephalosporins (ceftriaxone, cefotaxime, cefuroxime axetil) are recommended by the Infectious Diseases Society of America (IDSA), American Academy of Pediatrics (AAP), and other experts when a cephalosporin is used in the treatment of Lyme disease.185, 744, 745
Oral cefixime (8 mg/kg daily for 5 days) has been effective when used in children for the treatment of shigellosis† caused by susceptible Shigella 139, 148 and, in one study, was more effective than ampicillin and sulbactam sodium for the treatment of these infections.148 However, in a study in adults with shigellosis who received oral cefixime (400 mg once daily for 5 days), the clinical response rate to the drug was only 53% and the bacteriologic eradication rate was 40%.140 Anti-infective therapy generally is indicated in addition to fluid and electrolyte replacement for the treatment of severe cases of shigellosis since anti-infectives appear to shorten the duration of diarrhea and the period of fecal excretion of Shigella .82, 163, 753 Multiple-drug resistant strains of Shigella have been reported with increasing frequency.82, 753
For infections caused by Shigella , IDSA and AAP recommend azithromycin, ciprofloxacin, or ceftriaxone as first-line agents.217, 753 Alternative agents include oral ampicillin or co-trimoxazole if the isolate is susceptible.217, 753 A fluoroquinolone should not be used if the ciprofloxacin MIC is ≥0.12 mcg/mL, even if the laboratory report identifies the isolate as susceptible.217, 753 AAP recommends the use of oral antibiotics over parenteral treatment, except in seriously ill patients, those with underlying immunodeficiencies, and patients unable to take oral medications.753
For the treatment of Shigella infections in HIV-infected adults and adolescents, CDC, NIH, and IDSA state that the drug of choice is ciprofloxacin and alternatives are levofloxacin, moxifloxacin, co-trimoxazole, or azithromycin.440 Because antimicrobial resistance of Shigella is increasing and limited data demonstrate that antibiotic therapy limits transmission, NIH/CDC/IDSA state that antibiotic treatment may be withheld in patients with HIV and CD4+ T-cell counts >500 cells/mm3 whose diarrhea resolves before culture confirmation of Shigella infection.440
Cefixime has been used for the treatment of mild to moderate sinusitis† caused by S. pneumoniae ,2, 23, 44, 70, 72, 103 H. influenzae ,2, 23, 44, 70, 72, 103 M. catarrhalis ,2, 44, 70, 72, 103, 137, 166 E. coli , H. parahaemolyticus , or H. parainfluenzae .2, 23, 44, 75 Because of variable activity against S. pneumoniae and H. influenzae , IDSA no longer recommends second or third generation oral cephalosporins for empiric monotherapy of acute bacterial sinusitis.192 Oral amoxicillin or amoxicillin and clavulanate usually is recommended for empiric treatment.192, 193 If an oral cephalosporin is used as an alternative in children (e.g., in penicillin-allergic individuals), a combination regimen that includes a third generation cephalosporin (cefixime or cefpodoxime) and clindamycin (or linezolid) is recommended.192, 193
Typhoid Fever and Other Salmonella Infections
Oral cefixime has been used in children for the treatment of typhoid fever (enteric fever) or septicemia caused by multidrug-resistant strains of Salmonella typhi †.141, 142, 189, 190, 191 In a study in children 6 months to 13 years of age with typhoid fever caused by multidrug-resistant S. typhi who were randomized to receive a 14-day regimen of oral cefixime (5 mg/kg twice daily) or IV ceftriaxone (65 mg/kg once daily), the time to defervescence was 8.3 days in those who received cefixime and 8 days in those who received ceftriaxone; the relapse rate was 5 and 14%, respectively.141
Multidrug-resistant strains of S. typhi (i.e., strains resistant to ampicillin, chloramphenicol, and/or co-trimoxazole) have been reported with increasing frequency, and fluoroquinolones (e.g., ciprofloxacin, ofloxacin) and third generation cephalosporins (e.g., ceftriaxone, cefotaxime) have been considered the agents of first choice for the treatment of typhoid fever or other severe infections known or suspected to be caused by these strains.82, 104, 146, 147, 163, 174 AAP and CDC state that most typhoid fever infections diagnosed in the US are not susceptible to fluoroquinolones and that fluoroquinolones should not be used as empiric therapy.752, 766 AAP states that ceftriaxone is a drug of choice for empiric treatment of enteric fever pending results of in vitro susceptibility tests.752 Strains of S. typhi resistant to ceftriaxone have been reported rarely in the US.405, 752 Travel history and regional antibiotic resistance patterns should be considered carefully when selecting empiric antibiotic therapy for enteric fever.752, 765, 766 Clinicians should adjust treatment based on results of susceptibility testing.766
Cefixime is administered orally as capsules, conventional tablets, chewable tablets, or an oral suspension.1
Capsules containing 400 mg of cefixime are bioequivalent to conventional tablets containing 400 mg of the drug when administered under fasting conditions.1
Cefixime chewable tablets are bioequivalent to cefixime oral suspension.1
Cefixime conventional tablets and oral suspension are not bioequivalent.1
Store cefixime capsules, conventional tablets, or chewable tablets at 20-25°C.1
Store cefixime powder for oral suspension in tight containers at 20-25°C.1 After reconstitution, store the oral suspension in a tight container.1 The reconstituted suspension is stable for 14 days at room temperature or when refrigerated; discard any unused suspension after 14 days.1
Cefixime may be administered once or twice daily.1, 2, 3, 40, 51, 74, 75 Once- and twice-daily regimens reportedly are similarly effective for the treatment of otitis media,2, 56, 61, 75 tonsillitis,2, 56 or uncomplicated urinary tract infections.2, 51, 75 Relative efficacy of the 2 regimens has not been evaluated in other infections, and some clinicians suggest that twice-daily dosing may be preferable for the treatment of some lower respiratory tract infections70, 72, 75 or for complicated urinary tract infections†.75 Results of most studies indicate that the incidence of GI effects is similar with once- and twice-daily regimens.2, 23, 40, 41, 44, 56
Capsules, Conventional Tablets, and Chewable Tablets
Cefixime capsules and conventional tablets may be administered without regard to meals.1 Presence of food in the GI tract decreases the rate of absorption of cefixime, but generally does not affect the extent of absorption of the drug.1, 2, 3, 26
Cefixime chewable tablets must be chewed or crushed before swallowing.1
Reconstitute cefixime powder for oral suspension at the time of dispensing by adding the amount of water specified on the container to provide a suspension containing 100, 200, or 500 mg of cefixime per 5 mL.1 Add the water to the powder in 2 equal portions and shake he bottle well after each addition.1
Shake the suspension well just prior to administration of each dose.1
Cefixime is commercially available as the trihydrate;1, 2, 83 potency of the drug is expressed in terms of cefixime1, 83 (the free acid), calculated on the anhydrous basis.83
The usual adult dosage of cefixime for the treatment of uncomplicated urinary tract infections is 400 mg once daily or 200 mg every 12 hours.1 The usual duration of cefixime therapy for the treatment of uncomplicated urinary tract infections is 5-10 days.2, 40, 51, 74
The usual adult dosage of cefixime for the treatment of otitis media is 400 mg once daily or 200 mg every 12 hours1 for 10-14 days.23, 56, 62, 63
Only the chewable tablets or oral suspension should be used for the treatment of otitis media; cefixime capsules and conventional tablets should not be used for the treatment of otitis media.1
The usual adult dosage of cefixime for the treatment of pharyngitis and tonsillitis caused by Streptococcus pyogenes (group A β-hemolytic streptococci) is 400 mg once daily or 200 mg every 12 hours for ≥10 days.1
Acute Exacerbations of Chronic Bronchitis
The usual adult dosage of cefixime for the treatment of acute exacerbations of chronic bronchitis is 400 mg once daily or 200 mg every 12 hours.1 The usual duration of cefixime therapy for the treatment of upper respiratory tract infections is 10-14 days.44, 64, 72
If cefixime is used as an alternative for the treatment of uncomplicated urogenital or rectal† gonorrhea when ceftriaxone is not available or cannot be used, the US Centers for Disease Control and Prevention (CDC) recommends a single 800-mg dose of oral cefixime.130 Cefixime is not recommended by the CDC as first-line treatment for uncomplicated gonorrhea.130, 197 If chlamydia has not been excluded, CDC states that patients with gonorrhea also should be treated for chlamydia.130
The manufacturer recommends a single 400-mg dose of oral cefixime for the treatment of uncomplicated cervical/urethral gonococcal infections.1
For the treatment of Lyme disease†, adults have received cefixime in a dosage of 200 mg daily for 100 days (administered with oral probenecid 500 mg 3 times daily).181
Children >12 years of age or those weighing >45 kg may receive the usual adult dosage of cefixime.1
For pediatric patients beyond the neonatal period, the American Academy of Pediatrics (AAP) recommends a cefixime dosage of 8 mg/kg daily given in 1 or 2 divided doses for the treatment of mild to moderate infections.82, 757 The AAP states that cefixime is inappropriate for the treatment of severe infections.82
The oral suspension containing 100 mg of cefixime per 5 mL is the preferred preparation for use in children weighing 5-7.5 kg; oral suspensions containing 100 or 200 mg of cefixime per 5 mL are the preferred preparations in those weighing 7.6-10 kg.1
Cefixime chewable tablets are not recommended in children weighing <10 kg.1
The usual dosage of cefixime for the treatment of uncomplicated urinary tract infections in children 6 months to 12 years of age is 8 mg/kg once daily or 4 mg/kg every 12 hours.1 The usual duration of cefixime therapy for the treatment of uncomplicated urinary tract infections is 5-10 days.2, 40, 51, 74
The usual dosage of cefixime for the treatment of otitis media in children 6 months to 12 years of age is 8 mg/kg once daily or 4 mg/kg every 12 hours1 for 10-14 days.23, 56, 62, 63
In pediatric patients >12 years of age or weighing >45 kg, the usual dosage of cefixime for the treatment of otitis media is 400 mg daily1 for 10-14 days.44, 64, 72
Only the chewable tablets or oral suspension should be used for the treatment of otitis media; cefixime capsules and conventional tablets should not be used for the treatment of otitis media.1
The usual dosage of cefixime for the treatment of group A β-hemolytic streptococcal pharyngitis and tonsillitis in children 6 months to 12 years of age is 8 mg/kg once daily or 4 mg/kg every 12 hours for ≥10 days.1
Acute Exacerbations of Chronic Bronchitis
The usual dosage of cefixime for the treatment of acute exacerbations of chronic bronchitis in children 6 months to 12 years of age is 8 mg/kg once daily or 4 mg/kg every 12 hours.1 The usual duration of cefixime therapy for the treatment of upper respiratory tract infections is 10-14 days.44, 64, 72
For the treatment of uncomplicated gonorrhea when ceftriaxone is unavailable or cannot be used, CDC and AAP recommend a single cefixime dose of 800 mg in children or adolescents >12 years of age weighing ≥45 kg.130, 748
In pediatric patients weighing >45 kg or who are >12 years of age, the manufacturer recommends a single 400-mg dose of cefixime for the treatment of uncomplicated cervical/urethral gonococcal infections.1 In pediatric patients ≥6 months of age, the manufacturer recommends a dose of 8 mg/kg of the cefixime suspension.1
Cefixime is not recommended by the CDC as first-line treatment for uncomplicated gonorrhea.130, 197 If chlamydia has not been excluded, patients also should be treated for chlamydia.130, 748
For the treatment of shigellosis†, children have received cefixime in a dosage of 8 mg/kg daily for 5 days.139, 148
For empiric treatment of acute bacterial sinusitis† in children, a cefixime dosage of 8 mg/kg daily given in 2 equally divided doses for 10-14 days has been recommended.192
For the treatment of typhoid fever†, children 6 months to 16 years of age have received cefixime in a dosage of 5-10 mg/kg twice daily.141, 142, 189, 190, 191 Treatment usually is continued for 14 days;141, 142, 189 a high rate of treatment failure occurred when the drug was given for only 7 days.190
The manufacturer makes no specific dosage recommendations for patients with hepatic impairment.1
In patients with creatinine clearances <60 mL/minute, dose and/or frequency of administration of cefixime should be modified in response to the degree of renal impairment.1 The manufacturer recommends that adults with creatinine clearances of 21-59 mL/minute and those undergoing hemodialysis receive a cefixime dosage of 260 mg daily administered as oral suspension, preferably as oral suspension containing 200 or 500 mg of cefixime per 5 mL; cefixime conventional tablets and chewable tablets are not recommended in these patients.1 The manufacturer also recommends that adults with creatinine clearances of ≤20 mL/minute and those undergoing continuous peritoneal dialysis receive a cefixime dosage of 200 mg daily as conventional tablets or chewable tablets, 172 mg daily as oral suspension containing 100 mg/5 mL, 176 mg daily as oral suspension containing 200 mg/5 mL, or 180 mg daily as oral suspension containing 500 mg/5 mL.1 Because cefixime is not substantially removed by hemodialysis or peritoneal dialysis,1, 33, 37, 75 additional supplemental doses of the drug are not necessary during or after either procedure.33, 75
Modification of the usual dosage of cefixime is not necessary in geriatric adults based on age,35, 37 but may be required because of age-related decreases in renal function.35, 37
Hypersensitivity reactions have been reported in up to 7% of patients receiving cefixime1, 23, 40, 41, 75 and include rash,1, 40, 41, 43, 56, 64, 75 urticaria,1, 41, 43, 44, 62, 63, 75 drug fever,1, 41, 64 pruritus,1, 39, 40, 41, 44, 75 and arthralgia.39, 41
Anaphylaxis, angioedema, facial edema, Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, and serum sickness-like reactions1, 41 have been reported in <2% of patients receiving cefixime.1
If an allergic reaction to cefixime occurs, discontinue the drug.1 Prior to initiation of cefixime therapy, careful inquiry should be made concerning previous hypersensitivity reactions to cephalosporins, penicillins, or other drugs.1 There is clinical and laboratory evidence of partial cross-allergenicity among β-lactam antibiotics including penicillins, cephalosporins, and cephamycins.1, 172, 173 Caution is advised.1 Cefixime is contraindicated in individuals who are hypersensitive to the drug or other cephalosporins.1 Use of cephalosporins should be avoided in patients who have had an immediate-type (anaphylactic) hypersensitivity reaction to penicillins.173
Clostridioides difficile-associated Diarrhea
Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridioides difficile .1, 42, 177, 178
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 cefixime, and may range in severity from mild diarrhea to fatal colitis.1, 2, 39, 41, 42, 67C. difficile produces toxins A and B which contribute to the development of CDAD;1, 42 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
CDAD should be considered in the differential diagnosis in patients who develop diarrhea during or after anti-infective therapy and managed accordingly.1, 42, 177, 178 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, 42
If CDAD is suspected or confirmed, anti-infectives not directed against C. difficile should be discontinued whenever possible.1, 42, 177, 178 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, 42, 177, 178
Dose Adjustment in Renal Impairment
Because serum concentrations of cefixime are higher and more prolonged in patients with moderate or severe renal impairment than in patients with normal renal function, doses and/or frequency of administration of the drug should be decreased in patients with impaired renal function, including those undergoing continuous ambulatory peritoneal dialysis (CAPD) or hemodialysis.1, 2, 23, 33, 37, 75 Patients undergoing dialysis should be monitored carefully during cefixime therapy.1
Because decreased prothrombin activity has been reported with cephalosporins, including cefixime, prothrombin time should be monitored in patients at risk and exogenous vitamin K administered as indicated.1 Patients at risk for such coagulation effects include those with renal or hepatic impairment or poor nutritional status, patients receiving prolonged anti-infective therapy, and patients previously stabilized on anticoagulant therapy.1
Development of Drug-resistant Bacteria
To reduce development of drug-resistant bacteria and maintain effectiveness of cefixime 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 When selecting or modifying anti-infective therapy, results of culture and in vitro susceptibility testing should be used.1 In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.1
Individuals with phenylketonuria should be cautioned that cefixime chewable tablets containing 100, 150, and 200 mg of the drug contain aspartame, which is metabolized in the GI tract to provide 3.3, 5, and 6.7 mg of phenylalanine, respectively.1 Phenylalanine can be harmful to patients with phenylketonuria.1 Consider the combined daily amount of phenylalanine from all sources before prescribing cefixime chewable tablets in a patient with phenylketonuria.1
Reproduction studies in mice and rats using oral cefixime dosages up to 40 times the usual human dosage have not revealed evidence of harm to the fetus.1 Cefixime has been reported to cross the placenta.2, 23 There are no adequate and controlled studies to date using cefixime in pregnant women, and the drug should be used during pregnancy only when clearly needed.1 Use of cefixime during labor and delivery has not been studied to date, and the drug should be used in these circumstances only when clearly needed.1
Cefixime is distributed into milk in rats.36 Although the drug reportedly was not detected in milk following a single dose in lactating women in one study,2 it is not known whether cefixime is distributed into milk in humans.1 Therefore, consideration should be given to temporarily discontinuing nursing during therapy with the drug.1
Safety and efficacy of cefixime in children <6 months of age have not been established.1
The frequency of adverse GI effects (e.g., diarrhea, loose stools) reported in pediatric patients receiving cefixime oral suspension is similar to that reported in adults receiving cefixime tablets.1 Diarrhea or loose stools has been reported in up to 15% of children 6 months to 13 years of age receiving oral cefixime.2, 41, 75 CDAD has been reported rarely in children receiving cefixime.144 In 3 reported cases, the onset of symptoms (abdominal pain, diarrhea) occurred 4-14 days after the first dose of cefixime.144
Clinical studies did not include sufficient numbers of patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.1 Other reported clinical experience has not identified differences in responses between geriatric and younger patients.1
Some evidence indicates that oral bioavailability of the drug may be increased in geriatric patients,1, 2, 35, 37 but such increases are not considered clinically important.2, 35, 37
Because renal function decreases with age and may be impaired in geriatric patients, the possibility that adjustment of cefixime dosage may be necessary in this age group should be considered.35, 37
Although the difference was not considered clinically important,2, 35, 37 one study in geriatric patients >64 years of age receiving 400-mg doses of cefixime once daily for 5 days indicated that peak serum concentrations of cefixime were 20-26% higher and AUCs were approximately 40-42% higher in these geriatric adults than in healthy adults 18-35 years of age.1, 35
It is not known whether impaired hepatic function has an effect on the pharmacokinetics of cefixime.75 There is no evidence of metabolism of cefixime in vivo.1 Hepatic impairment is not expected to affect clearance of cefixime.1
The serum half-life of cefixime is prolonged in patients with impaired renal function.1, 2, 23, 33, 37, 75 In adults with moderate renal impairment (creatinine clearances of 20-40 mL/minute), serum half-life averages 6.4 hours.1 In adults with severe renal impairment (creatinine clearances of 5-20 mL/minute), half-life averages 11.5 hours.1
Cefixime is not substantially removed by hemodialysis or peritoneal dialysis.1 In one study in a limited number of adults undergoing hemodialysis and receiving 400-mg oral doses of cefixime, pharmacokinetics of the drug were similar to those reported for patients with creatinine clearances of 21-60 mL/minute.1
The most common adverse reactions in patients receiving cefixime are diarrhea (16%), nausea (7%), loose stools (6%), abdominal pain (3%), dyspepsia (3%), and vomiting.1
Results of a study in healthy men indicate that administration of an antacid containing aluminum hydroxide and magnesium hydroxide either simultaneously with or 2 hours before or after a single 400-mg oral dose of cefixime has no clinically important effects on the pharmacokinetics of the anti-infective agent.32
Increased prothrombin time (with or without bleeding) has been reported following concomitant use of cefixime with an anticoagulant (e.g., warfarin).1
Concomitant administration of cefixime and carbamazepine has resulted in increased plasma carbamazepine concentrations.1 Carbamazepine concentrations should be monitored if the drug is used concomitantly with cefixime.1
Concomitant administration of cefixime and nifedipine increases oral bioavailability of cefixime, with higher peak plasma concentrations and AUC.143
Although specific information is unavailable, concomitant administration of probenecid reportedly increases peak serum concentrations and the AUC of cefixime and decreases renal clearance and volume of distribution of the drug.2
In one in vitro study in pooled serum, salicylic acid apparently displaced cefixime from protein binding sites, resulting in more than a 50% increase in concentrations of free cefixime; this effect appeared to be concentration-dependent.25 Concomitant administration of a 650-mg oral dose of aspirin and a 400-mg oral dose of cefixime in healthy adult men did not appear to affect protein binding, serum half-life, or renal clearance of cefixime but did result in a 20-25% decrease in peak serum concentrations and AUCs of the anti-infective agent.2 Although the manufacturer states that this effect was not considered clinically important since serum concentrations of cefixime remained higher than the MIC values reported for most susceptible organisms,2 some clinicians state that this potential interaction may be clinically important in certain infections.102
A false-positive reaction for ketones in the urine may occur with tests using nitroprusside but not with those using nitroferricyanide.1
Administration of cefixime may result in a false-positive reaction for glucose in the urine using Clinitest®, Benedict's solution, or Fehling's solution.1 Use of glucose tests based on enzymatic glucose oxidase reactions (such as Clinistix® or TesTape®) is recommended in patients receiving cefixime.1
A false-positive direct Coombs test has been reported during treatment with cephalosporins.1
Cefixime is a semisynthetic oral aminothiazolyl methoxyimino cephalosporin antibiotic.1, 2, 3, 4, 6, 7, 13, 23, 57, 60, 75, 83 Based on its spectrum of activity, cefixime is classified as a third generation cephalosporin.3, 13, 15, 50, 69, 75 Cefixime is structurally similar to other oral (cefdinir, cefpodoxime proxetil, ceftibuten) or parenteral (cefotaxime, ceftazidime, ceftriaxone) cephalosporins that contain an aminothiazolyl side chain at position 7 of the cephalosporin nucleus.2, 4, 7, 13, 23, 57, 83 The aminothiazolyl side chain enhances antibacterial activity, particularly against Enterobacteriaceae, and the methoxyimino group imparts stability against hydrolysis by many β-lactamases.4, 57, 60, 75 Cefixime contains a vinyl moiety at position 3 of the cephalosporin nucleus, which is partially responsible for the GI absorption characteristics of the drug.2, 75 The vinyl moiety also may contribute to cefixime's potent bactericidal activity,60 although it appears to be partially responsible for the drug's poor in vitro activity against staphylococci.60
Cefixime is usually bactericidal in action.1, 2, 14, 34, 65, 69, 78 Like other cephalosporins, the antibacterial activity of the drug results from inhibition of mucopeptide synthesis in the bacterial cell wall.1, 2, 75
Cefixime has a high affinity for penicillin-binding proteins (PBPs) 3, 1a, and 1b of Escherichia coli .2, 14, 23, 60, 65, 75 Since PBP 1b is a killing site for β-lactam anti-infectives, cefixime's high affinity for this site may be a major factor in the drug's potent bactericidal activity against this organism.2, 14, 23, 60, 75 Cefixime has only low affinity for PBP 2 of staphylococci2, 23, 60, 75 and little or no affinity for PBP 4 or 5.60
In vitro studies indicate that low concentrations of cefixime usually cause the formation of filamentous cells in susceptible E. coli or Klebsiella pneumoniae .2, 9 At higher concentrations, direct lysis of the organisms may occur as well as spheroplast formation and rupture.2 Following in vitro exposure to cefixime, morphologic changes in β-lactamase-producing E. coli are the same as those seen in non-β-lactamase-producing strains of the organism.2 Lysis occurs in susceptible anaerobic bacteria following in vitro exposure to cefixime.2
For most susceptible organisms, the minimum bactericidal concentration (MBC) of cefixime is only 1-4 times higher than the minimum inhibitory concentration (MIC).2, 8, 14, 15, 20, 23, 60 However, for some strains of Enterobacter , Klebsiella , Morganella , Proteus , Providencia , and Serratia , the MBC may be 9-32 times higher than the MIC.14, 60
Like other currently available third generation cephalosporins (e.g., cefdinir, cefoperazone, cefotaxime, cefpodoxime, ceftazidime, ceftibuten, ceftriaxone), cefixime has an expanded spectrum of activity against gram-negative bacteria compared with first and second generation cephalosporins.2, 3, 14, 23, 59, 60, 75 In vitro on a weight basis, however, cefixime usually is less active than many other currently available third generation cephalosporins against susceptible Enterobacteriaceae15, 75, 101 and is inactive in vitro against most strains of Enterobacter 60, 75 and Pseudomonas .2, 13, 14, 15, 20, 23, 59, 60, 66, 75, 101 Although some other currently available third generation cephalosporins have some activity against staphylococci, cefixime usually is inactive against these organisms.1, 2, 3, 13, 14, 18, 20, 23, 59, 60, 69, 75, 78, 101
Cefixime generally is active in vitro against Streptococcus pyogenes (group A β-hemolytic streptococci),1, 2, 3, 13, 14, 20, 23, 50, 59, 60, 66, 77, 78, 79 S. agalactiae (group B streptococci),1, 2, 13, 15, 18, 23, 50, 59, 60, 66, 75 and groups C, F, and G streptococci.13, 23, 59, 60, 66 The MIC90 (minimum inhibitory concentration of the drug at which 90% of strains tested are inhibited) of cefixime reported for S. pyogenes and S. agalactiae is 0.1-0.5 mcg/mL,2, 3, 13, 14, 20, 23, 50, 59, 60, 66, 75, 78, 161 and the MIC90 reported for groups C, F, and G streptococci is 0.05-1 mcg/mL.23, 59, 60, 66, 75 In vitro on a weight basis, cefixime is either equally or more active than most first and second generation cephalosporins (e.g., cephalexin, cefadroxil, cefaclor, cefuroxime) against S. pyogenes ,3, 75 but is less active than ampicillin or amoxicillin against these organisms.2, 23
Cefixime is active in vitro against some strains of S. pneumoniae ;1, 2, 14, 20, 23, 50, 59, 60, 66, 167, 168 however, in vitro on a weight basis, the drug generally is less active against this organism than some other oral cephalosporins (e.g., cefdinir, cefpodoxime, cefprozil, cefuroxime).167, 168 While penicillin-susceptible S. pneumoniae may be inhibited in vitro by cefixime concentrations of ≤4 mcg/mL, the MIC90 of cefixime reported for strains of S. pneumoniae that have intermediate resistance to penicillin (relatively resistant) and strains that are highly resistant to penicillin is 16-32 mcg/mL and these strains are considered resistant to cefixime.137, 167, 168
Nonenterococcal group D streptococci (e.g., S. bovis ) and viridans streptococci (e.g., S. mitis ) generally require cefixime concentrations of 1-32 mcg/mL for in vitro inhibition, and most strains are considered resistant to the drug.2, 13, 19, 23, 50, 59, 60, 66, 75 In one study, the MIC50 and MIC90 of cefixime for the S. milleri group of viridans streptococci ( S. anginosus , S. constellatus , S. intermedius ) were 4 and 8 mcg/mL, respectively.183 Enterococci, including Enterococcus faecalis (formerly S. faecalis ) and E. faecium (formerly S. faecium ), are resistant to cefixime.1, 2, 3, 13, 20, 23, 59, 60, 66, 75
Unlike other currently available cephalosporins, cefixime is inactive in vitro against penicillinase-producing and nonpenicillinase-producing staphylococci, including Staphylococcus aureus ,1, 2, 3, 13, 14, 18, 20, 23, 59, 60, 66, 75, 78 S. epidermidis ,1, 2, 3, 4, 13, 14, 20, 23, 59, 60, 75, 78 and S. saprophyticus .23, 60 Although some staphylococci may be inhibited in vitro by cefixime concentrations of 3-16 mcg/mL, most strains require high concentrations of cefixime for in vitro inhibition and are considered resistant to the drug.59, 60, 75 Like other cephalosporins, cefixime is inactive against methicillin-resistant (oxacillin-resistant) staphylococci.3, 4, 20, 59, 60, 75, 78
Corynebacterium ,19, 23 including JK strains of Corynebacterium JK ,13, 19, 60 generally are resistant to cefixime and have MIC90s of ≥32 mcg/mL.13, 23, 19, 60 Listeria monocytogenes generally are resistant to cefixime in vitro.1, 13, 23, 59, 60, 66, 75
Cefixime is active in vitro against Neisseria meningitidis ,2, 3, 13, 20, 59, 60, 75 and most strains of this organism are inhibited by cefixime concentrations of 0.01-0.06 mcg/mL.2, 3, 13, 20, 59, 60, 75
Cefixime is active in vitro against penicillinase-producing (PPNG) and nonpenicillinase-producing N. gonorrhoeae .1, 2, 3, 11, 14, 23, 59, 60, 75 The drug also is active in vitro against N. gonorrhoeae with chromosomally mediated resistance to penicillin (CMRNG) or plasmid-mediated tetracycline resistance (TRNG).2, 11, 60 The MIC90 of cefixime reported for nonpenicillinase-producing N. gonorrhoeae , PPNG, or CMRNG usually has ranged from 0.001-0.06 mcg/mL.2, 3, 11, 14, 23, 59, 75 However, N. gonorrhoeae with reduced susceptibility to cefixime (MICs ≥0.25 mcg/mL) have been reported in the US and other countries with increasing frequency during the last decade;194, 195, 196, 197, 198 treatment failures have been reported.194
Cefixime is active in vitro against most β-lactamase-producing and non-β-lactamase-producing strains of Haemophilus influenzae 1, 2, 3, 8, 10, 13, 14, 18, 20, 23, 50, 59, 65, 66, 68, 75, 76, 77, 78 and H. parainfluenzae .1, 2, 8, 13 The MIC90 reported for β-lactamase-producing and non-β-lactamase-producing H. influenzae is 0.015-0.25 mcg/mL.2, 3, 8, 10, 13, 14, 18, 20, 23, 50, 59, 65, 66, 68, 75, 76, 77, 78
In vitro on a weight basis, cefixime is more active against β-lactamase-producing H. influenzae than is cefaclor, cephalexin, cefuroxime, or amoxicillin and clavulanate potassium, but may be equally or slightly less active than is ciprofloxacin, ceftriaxone, or co-trimoxazole against these organisms.2, 23, 60, 75, 76 Cefixime is active in vitro against multiple-drug resistant strains of H. influenzae that are resistant to ampicillin, chloramphenicol, tetracycline, co-trimoxazole, cefaclor, and/or erythromycin.2, 8, 17, 23, 60, 68, 76 However, some strains of non-β-lactamase-producing H. influenzae that are resistant to ampicillin and second generation cephalosporins also may have reduced susceptibility to cefixime.2, 23
Cefixime is active in vitro against both β-lactamase- and non-β-lactamase-producing Moraxella catarrhalis ,1, 2, 3, 13, 20, 23, 58, 59, 66, 75, 77, 78 and the MIC90 of the drug reported for this organism is 0.03-0.4 mcg/mL.2, 3, 13, 20, 23, 58, 59, 66, 75, 77, 78 Cefixime is active in vitro against strains of M. catarrhalis resistant to ampicillin, cephalexin, and cefaclor.2, 60, 75
Cefixime is active in vitro against most clinically important Enterobacteriaceae.15, 21, 23, 59, 60, 75 Cefixime is active in vitro against Citrobacter amalonaticus and C. diversus .1 With the exception of C. freundii , Enterobacter , Morganella morganii , and Serratia , the MIC90 of cefixime for Enterobacteriaceae is generally ≤2 mcg/mL15, 21, 23, 50, 59, 60, 66, 75
Cefixime is also active in vitro against Proteus vulgaris , Providencia , Salmonella, Serratia marcescens , and Shigella .1
In vitro on a weight basis, cefixime is equally or less active than other third generation cephalosporins (e.g., cefotaxime, ceftriaxone) or ciprofloxacin against Enterobacteriaceae.23, 60 Cefixime is active in vitro against many strains of E. coli , Citrobacter freundii , K. pneumoniae , and P. mirabilis resistant to other anti-infectives (e.g., aminoglycosides, tetracycline, ampicillin, amoxicillin, cefaclor, cephalexin).2, 14 Cefixime is active in vitro against strains of Salmonella typhi resistant to ampicillin, chloramphenicol, and/or co-trimoxazole.60
Some strains of Pseudomonas cepacia ,2, 13, 14, 20, 23, 78 Ps. pseudomallei ,54 and Ps. stutzeri 60 are inhibited in vitro by cefixime concentrations of 1.56-8 mcg/mL. However, the MIC90 of cefixime for Ps. aeruginosa 2, 13, 14, 15, 20, 23, 59, 60, 66, 75 and for most other Pseudomonas , including Ps. fluorescens ,13, 59 Ps. putida ,13, 15, 59 Ps. maltophilia ( Xanthomonas maltophilia ),13, 20, 59 and most strains of Ps. stutzeri ,13, 15 usually exceeds 16 mcg/mL and these organisms are considered resistant to the drug.14, 23, 59, 60, 75
Cefixime has some in vitro activity against Acinetobacter ; however, the MIC90 reported for A. calcoaceticus var. lwoffi and A. calcoaceticus var. anitratus generally ranges from 3.1-100 mcg/mL.2, 13, 20, 23, 60, 78 Aeromonas hydrophila generally is inhibited in vitro by cefixime concentrations of 0.01-4 mcg/mL.13, 23, 59, 60, 66 Some strains of Alcaligenes are inhibited in vitro by cefixime concentrations of 8 mcg/mL.60
Some strains of Campylobacter fetus subsp. jejuni are inhibited in vitro by cefixime concentrations of 1.6-8 mcg/mL,2, 13, 60, 75 but many strains of the organism are resistant to the drug.2, 13, 23, 75 Cefixime is active against Helicobacter pylori (formerly Campylobacter pylori or C. pyloridis ).22, 114, 115, 121, 122, 123 The MIC90 of cefixime for H. pylori has been reported as 0.25-0.5 mcg/mL.22, 115
Cefixime concentrations of 12.5-16 mcg/mL inhibit some strains of Bordetella pertussis ;81 however, B. bronchiseptica 13 and B. parapertussis 81 are resistant to the drug. Pasteurella multocida is inhibited in vitro by cefixime1, 2, 12, 23 concentrations of 0.012-1 mcg/mL.2, 12, 23
Achromobacter xylosoxidans 13, 19, 23 and Flavobacterium meningosepticum , F. adoratum , and F. indologenes are resistant to cefixime.13, 23
Cefixime has only limited in vitro activity against anaerobic bacteria.2, 14, 23, 59, 60, 75 Some strains (45-91% of those tested) of Lactobacillus , Peptococcus , Peptostreptococcus , Actinomyces , Propionibacterium , Fusobacterium , and Veillonella are inhibited in vitro by cefixime concentrations of 1-4 mcg/mL.2, 14, 23, 59, 60 Most strains of Bacteroides fragilis 1, 2, 14, 15, 23, 59, 75 and other Bacteroides species2, 23, 75 are resistant to cefixime in vitro. Although some Clostridium are inhibited in vitro by cefixime concentrations of 1.56-8 mcg/mL, most strains of Clostridia (including C. difficile ) are considered resistant to the drug.1, 2, 14, 59, 60, 66, 75, 78
Cefixime may have limited activity against Pseudomonas species, Enterococcus species, strains of group D streptococci, Listeria monocytogenes , most strains of staphylococci (including methicillin-resistant strains), most strains of Enterobacter species, and most strains of B. fragilis ; in addition, most strains of Clostridium species are resistant to cefixime.1
Cefixime has a high degree of β-lactamase stability1, 2, 13, 14, 21, 23, 60, 75 and is stable against hydrolysis by many plasmid- and chromosomally mediated β-lactamases.2, 13, 14, 21, 23, 60, 66, 75 The drug generally is more stable against inactivation by β-lactamases than are cefaclor, cefoxitin, cefuroxime, and cephalexin.13, 21, 79 Cefixime generally is not hydrolyzed by β-lactamases classified as Richmond-Sykes types Ia (P99), III (TEM-1, TEM-2, SHV-1), IV (K-1), and V (OXA-2, OXA-3, PSE-1, PSE-4).2, 13, 21, 23, 66, 75 Cefixime may have limited activity against Enterobacteriaceae producing extended spectrum β-lactamases.1 The drug is hydrolyzed by some β-lactamases produced by Enterobacter ,57, 60 Klebsiella oxytoca ,57 Proteus vulgaris ,2, 13 and Pseudomonas cepacia .2 The drug is hydrolyzed by Richmond-Sykes type I produced by Pseudomonas cepacia 60 and Ia produced by Citrobacter freundii and Enterobacter cloacae .13, 21 The drug also is hydrolyzed by β-lactamases produced by Flavobacterium 2 and Bacteroides fragilis .2, 13, 14, 23, 57, 60
Resistance to cefixime in staphylococci appears to be related to the drug's poor affinity for PBP 2 of these organisms.23, 60, 75 Resistance in enterococci and Listeria monocytogenes may also be related to poor binding of cefixime to the PBPs of these organisms.60, 75 Resistance to cefixime in isolates of H. influenzae and N. gonorrhoeae is most often associated with alterations in PBPs.1 In vitro studies indicate that resistance to cefixime in C. freundii 60 and Enterobacter 60 apparently is related to factors that affect permeability of the organisms to the drug and also is related to the production of β-lactamases.60 Resistance to cefixime in Pseudomonas and Acinetobacter is related to permeability factors.60, 75
Unlike some β-lactam anti-infectives (e.g., cefoxitin, imipenem), cefixime is a weak inducer of β-lactamases21 and does not derepress inducible, chromosomally mediated enzymes in C. freundii , E. cloacae , E. aerogenes , Providencia stuartii , Serratia liquefaciens , or S. marcescens .21 Cefixime does, however, induce β-lactamase production in some strains of Morganella morganii , but the drug remains active in vitro against these M. morganii strains following derepression of inducible β-lactamases.21
Capsules containing 400 mg of cefixime are bioequivalent to conventional tablets containing 400 mg of the drug when administered under fasting conditions.1 Cefixime chewable tablets are bioequivalent to cefixime oral suspension.1 Cefixime conventional tablets and oral suspension are not bioequivalent;1 in studies in adults, the oral suspension results in peak serum concentrations 25-50% higher than concentrations attained with the tablets.1 The AUC is greater by approximately 10-25% with the oral suspension than with the tablets after doses of 100-400 mg, when tested in healthy adults.1
When cefixime is administered as conventional tablets or oral suspension, about 40-50% of a dose is absorbed whether the drug is given with or without food;1 however, the time to peak concentrations is increased approximately 0.8 hours when the drug is given with food.1 When cefixime is administered as capsules with food, absorption of the drug is decreased by approximately 15% based on AUC or approximately 25% based on peak serum concentrations.1
Following oral administration of a single 200- or 400-mg dose of cefixime as capsules, tablets, or oral suspension, the time to peak serum concentrations averages 3.1-4.4 hours (range: 2-6 hours).1, 2, 26, 30, 31, 35, 37, 100 In one study in healthy, fasting adults, time to peak serum concentrations of cefixime was dose dependent and averaged 2.7, 3.4, 3.9, and 4.3 hours following a single 50-, 100-, 200-, and 400-mg oral dose, respectively.2, 3, 31 Studies in healthy adults using cefixime doses of 100 mg to 2 g given as capsules or an oral solution or suspension indicate that peak serum concentrations and AUCs increase with increasing dose but are not directly dose proportional;23, 37, 75, 100 there is some evidence that decreased GI absorption occurs with increasing dose.2, 37 Studies in children using cefixime doses of 4-8 mg/kg also indicate that serum concentrations of cefixime are not directly dose proportional.37
There is no evidence that cefixime accumulates in serum or urine of patients with normal renal function following multiple doses of the drug given once or twice daily.2, 23, 29, 30, 75 In one study in healthy adults receiving 400 mg once daily or 200 mg twice daily as cefixime capsules, peak serum concentrations and AUCs determined after 8 and 14-15 days of therapy were similar to those reported on the first day of therapy.2, 29, 30
Information on distribution of cefixime is limited.1, 34, 75 Cefixime has been reported to cross the placenta.2, 23 Following oral administration, cefixime is distributed into bile,1, 2 sputum,2, 23 tonsils,23 maxillary sinus mucosa,23 middle ear discharge,23 blister fluid,2, 75 and prostatic fluid.2 It is not known whether cefixime is distributed into CSF following oral administration.1 Cefixime is approximately 65-70% bound to serum proteins,1, 2, 23, 27, 33, 37, 75 principally albumin,2 and such binding is not concentration dependent over the range of 0.5-30 mcg/mL.1, 2, 23, 27, 37
The serum elimination half-life of cefixime in adults with normal renal function averages 2.4-4 hours.1, 2, 23, 24, 26, 27, 29, 31, 33, 37, 75, 100 Although not reported in published studies, the manufacturer states that the serum elimination half-life of cefixime may range up to 9 hours in some healthy adults.1 Serum half-life of cefixime is independent of dosage form1, 100 and is not dose dependent.2
There is no evidence that cefixime is metabolized in vivo;1, 2, 23, 30 no microbiologically active metabolites have been detected in serum or urine following oral administration of the drug.23, 30, 75
Cefixime is eliminated by renal and nonrenal mechanisms.1, 2, 23, 24, 26, 27, 29, 30, 31, 37, 52, 75 Approximately 7-50% of a single oral dose of the drug is excreted unchanged in urine within 24 hours;1, 2, 23, 24, 26, 27, 29, 31, 37, 75, 100 the drug is excreted principally by glomerular filtration27, 75 and to a lesser extent by tubular secretion.2 The remainder of the dose (up to 60%) is eliminated by nonrenal mechanisms.1, 2, 27, 30, 37, 75 Studies in animals indicate that >10% of a single oral dose of cefixime is excreted unchanged in bile.1, 2, 52 Fecal concentrations of cefixime in healthy adults may range from 0.237-1.55 g/kg following usual oral doses of the drug as capsules or tablets.30, 67
The serum half-life of cefixime averages 6.4 or 11.5 hours in adults with moderate (creatinine clearance 20-40 mL/minute) or severe (creatinine clearance 5-20 mL/minute) renal impairment, respectively.1 Cefixime is not substantially removed by hemodialysis or peritoneal dialysis.1, 2, 33, 37, 75 Average cefixime AUC at steady state is approximately 40% higher in geriatric patients compared with younger adults; this difference is not considered clinically important.1
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
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.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Capsules | 400 mg (of cefixime) | ||
For suspension | 100 mg (of cefixime) per 5 mL | Suprax® | Lupin | |
200 mg (of cefixime) per 5 mL | Suprax® | Lupin | ||
500 mg (of cefixime) per 5 mL | Suprax® | Lupin | ||
Tablets, chewable | 100 mg (of cefixime) | Suprax® | Lupin | |
150 mg (of cefixime) | Suprax® | Lupin | ||
200 mg (of cefixime) | Suprax® | Lupin | ||
Tablets, film-coated | 400 mg (of cefixime) | Suprax® (scored) | Lupin |
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