VA Class:AM117
Ceftazidime is a semisynthetic, third generation cephalosporin antibiotic.1, 3, 7, 10, 45, 50, 53, 54, 56, 147, 150, 203, 217
Ceftazidime is used for the treatment of bone and joint infections,1, 217, 251 intra-abdominal and gynecologic infections,1, 217, 251 meningitis and other CNS infections,1, 217, 251 lower respiratory tract infections,1, 217, 251 skin and skin structure infections,1, 217, 251 septicemia,1, 217, 251 and complicated or uncomplicated urinary tract infections caused by susceptible bacteria.1, 217 The drug also is used for empiric anti-infective agent therapy in febrile neutropenic patients†122, 123, 124, 138, 139, 140, 211, 212, 228, 231, 247, 248, 249, 279, 280 and has been used for perioperative prophylaxis†.142, 151, 167, 169
Ceftazidime therapy may be started pending results of susceptibility tests, but should be discontinued if the organism is found to be resistant to the drug.1, 217 When the causative organism is unknown, concomitant therapy with another anti-infective agent may be indicated pending results of in vitro susceptibility tests.1, 217 In severe or life-threatening infections or in immunocompromised patients, ceftazidime may be used concomitantly with other anti-infectives such as aminoglycosides, vancomycin, or clindamycin.1, 28, 50, 114, 122, 123, 133, 138, 139, 149, 217
Gram-positive Aerobic Bacterial Infections
Like other parenteral third generation cephalosporins (cefotaxime, ceftriaxone), ceftazidime is less active than first and second generation cephalosporins against some gram-positive bacteria (e.g., staphylococci) and generally should not be used in the treatment of infections caused by these organisms when a penicillin or first or second generation cephalosporin could be used.10, 50, 52, 53, 55, 57, 60, 196, 108, 150, 197, 200, 201 Although ceftazidime has been effective when used alone in adults or children for the treatment of septicemia,103, 123, 139 cellulitis,104, 107, 108, 117, 137 urinary tract infections,103, 106, 113, 141 osteomyelitis,103, 104, 108 or respiratory tract infections (including pneumonia)102, 103, 108, 117, 137, 146, 147, 148 caused by susceptible gram-positive cocci (e.g., Staphylococcus aureus , S. epidermidis , groups A and B streptococci, Streptococcus pneumoniae ), treatment failures also have been reported in some of these infections,103, 104, 137, 138, 139, 144, 147, 148, 224 especially in immunocompromised patients138, 139, 147 or patients with cystic fibrosis.28, 103 Therefore, ceftazidime is not used alone for empiric therapy in infections where gram-positive bacteria may be involved (e.g., community-acquired pneumonia).115, 119, 150
Gram-negative Aerobic Bacterial Infections
Ceftazidime generally has been effective when used alone in adults or children for the treatment of respiratory tract infections (including pneumonia),102, 118, 119, 120, 137, 143, 144, 146, 148 skin and skin structure infections,115, 119, 136 osteomyelitis,104, 118, 136, 298 septicemia,115, 118, 119, 120, 146 intra-abdominal infections,136, 137 or urinary tract infections106, 113, 115, 118, 119, 137, 141, 145, 153 caused by susceptible Enterobacteriaceae (e.g., Enterobacter , Escherichia coli , Klebsiella , Morganella , Proteus , Serratia ). A principal use of ceftazidime is for the treatment of infections known or suspected to be caused by multidrug-resistant Enterobacteriaceae (e.g., nosocomial urinary tract infections or pneumonia, suspected septicemia in non-neutropenic patients) and serious gram-negative infections when other anti-infectives are contraindicated or ineffective.50, 103, 115, 118, 119, 147, 214, 313, 316, 317 It has been suggested that certain parenteral cephalosporins (i.e., cefepime, cefotaxime, ceftriaxone, ceftazidime) may be drugs of choice for the treatment of infections caused by susceptible E. coli , K. pneumoniae , P. rettgeri , M. morganii , P. vulgaris , P. stuartii , or Serratia ; an aminoglycoside (amikacin, gentamicin, tobramycin) should be used concomitantly in severe infections.197 There is some evidence that for the treatment of some infections (e.g., pneumonia, bacteremia) caused by susceptible Enterobacteriaceae, ceftazidime used alone can be as effective as a 2-drug regimen of a third generation cephalosporin or an extended-spectrum penicillin used in conjunction with an aminoglycoside.102, 143, 144, 146, 214, 317
Mixed Aerobic-Anaerobic Bacterial Infections
Ceftazidime has been used with some success in the treatment of mixed aerobic-anaerobic bacterial infections.50, 109, 147, 150 The manufacturers indicate that ceftazidime may be used in the treatment of polymicrobial intra-abdominal infections caused by aerobic and anaerobic bacteria, including Bacteroides ;1, 217 however, the drug should not be used alone for the treatment of any infection when B. fragilis may be present, since it generally is inactive against this organism.49, 57, 109, 115, 119, 147, 150
Intra-abdominal and Gynecologic Infections
Ceftazidime is used for the treatment of gynecologic infections (including endometritis, pelvic cellulitis, other infections of the female genital tract) caused by susceptible E. coli .1, 217, 251
Ceftazidime also is used for the treatment of intra-abdominal infections (including peritonitis) caused by susceptible S. aureus (oxacillin-susceptible strains only), E. coli , or Klebsiella .1, 217, 251 and polymicrobial infections caused by aerobic and anaerobic bacteria.1, 217, 251
For initial empiric treatment of high-risk or severe community-acquired extrabiliary intra-abdominal infections in adults (e.g., those with advanced age, immunocompromise, severe physiologic disturbance), the Infectious Diseases Society of America (IDSA) recommends either monotherapy with a carbapenem (doripenem, imipenem, meropenem) or the fixed combination of piperacillin and tazobactam, or a combination regimen that includes either a cephalosporin (cefepime, ceftazidime) or fluoroquinolone (ciprofloxacin, levofloxacin) in conjunction with metronidazole.70 IDSA also recommends ceftazidime in conjunction with metronidazole as one of several regimens that can be used for initial empiric treatment of health-care-associated complicated intra-abdominal infections in adults and community-acquired complicated intra-abdominal infections in pediatric patients.70
For additional information regarding management of intra-abdominal infections, the current IDSA clinical practice guidelines available at [Web] should be consulted.70
Meningitis and Other CNS Infections
Ceftazidime used in conjunction with an aminoglycoside is considered a regimen of choice for the treatment of meningitis caused by susceptible Pseudomonas aeruginosa 13, 14, 112, 147, 197, 337, 354 or susceptible Enterobacteriaceae† (e.g., E. coli , P. mirabilis , Enterobacter , S. marcescens ).46, 47, 222, 223, 224, 335 While ceftazidime also has been effective when used alone for the treatment of meningitis caused by susceptible Haemophilus influenzae , Neisseria meningitidis , or S. pneumoniae ,1, 46, 47, 50, 137, 254 cefotaxime or ceftriaxone generally is preferred when a cephalosporin is indicated for the treatment of meningitis caused by these organisms.47, 150, 197, 216, 335, 336, 337, 338 (See Uses: Meningitis and Other CNS Infections in the Cephalosporins General Statement 8:12.06.)
Because preterm, low-birthweight neonates are at increased risk for nosocomial infection caused by staphylococci or gram-negative bacilli,331 some clinicians suggest that these neonates receive an empiric regimen of IV ceftazidime and IV vancomycin for suspected bacterial meningitis.335, 337, 338 Immunocompromised individuals, geriatric individuals, and individuals with recent head trauma, neurosurgery, or CSF shunts also are at increased risk for meningitis caused by gram-negative bacilli and some clinicians recommend that IV ceftazidime be use for empiric therapy in these patients. If ceftazidime is used for empiric therapy in individuals with meningitis, concomitant use of IV ampicillin should be considered to provide coverage against Listeria monocytogenes , especially in patients who are immunocompromised, infants younger than 3 months of age, or adults older than 50 years of age.335, 337 In addition, for empiric therapy of meningitis in individuals with recent head trauma, neurosurgery, or CSF shunts, concomitant use of vancomycin should be considered to provide coverage against gram-positive bacteria.335 When results of culture and in vitro susceptibility tests become available and the pathogen is identified, the empiric anti-infective regimen should be modified (if necessary) to ensure that the most effective regimen is being administered.335, 337
In patients with meningitis caused by Ps. aeruginosa , many clinicians recommend that therapy be initiated with a regimen of ceftazidime and a parenteral aminoglycoside (amikacin, gentamicin, tobramycin).197, 335, 337, 354 If the patient fails to respond to this regimen, concomitant use of intrathecal or intraventricular aminoglycoside therapy or use of an alternative parenteral anti-infective (e.g., aztreonam, meropenem, a fluoroquinolone) should be considered based on results of in vitro susceptibility tests.335, 337, 354
Ceftazidime is used in adult and pediatric patients for the treatment of septicemia caused by S. aureus , S. pneumoniae , E. coli , H. influenzae , K. pneumoniae , or Ps. aeruginosa .1, 115, 118, 119, 120, 146, 217, 251 Some clinicians recommend that an aminoglycoside (amikacin, gentamicin, tobramycin) be used concomitantly for the treatment of gram-negative bacteremia in seriously ill patients.197, 222
The choice of anti-infective agent for the treatment of sepsis syndrome should be based on the probable source of infection, causative organism, immune status of the patient, and local patterns of bacterial resistance.197 For initial treatment of life-threatening sepsis in adults, some clinicians recommend that a third or fourth generation cephalosporin (cefepime, cefotaxime, ceftriaxone, ceftazidime), the fixed combination of piperacillin and tazobactam, or a carbapenem (doripenem, imipenem, meropenem) be used in conjunction with vancomycin; some experts also suggest including an aminoglycoside or fluoroquinolone during the initial few days of treatment.197
Ceftazidime is used in adult and pediatric patients for the treatment of complicated and uncomplicated urinary tract infections caused by Enterobacter , E. coli , Klebsiella , M. morganii , P. mirabilis , P. vulgaris , or Ps. aeruginosa .1, 197, 217 The most appropriate agent for the treatment of urinary tract infections should be selected based on the severity of the infection and results of culture and in vitro susceptibility testing.197, 296 It has been suggested that certain parenteral cephalosporins (i.e., cefepime, cefotaxime, ceftriaxone, ceftazidime) may be drugs of choice for the treatment of infections caused by susceptible Enterobacteriaceae, including susceptible E. coli , K. pneumoniae , P. rettgeri , M. morganii , P. vulgaris , P. stuartii , or Serratia ; an aminoglycoside should be used concomitantly in severe infections.197 However, ceftazidime, like other third generation cephalosporins, generally should not be used in the treatment of uncomplicated urinary tract infections when other anti-infectives with a narrower spectrum of activity could be used.197, 296
Pseudomonas aeruginosa Infections
Ceftazidime is used in adult and pediatric patients for the treatment of septicemia,115, 119, 120, 146, 197 osteomyelitis,104, 118, 119, 120, 136, 137, 197, 298 respiratory tract,102, 105, 120, 135, 136, 227, 348 skin and skin structure,119, 135, 136, 137 or urinary tract106, 113, 115, 116, 119, 137, 141, 145, 152, 153, 197 infections caused by susceptible Ps. aeruginosa . The drug also is used for the treatment of meningitis caused by Ps. aeruginosa (see Uses: Meningitis and Other CNS Infections)197, 335, 337, 354 and has been used for the treatment of malignant otitis externa† caused by Ps. aeruginosa (see Otitis Externa under Uses: Otitis, in the Cephalosporins General Statement 8:12.06).352, 353
Ceftazidime generally has been considered a drug of choice for the treatment of infections caused by Ps. aeruginosa since it is more active in vitro on a weight basis against the organism than most other currently available cephalosporins and is active against some strains resistant to many other cephalosporins, aminoglycosides, and extended-spectrum penicillins.50, 57, 147, 186, 198 However, ceftazidime-resistant strains of Ps. aeruginosa can emerge during therapy with the drug, and superinfection with resistant strains has occurred.50, 111, 115, 147 In severe infections, especially in immunocompromised patients, concomitant use of ceftazidime and an aminoglycoside (e.g., amikacin, gentamicin, tobramycin) is recommended.197
For the treatment of community-acquired pneumonia (CAP) caused by Ps. aeruginosa , the American Thoracic Society (ATS) and IDSA recommend a combination regimen that includes an antipseudomonal β-lactam (cefepime, ceftazidime, aztreonam, imipenem, meropenem, piperacillin, ticarcillin) given in conjunction with ciprofloxacin, levofloxacin, or an aminoglycoside.227 For additional information on treatment of CAP, see Community-Acquired Pneumonia under Uses: Respiratory Tract Infections, in the Cephalosporins General Statement 8:12.06.
Ceftazidime is used alone or in conjunction with an aminoglycoside for the treatment of acute exacerbations of bronchopulmonary Ps. aeruginosa infections in children and adults with cystic fibrosis and generally is considered a drug of choice for these infections.28, 119, 125, 126, 128, 129, 130, 132, 134, 147, 150, 154, 208, 246, 313, 332, 348 In cystic fibrosis patients with acute exacerbations of Ps. aeruginosa infection, there is some evidence that an empiric regimen of ceftazidime and an aminoglycoside may be more effective than ceftazidime monotherapy; however, ceftazidime monotherapy appears to be as effective or more effective than monotherapy with aztreonam, ciprofloxacin, or meropenem or combination therapy with ticarcillin and tobramycin.312, 313, 315 Although anti-infective therapy in patients with cystic fibrosis may result in clinical improvement and Ps. aeruginosa may be temporarily cleared from the sputum, a bacteriologic cure is rarely obtained and should not be expected.28, 119, 125, 126, 132, 149, 150, 208, 246, 313 Continuous IV infusion of ceftazidime has been used effectively for the treatment of Ps. aeruginosa infections in some adult and pediatric cystic fibrosis patients, including patients who failed to respond to ceftazidime administered by intermittent IV injection or infusion.302, 332, 348 Because a ceftazidime dosing regimen that consists of an IV loading dose followed by continuous IV infusion may provide more consistent concentrations of the drug than an intermittent dosing regimen, it has been suggested that such a regimen theoretically would be more effective in suppressing Ps. aeruginosa and possibly may decrease emergence of drug-resistant strains of the organism.310, 329, 348 Ceftazidime has been administered on an outpatient basis for the treatment of acute exacerbations of Ps. aeruginosa infections in cystic fibrosis patients; such community-based parenteral therapy generally is used to complete a course of ceftazidime therapy initiated during hospitalization.310, 313, 333
Burkholderia cepacia Infections
Ceftazidime has been used alone or in conjunction with an aminoglycoside for the treatment of septicemia or pulmonary infections caused by Burkholderia cepacia (formerly Ps. cepacia )†.147, 197, 208, 345 Patients with cystic fibrosis often are colonized with B. cepacia (with or without Ps. aeruginosa colonization).297, 308, 314 In addition, B. cepacia has recently been recognized as a cause of nosocomial pneumonia or nosocomial bacteremia in immunocompromised patients (e.g., patients with malignancy)297, 308, 314, 345 B. cepacia is an aerobic, nonfermentative gram-negative bacilli resistant to many anti-infective agents, and no anti-infective regimen has been identified that effectively eradicates the organism in colonized cystic fibrosis patients.133, 246, 314 The optimum regimen for the treatment of infections caused by B. cepacia has not been identified.314 Some clinicians consider co-trimoxazole the drug of choice and ceftazidime, chloramphenicol, and imipenem alternative agents for the treatment of B. cepacia infections.197 Ceftazidime monotherapy has been used effectively to treat nosocomial B. cepacia bacteremia in a limited number of patients with severe underlying disease (e.g., malignancy); many of these patients had indwelling central venous catheters or recent surgery that may have precipitated the infection.345
Ceftazidime is considered by many clinicians to be a drug of choice for the treatment of severe melioidosis†, a potentially life-threatening disease caused by B. pseudomallei (formerly Ps. pseudomallei ).197, 264, 266, 267, 275, 276, 277, 346, 355, 356, 357, 358
B. pseudomallei is an aerobic, nonfermentative gram-negative bacilli resistant to many anti-infective agents (e.g., penicillins, first and second generation cephalosporins, aminoglycosides).197, 267, 275, 325, 355, 356, 357B. pseudomallei may cause subclinical illness and localized infections or fulminant septicemia; disseminated infections may include hepatic and splenic abscesses.275, 355, 356, 357 The incubation period usually is 1-21 days (median 9 days), but can be prolonged (years).275, 355, 356, 357 In some asymptomatic individuals, the disease has remained dormant and active melioidosis was not evident for more than 20 years, usually at a time when the patient was immunosuppressed.355, 356 If left untreated, severe septicemic infections can be fatal within 24-48 hours after onset.356, 357 B. pseudomallei is widely distributed in water and soil in many tropical and subtropical countries and melioidosis is endemic in Southeast Asia (e.g., Thailand, Malaysia, Singapore) and northern Australia,275, 355, 356, 357 and also is found in the Indian subcontinent and South and Central America.275 The disease occurs only rarely in the US.358 Person-to-person spread occurs only rarely.355, 356, 357 B. pseudomallei usually is transmitted to humans from contaminated materials (e.g., soil) via contact with nasal, oral, or conjunctival mucous membranes, contact with abraded or lacerated skin, or, rarely, by inhalation.355, 356, 357 Laboratory workers have become infected via aerosols from B. pseudomallei cultures.356
Melioidosis, regardless of severity, should be treated with an initial parenteral regimen of ceftazidime, imipenem, or meropenem (some clinicians recommend that co-trimoxazole also be included, especially if the patient is septicemic) followed by a prolonged maintenance regimen of oral anti-infectives (e.g., co-trimoxazole with or without doxycycline).275, 355, 356, 357, 358 In patients with melioidosis septic shock, adjunctive use of filgrastim (granulocyte colony-stimulating factor; G-CSF) during initial treatment has been suggested.355, 356 B. pseudomallei is difficult to eradicate, and relapse of melioidosis commonly occurs.264, 266, 275, 276, 346, 355 Therefore, after the maintenance regimen is completed, life-long follow-up is recommended since relapse of melioidosis can occur despite effective anti-infective therapy.264, 266, 276, 346, 355, 356 The fact that resistant strains of B. pseudomallei have developed during ceftazidime therapy should be considered.325, 326
B. pseudomallei has been studied for and is considered a potential pathogen for aerosol distribution in the context of biologic warfare or bioterrorism.355, 356, 357, 358 Acute respiratory or systemic infection probably would occur following high-dose aerosol exposure to B. pseudomallei .356 Some experts (e.g., US Army Medical Research Institute of Infectious Diseases [USAMRIID], European Commission's Task Force on Biological and Chemical Agent Threats [BICHAT]) state that the same treatment regimens recommended for naturally occurring melioidosis should be used if the disease occurs in the context of biologic warfare or bioterrorism.356, 357
Ceftazidime monotherapy (40 mg/kg or 2 g IV 3 times daily) has been effective for the treatment of severe septicemic or pulmonary melioidosis,264, 267, 346 and has been associated with a lower mortality rate than a 3-drug regimen of IV chloramphenicol, oral doxycycline, and oral co-trimoxazole.266, 276 In an open, prospective study in adults with acute severe melioidosis randomized to receive an initial parenteral regimen of IV ceftazidime or IV imipenem followed by an oral maintenance regimen, the survival rate at 48 hours was similar with both drugs (20.8% of those receiving ceftazidime and 25% of those receiving imipenem died within the first 48 hours), and the choice of initial drug did not appear to influence the final outcome; however, a higher percentage of patients receiving ceftazidime were considered to be treatment failures after 48 hours and had to be switched to an alternative drug because of primary treatment failure.346
Ceftazidime is considered by some clinicians to be a drug of choice for the treatment of infections caused by Vibrio vulnificus †.219, 256 V. vulnificus , a gram-negative aerobic bacteria that can cause potentially fatal septicemia, wound infections, or gastroenteritis, generally is transmitted through ingestion of contaminated raw or undercooked seafood (especially raw oysters) or through contamination of a wound with seawater or seafood drippings.219, 256, 262, 263 V. vulnificus is naturally present in marine environments, thrives in warm ocean water, and frequently is isolated from oysters and other shellfish harvested from the Gulf of Mexico and from US coastal waters along the Pacific and Atlantic ocean.256, 263 Individuals with preexisting liver disease are at high risk for developing fatal septicemia following ingestion of seafood contaminated with V. vulnificus and debilitated or immunocompromised individuals (e.g., those with chronic renal impairment, cancer, diabetes mellitus, steroid-dependent asthma, chronic GI disease) or individuals with iron overload states (e.g., thalassemia and hemochromatosis) also are at increased risk for fatal infections.219, 256, 262 The incubation period for V. vulnificus infection reportedly is 1-7 days and the duration of illness usually is 2-8 days.219 In immunocompromised individuals, fever, nausea, myalgia, and abdominal cramps may occur as soon as 24-48 hours after ingestion of seafood contaminated with V. vulnificus and sepsis and cutaneous bullae may be present within 36 hours of the onset of symptoms.256
Because the case fatality rate for V. vulnificus septicemia exceeds 50% in immunocompromised individuals or those with preexisting liver disease, these individuals should be informed about the health hazards of ingesting raw or undercooked seafood (especially oysters), the need to avoid contact with seawater during the warm months, and the importance of using protective clothing (e.g., gloves) when handling shellfish.256, 262 V. vulnificus infection should be considered in the differential diagnosis of fever of unknown etiology, and individuals who present with fever (especially when bullae, cellulitis, or wound infection is present) and who have preexisting liver disease or are immunocompromised should be questioned regarding a history of raw oyster ingestion or seawater contact.256 While optimum anti-infective therapy for the treatment of V. vulnificus infections has not been identified, use of a tetracycline or third generation cephalosporin (e.g., cefotaxime, ceftazidime) is recommended.197, 219, 256 Because the high fatality rate associated with V. vulnificus infections, anti-infective therapy should be initiated promptly if indicated.256, 262
Empiric Therapy in Febrile Neutropenic Patients
Ceftazidime has been effective when used alone or in conjunction with other anti-infectives for empiric anti-infective therapy of presumed bacterial infections in febrile granulocytopenic adults or children†.122, 123, 124, 138, 139, 140, 212, 228, 247, 248, 249, 261, 279, 280, 286, 287, 288, 289, 290, 291, 292, 294, 295, 347, 349
Results of several studies in febrile granulocytopenic patients indicate that ceftazidime used alone may be as effective as combination regimens that include ceftazidime and an aminoglycoside (e.g., amikacin, gentamicin, tobramycin) or combination regimens that include some other β-lactam antibiotic (e.g., cefepime, ceftriaxone, piperacillin) and an aminoglycoside for empiric therapy in these patients.124, 138, 139, 140, 212, 228, 247, 248, 249, 261, 290, 292, 295 Results of a randomized study in adults indicate that ceftazidime monotherapy (2 g IV every 8 hours) is as effective as meropenem monotherapy (1 g IV every 8 hours) for empiric anti-infective therapy in febrile neutropenic patients; at the end of therapy, a satisfactory response was obtained in 49 or 46% of those receiving ceftazidime or meropenem, respectively.349 Because gram-positive bacteria are being reported with increasing frequency in febrile granulocytopenic patients and because ceftazidime is less active against these organisms than many other cephalosporins and β-lactam antibiotics, some clinicians suggest that an anti-infective agent active against staphylococci (e.g., vancomycin) probably should be used concomitantly if ceftazidime is used for empiric therapy in these patients.122, 124, 132, 138, 139, 140, 212, 222, 229, 247 However, unlike ceftazidime, other anti-infectives used for empiric therapy (e.g., cefepime, imipenem, meropenem) have good activity against viridans streptococci and S. pneumoniae .390
Successful treatment of infections in granulocytopenic patients requires prompt initiation of empiric anti-infective therapy (even when fever is the only sign or symptom of infection) and appropriate modification of the initial regimen if the duration of fever and neutropenia is protracted, if a specific site of infection is identified, or if organisms resistant to the initial regimen are present.121, 249, 283, 284, 286, 390 The initial empiric regimen should be chosen based on the underlying disease and other host factors that may affect the degree of risk; local epidemiologic data regarding the type, frequency of occurrence, and in vitro susceptibility of bacterial isolates recovered from other patients in the same health-care facility; and the individual patient's pattern of colonization and resistance.121, 229, 230, 249, 284, 285, 286, 390 No empiric regimen has been identified that would be appropriate for initial treatment of all febrile neutropenic patients.284, 286, 390 Regardless of the initial regimen selected, patients should be reassessed daily and the anti-infective regimen altered (if indicated) based on the presence or absence of fever, identification of the causative organism, and the clinical condition of the patient.390
The fact that gram-positive bacteria have become a predominant pathogen in febrile neutropenic patients should be considered when selecting an empiric anti-infective regimen.122, 124, 212, 222, 229, 390, 284 The IDSA states that ceftazidime is no longer a reliable agent for empiric monotherapy in febrile neutropenic patients because of decreasing potency against gram-negative bacteria and poor activity against many gram-positive bacteria (e.g., streptococci).390
Published protocols for the treatment of infections in febrile neutropenic patients should be consulted for specific recommendations regarding selection of the initial empiric anti-infective regimen, when to change the initial regimen, possible subsequent regimens, and duration of therapy in these patients.390 In addition, consultation with an infectious disease expert knowledgeable about infections in immunocompromised patients is advised.390
Ceftazidime has been used for perioperative prophylaxis† in patients undergoing vaginal hysterectomy,151 biliary or intra-abdominal surgery,167, 169 or transurethral resection of the prostate;142 however, many clinicians state that ceftazidime should not be used prophylactically.147, 168, 222
A first or second generation cephalosporin (cefazolin, cefoxitin, cefotetan, cefuroxime) generally is preferred when a cephalosporin is used for perioperative prophylaxis.168, 169 Third generation cephalosporins (cefotaxime, ceftriaxone, ceftazidime) and fourth generation cephalosporins (cefepime) are not usually recommended for perioperative prophylaxis because they are expensive, some are less active than first or second generation cephalosporins against staphylococci, they have spectrums of activity wider than necessary for organisms encountered in elective surgery, and their use for prophylaxis may promote emergence of resistant organisms.168, 169 (See Uses: Perioperative Prophylaxis, in the Cephalosporins General Statement 8:12.06.)
Reconstitution and Administration
Ceftazidime sodium (as commercially available formulations of ceftazidime with sodium carbonate) is administered by intermittent IV injection or infusion or by deep IM injection.1, 217 Ceftazidime sodium premixed with dextrose injection is administered by continuous or intermittent IV infusion.1 Ceftazidime sodium also has been administered by continuous IV infusion†299, 300, 301, 302, 310, 332, 348 and has been administered intraperitoneally in dialysis solutions.1, 27, 217 Intra-arterial injection should be avoided since distal necrosis can occur .1, 217
The IV route usually is preferred in patients with septicemia, meningitis, peritonitis, or other severe or life-threatening infections and in patients with lowered resistance resulting from malnutrition, trauma, surgery, diabetes, heart failure, or malignancy, particularly if shock is present or impending.1, 217
If an aminoglycoside or vancomycin is administered concomitantly with ceftazidime or ceftazidime sodium, the drugs should be administered at separate sites.1, 217 Reconstituted and diluted solutions of ceftazidime or ceftazidime sodium should be inspected visually for particulate matter prior to administration whenever solution and container permit.1, 217
Vials labeled as containing 500 mg, 1 g, or 2 g of ceftazidime with sodium carbonate should be reconstituted with 5.3, 10, or 10 mL, respectively, of sterile water for injection or a compatible IV solution to provide solutions containing approximately 100, 100, or 170 mg/mL, respectively.1, 217 After adding the diluent to the vial, the vial should be shaken to dissolve the drug.1, 217 With sodium carbonate formulations of ceftazidime, carbon dioxide is released as the drug dissolves and the solution will become clear within 1-2 minutes.1, 217 The appropriate dose of the drug should then be added to a compatible IV solution.1, 217 When withdrawing a dose from reconstituted vials, ensure that the syringe needle opening remains within the solution.1, 217 The withdrawn solution may contain some carbon dioxide bubbles, which should be expelled from the syringe before injection.1, 217
Alternatively, TwistVial® (Fortaz®) or ADD-Vantage® (Tazicef®) vials labeled as containing 1 or 2 g of ceftazidime with sodium carbonate should be reconstituted according to the manufacturer's directions.1, 217 Carbon dioxide that forms inside the package in sodium carbonate formulations of ceftazidime should be relieved by inserting a vent needle; to preserve sterility, it is important that the vent needle be inserted through the vial closure only after the drug has dissolved.1 The vent needle should be removed prior to use of the solution.1
Alternatively, the commercially available Duplex® drug delivery system containing 1 or 2 g of ceftazidime and 50 mL of 5% dextrose injection in separate chambers should be reconstituted (activated) according to the manufacturer's directions and administered by IV infusion.251 If stored in the refrigerator after reconstitution (see Chemistry and Stability: Stability), the solution should be allowed to reach room temperature prior to administration.251
The 6-g pharmacy bulk vial of ceftazidime as a sodium carbonate formulation should be reconstituted with sterile water for injection according to the manufacturer's directions.1, 233 The pharmacy bulk vial is not intended for direct IV infusion.233
Thawed solutions of the commercially available frozen premixed ceftazidime sodium injection in dextrose may be administered by continuous or intermittent IV infusion.1 The frozen injections should be thawed at room temperature (25°C) or under refrigeration (5°C); the injections 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 injections usually will dissolve with little or no agitation when the injections reach 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 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 injections 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
If a Y-type administration set is used, the other solution flowing through the tubing should be discontinued while ceftazidime or ceftazidime sodium is being infused.1, 217, 262
Intermittent IV infusions of ceftazidime sodium have generally been infused over 15-30 minutes in adults,8, 102, 104, 105, 115, 116, 118, 119, 133, 137, 139, 144, 251 neonates,34 and children.108, 157
For direct intermittent IV injection, vials labeled as containing 500 mg, 1 g, or 2 g of ceftazidime with sodium carbonate should be reconstituted with sterile water for injection as for initial reconstitution for IV infusion to provide solutions containing 100, 100, or 170 mg/mL, respectively.1, 217 (See Reconstitution and Administration: Intermittent IV Infusion, in Dosage and Administration.) When withdrawing a dose from reconstituted vials of ceftazidime sodium, ensure that the syringe needle opening remains within the solution.1, 217 Any carbon dioxide bubbles that may be present in the withdrawn solution of ceftazidime sodium should be expelled from the syringe prior to injection.1, 217
The appropriate dose of reconstituted ceftazidime sodium should be injected over a period of 3-5 minutes directly into a vein or the tubing of a compatible IV solution.1, 217
For IM injection, vials labeled as containing 500 mg or 1 g of ceftazidime with sodium carbonate (Fortaz®) are prepared by adding 1.5 or 3 mL of sterile or bacteriostatic water for injection or 0.5 or 1% lidocaine hydrochloride injection, respectively, to provide solutions containing approximately 280 mg/mL.1, 217 When withdrawing a dose from reconstituted vials of ceftazidime sodium, ensure that the syringe needle opening remains within the solution.1, 217 Any carbon dioxide bubbles that may be present in the withdrawn solution of ceftazidime sodium should be expelled from the syringe prior to injection.1, 217
IM injections should be made deeply into a large muscle mass, such as the upper outer quadrant of the gluteus maximus or lateral part of the thigh, using usual techniques and precautions.1, 217
For intraperitoneal instillation, a sodium carbonate formulation of ceftazidime powder for injection can be reconstituted with sterile water for injection as for initial reconstitution for IV infusion.221 (See Reconstitution and Administration: Intermittent IV Infusion, in Dosage and Administration.) The manufacturers of the sodium carbonate formulations of ceftazidime recommend that the drug then be further diluted in a compatible peritoneal dialysis solution to provide a solution containing 250 mg of ceftazidime in each 2 L of dialysis solution.1, 217
Following reconstitution of the commercially available powders for injection containing a mixture of ceftazidime (as the pentahydrate) and sodium carbonate, solutions contain ceftazidime sodium;56, 221, 225 dosage of the drug is expressed in terms of anhydrous ceftazidime.1, 3, 217
To avoid unintentional overdosage, the commercially available Duplex® drug delivery system containing ceftazidime and dextrose injection should not be used in patients who require less than the entire 1- or 2-g dose in the container.251
The usual adult dosage of ceftazidime for the treatment of less severe infections caused by susceptible organisms is 1 g given IV or IM every 8 or 12 hours; however, the dosage and route of administration should be determined by the susceptibility of the causative organism, the severity of the infection, and the condition and renal function of the patient.1, 217 For severe or life-threatening infections, especially in immunocompromised patients, a dosage of 2 g every 8 hours is recommended.1, 217
The maximum adult dosage of ceftazidime recommended by the manufacturers is 6 g daily.1, 217, 221, 225
For the treatment of bone and joint infections, the usual adult dosage is 2 g IV every 12 hours.1, 104, 217, 251
Intra-abdominal and Gynecologic Infections
For the treatment of serious gynecologic and intra-abdominal infections, the usual adult dosage of ceftazidime is 2 g IV every 8 hours.1, 217, 251
For the treatment of meningitis, the usual dosage of ceftazidime is 2 g IV every 8 hours.1, 217, 354, 251 Because of a high rate of relapse, anti-infective therapy in patients with meningitis caused by gram-negative bacilli generally should be continued for at least 3 weeks.335, 337, 354
The usual adult dosage of the drug for the treatment of uncomplicated pneumonia is 0.5-1 g IV or IM every 8 hours.1, 217, 251
Skin and Skin Structure Infections
The usual adult dosage of the drug for the treatment of mild skin and skin structure infections is 0.5-1 g IV or IM every 8 hours.1, 217, 251
The manufacturers recommend that adults with uncomplicated urinary tract infections receive 250 mg of ceftazidime IV or IM every 12 hours and that adults with complicated urinary tract infections receive 500 mg IV or IM every 8 or 12 hours.1, 217
Pseudomonas aeruginosa Infections
For the treatment of pulmonary infections caused by Pseudomonas aeruginosa in patients with cystic fibrosis and normal renal function, the usual dosage of ceftazidime is 30-50 mg/kg given IV every 8 hours up to a maximum dosage of 6 g daily.1, 28, 30, 50, 125, 126, 128, 129, 149, 217, 246, 348 Clinical improvement may occur, but bacteriologic cures should not be expected in patients with chronic respiratory disease and cystic fibrosis.1, 28, 119, 125, 126, 132, 149, 150, 208, 217
For the treatment of melioidosis† caused by Burkholderia pseudomallei , the US Army Medical Research Institute of Infectious Diseases (USAMRIID) recommends a ceftazidime dosage of 40 mg/kg every 8 hours.356 Other clinicians recommend a ceftazidime dosage of 2 g IV every 8 hours (up to 6 g daily)357 or 50 mg/kg (up to 2 g) IV every 6 hours.355, 358 Concomitant co-trimoxazole (6-8 mg/kg of trimethoprim daily in 4 divided doses) or doxycycline (100 mg IV twice daily) may be indicated in septicemic or other severe cases.355, 356, 357, 358 The initial parenteral regimen should be continued for at least 10-14 days and until there is clinical improvement.275, 355, 356, 357, 358 Although the median time to fever resolution is 9 days, some patients may remain febrile for prolonged periods despite appropriate antimicrobial therapy.356 When appropriate, treatment may be changed to an oral maintenance regimen (e.g., oral co-trimoxazole with or without oral doxycycline) and continued for at least 3-6 months to prevent recrudence or relapse.275, 355, 356, 357, 358 More prolonged oral maintenance therapy (up to 12 months) may be necessary, depending on the response to therapy and severity of initial illness.356, 357
Although only limited experience is available regarding the treatment of human cases of glanders†, some clinicians suggest that the regimens recommended for the treatment of severe melioidosis also can be used for the treatment of glanders.356
Empiric Therapy in Febrile Neutropenic Patients
If ceftazidime is used for empiric anti-infective therapy in febrile neutropenic patients† (see Uses: Empiric Therapy in Febrile Neutropenic Patients), the usual dosage of the drug is 100 mg/kg daily given IV in 3 divided doses or 2 g IV every 8 hours either alone or in conjunction with an aminoglycoside (amikacin, gentamicin, tobramycin).261, 279, 280, 286, 290, 292, 295, 349
Children 12 years of age and older may receive the usual adult dosage of ceftazidime.1, 217
The usual dosage of ceftazidime recommended by the manufacturers for neonates up to 4 weeks of age is 30 mg/kg IV every 12 hours.1, 217
The American Academy of Pediatrics (AAP) recommends that neonates 7 days of age or younger receive 50 mg/kg of ceftazidime every 12 hours, regardless of weight.275 For neonates 8-28 days of age, the AAP recommends a dosage of 50 mg every 8-12 hours for those weighing 2 kg or less and 50 mg/kg every 8 hours for those weighing more than 2 kg.275
General Dosage for Infants and Children
The usual dosage of ceftazidime for children 1 month to 12 years of age is 25-50 mg/kg IV every 8 hours, depending on the type and severity of infection.1, 38, 103, 107, 217, 254, 275 The manufacturers state that the maximum ceftazidime dosage for children 1 month to 12 years of age is 6 g daily, and that the higher dosage (i.e., 50 mg/kg every 8 hours) should be used in immunocompromised children or children with cystic fibrosis or meningitis.1, 28, 30, 108, 126, 128, 129, 149, 217
The AAP recommends that children beyond the neonatal period receive ceftazidime in a dosage of 90-150 mg/kg daily in 3 equally divided doses for the treatment of mild to moderate infections or 200-300 mg/kg daily in 3 equally divided doses for the treatment of severe infections.275
For the treatment of meningitis, some clinicians recommend a ceftazidime dosage of 100-150 mg/kg daily in 2 or 3 equally divided doses for neonates 7 days of age or younger and 150 mg/kg daily in 3 divided doses in older neonates and children.354 Because of a high rate of relapse, anti-infective therapy in patients with meningitis caused by gram-negative bacilli generally should be continued for at least 3 weeks.335, 337, 354 For treatment of meningitis in neonates, some clinicians recommend that anti-infective treatment be continued for 2 weeks beyond the first sterile CSF culture or at least 3 weeks, whichever is longer.354
For the treatment of melioidosis† caused by B. pseudomallei , some clinicians recommend a ceftazidime dosage of 60 mg/kg daily given IV in 2 equally divided doses in children younger than 2 months of age or 100 mg/kg daily given IV in 3 equally divided doses in children 2 months of age or older.357 Concomitant co-trimoxazole (6-8 mg/kg of trimethoprim daily) or doxycycline may be indicated in septicemic or other severe cases.357 The initial parenteral regimen should be continued for at least 10-14 days and until there is clinical improvement.275, 355, 356, 357 When appropriate, treatment may be changed to an oral maintenance regimen (e.g., oral co-trimoxazole with or without oral doxycycline) and continued for at least 3-6 months to prevent recrudence or relapse.275, 355, 356, 357 More prolonged oral maintenance therapy (up to 12 months) may be necessary, depending on the response to therapy and severity of initial illness.356, 357
Empiric Therapy in Febrile Neutropenic Patients
For empiric anti-infective therapy in febrile neutropenic patients†, pediatric patients 2 years of age or older have received ceftazidime in a dosage of 50 mg/kg (maximum 2 g) every 8 hours.347 (See Uses: Empiric Therapy in Febrile Neutropenic Patients.)
The duration of ceftazidime therapy depends on the type and severity of infection and should be determined by the clinical and bacteriologic response of the patient.1, 217 For most infections, therapy generally should be continued for at least 48 hours after the patient becomes asymptomatic or evidence of eradication of the infection has been obtained.1, 217 Complicated infections may require more prolonged therapy.1, 217
Dosage in Renal and Hepatic Impairment
In patients with renal impairment, doses and/or frequency of administration of ceftazidime should be modified in response to the degree of renal impairment, severity of the infection, and susceptibility of the causative organism.1, 9, 11, 37, 50, 159, 161, 162, 217 Excessive dosage and elevated plasma concentrations of the drug in patients with renal impairment can precipitate serious neurotoxicity (e.g., seizures, encephalopathy, coma, asterixis, neuromuscular excitability, myoclonia).1
The manufacturers recommend that adults with creatinine clearances of 50 mL/minute or less receive an initial loading dose of 1 g of ceftazidime and a maintenance dosage based on the patient's creatinine clearance.1, 217 (See Table 1.)
Creatinine Clearance (mL/minute) | Dosage |
|---|---|
31-50 | 1 g every 12 h |
16-30 | 1 g every 24 h |
6-15 | 500 mg every 24 h |
<5 | 500 mg every 48 h |
In patients with renal impairment and severe infections who would generally receive a ceftazidime dosage of 6 g daily if their renal function were normal, the manufacturers state that doses in the above table may be increased by 50% or the dosing frequency may be increased appropriately.1, 217
Alternatively, some clinicians recommend that adults with creatinine clearances of 30-80 mL/minute receive the usual doses of ceftazidime every 12-24 hours, adults with creatinine clearances of 10-29 mL/minute receive the usual doses every 24-36 hours, and adults with creatinine clearances less than 10 mL/minute receive the usual doses every 36-48 hours.161
Because ceftazidime is removed by hemodialysis, a supplemental dose of the drug is generally indicated after each dialysis period.1, 161, 217 The manufacturers recommend that adults undergoing hemodialysis receive an initial 1-g loading dose of ceftazidime followed by a 1-g dose after each dialysis period.1, 217, 221
In adults undergoing intraperitoneal dialysis or continuous ambulatory peritoneal dialysis, the manufacturers recommend that an initial 1-g loading dose of ceftazidime be given followed by a 500-mg dose every 24 hours.1, 217, 221 Some clinicians recommend that patients undergoing peritoneal dialysis receive 500 mg of ceftazidime every 24 hours and a supplemental 500-mg dose of the drug at the end of each dialysis period.27 If ceftazidime (as a sodium carbonate formulation) is administered intraperitoneally in the dialysis solution, the manufacturers recommend that 250 mg of the drug be added to each 2 L of dialysis solution.1, 217
In children with impaired renal function, the frequency of dosing should be decreased based on the degree of impairment.1, 217
Modification of the usual dosage of ceftazidime is generally unnecessary in patients with impaired hepatic function, unless renal function is also impaired.1, 150, 217
Adverse effects reported with ceftazidime are similar to those reported with other cephalosporins.1, 44, 48, 50, 103, 132, 147, 150, 208, 217 For information on adverse effects reported with cephalosporins, see Cautions in the Cephalosporins General Statement and other monographs in 8:12.06. Ceftazidime is generally well tolerated;1, 44, 48, 50, 103, 150, 208, 217 adverse effects have been reported in about 9% of patients receiving the drug and have required discontinuance in about 2% of patients.44, 50
Eosinophilia1, 48, 49, 50, 104, 107, 117, 119, 120, 132, 133, 134, 135, 136, 154, 217 has generally been reported in less than 7% of patients receiving ceftazidime.1, 44, 48, 217 Thrombocytosis1, 44, 48, 108, 117, 136, 217 has occurred in about 2%1, 48, 217 of patients receiving the drug. Transient leukopenia,1, 48, 117, 134, 136, 217 neutropenia,1, 132, 171, 217 thrombocytopenia,1, 48, 217 agranulocytosis,1 and lymphocytosis1, 217 have been reported rarely.
Positive direct antiglobulin (Coombs') test results1, 44, 48, 49, 50, 116, 120, 123, 132, 133, 137, 144, 146, 148, 217 have occurred in about 5% of patients receiving ceftazidime.1, 44, 48, 50, 217 In most reported cases, there was no clinical or laboratory evidence of hemolysis.1, 48, 50, 116, 120, 123, 132, 133, 137, 144, 146, 148, 217 However, hemolytic anemia has been reported rarely.1, 133, 217 In one patient with a positive direct antiglobulin test, mild hemolytic anemia occurred;1, 133, 217 the serum of this patient reacted with ceftazidime-treated erythrocytes, but did not react with untreated erythrocytes.133
Cephalosporins have been reported to cause hypothrombinemia.1, 217 Patients with renal or hepatic impairment, poor nutritional status, or those receiving a protracted course of anti-infective therapy are at particular risk of cephalosporin-induced hypothrombinemia.1, 217 Prothrombin time should be monitored and vitamin K administered as indicated in patients who are at risk of developing hypothrombinemia.1, 217
Adverse GI effects, including diarrhea,1, 48, 50, 103, 108, 117, 123, 132, 136, 137, 208, 217 nausea,1, 50, 134, 208, 217 vomiting,1, 50, 134, 217 abdominal pain,1, 50, 217 and a metallic taste,147 have been reported in less than 2% of patients receiving ceftazidime.1, 44, 50, 103, 217
Clostridium difficile-associated Diarrhea and Colitis
Treatment with anti-infectives alters the normal flora of the colon and may permit overgrowth of Clostridium difficile .1, 217
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 ceftazidime, and may range in severity from mild diarrhea to fatal colitis.1, 48, 50, 117, 123, 132, 136, 137, 145, 147, 217, 340, 341, 342C. difficile produces toxins A and B which contribute to the development of CDAD;1, 217, 340 hypertoxin-producing strains cause increased morbidity and mortality since these infections may be refractory to anti-infective therapy and may require colectomy.1
CDAD should be considered in the differential diagnosis in patients who develop diarrhea during or after anti-infective therapy and managed accordingly.1, 217, 340, 341, 342 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, 217, 340
If CDAD is suspected or confirmed, anti-infectives not directed against C. difficile should be discontinued whenever possible.1, 217, 340 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, 217, 340, 341, 342
Dermatologic and Sensitivity Reactions
Hypersensitivity reactions have been reported in 1-3% of patients receiving ceftazidime1, 44, 48, 50, 132, 217 and include pruritus,1, 50, 104, 107, 116, 137, 217 rash (maculopapular or erythematous),1, 48, 50, 103, 104, 107, 116, 117, 119, 120, 123, 136, 137, 138, 208, 217 urticaria,1, 12, 133 photosensitivity,268 angioedema,1, 262 and fever.1, 48, 50, 217
Immediate hypersensitivity reactions, including anaphylaxis (manifested as bronchospasm and/or hypotension), have occurred rarely with ceftazidime.1, 12, 50, 105, 120, 217 Toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme have been reported with cephalosporins,1, 217 including ceftazidime.1
The manufacturer of the commercially available Duplex® drug delivery system containing ceftazidime and 5% dextrose injection cautions that hypersensitivity reactions, including anaphylaxis, have been reported with administration of dextrose-containing solutions.251 These reactions have been reported in patients receiving high concentrations of dextrose (i.e., 50% dextrose) and also have been reported when corn-derived dextrose solutions were administered to patients with or without a history of hypersensitivity to corn products.251
If a hypersensitivity reaction occurs during ceftazidime therapy, the drug should be discontinued.1, 217 Severe acute hypersensitivity reactions should be treated with appropriate therapy (e.g., epinephrine, oxygen, antihistamines, corticosteroids, IV fluids, vasopressors, airway management) as indicated.1, 217
Transient increases in serum concentrations of AST (SGOT),1, 48, 50, 104, 107, 117, 134, 137, 139, 145, 152, 154, 208, 217 ALT (SGPT),1, 48, 50, 104, 134, 137, 139, 145, 152, 154, 208, 217 alkaline phosphatase,1, 48, 104, 142, 145, 152, 154, 217 LDH,1, 104, 217 and/or γ-glutamyltransferase (γ-glutamyl transpeptidase, GGT, GGTP)48, 104, 107, 145 have been reported in 3-9% of patients receiving ceftazidime.1, 48, 50, 103, 132, 217 Increased serum concentrations of bilirubin have occurred1, 48, 217 in less than 1% of patients receiving the drug.48 Jaundice has been reported with ceftazidime.1
Transient increases in BUN and/or serum creatinine concentrations1, 48, 50, 117, 126, 132, 136, 144, 147, 217 have been reported in less than 2% of patients receiving ceftazidime.48, 50
A transient, mild to moderate decrease in glomerular filtration rate has occurred in a few patients receiving ceftazidime.37, 50, 132 Although excretion of thermophilic aminopeptidase (alanine aminopeptidase), an enzyme originating from renal proximal tubular cells, was increased slightly in some of these patients, serum creatinine and urinary β2-microglobulin concentrations were generally unaffected, suggesting that ceftazidime did not adversely affect proximal tubular cells.37, 132 In healthy adults who received 6 g of ceftazidime daily for 3 days, urinary excretion of thermophilic aminopeptidase was unaffected by the drug.43 It has been suggested that ceftazidime's potential to slightly decrease glomerular filtration rate may be clinically important in patients with preexisting renal impairment if adequate dosage adjustments are not made in these patients.37 (See Dosage and Administration: Dosage in Renal and Hepatic Impairment.)
Renal failure has been reported in a few patients receiving ceftazidime; however, a causal relationship to the drug has not been established.117, 120, 136, 214 Like cephaloridine (a cephalosporin known to be nephrotoxic; no longer commercially available in the US), ceftazidime contains a methylpyridinium at position 3 of the cephalosporin nucleus;45, 48, 53, 54, 117, 120, 136, 203, 214 however, there is no evidence to date that this group is associated with nephrotoxicity,120, 214 and the manufacturers state that ceftazidime has not been shown to be nephrotoxic.1, 217 Nephrotoxicity of cephaloridine apparently results from accumulation of the drug in renal proximal tubular cells;39, 209 there is no evidence to date that ceftazidime accumulates in renal tubular cells.39, 221
Coma, encephalopathy, asterixis, hallucinations, neuromuscular excitability, and myoclonia have been reported in patients with renal impairment who received usual dosages of ceftazidime.1, 217, 257
Adverse local reactions, including phlebitis and pain or inflammation at the injection site,1, 6, 48, 50, 103, 105, 126, 137, 217 have been reported in less than 3% of patients receiving ceftazidime.1, 44, 48, 50, 217 Following IM injection of the drug, pain at the injection site is reportedly mild to moderate for about 2-5 minutes and subsides within 10-20 minutes.12
Distal necrosis can occur after inadvertent intra-arterial administration of ceftazidime.1, 217
Other adverse effects that have been reported in less than 1% of patients receiving ceftazidime include candidiasis (e.g., oral thrush) and vaginitis.1, 217
Precautions and Contraindications
Ceftazidime shares the toxic potentials of the cephalosporins, and the usual precautions of cephalosporin therapy should be observed.1, 217 Prior to initiation of therapy with ceftazidime, careful inquiry should be made concerning previous hypersensitivity reactions to cephalosporins, penicillins, or other drugs.1, 217 There is clinical and laboratory evidence of partial cross-allergenicity among cephalosporins and other β-lactam antibiotics including penicillins and cephamycins.1, 10, 207, 217, 244, 245 Ceftazidime is contraindicated in patients who are hypersensitive to any cephalosporin and should be used with caution in patients with a history of hypersensitivity reactions to penicillins.1, 217 Use of cephalosporins should be avoided in patients who have had an immediate-type (anaphylactic) hypersensitivity reaction to penicillins.245
To reduce development of drug-resistant bacteria and maintain effectiveness of ceftazidime 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, 217 When selecting or modifying anti-infective therapy, results of culture and in vitro susceptibility testing should be used.1, 217 In the absence of such data, local epidemiology and susceptibility patterns should be considered when selecting anti-infectives for empiric therapy should be considered.1, 217
Patients should be advised that antibacterials (including ceftazidime) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).1, 217 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 ceftazidime or other antibacterials in the future.1, 217
Like other dextrose-containing solutions, the commercially available Duplex® drug delivery system containing ceftazidime and 5% 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.251
Use of ceftazidime may result in overgrowth of nonsusceptible organisms, especially Candida, Staphylococcus aureus , enterococci, Enterobacter , or Pseudomonas .1, 44, 48, 111, 116, 119, 120, 132, 135, 136, 137, 138, 139, 154, 217 Resistant strains of Ps. aeruginosa and Enterobacter have developed during therapy with ceftazidime.44, 55, 111, 116, 117, 118, 132, 136, 137 (See Resistance.) Careful observation of the patient during ceftazidime therapy is essential.1, 117, 118, 217 If superinfection or suprainfection occurs, appropriate therapy should be instituted.1, 217
Because CDAD has been reported with the use of ceftazidime and other cephalosporins, it should be considered in the differential diagnosis of patients who develop diarrhea during or after ceftazidime therapy.1, 217, 340, 341, 342 (See Cautions: GI Effects.) Patients should be advised that diarrhea is a common problem caused by anti-infectives and usually ends 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, 217 Ceftazidime should be used with caution in patients with a history of GI disease, especially colitis.1, 217
As with other extended-spectrum β-lactams, resistance to ceftazidime in some gram-negative bacteria (e.g., Enterobacter , Pseudomonas ) can develop during therapy, leading to clinical failure in some cases.1, 217 When ceftazidime is used to treat infections caused by these gram-negative bacteria, periodic susceptibility testing should be performed when clinically appropriate.1, 217 If patients fail to respond to ceftazidime monotherapy, adding an aminoglycoside or similar agent to the regimen should be considered.1, 217
High and prolonged serum ceftazidime concentrations may occur if usual dosages of the drug are used in patients with transient or persistent reduction in urinary output because of renal insufficiency. Doses and/or frequency of administration of ceftazidime should be decreased in patients with transient or persistent renal impairment.1, 9, 11, 37, 50, 132 (See Dosage and Administration: Dosage in Renal and Hepatic Impairment.) Increased serum ceftazidime concentrations can result in serious adverse nervous system effects (e.g., seizures, encephalopathy, coma, asterixis, neuromuscular excitability, myoclonia).1 (See Cautions: Nervous System Effects.) Continued dosage should be determined by degree of renal impairment, severity of infection, and susceptibility of the causative organisms.
Clinical studies of ceftazidime did not include sufficient numbers of patients 65 years of age or older to determine whether geriatric patients respond differently than younger patients. Of the 2221 adults who received ceftazidime in clinical studies, 37% were 65 years of age or older, while 18% were 75 years of age or older.1 Although no overall differences in efficacy or safety were observed between geriatric and younger patients and other clinical experience revealed no age-related differences, the possibility that some older patients may exhibit increased sensitivity to the drug cannot be ruled out.1
Ceftazidime is known to be substantially excreted by the kidney, and the risk of ceftazidime-induced toxicity may be greater in patients with renal impairment.1 Because geriatric patients may have decreased renal function, initial dosage should be selected carefully and it may be useful to monitor renal function.1 (See Dosage and Administration: Dosage in Renal and Hepatic Impairment.)
Mutagenicity and Carcinogenicity
In vitro studies using microbial (i.e., Ames test) or mammalian cell (i.e., mouse micronucleus) systems have not shown ceftazidime to be mutagenic.1, 217 Studies have not been performed to date to evaluate the carcinogenic potential of ceftazidime.1, 217
Pregnancy, Fertility, and Lactation
Safe use of ceftazidime during pregnancy has not been definitely established.1, 217 Reproduction studies in mice and rats using ceftazidime dosages up to 40 times the usual human dosage have not revealed evidence of harm to the fetus.1, 217 There are no adequate or controlled studies using ceftazidime in pregnant women, and the drug should be used during pregnancy only when clearly needed.1, 217
Reproduction studies in mice and rats using ceftazidime dosages up to 40 times the usual human dosage have not revealed evidence of impaired fertility.1, 217
Because ceftazidime is distributed into milk,1, 17, 50, 203, 217 sodium carbonate formulations of the drug should be used with caution in nursing women.1, 217
Concomitant administration of 2 g of oral probenecid does not affect the pharmacokinetics of ceftazidime, presumably because ceftazidime is excreted principally by glomerular filtration.1, 5, 10, 24, 50, 130, 147, 164, 217
In vitro studies indicate that the antibacterial activity of ceftazidime and an aminoglycoside may be additive or synergistic against some strains of Enterobacteriaceae and Pseudomonas aeruginosa .1, 50, 63, 90, 147, 186, 187, 191, 217 Organisms with high-level resistance to both ceftazidime and the aminoglycoside alone are unlikely to be synergistically inhibited by concomitant use of the drugs.90
Concomitant use of aminoglycosides and certain cephalosporins reportedly may increase the risk of nephrotoxicity during therapy.1, 209, 217 Although this effect has not been reported to date with ceftazidime,43 the manufacturers suggest that renal function be carefully monitored when an aminoglycoside is used concomitantly with ceftazidime, especially if high aminoglycoside dosage is used or if therapy is prolonged.1, 217
Although a synergistic or partially synergistic effect has occurred in vitro against a few strains of Ps. aeruginosa when ceftazidime and carbenicillin, cefsulodin, mezlocillin, or piperacillin were used concomitantly,1, 50, 187, 217 use of ceftazidime and another cephalosporin or an extended-spectrum penicillin has generally resulted in an effect that was only slightly additive or indifferent against Ps. aeruginosa .50, 147, 186, 187 In addition, the combination of ceftazidime and cefoxitin has been antagonistic in vitro against Ps. aeruginosa .50
The clinical importance is unclear, but concomitant use of ceftazidime and ampicillin in vitro has resulted in antagonism against group B streptococci and Listeria monocytogenes .193
Although the clinical importance is unclear, in vitro studies indicate that the combination of ceftazidime and ciprofloxacin exerts a synergistic effect against Burkholderia cepacia .297, 344 In an in vitro study using B. cepacia isolates from patients with cystic fibrosis, the combination of ceftazidime and ciprofloxacin resulted in increased killing activity against most isolates (except ciprofloxacin-resistant strains).344 While a 3-drug combination (ceftazidime, ciprofloxacin, and tobramycin or rifampin) resulted in increased killing activity against B. cepacia isolates compared with ceftazidime alone, this effect was not substantially greater than that attained with the 2-drug combination of ceftazidime and ciprofloxacin.244
In vitro, the combination of ceftazidime and clindamycin has been reported to be neither synergistic nor antagonistic against Bacteroides fragilis .63
In vitro results indicate that the combination of ceftazidime and metronidazole may be at least partially synergistic against Clostridium , but results against B. fragilis are conflicting.50, 63
Chloramphenicol has been reported to antagonize the bactericidal activity of β-lactam antibiotics including ceftazidime,1, 270, 271, 272, 273, 274 in vitro, and the possibility of in vivo antagonism should be considered.1 Therefore, the manufacturers recommend that combined therapy with chloramphenicol and ceftazidime be avoided, particularly when bactericidal activity is considered important.1, 274
In vitro studies indicate that the combination of ceftazidime and clavulanic acid, a β-lactamase inhibitor, is synergistic against some strains of B. fragilis resistant to ceftazidime alone.50, 210 The combination was not effective against other Bacteroides , such as B. distasonis , that are not β-lactamase producers.50, 210 In vitro studies indicate that the combination of ceftazidime and chloramphenicol may be antagonistic against some organisms.264
Although concomitant use of cephalosporins and potent diuretics (e.g., furosemide) reportedly may adversely affect renal function,1, 217 this effect apparently did not occur when furosemide was used concomitantly with ceftazidime in a few patients.26, 49
Positive direct antiglobulin (Coombs') test results have been reported in patients receiving ceftazidime.1, 44, 48, 49, 50, 116, 120, 123, 132, 133, 137, 144, 146, 148, 217 This reaction may interfere with hematologic studies or transfusion cross-matching procedures.215
Like most cephalosporins, ceftazidime interferes with urinary glucose determinations using cupric sulfate (e.g., Benedict's solution, Fehling's solution, Clinitest®).1, 173 Urinary glucose determinations using glucose oxidase methods (e.g., Clinistix®) are unaffected by the drug.1, 173 In addition, ceftazidime does not interfere with glucose oxidase or hexokinase methods used to determine serum glucose concentrations.170
Ceftazidime does not appear to interfere with manual or automated methods used to determine serum or urinary creatinine concentrations, including those using the Jaffé reaction.40, 41, 42
Limited information is available on the acute toxicity of ceftazidime. Inappropriately large doses of parenteral cephalosporins may cause seizures, especially in patients with renal impairment. Overdosage of ceftazidime in patients with renal failure has produced seizures, encephalopathy, coma, asterixis, neuromuscular excitability, and myoclonia.1, 217 The drug should be discontinued promptly if seizures occur; anticonvulsant therapy may be administered if indicated. If acute overdosage of ceftazidime occurs, hemodialysis or peritoneal dialysis may be used to enhance elimination of the drug.1, 217
Ceftazidime usually is bactericidal in action.1, 50, 52, 55, 56, 95, 147, 150, 217 Like other cephalosporins, the antibacterial activity of the drug results from inhibition of mucopeptide synthesis in the bacterial cell wall.1, 3, 50, 150, 217 For information on the mechanism of action of cephalosporins, see Mechanism of Action in the Cephalosporins General Statement 8:12.06.
Studies evaluating the binding of ceftazidime to penicillin-binding proteins (PBPs), the target enzymes of β-lactam antibiotics, indicate that ceftazidime binds principally to PBP 3 of Escherichia coli and Pseudomonas aeruginosa .45, 50 The drug also has some affinity for PBP 1a of these organisms, but has little affinity for PBPs 2, 4, 5, and 6.45, 50 Ceftazidime binds less well than cefuroxime to PBPs 1, 2, and 3 of Staphylococcus aureus .45
Based on its spectrum of activity, ceftazidime is classified as a third generation cephalosporin.45, 50, 51, 52, 53, 57, 58, 59, 60, 63, 147, 150 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 parenteral third generation cephalosporins (e.g., cefotaxime, ceftriaxone), ceftazidime generally is less active in vitro against susceptible staphylococci than first generation cephalosporins but has an expanded spectrum of activity against gram-negative bacteria compared with first and second generation cephalosporins.50, 52, 53, 57, 58, 59, 60, 63, 147, 150, 195, 196, 200, 201 The spectrum of activity of ceftazidime resembles that of cefotaxime and ceftriaxone;52, 53, 55, 58, 59, 63, 196, 200 however, ceftazidime is more active in vitro on a weight basis against Pseudomonas than most other currently available parenteral third generation cephalosporins,50, 52, 53, 54, 55, 56, 58, 59, 60, 62, 150, 195, 196, 200, 201 but less active in vitro on a weight basis against anaerobes and gram-positive aerobic cocci than these drugs.50, 52, 53, 55, 58, 60, 195, 196, 200, 201
In Vitro Susceptibility Testing
Results of in vitro susceptibility tests with ceftazidime for some Enterobacteriaceae,50, 52, 63, 87, 89, 178 Pseudomonas aeruginosa ,50, 63, 65 and Bacteroides 87 may be affected by the size of the inoculum. For most organisms there is generally little difference in MICs of ceftazidime when the size of the inoculum is increased from 103 to 105 colony-forming units (CFU) per mL,52, 55, 63, 89, 195 but MICs of some organisms (e.g., Citrobacter freundii, Enterobacter, Morganella morganii, Proteus, Ps. aeruginosa ) may be 8-128 times greater when the size of the inoculum is increased from 105 to 107 CFU/mL.52, 55, 65, 89, 195 Results of ceftazidime susceptibility tests are generally unaffected by culture media,50, 63, 147 pH,63, 147 or presence of serum.50, 63, 147, 195, 199
Strains of staphylococci resistant to penicillinase-resistant penicillins (oxacillin-resistant [methicillin-resistant] staphylococci) should be considered resistant to ceftazidime, although results of in vitro susceptibility tests may indicate that the organisms are susceptible to the drug.204
For information on interpreting results of in vitro susceptibility testing (disk susceptibility tests, dilution susceptibility tests) when ceftazidime 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
Ceftazidime generally is active in vitro against the following gram-positive aerobic cocci: penicillinase-producing and nonpenicillinase-producing strains of Staphylococcus aureus 1, 50, 52, 54, 55, 56, 57, 58, 59, 60, 63, 92, 93, 94, 95, 96, 177, 179, 180, 217 and S. epidermidis ,1, 52, 54, 55, 56, 57, 58, 63, 92, 93, 94, 96, 179, 180, 200, 202, 217 Streptococcus pneumoniae ,1, 50, 54, 55, 56, 60, 63, 91, 93, 94, 96, 98, 177, 184, 194, 199, 217 S. pyogenes (group A β-hemolytic streptococci),1, 50, 52, 54, 55, 56, 57, 60, 63, 92, 93, 94, 177, 184, 195, 199, 217 S. agalactiae (group B streptococci),1, 50, 54, 55, 56, 60, 63, 74, 92, 93, 177, 217 and viridans streptococci.50, 55, 60, 63, 351 However, in vitro on a weight basis, ceftazidime is slightly less active than most other currently available third generation cephalosporins against these gram-positive bacteria.50, 52, 53, 55, 60, 196, 200, 201
Staphylococci resistant to penicillinase-resistant penicillins are resistant to ceftazidime.1, 50, 52, 55, 177, 179, 180, 202, 217 Listeria monocytogenes 1, 52, 55, 57, 63, 182, 217 and enterococci, including E. faecalis (formerly S. faecalis ), also are generally resistant to the drug.1, 50, 52, 54, 55, 60, 63, 92, 93, 94, 96, 177, 180, 184, 195, 199, 202, 217
The MIC90 (minimum inhibitory concentration of the drug at which 90% of strains tested are inhibited) of ceftazidime for penicillinase-producing and nonpenicillinase-producing S. aureus is 8-25 mcg/mL.52, 54, 55, 56, 57, 58, 59, 60, 63, 92, 93, 94, 95, 96, 177, 179, 180, 334 Although the MIC50 of ceftazidime reported for S. epidermidis is 8-16 mcg/mL,63, 180 the MIC90 of the drug for S. epidermidis 52, 54, 55, 56, 57, 58, 63, 92, 93, 94, 96, 179, 180, 200, 202, 334 or S. saprophyticus 55, 96 usually is 8-50 mcg/mL. The MIC90 of ceftazidime for group A β-hemolytic streptococci50, 52, 54, 55, 56, 57, 60, 63, 92, 93, 94, 177, 184, 195, 199 or group B streptococci50, 54, 55, 56, 59, 60, 63, 74, 92, 93, 177 is 0.06-2 mcg/mL. The MIC90 of the drug reported for Streptococcus pneumoniae is 0.13-4 mcg/mL,50, 52, 54, 55, 56, 60, 63, 91, 93, 94, 96, 98, 177, 184, 194, 199, 334 and the MIC90 reported for viridans streptococci is 3.1-8 mcg/mL.50, 55, 60, 63, 351 In one study, the MIC50 and MIC90 of ceftazidime for the S. milleri group of viridans streptococci ( S. anginosus , S. constellatus , S. intermedius ) were 4 and 8 mcg/mL, respectively.351
Gram-negative Aerobic Bacteria
Ceftazidime is active in vitro against Neisseria meningitidis 1, 50, 52, 54, 55, 56, 63, 188, 217 and most strains of penicillinase-producing and nonpenicillinase-producing Neisseria gonorrhoeae .1, 50, 52, 54, 55, 56, 63, 68, 71, 72, 91, 92, 98, 99, 189, 194, 195, 217 Ceftazidime concentrations of 0.001-0.06 mcg/mL generally inhibit N. meningitidis .52, 54, 55, 56, 63, 188 The MIC90 of ceftazidime is 0.02-0.25 mcg/mL for nonpenicillinase-producing N. gonorrhoeae 52, 68, 72, 92 and 0.001-0.03 mcg/mL for penicillinase-producing strains of the organism.52, 55, 68, 72, 98, 194
Ceftazidime is active in vitro against most β-lactamase-producing and non-β-lactamase-producing strains of Haemophilus influenzae ,1, 50, 52, 54, 55, 56, 57, 58, 63, 77, 79, 91, 92, 94, 96, 99, 180, 184, 189, 194, 195, 217 H. parainfluenzae ,1, 217 and H. ducreyi .56 The MIC90 of the drug reported for H. influenzae is 0.1-1 mcg/mL.52, 54, 55, 56, 57, 58, 63, 77, 79, 91, 92, 94, 96, 99, 180, 184, 189, 194, 195, 334 In one study, the MIC90 of ceftazidime for H. ducreyi was 0.13 mcg/mL.56
Generally, ceftazidime is active in vitro against the following Enterobacteriaceae: Citrobacter diversus ,1, 52, 54, 55, 60, 63, 97, 99, 101, 217 C. freundii ,1, 52, 54, 55, 60, 63, 92, 93, 95, 96, 97, 101, 200, 217 Enterobacter agglomerans ,52, 55, 57, 63, 92, 97, 99 E. cloacae ,1, 52, 54, 55, 63, 94, 95, 97, 99, 101, 217 E. aerogenes ,1, 52, 55, 60, 63, 93, 94, 95, 97, 99, 101, 199, 217 Escherichia coli ,1, 52, 55, 56, 57, 58, 59, 60, 63, 82, 91, 93, 94, 95, 96, 97, 98, 99, 100, 180, 189, 194, 195, 199, 201, 202, 217 Klebsiella oxytoca ,63, 95, 96, 97, 99, 101 K. pneumoniae ,1, 52, 55, 56, 58, 60, 63, 82, 94, 95, 96, 97, 99, 101, 180, 189, 195, 199, 200, 202, 217 Morganella morganii (formerly Proteus morganii ),1, 52, 54, 55, 60, 63, 93, 94, 97, 99, 101, 180, 184, 200, 201, 202, 217 Proteus mirabilis ,1, 52, 54, 55, 56, 57, 59, 60, 63, 82, 91, 92, 93, 94, 95, 96, 97, 98, 99, 101, 184, 189, 194, 199, 202, 217 P. vulgaris ,1, 52, 55, 60, 63, 82, 93, 94, 97, 99, 101, 180, 184, 195, 200, 201, 217 Providencia rettgeri (formerly Proteus rettgeri ),1, 52, 55, 63, 94, 97, 99, 101, 184, 200, 201, 202, 217 P. stuartii ,52, 55, 60, 91, 92, 93, 94, 97, 98, 99, 101, 180, 189, 194, 195, 200 Serratia marcescens ,1, 52, 54, 55, 58, 60, 63, 92, 93, 94, 95, 96, 97, 99, 180, 189, 195, 200, 201, 202, 217 Salmonella ,1, 52, 55, 56, 57, 63, 69, 93, 97, 99, 180, 202, 217, 252 Shigella ,1, 52, 55, 56, 57, 63, 97, 99, 180, 202, 217 and Yersinia enterocolitica .1, 56, 63, 75, 76, 92, 99, 201, 202, 217
The MIC90 of ceftazidime for E. coli ,52, 55, 56, 57, 58, 59, 60, 63, 82, 91, 93, 94, 95, 96, 97, 98, 99, 100, 180, 189, 194, 195, 199 Klebsiella (including K. pneumoniae ),52, 55, 56, 58, 60, 63, 82, 94, 95, 96, 97, 99, 101, 180, 189, 195, 199, 200, 202 M. morganii ,52, 54, 55, 60, 63, 93, 94, 97, 99, 101, 180, 184, 200, 201, 202 Providencia ,52, 55, 60, 63, 91, 92, 93, 94, 97, 98, 99, 101, 180, 184, 189, 195, 200, 201, 202 and S. marcescens 52, 54, 55, 58, 60, 63, 92, 93, 94, 95, 96, 97, 99, 180, 189, 195, 200, 201, 202 is 0.2-6.3 mcg/mL. The MIC90 of the drug for P. mirabilis ,52, 54, 55, 56, 57, 59, 60, 63, 82, 91, 92, 93, 94, 95, 96, 97, 98, 99, 101, 184, 189, 194, 199, 202 P. vulgaris ,52, 55, 60, 63, 82, 93, 94, 97, 99, 101, 180, 184, 195, 200, 201 and Y. enterocolitica 56, 63, 75, 76, 92, 99, 201, 202 is 0.05-0.8 mcg/mL.
The MIC90 of ceftazidime reported for C. diversus is 0.2-1 mcg/mL.52, 54, 55, 60, 63, 97, 99, 101, 334 The in vitro activity of ceftazidime against C. freundii , however, varies considerably.50, 52, 54, 92, 93, 94, 95, 96, 97, 99, 101, 200 In some studies the MIC90 of ceftazidime for C. freundii was 0.2-8 mcg/mL,52, 54, 63, 92, 93, 99, 101, 200 and in other studies it was 32 mcg/mL or greater.94, 95, 96, 97 The in vitro activity of ceftazidime against Enterobacter also varies considerably.50, 52, 55, 60, 93, 94, 95, 99, 101 The MIC90 of ceftazidime reported for E. agglomerans is 0.5-6.3 mcg/mL,52, 55, 57, 63, 92, 97, 99 and the MIC90 of the drug reported for E. aerogenes is 0.2-32 mcg/mL.52, 55, 60, 63, 93, 94, 95, 99, 101 In some studies the MIC90of ceftazidime reported for E. cloacae was 0.5-12.5 mcg/mL,54, 63, 93, 95, 99, 101 but in other studies it was 32-64 mcg/mL or greater.50, 52, 55, 60, 94, 97, 334
The MIC90 of ceftazidime reported for Salmonella enteritidis ,55, 180, 252 S. newport ,69 and S. typhi 69, 252 is 0.1-6.5 mcg/mL. In one study, strains of S. typhi resistant to ampicillin and chloramphenicol were susceptible in vitro to ceftazidime concentrations of 0.1-0.2 mcg/mL.69 The MIC90 of ceftazidime reported for Shigella , including Sh. flexneri and Sh. sonnei , is 0.12-6.3 mcg/mL.52, 55, 56, 57, 97, 99, 180, 202
Ceftazidime is active in vitro against Pseudomonas aeruginosa .1, 50, 54, 56, 61, 62, 63, 67, 147, 150, 187, 192, 198, 217, 306 In vitro on a weight basis, ceftazidime is more active against Ps. aeruginosa than most other cephalosporins.50, 54, 56, 61, 62, 63, 67, 147, 150, 187, 192, 198 In addition, ceftazidime is active in vitro against some strains of Ps. aeruginosa resistant to other third generation cephalosporins, aminoglycosides, and extended-spectrum penicillins.50, 147, 186, 198 The MIC90 of ceftazidime reported for Ps. aeruginosa is 0.5-32 mcg/mL.50, 52, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 67, 84, 91, 92, 93, 94, 95, 96, 147, 150, 177, 179, 180, 184, 186, 187, 189, 192, 194, 195, 198, 201, 202, 306, 334
Ceftazidime is also active against Pseudomonas other than Ps. aeruginosa .1, 50, 52, 55, 57, 60, 63, 93, 100, 131, 217, 246 The MIC90 of ceftazidime reported for Ps. acidovorans ,61 Ps. fluorescens ,55, 57, 61, 324 Ps. putida ,61, 100, 324 and Ps. stutzeri 55, 61, 100, 306, 324 is 0.5-16 mcg/mL.
Ceftazidime is active in vitro against some strains of Burkholderia cepacia (formerly Ps. cepacia ).55, 57, 60, 61, 297, 307, 309, 314, 324, 334, 344 The MIC50 and MIC90 of ceftazidime reported for some strains of B. cepacia are 2-8 and 4-32 mcg/mL, respectively;314, 309, 324, 334, 344 however, strains of B. cepacia isolated from patients with cystic fibrosis generally require higher ceftazidime concentrations for in vitro inhibition than strains isolated from patients who do not have cystic fibrosis and many of these strains have MIC90s of 64 mcg/mL or greater and are resistant to the drug.314, 324, 344 Although the clinical importance is unclear, in vitro studies indicate that the combination of ceftazidime and amikacin297 or ciprofloxacin297, 344 exerts a synergistic effect against B. cepacia . (See Quinolones under Drug Interactions: Anti-infective Agents.)
Ceftazidime also has in vitro activity against some strains of B. pseudomallei (formerly Ps. pseudomallei ).113, 325, 326, 330 Susceptible strains of B. pseudomallei are inhibited in vitro by ceftazidime concentrations of 1-8 mcg/mL;326, 330 other strains are resistant to the drug.325, 326, 330
Other Gram-negative Aerobic Bacteria
Ceftazidime has some activity in vitro against Acinetobacter .1, 50, 52, 55, 57, 61, 63, 92, 93, 95, 97, 99, 100, 177, 180, 201, 217 The MIC90 of ceftazidime reported for A. calcoaceticus , A. lwoffi , and A. baumannii 306 is 8-32 mcg/mL.50, 55, 92, 100, 180
Moraxella catarrhalis generally is inhibited in vitro by ceftazidime concentrations of 0.06-0.13 mcg/mL.56, 83 Some strains of M. osloensis and M. nonliquefaciens are inhibited in vitro by ceftazidime concentrations of 8 mcg/mL.324
Ceftazidime also is active in vitro against Eikenella corrodens 78 and Pasteurella multocida .55, 56, 63, 180 The MIC90 of the drug is 16 mcg/mL for E. corrodens 78 and 0.13-1.6 mcg/mL for P. multocida .55, 56, 63, 180
Campylobacter fetus subsp. jejuni , an organism that can be microaerophilic or anaerobic, may be inhibited in vitro by ceftazidime concentrations of 3.1-6.25 mcg/mL.181
While some strains of Alcaligenes denitrificans , A. faecalis , and A. xylosoxidans may be inhibited in vitro by ceftazidime concentrations of 1-16 mcg/mL,306, 324 the MIC90 of the drug reported for Alcaligenes ranges from 2 to more than 64 mcg/mL.324
In vitro, some strains of Bartonella bacilliformis are inhibited by ceftazidime concentrations of 0.12-0.25 mcg/mL.350
The MIC90 of ceftazidime reported for some strains of Chryseobacterium gleum (formerly Flavobacterium gleum , CDC group IIb) and C. indologenes (formerly F. indologenes , CDC group IIb) is 8 mcg/mL and the MIC90 reported for Sphingobacterium multivorum (formerly F. multivorum ) is 32 mcg/mL.324 C. meningosepticum (formerly F. meningosepticum ) generally are resistant to ceftazidime.324
Rare strains of Stenotrophomonas maltophilia (formerly Ps. maltophilia or Xanthomonas maltophilia ) are inhibited in vitro by ceftazidime concentrations of 4-16 mcg/mL;278, 304, 305 however, most strains require ceftazidime concentrations of 32 mcg/mL or greater for in vitro inhibition and are considered resistant to the drug.55, 61, 97, 99, 100, 222, 278, 304, 305, 306, 324, 328 Although the clinical importance is unclear, in vitro studies indicate that the combination of ceftazidime and a quinolone (e.g., ciprofloxacin, levofloxacin, trovafloxacin) exerts a synergistic bactericidal activity against some strains of S. maltophilia .304, 331
Ceftazidime is active in vitro against some gram-positive anaerobic bacteria including some strains of Bifidobacterium ,56, 60, 174 Clostridium ,50, 54, 56, 57, 60, 63, 92, 174 Eubacterium ,60, 174, 218 Lactobacillus ,60 Peptococcus ,1, 52, 54, 56, 60, 63, 174, 177, 217, 218 Peptostreptococcus ,1, 50, 54, 56, 60, 174, 217 and Propionibacterium .50, 56, 60, 81 The MIC90 of ceftazidime reported for most of these gram-positive anaerobic bacteria is 4-32 mcg/mL.50, 52, 54, 56, 60, 63, 81, 174, 177, 218 C. perfringens generally is inhibited in vitro by ceftazidime concentrations of 2-16 mcg/mL;54, 56, 57, 60, 63, 92, 174 however, C. difficile is resistant to the drug.1, 50, 56, 63, 217, 218 The MIC50 of ceftazidime for Actinomyces is reportedly 6-8 mcg/mL, but the MIC90 is 48-64 mcg/mL.54, 174
Ceftazidime has little in vitro activity against gram-negative anaerobic bacteria.50, 73, 96, 174 Although the MIC90 of ceftazidime reported for Bacteroides melaninogenicus is 4-16 mcg/mL,60, 218 other Bacteroides (including B. fragilis ) are generally resistant to the drug.1, 50, 73, 96, 98, 174, 184, 189, 194, 195, 217 The MIC50 of ceftazidime reported for B. fragilis, B. distasonis, B. ovatus , and B. thetaiotaomicron is 8-32 mcg/mL, and the MIC90 of the drug reported for these organisms is usually 64 mcg/mL or greater.50, 52, 57, 60, 73, 96, 98, 174, 177, 189, 194, 195, 218 Although the MIC50 of ceftazidime reported for Fusobacterium and Veillonella is 4-16 mcg/mL, the MIC90 of the drug for these organisms is 32 mcg/mL or greater and many strains are considered resistant to the drug.52, 56, 60, 174, 177
For information on possible mechanisms of bacterial resistance to cephalosporins, see Resistance in the Cephalosporins General Statement 8:12.06.
Ceftazidime generally is stable against hydrolysis by β-lactamases classified as Richmond-Sykes types I, II, III (TEM type), IV, and V45, 50, 55, 62, 63, 87, 88, 94, 96, 101, 175, 176, 177, 189 and most PSE types.45, 50, 62, 63, 87, 88, 176 The drug is hydrolyzed to some extent by chromosomally mediated β-lactamases isolated from Bacteroides and Providencia .87, 177 Ceftazidime is more stable than cefotaxime56, 63, 87, 88, 147, 175 against hydrolysis by β-lactamases, but as stable as or slightly less stable than cefoxitin.50, 147
Resistant strains of Enterobacter and Pseudomonas have developed during therapy with ceftazidime.44, 50, 111, 116, 117, 118, 132, 136, 137 Resistance to ceftazidime in some Enterobacteriaceae (e.g., Enterobacter cloacae, Citrobacter freundii ) reportedly results from increased production of chromosomally mediated β-lactamases, nonspecific binding of PBPs, and permeability factors.45, 50, 265 In vitro studies indicate that resistance to ceftazidime in Ps. aeruginosa, Acinetobacter , and some strains of Serratia is generally related to permeability factors;45 however, in a few strains of Ps. aeruginosa that developed resistance to ceftazidime during therapy with the drug, resistance appeared to result partly from increased production of chromosomally mediated β-lactamases.50, 111 Bacteroides are generally resistant to ceftazidime because of permeability factors and because the drug has little affinity for the PBPs of this organism.45
Ceftazidime-resistant strains of Klebsiella pneumoniae have been reported, and these strains have been involved in nosocomial outbreaks in hospitals and chronic care facilities.318, 319, 320, 321, 322, 323 Resistance in these strains results from acquisition of plasmid-mediated extended-spectrum β-lactamases (TEM- or SHV-derived extended-spectrum β-lactamases).318, 320, 321, 322, 323
In vitro studies indicate that ceftazidime can induce β-lactamase production in some strains of Enterobacter and Ps. aeruginosa that possess these inducible, chromosomally mediated enzymes; however, the drug is not an efficient inducer when compared with cefoxitin.45, 163, 176
In all studies described in the Pharmacokinetics section, ceftazidime was administered as ceftazidime sodium; dosages and concentrations of the drug are expressed in terms of ceftazidime.
Ceftazidime is not absorbed from the GI tract and must be given parenterally.3, 50
Following IM administration of a single 0.5- or 1-g dose of ceftazidime in healthy adults, peak serum concentrations of the drug are attained approximately 1 hour after the dose and average 17 or 29-39 mcg/mL, respectively.1, 6, 12, 217 Following IM injection into the gluteus maximus or vastus lateralis, ceftazidime may be absorbed more slowly in women than in men.6 In women, peak serum concentrations of the drug may be lower following IM injection into the gluteus maximus than into the vastus lateralis.6
Following IV infusion over 20-30 minutes of a single 0.5- or 1-g dose of ceftazidime in healthy men, peak serum concentrations of the drug at completion of the infusion average 42 or 69 mcg/mL, respectively.1, 12, 217 IV infusion over 20-30 minutes of a single 2-g dose in healthy adults results in peak serum ceftazidime concentrations at completion of the infusion that average 159-185.5 mcg/mL1, 4, 7, 8, 12, 217 and serum concentrations at 0.5, 1, 2, 4, and 6 hours after completion of the infusion that average 87.9, 65.2-70.6, 38.7, 16.7-16.9, and 7.7 mcg/mL, respectively.4, 7, 8
Following IV injection over 3-5 minutes of a single 0.5- or 1-g dose of ceftazidime in healthy men, serum concentrations of the drug at 0.25, 0.5, 1, 2, 4, 6, and 8 hours after the dose average 34.1, 24.5, 17.1, 11.2, 5.6, 2.1-2.4, and 0.9-1.3 mcg/mL, respectively, after the 0.5-g dose and 59.9-83.3, 45.3-60.9, 32.1-40.9, 22.9-23.2, 9.7, 4.4-5.3, and 1.9-3.2 mcg/mL, respectively, after the 1-g dose.5, 12, 24, 165
In adults with suspected gram-negative infections who received a 2-g IV loading dose of ceftazidime followed by 3 g given by continuous IV infusion over 24 hours, steady-state serum concentrations averaged 29.7 mcg/mL.300 Serum concentrations averaged 21.3-56.4 mcg/mL in cystic fibrosis patients 9-25 years of age who received a 7.5- or 10-mg/kg IV loading dose of ceftazidime followed by 3.4 or 4.5 mg/kg hourly given by continuous IV infusion over 24 hours.301
In neonates 1-15 days of age with infections who received a single 50-mg/kg dose of ceftazidime by IM injection, serum concentrations of the drug averaged 67.2, 68.2, 42.1, 23.7, and 8.9 mcg/mL at 0.5, 1, 3, 6, and 12 hours, respectively, after the dose.35 In neonates and children with infections who received a single 30-mg/kg dose by IV injection, serum concentrations of ceftazidime averaged 54.1, 31.2, and 18.6 mcg/mL at 3, 6, and 9 hours, respectively, after the dose in those less than 2 months of age and 26.5, 12.3, 6.4, and 3.3 mcg/mL at 3, 5, 7, and 9 hours, respectively, after the dose in those 2-12 months of age.155 In neonates who received 25-mg/kg doses every 12 hours by IV injection, serum ceftazidime concentrations on the third or fourth day of therapy averaged 81.7, 70, 68, 50, 39.5, and 16.1 mcg/mL at 0.25, 0.5, 1, 3, 5, and 12 hours, respectively, after a dose.33
In children 5-14 years of age with cystic fibrosis who received 35-mg/kg doses of ceftazidime every 8 hours by IV injection, serum concentrations averaged 110, 86, 50, 25.5, 8.1, 4.3, and 2.3 mcg/mL at 0.25, 0.5, 1, 2, 4, 6, and 8 hours, respectively, after the eighth dose.30
In patients with end-stage chronic renal failure who received a single 1-g dose of ceftazidime via an intraperitoneal catheter, peak serum concentrations were attained 2.75 hours after the dose and averaged 44.7 mcg/mL; serum ceftazidime concentrations at 0.25, 2, and 8 hours after the dose averaged 14.2, 40, and 32 mcg/mL, respectively.27 Following intraperitoneal administration of a 200-mg dose of ceftazidime in 2 L of dialysis fluid in patients with end-stage chronic renal failure undergoing a 12-hour period of peritoneal dialysis (12 cycles of dialysis, each exchanging 2 L of dialysate for 15-20 minutes), serum ceftazidime concentrations averaged 1.3, 25.3, and 18.7 mcg/mL at 1, 12, and 24 hours, respectively, after the start of dialysis.27 Concentrations of the drug in the dialysis effluent averaged 42.2 mcg/mL.27
Following IM or IV administration, ceftazidime is widely distributed into body tissues and fluids including the gallbladder,24, 234, 255 bone,1, 3, 23, 147, 203, 217, 220 bile,1, 3, 10, 11, 18, 24, 49, 50, 147, 203, 217, 255 skeletal muscle,1, 3, 23, 50, 203, 217, 234 prostatic tissue,21, 217, 234 endometrium,25 myometrium,1, 3, 25, 217, 234 heart,1, 3, 23, 50, 203, 217 skin,1, 3, 23, 50, 217, 234 adipose tissue,23, 50, 234 aqueous humor,1, 3, 16, 22, 147, 203, 217 and sputum,1, 3, 28, 30, 49, 147, 154, 203, 217 and pleural,22, 203 peritoneal,1, 3, 15, 50, 166, 167, 217 synovial,1, 3, 217 ascitic,160, 166 lymphatic,1, 3, 22, 217 and blister1, 3, 22, 165, 217 fluids.
The volume of distribution of ceftazidime at steady state (Vss) averages 0.18-0.31 L/kg in healthy adults.4, 7, 9, 156, 161 In neonates 2-9 days of age, the Vss of ceftazidime averaged 0.42-0.55 L/kg.34 In patients with cystic fibrosis, the volume of distribution of ceftazidime reportedly averages 0.15-0.19 L/kg in the central compartment and 0.17-0.27 L/kg in the peripheral compartment.130, 154, 157
Ceftazidime generally diffuses into CSF following IV administration;1, 11, 13, 19, 20, 22, 50, 147, 158, 217, 223, 224, 226 however, CSF concentrations of the drug are higher in patients with inflamed meninges than in those with uninflamed meninges.10, 13, 19, 20, 22, 50, 147, 158 CSF concentrations of ceftazidime do not appear to correlate with CSF leukocyte cell counts or CSF protein concentrations.20, 226 In adults with meningitis who received 2 g of ceftazidime every 8 hours by IV infusion over 30 minutes, CSF concentrations of the drug on days 2-4 of therapy averaged 9.8 mcg/mL in samples obtained 2 hours after a dose and 9.4 mcg/mL in samples obtained 3 hours after a dose.19 On days 11-20 of therapy, when the meninges were presumably healed, CSF concentrations of ceftazidime averaged 4.1 and 7.2 mcg/mL in samples obtained 2 and 3 hours, respectively, after a dose.19 In neonates with meningitis who received IV ceftazidime in a dosage of 90-150 mg/kg daily, CSF concentrations 2-4 hours after a dose were 22-30 mcg/mL.223
Ceftazidime generally is distributed into bile, but biliary concentrations of the drug following IM or IV administration may be lower than concurrent serum concentrations.10, 11, 18, 255 In women 36-70 years of age undergoing cholecystectomy who received a single 2-g dose of ceftazidime by IV infusion over 15 minutes, ceftazidime concentrations in gallbladder bile 25-160 minutes after the dose ranged from 6.6-58 mcg/mL and concurrent serum concentrations of the drug ranged from 51.6-108 mcg/mL.18 In another study in patients 34-72 years of age also undergoing cholecystectomy who received a single 1-g IV dose of the drug, ceftazidime concentrations in gallbladder and bile duct bile 60 minutes following the dose averaged 3.9 mcg/mL (range: 0.1-15.2 mcg/mL) and 31.8 mcg/mL (range: 12.5-55.4 mcg/mL), respectively, and concurrent serum concentrations of the drug averaged 36.1 mcg/mL (range: 23.6-46.8 mcg/mL).255
In cystic fibrosis patients aged 5-32 years who received 35- or 50-mg/kg doses of ceftazidime every 8 hours by IV injection, concentrations of ceftazidime in sputum ranged from 0.7-9.8 mcg/mL;28, 30 peak sputum concentrations were usually attained 1 hour after a dose.30
In patients undergoing cataract surgery who received a single 2-g dose of ceftazidime by IV injection over 3-5 minutes, aqueous humor concentrations of the drug averaged 2.8, 4, 3.2, 3.4, and 1.9 mcg/mL at 0.5, 1, 2, 4, and 6 hours, respectively, after the dose.16
Ceftazidime is 5-24% bound to serum proteins.1, 4, 6, 8, 10, 11, 50, 147, 203 The degree of protein binding is independent of the concentration of the drug.1, 7, 50, 217
Ceftazidime crosses the placenta and is distributed into amniotic fluid.3, 32 Ceftazidime is also distributed into milk.1, 3, 17, 203 In lactating women with endometritis who received 2 g of ceftazidime IV every 8 hours, concentrations of the drug in milk obtained during days 2-4 of therapy averaged 3.8 mcg/mL immediately prior to a dose and 5.2 and 4.5 mcg/mL at 1 and 3 hours, respectively, after a dose.17
Plasma concentrations of ceftazidime decline in a biphasic manner.4, 6, 7, 12 In adults with normal renal and hepatic function, the distribution half-life (t½α) of ceftazidime is 0.1-0.6 hours4, 6, 7, 8, 24, 36, 161, 166 and the elimination half-life (t½β) is 1.4-2 hours.1, 4, 5, 6, 7, 24, 36, 161, 166, 203, 217
Ceftazidime is not metabolized1, 3, 4, 9, 10, 11, 12, 24, 50, 217 and is excreted unchanged principally in urine by glomerular filtration.1, 3, 7, 10, 11, 24, 47, 50, 203, 217 Following IM or IV administration of a single 0.5- or 1-g dose of ceftazidime in adults with normal renal function, 80-90% of the dose is excreted in urine unchanged within 24 hours;1, 12, 24, 161, 165, 203, 217 approximately 50% of the dose is excreted within 2 hours after the dose.1, 217
Serum clearance of ceftazidime averages 98-122 mL/minute in healthy adults.1, 12, 24, 165, 217 In geriatric patients 63-83 years of age with urinary tract infections, serum clearance of ceftazidime averaged 79 mL/minute and the serum half-life of the drug averaged 2.9 hours.153 In patients with cystic fibrosis, the serum clearance of ceftazidime ranges from 142-316 mL/minute per 1.73 m2;50 the serum half-life of the drug in these patients, however, ranges from 1-2.2 hours and is generally within the same range as that for healthy individuals.28, 30, 50, 154, 157
The serum half-life of ceftazidime is longer in neonates than in older children and adults,33, 34, 35, 38, 154, 155, 226 but does not appear to be related to gestational age or birthweight.33 The t½β of ceftazidime in neonates 1-23 days of age reportedly ranges from 2.2-4.7 hours.34, 35, 147, 226 In a group of children 2-12 months of age, the t½β of ceftazidime averaged 2 hours.155
Serum concentrations of ceftazidime are higher and the serum half-life of the drug is prolonged in patients with impaired renal function.1, 9, 24, 37, 153, 159, 161, 162, 217 The t½β of ceftazidime ranged from 3-4.6 hours in patients with creatinine clearances of 39-73 mL/minute and 9.4-10.3 hours in patients with creatinine clearances of 13-27 mL/minute.161 The t½β of ceftazidime in patients with creatinine clearances less than 10 mL/minute ranges from 11.9-35 hours.159, 161, 162, 221
The serum half-life of ceftazidime is only slightly prolonged in patients with impaired hepatic function and accumulation of the drug does not generally occur in these patients unless renal function is also impaired.1, 26, 166, 217 In a group of patients who had normal renal function but impaired hepatic function (e.g., alcoholic cirrhosis, chronic active hepatitis B, biliary cirrhosis), the serum half-life of ceftazidime averaged 2.9 hours.26 In another group of patients with ascites who had normal renal function, the t½α of ceftazidime averaged 0.4 hours and the t½β averaged 5.9 hours.166
Ceftazidime is readily removed by hemodialysis.50, 147, 161 The drug is also removed by peritoneal dialysis.27, 50, 147
Ceftazidime is a semisynthetic cephalosporin antibiotic.1, 3, 7, 10, 45, 50, 53, 54, 56, 147, 150, 203, 217 Like cefepime, cefotaxime, and ceftriaxone, ceftazidime is a parenteral aminothiazolyl cephalosporin.7, 45, 50, 56, 147, 150, 203 Ceftazidime contains an aminothiazolyl side chain at position 7 of the cephalosporin nucleus.45, 54, 56 The aminothiazolyl side chain enhances antibacterial activity, particularly against Enterobacteriaceae, and generally results in enhanced stability against β-lactamases.45, 54, 56 However, ceftazidime contains a carboxypropyl oxyimino group in the side chain rather than the methoxyimino group contained in many aminothiazolyl cephalosporins.45, 54, 56 This difference results in increased stability against hydrolysis by β-lactamases, increased activity against Pseudomonas , and decreased activity against gram-positive bacteria.45, 50, 54, 56, 150 Ceftazidime also contains a pyridine at position 3 of the cephalosporin nucleus.45, 48, 54, 117, 120, 136, 203, 214
Ceftazidime is commercially available as sterile powders for injection containing a mixture of ceftazidime (as the pentahydrate) and sodium carbonate.1, 217, 233 In these formulations, sodium carbonate has been admixed with ceftazidime to facilitate its dissolution;1, 217, 233 ceftazidime sodium is formed in situ following reconstitution of the powdered mixture as directed.56, 221, 225 These preparations contain 118 mg of sodium carbonate per gram of ceftazidime or 54 mg (2.3 mEq) of sodium per gram of ceftazidime.1, 3, 217, 233 Potency of ceftazidime sodium is expressed in terms of ceftazidime,1, 217, 233, 258 calculated on the anhydrous basis.
Ceftazidime occurs as a white to off-white powder.1, 3 The drug has solubilities of 5 mg/mL in water and less than 1 mg/mL in alcohol.3 Ceftazidime has pKas of 1.9, 2.7, and 4.1.221 When reconstituted as directed, ceftazidime sodium solutions have a pH of 5-8,1, 3, 217, 233 and are light yellow to amber in color depending on the diluent used, concentration of the drug, and length of storage.1, 217
When the commercially available Duplex® drug delivery system containing 1 or 2 g of ceftazidime and 50 mL of 5% dextrose injection in separate chambers is reconstituted (activated) according to the manufacturer's directions, the resultant solution has an osmolality of approximately 340 and 400 mOsm/kg, respectively.251 The solutions are light yellow to amber in color and have a pH of 5-7.5.251
Commercially available frozen premixed injections of ceftazidime sodium in dextrose are sterile, nonpyrogenic, iso-osmotic solutions of the drug provided in a plastic container (Galaxy® container) fabricated from specially formulated multilayered plastic (PL 2040).1 The 1- and 2-g frozen injections of ceftazidime contain approximately 2.2 or 1.6 g of dextrose, respectively, and have osmolalities of approximately 300 mOsm/kg;1 The frozen injections also contain hydrochloric acid and/or sodium hydroxide to adjust pH to 5-7.5;1 sodium hydroxide neutralizes ceftazidime pentahydrate free acid to the sodium salt.1
Ceftazidime powder and solutions of ceftazidime sodium tend to darken depending on storage conditions; however, color changes do not necessarily indicate loss of potency.1, 217, 233
The commercially available vials of Fortaz® sterile powder for injection containing ceftazidime (as the pentahydrate) with sodium carbonate should be stored at 15-30°C and protected from light.1 Following reconstitution with sterile water for injection according to the manufacturer's directions, Fortaz® solutions for IV administration containing 100, 170, or 200 mg of ceftazidime per mL are stable for 12 hours at room temperature or 3 days when refrigerated.1 IV solutions prepared according to the manufacturer's directions using Fortaz® TwistVial® vials containing 1 or 2 g of ceftazidime and 0.9 or 0.45% sodium chloride injection or 5% dextrose injection are stable for 12 hours at room temperature or 3 days under refrigeration.1
Following reconstitution with sterile water for injection, bacteriostatic water for injection, or 0.5 or 1% lidocaine hydrochloride injection, Fortaz® solutions for IM injection containing 280 mg/mL are stable for 12 hours at room temperature or 3 days when refrigerated.1
The manufacturer of Fortaz® states that ceftazidime at concentrations of 1-40 mg/mL is chemically and physically stable for 12 hours at room temperature or for 3 days when refrigerated in the following IV solutions: 0.9% sodium chloride; (1/6) M sodium lactate; 5 or 10% dextrose; 5% dextrose and 0.225, 0.45, or 0.9% sodium chloride; Ringer's; lactated Ringer's; 10% invert sugar; or Normosol®-M and 5% dextrose.1 Fortaz® solutions in 5% dextrose or 0.9% sodium chloride are stable for at least 6 hours at room temperature in plastic tubing, drip chambers, and volume control devices of common IV infusion sets.1
The commercially available vials of Tazicef® sterile powder for injection containing ceftazidime (as the pentahydrate) with sodium carbonate should be stored at 20-25°C and protected from light.217 Following reconstitution with sterile water for injection according to the manufacturer's directions, Tazicef® solutions for IV or IM administration containing 95, 180, or 280 mg of ceftazidime per mL are stable for 24 hours at room temperature or 7 days when refrigerated.217 IV solutions prepared according to the manufacturer's directions using Tazicef® ADD-Vantage® vials containing 1 or 2 g of ceftazidime and 0.45 or 0.9% sodium chloride injection or 5% dextrose injection are stable for 24 hours at room temperature.217
The commercially available Duplex® drug delivery system containing 1 or 2 g of ceftazidime and 50 mL of 5% dextrose injection in separate chambers should be stored at 20-25°C, but may be exposed to temperatures ranging from 15-30°C.251 Following reconstitution (activation), these IV solutions must be used within 12 hours if stored at room temperature or within 3 days if stored in a refrigerator and should not be frozen.251
The commercially available frozen premixed injections of ceftazidime sodium in dextrose (Fortaz®) should be stored at -20°C or lower.1 The frozen injections 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 injections are stable for 8 hours at room temperature or 7 days when refrigerated.1 The commercially available frozen injections of the drug are provided in plastic containers 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 injections; 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
Ceftazidime and ceftazidime sodium are potentially physically and/or chemically incompatible with some drugs, including aminoglycosides and vancomycin, but the compatibility depends on several factors (e.g., concentrations of the drugs, specific diluents used, resulting pH, temperature).1, 217 Specialized references should be consulted for specific compatibility information. Sodium bicarbonate injection should not be used as a diluent for ceftazidime or ceftazidime sodium since the drug is less stable in sodium bicarbonate than in other IV solutions.1, 217 Because of the potential for incompatibility, the manufacturers state that ceftazidime or ceftazidime sodium should not be admixed with aminoglycosides or vancomycin.1, 217
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 ceftazidime, see the Cephalosporins General Statement 8:12.06.
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 |
|---|---|---|---|---|
Parenteral | For injection | equivalent to anhydrous ceftazidime 500 mg (with sodium carbonate)* | ||
equivalent to anhydrous ceftazidime 1 g (with sodium carbonate)* | cefTAZidime for Injection | |||
Fortaz® | Covis | |||
equivalent to anhydrous ceftazidime 2 g (with sodium carbonate)* | cefTAZidime for Injection | |||
Fortaz® | Covis | |||
Tazicef® | Hospira | |||
equivalent to anhydrous ceftazidime 6 g pharmacy bulk package (with sodium carbonate)* | cefTAZidime for Injection | |||
Fortaz® | Covis | |||
Tazicef® | Hospira | |||
For injection, for IV infusion | equivalent to anhydrous ceftazidime 1 g (with sodium carbonate) | cefTAZidime for Injection (available in dual-chambered Duplex® drug delivery system with 5% dextrose injection) | ||
Fortaz® TwistVial® | Covis | |||
Tazicef® ADD-Vantage® | Hospira | |||
equivalent to anhydrous ceftazidime 2 g (with sodium carbonate) | cefTAZidime for Injection (available in dual-chambered Duplex® drug delivery system with 5% dextrose injection) | B Braun | ||
Fortaz® TwistVial® | Covis | |||
Tazicef® ADD-Vantage® | Hospira |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Injection (frozen), for IV infusion | equivalent to 20 mg (of anhydrous ceftazidime) per mL (1 g) in 4.4% Dextrose | Fortaz® Iso-osmotic in Dextrose Injection (Galaxy® [Baxter]) | Covis |
equivalent to 40 mg (of anhydrous ceftazidime) per mL (2 g) in 3.2% Dextrose | Fortaz® Iso-osmotic in Dextrose Injection (Galaxy® [Baxter]) | Covis |
1. Covis Pharmaceuticals Inc. Fortaz® (ceftazidime) powder for injection and injection prescribing information. Cary, NC; 2012 Apr.
3. Glaxo Inc. Product information form on Fortaz®. Research Triangle Park, NC; 1985 Jan.
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