Ceftazidime is a parenteral third-generation cephalosporin. As a rule, third-generation cephalosporins are more active and have a broader spectrum against aerobic gram-negative bacteria than do either first- or second-generation agents. Ceftazidime, like other third-generation cephalosporins, is less active against gram-positive organisms than are first-generation drugs. Ceftazidime is extremely active against Pseudomonas aeruginosa, and is used frequently for pulmonary infections, particularly in patients with cystic fibrosis. Other therapeutic uses of ceftazidime include meningitis, skin and soft-tissue infections, urinary tract infections, and bone and joint infections. Ceftazidime has been commonly used in the empiric treatment of fever in neutropenic patients. However, higher rates of resistance among viridans-group streptococci have been noted with ceftazidime compared with cefepime; therefore, ceftazidime monotherapy should not be used if there are concerns about gram-positive or resistant gram-negative infections. Ceftazidime was FDA-approved in July 1985.
General Administration Information
For storage information, see specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration whenever solution and container permit.
Intravenous Administration
Powder vials for injection
Reconstitution
-Vials are supplied under reduced pressure. Carbon dioxide gas is released upon reconstitution.
-Reconstitute 500 mg, 1 g, or 2 g vial with 5.3, 10, or 10 mL, respectively, of Sterile Water for Injection to give approximate concentrations of 100, 100, and 170 mg/mL, respectively.
-Shake well to dissolve the drug; the solution should become clear within 1 to 2 minutes.
-May be used for direct intermittent IV administration or further diluted for intermittent IV infusion.
-Storage: Storage recommendations for reconstituted and thawed solutions vary by manufacturer. Reconstituted solutions that are frozen immediately after reconstitution in the original container are stable for 3 months at -20 degrees C. Thaw frozen solutions at room temperature and do not refreeze. Do not force thaw by immersion in water baths or by microwave.
Dilution
-Withdraw the appropriate dose and dilute in compatible IV solution to a concentration of 1 to 40 mg/mL.
-Compatible solutions include 0.9% Sodium Chloride Injection, 5% Dextrose Injection, 5% Dextrose and 0.9% Sodium Chloride Injection, 5% Dextrose and 0.45% Sodium Chloride Injection, 5% Dextrose and 0.225% Sodium Chloride Injection, 10% Dextrose Injection, 10% Invert Sugar in Water for Injection, 1/6 M Sodium Lactate Injection, Lactated Ringer's Injection, and Normosol-M in 5% Dextrose Injection.
-Storage: Storage recommendations for diluted and thawed solutions vary by manufacturer. Solutions in 0.9% Sodium Chloride Injection in Viaflex small-volume containers that are frozen immediately after reconstitution are stable for 3 months when stored at -20 degrees C. Do not force thaw by immersion in water baths or by microwave irradiation. Thaw frozen solutions at room temperature and do not refreeze. Do not force thaw by immersion in water baths or by microwave.
Bulk vials for injection
Reconstitution
-Vials are supplied under reduced pressure. Carbon dioxide gas is released upon reconstitution.
-Reconstitute 6 g vial with 26 mL of a compatible solution to give a concentration of 200 mg/mL.
-Shake well to dissolve the drug; the solution should become clear within 1 to 2 minutes.
-Pressure inside the container will increase due to carbon dioxide gas production. To release pressure, insert a vent needle only after the drug has completely dissolved. Remove the vent needle before using solution.
-Further dilution is required. Withdraw vial contents within 4 hours.
-Storage: Storage recommendations for the reconstituted solution vary by manufacturer.
Dilution
-Withdraw the appropriate dose and dilute in compatible IV solution to a concentration of 1 to 40 mg/mL.
-Compatible solutions include 0.9% Sodium Chloride Injection, 5% Dextrose Injection, 5% Dextrose and 0.9% Sodium Chloride Injection, 5% Dextrose and 0.45% Sodium Chloride Injection, 5% Dextrose and 0.225% Sodium Chloride Injection, 10% Dextrose Injection, 10% Invert Sugar in Water for Injection, 1/6 M Sodium Lactate Injection, Lactated Ringer's Injection, and Normosol-M in 5% Dextrose Injection.
-Ceftazidime is not recommended for use in Sodium Bicarbonate Injection.
-Storage: Storage recommendations for diluted solutions vary by manufacturer. Solutions in 5% Dextrose Injection and 0.9% Sodium Chloride Injection are stable for at least 6 hours at room temperature when in plastic tubing, drip chambers, and volume control devices of common IV infusion sets.
ADD-Vantage vials
Reconstitution
-Reconstitute with 50 or 100 mL of 0.9% Sodium Chloride Injection or 5% Dextrose Injection or 50 mL of 0.45% Sodium Chloride Injection.
-Remove the protective covers from the top of the vial and vial port on the diluent container.
-Screw the vial into the vial port until it will go no further to assure a seal. Once vial is sealed to the port, do not remove.
-To activate the contents of the vial, squeeze the bottom of the diluent container gently to inflate the portion of the container surrounding the end of the drug vial. With the other hand, push the drug vial down into the container telescoping the walls of the container, and grasp the inner cap of the vial through the walls of the container. Pull the inner cap from the drug vial. Verify the rubber stopper has been pulled out, allowing the drug and diluent to mix.
-Mix the container contents thoroughly.
-Do not use in series connections with flexible containers.
-Storage: The admixture solution may be stored for up to 24 hours at room temperature. Solutions in 0.9% Sodium Chloride Injection or 5% Dextrose Injection are stable for at least 6 hours at room temperature in plastic tubing, drip chambers, and volume control devices of common IV infusion sets.
DUPLEX Drug Delivery System
-Use only if container and seals are intact. To inspect the drug powder for foreign matter or discoloration, peel the foil strip from the drug chamber.
-Protect from light after removal of foil strip. If the foil strip is removed and the container will not be used immediately, refold container and latch the side tab until ready to activate and use within 7 days.
-Once ready for activation, allow the product to reach room temperature before patient use.
-Unfold Duplex container and point the set port downward. Starting at the hanger tab end, fold the Duplex container just below the diluent meniscus trapping all air above the fold.
-To activate, squeeze the folded diluent chamber until the seal between the diluent and powder opens, releasing diluent into the drug powder chamber.
-Agitate the liquid-powder mixture until the drug powder completely dissolves.
-Storage: After reconstitution (activation), use within 12 hours if stored at room temperature or within 3 days if stored under refrigeration.
Intermittent IV Infusion
-Infuse IV over 30 minutes.
-Do not use plastic containers in series connections.
Direct Intermittent IV Injection
-Only with powder vials for injection.
-Withdraw the appropriate dose and inject directly into a vein over 3 to 5 minutes or slowly into the tubing of a freely-flowing compatible IV solution.
Plasmapheresis
-Administer IV doses at least 2 hours before plasmapheresis.
Intramuscular Administration
Powder vials for injection
Reconstitution
-Reconstitute 500 mg or 1 g vial with 1.5 or 3 mL, respectively, of Sterile or Bacteriostatic Water for Injection or 0.5% to 1% lidocaine to give solutions containing approximately 280 mg/mL.
-Storage: Storage recommendations for constituted and thawed solutions vary by manufacturer. Reconstituted solutions that are frozen immediately after reconstitution in the original container are stable for 3 months at -20 degrees. Once thawed, do not refreeze.
Intramuscular Injection
-Inject deeply into a large muscle (e.g., anterolateral thigh or deltoid).
-In general, IM administration of antibiotics in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.
Plasmapheresis
-Administer IM doses at least 3 hours before plasmapheresis.
An injection site reaction following intramuscular (IM) injection has been reported in fewer than 2% of ceftazidime patients. Phlebitis and inflammation at the injection site were the most common reactions. Pain and induration have also been reported post-marketing.
Gastrointestinal reactions were reported in fewer than 2% of ceftazidime patients. The most frequently reported were diarrhea, nausea, vomiting, and abdominal pain.
Transient agranulocytosis, neutropenia, leukopenia, lymphocytosis, and thrombocytopenia have been reported rarely with cephalosporin antibiotics. Other adverse effects seen with ceftazidime therapy include hemolytic anemia (rare), eosinophilia (7.7%), positive Coombs' test without hemolysis (4.3%), and thrombocytosis (2.2%). As with some other cephalosporins, transient elevations of blood urea, blood urea nitrogen, and/or serum creatinine were observed occasionally. Prolonged prothrombin time (hypoprothrombinemia), false-positive test for urinary glucose, pancytopenia, hemorrhage, and aplastic anemia were all reported during postmarketing surveillance.
Central nervous system adverse reactions reported in up to 2% of patients during ceftazidime therapy include dizziness, headache, and paresthesias. Seizures, nonconvulsive status epilepticus (NCSE), encephalopathy, coma, asterixis, neuromuscular excitability, and myoclonia have been reported in patients treated with ceftazidime, particularly in the setting of renal impairment.
Hypersensitivity reactions were reported in 2% of ceftazidime patients as pruritus, maculopapular rash, and fever. Immediate hypersensitivity reactions, generally manifested by rash and/or pruritus, occurred in 1 in 285 patients. Toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme have also been reported with cephalosporin antibiotics, including ceftazidime. Angioedema and anaphylaxis (bronchospasm and/or hypotension) have been reported very rarely. Interstitial nephritis, a hypersensitivity reaction, has been reported in < 1% of patients receiving other cephalosporins, but has not been reported with ceftazidime. Anaphylaxis; allergic reactions, which, in rare instances, were severe (e.g., cardiopulmonary arrest); and urticaria were reported during postmarketing surveillance.
Ceftazidime has been associated with acute generalized exanthematous pustulosis (AGEP). The nonfollicular, pustular, erythematous rash starts suddenly, is associated with fever above 38 degrees C, and is distinct from pustular psoriasis, although biopsy results in each reveal spongiform subcorneal pustules. Drugs are the main cause of AGEP. A period of 2-3 weeks after an inciting drug exposure appears necessary for a first episode of AGEP. Unintentional reexposure may cause a second episode within 2 days. Clinical presentation is diverse with cutaneous lesions beyond erythema and pustules present in half of the cases. For example, bullous lesions, edema, purpura, pruritus, and mucosal erosions are possible. The mean duration of the pustules is 9.7 days followed by an annular desquamation, as long as the causative drug or factor is discontinued. The physiopathological mechanisms of AGEP have not been determined but the pathological criteria of edema, leukocytoclastic vasculitis, eosinophil exocytosis, and keratinocyte focal necrosis are distinctive. Pustule confluence or very small pustules may lead a clinician to make an incorrect diagnosis of TEN, of drug-induced erythroderma, or of staphylococcal scalded skin syndrome.
Laboratory test changes during ceftazidime therapy were transient and included slight elevated hepatic enzymes of one or more tests: AST: 1 in 16, ALT: 1 in 15, LDH: 1 in 18, GGT: 1 in 19, and alkaline phosphatase: 1 in 23. Cholestasis, jaundice, and hyperbilirubinemia have been reported rarely during postmarketing surveillance of ceftazidime.
Microbial overgrowth and superinfection can occur with antibiotic use. C. difficile-associated diarrhea (CDAD) or pseudomembranous colitis has been reported with ceftazidime. If pseudomembranous colitis is suspected or confirmed, ongoing antibacterial therapy not directed against C. difficile may need to be discontinued. Institute appropriate fluid and electrolyte management, protein supplementation, C. difficile-directed antibacterial therapy, and surgical evaluation as clinically appropriate. Candidiasis (including oral thrush) and vaginitis were reported in fewer than 1% of patients.
Ceftazidime is contraindicated in patients who have a history of immediate hypersensitivity reactions (e.g., anaphylaxis, serious skin reactions) to ceftazidime or the cephalosporin class of antibacterial drugs (cephalosporin hypersensitivity), penicillins (penicillin hypersensitivity), or other beta-lactam antibacterial drugs (including carbapenem hypersensitivity). Immediate hypersensitivity reactions to ceftazidime have been reported. Make careful inquiry to determine whether the patient has had previous hypersensitivity reactions with cephalosporins or penicillins. Use caution if ceftazidime is to be given to penicillin-sensitive patients because cross-hypersensitivity among beta-lactam antibacterials has been clearly documented and may occur in up to 10% of patients with a history of penicillin allergy.
Consider pseudomembranous colitis in patients presenting with diarrhea after antibacterial use. Careful medical history is necessary as pseudomembranous colitis has been reported to occur over 2 months after the administration of antibacterial agents. Almost all antibacterial agents, including ceftazidime, have been associated with pseudomembranous colitis or C. difficile-associated diarrhea (CDAD) which may range in severity from mild to life-threatening. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
Ceftazidime is substantially eliminated by the kidneys, and the risk of adverse reactions to ceftazidime may be greater in patients with renal impairment due to slower elimination by the kidneys. Consequently, ceftazidime dosage adjustment is required in patients with moderate (CrCl 30 to 50 mL/minute) and severe (CrCl 16 to 29 mL/minute) renal impairment or renal failure. Also, many cephalosporins, including ceftazidime, have been associated with a fall in prothrombin activity. Those at risk include patients with renal impairment or hepatic disease, or malnutrition, as well as patients receiving a protracted course of antimicrobial therapy. Monitor prothrombin time in patients at risk, and administer exogenous vitamin K as indicated.
Administration of ceftazidime may result in laboratory test interference. A false-positive reaction for glucose in the urine has been observed in patients receiving cephalosporins, such as ceftazidime, and using glucose tests based on Benedict's copper reduction reactions, such as Benedict's solution, Fehling's solution, or Clinitest tablets for urine glucose testing. However, this reaction has not been observed with glucose oxidase tests (e.g., Tes-tape, Clinistix, Diastix). Patients with diabetes mellitus who test their urine for glucose should use glucose tests based on enzymatic glucose oxidase reactions while on ceftazidime treatment.
No overall differences in safety or effectiveness were observed between older and younger adult subjects in clinical trials or other reported clinical experience. Ceftazidime is known to be substantially excreted by the kidney, and the risk of adverse reactions may be greater in patients with impaired renal function. Because geriatric patients are more likely to have decreased renal function, take care in dose selection, and it may be useful to monitor renal function. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities. According to OBRA, use of antibiotics should be limited to confirmed or suspected bacterial infections. Antibiotics are non-selective and may result in the eradication of beneficial microorganisms while promoting the emergence of undesired ones, causing secondary infections such as oral thrush, colitis, or vaginitis. Any antibiotic may cause diarrhea, nausea, vomiting, anorexia, and hypersensitivity reactions.
Available data over several decades with cephalosporin use, including ceftazidime, during pregnancy have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Ceftazidime crosses the placenta. No adverse developmental effects were observed in animals administered ceftazidime at approximately 0.6 to 5 times the maximum recommended human dose (MRHD).
Ceftazidime in present in human breast milk, but is not expected to accumulate in the breast-fed infant. There are no data on the effects of ceftazidime on the breast-fed child or on milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for ceftazidime and any potential adverse effects on the breast-fed child from ceftazidime or the underlying maternal condition.
Ceftazidime may be associated with reproductive risk. Limited animal data suggests that ceftazidime may impair sperm motility. However, there are no reported effects of ceftazidime on human fertility.
Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Acinetobacter sp., Bacteroides sp., Citrobacter diversus, Citrobacter freundii, Citrobacter sp., Clostridium sp., Enterobacter sp., Escherichia coli, Haemophilus influenzae (beta-lactamase negative), Haemophilus influenzae (beta-lactamase positive), Haemophilus parainfluenzae, Klebsiella pneumoniae, Klebsiella sp., Morganella morganii, Neisseria gonorrhoeae, Neisseria meningitidis, Peptostreptococcus sp., Proteus mirabilis, Proteus vulgaris, Providencia rettgeri, Providencia sp., Pseudomonas aeruginosa, Pseudomonas sp., Salmonella sp., Serratia sp., Shigella sp., Staphylococcus aureus (MSSA), Staphylococcus epidermidis, Streptococcus agalactiae (group B streptococci), Streptococcus pneumoniae, Streptococcus pyogenes (group A beta-hemolytic streptococci), Yersinia enterocolitica
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.
This drug may also have activity against the following microorganisms: Burkholderia pseudomallei, Eikenella corrodens, Eubacterium sp., Haemophilus ducreyi, Klebsiella oxytoca, Lactobacillus sp., Moraxella catarrhalis, Pantoea agglomerans, Pasteurella multocida, Propionibacterium sp., Providencia stuartii, Serratia marcescens, Viridans streptococci
NOTE: Some organisms may not have been adequately studied during clinical trials; therefore, exclusion from this list does not necessarily negate the drug's activity against the organism.
For the treatment of intraabdominal infections, including peritonitis, appendicitis, intraabdominal abscess, and peritoneal dialysis-related peritonitis*:
-for the treatment of complicated community-acquired, healthcare-acquired, or hospital-acquired intraabdominal infections with adequate source control:
Intravenous dosage:
Adults: 1 to 2 g IV every 8 hours as part of combination therapy for 3 to 7 days. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.
Adolescents: 1 to 2 g IV every 8 hours as part of combination therapy for 3 to 7 days. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.
Infants and Children: 30 to 50 mg/kg/dose (Max: 2 g/dose) IV every 8 hours as part of combination therapy for 3 to 7 days. For serious Pseudomonas infections, 200 to 300 mg/kg/day (Max: 6 g/day) IV divided every 8 hours is recommended. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.
Neonates 32 weeks gestation and older and 8 days and older: 50 mg/kg/dose IV every 8 hours as part of combination therapy for 7 to 10 days. The FDA-approved dosage is 30 mg/kg/dose IV every 12 hours.
Neonates 32 weeks gestation and older and 0 to 7 days: 50 mg/kg/dose IV every 12 hours as part of combination therapy for 7 to 10 days. The FDA-approved dosage is 30 mg/kg/dose IV every 12 hours.
Neonates younger than 32 weeks gestation and 7 days and older: 50 mg/kg/dose IV every 8 hours as part of combination therapy for 7 to 10 days. The FDA-approved dosage is 30 mg/kg/dose IV every 12 hours.
Neonates younger than 32 weeks gestation and 0 to 6 days: 50 mg/kg/dose IV every 12 hours as part of combination therapy for 7 to 10 days. The FDA-approved dosage is 30 mg/kg/dose IV every 12 hours.
-for the treatment of uncomplicated intraabdominal infections:
Intravenous dosage:
Adults: 1 to 2 g IV every 8 hours as part of combination therapy. Antibiotics should be discontinued within 24 hours. Uncomplicated infections include acute appendicitis without perforation, abscess, or local peritonitis; traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.
Adolescents: 1 to 2 g IV every 8 hours as part of combination therapy. Antibiotics should be discontinued within 24 hours. Uncomplicated infections include acute appendicitis without perforation, abscess, or local peritonitis; traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.
Infants and Children: 30 to 50 mg/kg/dose (Max: 2 g/dose) IV every 8 hours. Antibiotics should be discontinued within 24 hours. Uncomplicated infections include acute appendicitis without perforation, abscess, or local peritonitis; traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.
-for the treatment of peritoneal dialysis-related peritonitis*:
Intermittent Intraperitoneal dosage*:
Adults: 1 to 1.5 g intraperitoneally every 24 hours for 21 to 28 days.
Infants, Children, and Adolescents: 20 mg/kg/dose (Max: 1.5 g/dose) intraperitoneally every 24 hours for 14 to 21 days.
Continuous Intraperitoneal dosage*:
Adults: 500 mg/L intraperitoneal loading dose, followed by 125 mg/L in each dialysate exchange. Treat for 21 to 28 days.
Infants, Children, and Adolescents: 500 mg/L intraperitoneal loading dose, followed by 125 mg/L in each dialysate exchange. Treat for 14 to 21 days.
For the treatment of bone and joint infections, including osteomyelitis, infectious arthritis, and orthopedic device-related infection*:
-for the treatment of unspecified osteomyelitis:
Intravenous dosage:
Adults: 2 g IV every 8 hours for 4 to 6 weeks. The FDA-approved dosage is 2 g IV every 12 hours.
Infants, Children, and Adolescents 3 months to 17 years: 150 mg/kg/day (Max: 6 g/day) IV divided every 8 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 3 to 4 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for severe or complicated infections.
Infants 1 to 2 months: 150 mg/kg/day IV divided every 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates 32 weeks gestation and older and 8 days and older: 50 mg/kg/dose IV every 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 30 mg/kg/dose IV every 12 hours.
Neonates 32 weeks gestation and older and 0 to 7 days: 50 mg/kg/dose IV every 12 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 30 mg/kg/dose IV every 12 hours.
Neonates younger than 32 weeks gestation and 7 days and older: 50 mg/kg/dose IV every 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 30 mg/kg/dose IV every 12 hours.
Neonates younger than 32 weeks gestation and 0 to 6 days: 50 mg/kg/dose IV every 12 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 30 mg/kg/dose IV every 12 hours.
-for the treatment of native vertebral osteomyelitis:
Intravenous dosage:
Adults: 2 g IV every 8 hours for 6 weeks. May consider addition of ciprofloxacin or aminoglycoside for P. aeruginosa infections. The FDA-approved dosage is 2 g IV every 12 hours.
-for the treatment of infectious arthritis:
Intravenous dosage:
Adults: 2 g IV every 8 hours. Treat for 1 to 2 weeks or until clinically improved, followed by oral step-down therapy for 2 to 4 weeks. The FDA-approved dosage is 2 g IV every 12 hours.
Infants, Children, and Adolescents 3 months to 17 years: 150 mg/kg/day (Max: 6 g/day) IV divided every 8 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 2 to 3 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for septic hip arthritis or severe or complicated infections.
Infants 1 to 2 months: 150 mg/kg/day IV divided every 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates 32 weeks gestation and older and 8 days and older: 50 mg/kg/dose IV every 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 30 mg/kg/dose IV every 12 hours.
Neonates 32 weeks gestation and older and 0 to 7 days: 50 mg/kg/dose IV every 12 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 30 mg/kg/dose IV every 12 hours.
Neonates younger than 32 weeks gestation and 7 days and older: 50 mg/kg/dose IV every 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 30 mg/kg/dose IV every 12 hours.
Neonates younger than 32 weeks gestation and 0 to 6 days: 50 mg/kg/dose IV every 12 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections. The FDA-approved dosage is 30 mg/kg/dose IV every 12 hours.
-for the treatment of prosthetic joint infections*:
Intravenous dosage:
Adults: 2 g IV every 8 hours for 4 to 6 weeks, which may be followed by long-term suppressive therapy. May consider addition of an aminoglycoside for P. aeruginosa infections; if aminoglycoside is in spacer and organism is aminoglycoside-susceptible, then double coverage is provided with IV or oral monotherapy.
For the empiric treatment of febrile neutropenia*:
Intravenous dosage:
Adults: 2 g IV every 8 hours with or without an aminoglycoside. Ceftazidime, an antipseudomonal cephalosporin, has been successfully used for the empiric treatment of febrile neutropenia as monotherapy or in combination with an aminoglycoside. Higher rates of resistance among viridans-group streptococci have been noted with ceftazidime compared with cefepime; therefore, ceftazidime monotherapy should not be used if there are concerns about gram-positive or resistant gram-negative infections.
Infants, Children, and Adolescents: 100 to 150 mg/kg/day IV divided every 8 hours (Max: 2 g/dose) with or without an aminoglycoside. Ceftazidime, an antipseudomonal cephalosporin, has been successfully used for the empiric treatment of febrile neutropenia in pediatric patients as monotherapy or in combination with an aminoglycoside. Higher rates of resistance among viridans-group streptococci have been noted with ceftazidime compared with cefepime in adult studies; therefore, ceftazidime monotherapy should not be used if there are concerns about gram-positive or resistant gram-negative infections.
For the treatment of lower respiratory tract infections (LRTIs), including pneumonia, community-acquired pneumonia (CAP), and nosocomial pneumonia:
-for the treatment of uncomplicated nonspecific pneumonia:
Intravenous or Intramuscular dosage:
Adults: 500 mg to 1 g IV or IM every 8 hours.
Adolescents: 500 mg to 1 g IV or IM every 8 hours.
Infants and Children: 90 to 150 mg/kg/day IV or IM divided every 8 hours (Max: 3 g/day).
Neonates 32 weeks gestation and older and 8 days and older: 50 mg/kg/dose IV or IM every 8 hours. The FDA-approved dose is 30 mg/kg/dose IV every 12 hours.
Neonates 32 weeks gestation and older and 0 to 7 days: 50 mg/kg/dose IV or IM every 12 hours. The FDA-approved dose is 30 mg/kg/dose IV every 12 hours.
Neonates younger than 32 weeks gestation and 7 days and older: 50 mg/kg/dose IV or IM every 8 hours. The FDA-approved dose is 30 mg/kg/dose IV every 12 hours.
Neonates younger than 32 weeks gestation and 0 to 6 days: 50 mg/kg/dose IV or IM every 12 hours. The FDA-approved dose is 30 mg/kg/dose IV every 12 hours.
-for the treatment of severe or life-threatening nonspecific pneumonia:
Intravenous or Intramuscular dosage:
Adults: 2 g IV every 8 hours.
Adolescents: 2 g IV every 8 hours.
Infants and Children: 200 to 300 mg/kg/day IV or IM divided every 8 hours (Max: 6 g/day). The FDA-approved dose is 90 to 150 mg/kg/day IV or IM divided every 8 hours (Max: 6 g/day).
Neonates 32 weeks gestation and older and 8 days and older: 50 mg/kg/dose IV or IM every 8 hours. The FDA-approved dose is 30 mg/kg/dose IV every 12 hours.
Neonates 32 weeks gestation and older and 0 to 7 days: 50 mg/kg/dose IV or IM every 12 hours. The FDA-approved dose is 30 mg/kg/dose IV every 12 hours.
Neonates younger than 32 weeks gestation and 7 days and older: 50 mg/kg/dose IV or IM every 8 hours. The FDA-approved dose is 30 mg/kg/dose IV every 12 hours.
Neonates younger than 32 weeks gestation and 0 to 6 days: 50 mg/kg/dose IV or IM every 12 hours. The FDA-approved dose is 30 mg/kg/dose IV every 12 hours.
-for the treatment of community-acquired pneumonia (CAP):
Intravenous dosage:
Adults: 2 g IV every 8 hours for at least 7 days.
-for the treatment of nosocomial pneumonia:
Intravenous dosage:
Adults: 2 g IV every 8 hours for 7 days.
For the treatment of urinary tract infection (UTI), including pyelonephritis:
Intravenous or Intramuscular dosage:
Adults: 1 to 2 g IV or IM every 8 hours for 7 to 14 days with or without an aminoglycoside. The FDA-approved dosage is 250 mg IV or IM every 12 hours for uncomplicated UTI or 500 mg IV or IM every 8 to 12 hours for complicated UTI.
Infants, Children, and Adolescents 2 months to 17 years: 90 to 150 mg/kg/day (Max: 6 g/day) IV or IM divided every 8 hours. Treat for 24 to 48 hours or until patient is clinically stable and afebrile, followed by oral antibiotics for a total duration of 7 to 14 days.
Infants 1 month: 90 to 150 mg/kg/day IV or IM divided every 8 hours. Infants younger than 2 to 3 months are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Neonates 32 weeks gestation and older and 8 days and older: 50 mg/kg/dose IV or IM every 8 hours. The FDA-approved dosage is 30 mg/kg/dose IV every 12 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Neonates 32 weeks gestation and older and 0 to 7 days: 50 mg/kg/dose IV or IM every 12 hours. The FDA-approved dosage is 30 mg/kg/dose IV every 12 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Neonates younger than 32 weeks gestation and 7 days and older: 50 mg/kg/dose IV or IM every 8 hours. The FDA-approved dosage is 30 mg/kg/dose IV every 12 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Neonates younger than 32 weeks gestation and 0 to 6 days: 50 mg/kg/dose IV or IM every 12 hours. The FDA-approved dosage is 30 mg/kg/dose IV every 12 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
For the treatment of melioidosis* due to Burkholderia pseudomallei:
Intravenous dosage:
Adults: 100 to 120 mg/kg/day IV divided every 8 hours (Max: 2 g/dose) given alone or in combination with sulfamethoxazole; trimethoprim or ciprofloxacin for at least 10 to 14 days. If clinical improvement is achieved, switch to oral maintenance combination therapy with sulfamethoxazole; trimethoprim and doxycycline for 3 to 6 months (with or without an initial 8-week regimen of chloramphenicol). In pregnant patients, the preferred oral therapy is amoxicillin; clavulanic acid.
Infants, Children, and Adolescents: 100 to 120 mg/kg/day IV divided every 8 hours (Max: 2 g/dose) given alone or in combination with sulfamethoxazole; trimethoprim or ciprofloxacin for at least 10 to 14 days. If clinical improvement is achieved, switch to oral maintenance combination therapy with sulfamethoxazole; trimethoprim and doxycycline for 3 to 6 months (with or without an initial 8-week regimen of chloramphenicol). In children 1 to 7 years, the preferred oral therapy is amoxicillin; clavulanic acid.
For the treatment of bacteremia and sepsis:
Intravenous dosage:
Adults: 2 g IV every 8 hours. Start within 1 hour for septic shock or within 3 hours for possible sepsis without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.
Adolescents: 2 g IV every 8 hours. Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for de-escalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.
Infants and Children: 90 to 150 mg/kg/day (Max: 6 g/day) IV divided every 8 hours. 200 to 300 mg/kg/day (Max: 6 g/day) IV divided every 8 hours for serious P. aeruginosa infections. Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for de-escalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.
Neonates 32 weeks gestation and older and 8 days and older: 50 mg/kg/dose IV every 8 hours. The FDA-approved dosage is 30 mg/kg/dose IV every 12 hours. Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response. Neonates younger than 37 weeks gestational age were excluded from guideline scope.
Neonates 32 weeks gestation and older and 0 to 7 days: 50 mg/kg/dose IV every 12 hours. The FDA-approved dosage is 30 mg/kg/dose IV every 12 hours. Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response. Neonates younger than 37 weeks gestational age were excluded from guideline scope.
Neonates younger than 32 weeks gestation and 7 days and older: 50 mg/kg/dose IV every 8 hours. The FDA-approved dosage is 30 mg/kg/dose IV every 12 hours.
Neonates younger than 32 weeks gestation and 0 to 6 days: 50 mg/kg/dose IV every 12 hours. The FDA-approved dosage is 30 mg/kg/dose IV every 12 hours.
For the treatment of gynecologic infections, including endometritis and pelvic cellulitis:
Intravenous or Intramuscular dosage:
Adults: 1 g IV or IM every 8 hours. For serious infections, 2 g IV every 8 hours.
Adolescents: 1 g IV or IM every 8 hours. For serious infections, 2 g IV every 8 hours.
For the treatment of central nervous system infections, including meningitis:
Intravenous dosage:
Adults: 2 g IV every 8 hours for 21 days for aerobic gram-negative infections. Guidelines suggest ceftazidime for documented or suspected P. aeruginosa infections or in combination with vancomycin for patients with penetrating head trauma, postneurosurgery, and for those with a cerebrospinal fluid (CSF) shunt.
Adolescents: 2 g IV every 8 hours for 21 days for aerobic gram-negative infections. Guidelines suggest ceftazidime for documented or suspected P. aeruginosa infections or in combination with vancomycin for patients with penetrating head trauma, postneurosurgery, and for those with a cerebrospinal fluid (CSF) shunt.
Infants and Children: 150 to 300 mg/kg/day (Max: 6 g/day) IV divided every 8 hours for 21 days for aerobic gram-negative infections. Guidelines suggest ceftazidime for documented or suspected P. aeruginosa infections or in combination with vancomycin for patients with penetrating head trauma, postneurosurgery, and for those with a cerebrospinal fluid (CSF) shunt.
Neonates 32 weeks gestation and older and 8 days and older: 50 mg/kg/dose IV every 8 hours for at least 21 days. The FDA-approved dosage is 30 mg/kg/dose IV every 12 hours.
Neonates 32 weeks gestation and older and 0 to 7 days: 50 mg/kg/dose IV every 12 hours for at least 21 days. The FDA-approved dosage is 30 mg/kg/dose IV every 12 hours.
Neonates younger than 32 weeks gestation and 7 days and older: 50 mg/kg/dose IV every 8 hours for at least 21 days. The FDA-approved dosage is 30 mg/kg/dose IV every 12 hours.
Neonates younger than 32 weeks gestation and 0 to 6 days: 50 mg/kg/dose IV every 12 hours for at least 21 days. The FDA-approved dosage is 30 mg/kg/dose IV every 12 hours.
For the treatment of skin and skin structure infections, including necrotizing infections and diabetic foot ulcer:
-for the treatment of mild skin and skin structure infections:
Intravenous or Intramuscular dosage:
Adults: 500 mg to 1 g IV or IM every 8 hours.
Adolescents: 500 mg to 1 g IV or IM every 8 hours.
Infants and Children: 90 to 150 mg/kg/day (Max: 3 g/day) IV or IM divided every 8 hours.
Neonates 32 weeks gestation and older and 8 days and older: 50 mg/kg/dose IV or IM every 8 hours. The FDA-approved dosage is 30 mg/kg/dose IV every 12 hours.
Neonates 32 weeks gestation and older and 0 to 7 days: 50 mg/kg/dose IV or IM every 12 hours. The FDA-approved dosage is 30 mg/kg/dose IV every 12 hours.
Neonates younger than 32 weeks gestation and 7 days and older: 50 mg/kg/dose IV or IM every 8 hours. The FDA-approved dosage is 30 mg/kg/dose IV every 12 hours.
Neonates younger than 32 weeks gestation and 0 to 6 days: 50 mg/kg/dose IV or IM every 12 hours. The FDA-approved dosage is 30 mg/kg/dose IV every 12 hours.
-for the treatment of severe or life-threatening skin and skin structure infections:
Intravenous dosage:
Adults: 2 g IV every 8 hours.
Adolescents: 2 g IV every 8 hours.
Infants and Children: 90 to 150 mg/kg/day (Max: 6 g/day) IV divided every 8 hours. 200 to 300 mg/kg/day (Max: 6 g/day) IV divided every 8 hours for serious Pseudomonas infections.
Neonates 32 weeks gestation and older and 8 days and older: 50 mg/kg/dose IV every 8 hours. The FDA-approved dose is 30 mg/kg/dosage IV every 12 hours.
Neonates 32 weeks gestation and older and 0 to 7 days: 50 mg/kg/dose IV every 12 hours. The FDA-approved dosage is 30 mg/kg/dose IV every 12 hours.
Neonates younger than 32 weeks gestation and 7 days and older: 50 mg/kg/dose IV every 8 hours. The FDA-approved dosage is 30 mg/kg/dose IV every 12 hours.
Neonates younger than 32 weeks gestation and 0 to 6 days: 50 mg/kg/dose IV every 12 hours. The FDA-approved dosage is 30 mg/kg/dose IV every 12 hours.
-for the treatment of necrotizing infections of the skin, fascia, and muscle:
Intravenous dosage:
Adults: 2 g IV every 8 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus clindamycin or metronidazole for mixed necrotizing infections.
Adolescents: 2 g IV every 8 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus metronidazole for mixed necrotizing infections.
Infants and Children: 90 to 150 mg/kg/day (Max: 6 g/day) IV divided every 8 hours. 200 to 300 mg/kg/day (Max: 6 g/day) IV divided every 8 hours for serious Pseudomonas infections. Treat until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus metronidazole for mixed necrotizing infections.
Neonates 32 weeks gestation and older and 8 days and older: 50 mg/kg/dose IV every 8 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus metronidazole for mixed necrotizing infections. The FDA-approved dosage is 30 mg/kg/dose IV every 12 hours.
Neonates 32 weeks gestation and older and 0 to 7 days: 50 mg/kg/dose IV every 12 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus metronidazole for mixed necrotizing infections. The FDA-approved dosage is 30 mg/kg/dose IV every 12 hours.
Neonates younger than 32 weeks gestation and 7 days and older: 50 mg/kg/dose IV every 8 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus metronidazole for mixed necrotizing infections. The FDA-approved dosage is 30 mg/kg/dose IV every 12 hours.
Neonates younger than 32 weeks gestation and 0 to 6 days: 50 mg/kg/dose IV every 12 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus metronidazole for mixed necrotizing infections. The FDA-approved dosage is 30 mg/kg/dose IV every 12 hours.
-for the treatment of diabetic foot ulcer:
Intravenous dosage:
Adults: 2 g IV every 8 hours for 7 to 14 days for moderate or severe infections in patients with recent antibiotic exposure or infections with no complicating features or with ischemic limb/necrosis/gas forming. Continue treatment for up to 28 days if infection is improving but is extensive and resolving slower than expected or if patient has severe peripheral artery disease.
For the management of pulmonary infections in patients with cystic fibrosis:
Intravenous dosage:
Adults: 200 to 400 mg/kg/day (Max: 12 g/day) IV divided every 6 to 8 hours. The FDA-approved dosage is 150 mg/kg/day (Max: 6 g/day) IV divided every 8 hours; however, pharmacokinetic/pharmacodynamic data have suggested this dose to be suboptimal in treating Pseudomonas infections in acute pulmonary exacerbations.
Infants, Children, and Adolescents: 200 to 400 mg/kg/day (Max: 12 g/day) IV divided every 6 to 8 hours. The FDA-approved dosage is 150 mg/kg/day (Max: 6 g/day) IV divided every 8 hours; however, pharmacokinetic/pharmacodynamic data have suggested this dose to be suboptimal in treating Pseudomonas infections in acute pulmonary exacerbations.
For the treatment of infective endocarditis*:
Intravenous dosage:
Adults: 2 g IV every 8 hours is recommended in the FDA-approved labeling for very severe, life-threatening infections. Guidelines recommend a third- or fourth-generation cephalosporin as an alternate therapy for 4 weeks for native valve endocarditis (NVE) and for 6 weeks for prosthetic valve endocarditis (PVE) caused by HACEK microorganisms. A cephalosporin in combination with an aminoglycoside for 6 weeks is also recommended for endocarditis due to non-HACEK gram-negative microorganisms.
Children and Adolescents: 100 to 150 mg/kg/day IV divided every 8 hours (Max: 6 g/day) is the general dosage. 200 to 300 mg/kg/day IV divided every 8 hours (Max: 12 g/day) is recommended by the American Academy of Pediatrics (AAP) for serious Pseudomonas infections. Guidelines recommend ceftazidime plus vancomycin, gentamicin, and rifampin (if prosthetic material is present) for culture-negative nosocomial endocarditis associated with vascular cannulae or early (less than 1 year after surgery) prosthetic valve endocarditis (PVE); treat for 4 to 6 weeks, with a longer course for PVE. Ceftazidime is also a preferred therapy in combination with an aminoglycoside for at least 6 weeks for non-HACEK gram-negative microorganisms.
Infants: 90 to 150 mg/kg/day IV divided every 8 hours is the general dosage recommended by the American Academy of Pediatrics (AAP); 200 to 300 mg/kg/day IV divided every 8 hours (Max: 12 g/day) is recommended for serious Pseudomonas infections.
Neonates 32 weeks gestation and older and 8 days and older: 50 mg/kg/dose IV every 8 hours is the general dosage recommended by the American Academy of Pediatrics (AAP).
Neonates 32 weeks gestation and older and 0 to 7 days: 50 mg/kg/dose IV every 12 hours is the general dosage recommended by the American Academy of Pediatrics (AAP).
Neonates younger than 32 weeks gestation and 14 days and older: 50 mg/kg/dose IV every 8 hours is the general dosage recommended by the American Academy of Pediatrics (AAP).
Neonates younger than 32 weeks gestation and 0 to 13 days: 50 mg/kg/dose IV every 12 hours is the general dosage recommended by the American Academy of Pediatrics (AAP).
For the treatment of bartonellosis*, including severe Oroya fever*:
Intravenous dosage:
Adults: 1 g IV every 8 hours for 7 days plus ciprofloxacin as second-line therapy.
Pregnant or Breast-feeding Persons: 1 g IV every 12 hours for 10 days plus amikacin as second-line therapy.
Infants, Children, and Adolescents: 30 to 50 mg/kg/dose (Max: 1 g/dose) IV every 8 hours for 7 to 10 days plus ciprofloxacin as second-line therapy.
For the treatment of invasive vibriosis*:
Intravenous dosage:
Adults: 1 to 2 g IV every 8 hours in combination with doxycycline for 7 to 14 days.
Infants, Children, and Adolescents: 30 to 50 mg/kg/dose (Max: 2 g/dose) IV every 8 hours in combination with doxycycline for 7 to 14 days.
For the treatment of bronchiectasis*:
-for the treatment of acute exacerbations of bronchiectasis*:
Intravenous dosage:
Adults: 2 g IV every 8 hours for 14 days with or without an aminoglycoside.
Infants, Children, and Adolescents: 200 to 300 mg/kg/day (Max: 6 g/day) IV divided every 8 hours for 14 days with or without an aminoglycoside.
-for the eradication of first or new isolates of Pseudomonas aeruginosa in patients with bronchiectasis*:
Intravenous dosage:
Adults: 2 g IV every 8 hours for 14 days with or without a systemic aminoglycoside or inhaled antibiotics, followed by inhaled antibiotics for 4 to 12 weeks.
Infants, Children, and Adolescents: 200 to 300 mg/kg/day (Max: 6 g/day) IV divided every 8 hours for 14 days with or without a systemic aminoglycoside or inhaled antibiotics, followed by inhaled antibiotics for 4 to 12 weeks.
Maximum Dosage Limits:
-Adults
6 g/day IV/IM is FDA-approved maximum dosage; however, doses up to 12 g/day have been used off-label for cystic fibrosis.
-Geriatric
6 g/day IV/IM is FDA-approved maximum dosage; however, doses up to 12 g/day have been used off-label for cystic fibrosis.
-Adolescents
6 g/day IV/IM is FDA-approved maximum dosage; however, doses up to 400 mg/kg/day (Max: 12 g/day) have been used off-label for cystic fibrosis.
-Children
150 mg/kg/day (Max: 6 g/day) IV/IM is FDA-approved maximum dosage; however, doses up to 400 mg/kg/day (Max: 12 g/day) have been used off-label for cystic fibrosis.
-Infants
150 mg/kg/day IV/IM is FDA-approved maximum dosage; however, doses up to 400 mg/kg/day have been used off-label for cystic fibrosis.
-Neonates
8 days and older: 60 mg/kg/day IV/IM is FDA-approved maximum dosage; however, doses up to 150 mg/kg/day have been used off-label.
0 to 7 days: 60 mg/kg/day IV/IM is FDA-approved maximum dosage; however, doses up to 100 mg/kg/day have been used off-label.
Patients with Hepatic Impairment Dosing
No dosage adjustment needed.
Patients with Renal Impairment Dosing
Adult patients
FDA-approved labeling renal adjustment:
NOTE: In patients with severe infections who would normally receive a 6 g/day dose were it not for renal impairment, the adjusted renal dose listed below may be increased by 50% or the dosing frequency listed below may be increased appropriately. Further dosing should be determined by therapeutic monitoring, severity of the infection, and susceptibility of the causative organism.
CrCl more than 50 mL/minute: no dosage adjustment needed.
CrCl 31 to 50 mL/minute: 1 g IV/IM every 12 hours.
CrCl 16 to 30 mL/minute: 1 g IV/IM every 24 hours.
CrCl 6 to 15 mL/minute: 1 g IV/IM loading dose, then 500 mg IV/IM every 24 hours.
CrCl less than 5 mL/minute: 1 g IV/IM loading dose, then 500 mg IV/IM every 48 hours.
Alternative renal adjustment:
CrCl more than 50 mL/minute: 1 to 2 g IV/IM every 8 to 12 hours.
CrCl 10 to 50 mL/minute: 1 to 2 g IV/IM every 12 to 24 hours.
CrCl less than 10 mL/minute: 1 to 2 g IV/IM every 24 to 48 hours.
Pediatric patients
The following dose adjustments are based on the usual recommended dose in children of 75 to 150 mg/kg/day IV divided every 8 hours.
CrCl more than 50 mL/minute/1.73 m2: no dosage adjustment needed.
CrCl 30 to 50 mL/minute/1.73 m2: 50 mg/kg/dose IV every 12 hours (Max: 2 g/dose).
CrCl 10 to 29 mL/minute/1.73 m2: 50 mg/kg/dose IV every 24 hours (Max: 2 g/dose).
CrCl less than 10 mL/minute/1.73 m2: 50 mg/kg/dose IV every 48 hours (Max: 2 g/dose).
Intermittent hemodialysis
In adults, 1 g IV loading dose, then 1 g IV dose after each standard dialysis session. For children receiving hemodialysis, 50 mg/kg/dose IV every 48 hours (Max: 2 g/dose), given after hemodialysis on dialysis days. During a standard intermittent hemodialysis session, 50% to 100% of a dose of ceftazidime is removed.
Continuous renal replacement therapy (CRRT)
1 to 2 g IV every 12 hours, or a 2 g IV loading dose then 3 g/day continuous IV infusion. Ceftazidime is significantly removed by CRRT. A daily dose 2.4 times that used for anuric non dialyzed patients has been recommended, assuming a combined dialysis and ultrafiltrate flow rate of 1.5 L/hour. For children receiving CRRT, 50 mg/kg/dose IV every 12 hours (Max: 2 g/dose).
Peritoneal dialysis:
In adults and adolescents old enough to receive adult dosage, 1 g IV/IM loading dose, then 500 mg IV/IM every 24 hours. For children receiving peritoneal dialysis, 50 mg/kg/dose IV every 48 hours (Max: 2 g/dose).
*non-FDA-approved indication
Amikacin: (Minor) Ceftazidime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
Aminoglycosides: (Minor) Ceftazidime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
Bumetanide: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
Desogestrel; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Dienogest; Estradiol valerate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Estetrol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Elagolix; Estradiol; Norethindrone acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Estradiol; Levonorgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Estradiol; Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Estradiol; Norgestimate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethacrynic Acid: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
Ethinyl Estradiol; Norelgestromin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethinyl Estradiol; Norethindrone Acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethinyl Estradiol; Norgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethynodiol Diacetate; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Etonogestrel; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Furosemide: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
Gentamicin: (Minor) Ceftazidime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
Leuprolide; Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Levonorgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Levonorgestrel; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Loop diuretics: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norethindrone; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norgestimate; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Oral Contraceptives: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Paromomycin: (Minor) Ceftazidime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
Plazomicin: (Minor) Ceftazidime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
Relugolix; Estradiol; Norethindrone acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Segesterone Acetate; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Major) Prior or concomitant use of antibiotics with sodium picosulfate; magnesium oxide; anhydrous citric acid may reduce efficacy of the bowel preparation as conversion of sodium picosulfate to its active metabolite bis-(p-hydroxy-phenyl)-pyridyl-2-methane (BHPM) is mediated by colonic bacteria. If possible, avoid coadministration. Certain antibiotics (i.e., tetracyclines and quinolones) may chelate with the magnesium in sodium picosulfate; magnesium oxide; anhydrous citric acid solution. Therefore, these antibiotics should be taken at least 2 hours before and not less than 6 hours after the administration of sodium picosulfate; magnesium oxide; anhydrous citric acid solution.
Streptomycin: (Minor) Ceftazidime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
Tobramycin: (Minor) Ceftazidime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
Torsemide: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
Warfarin: (Moderate) The concomitant use of warfarin with many classes of antibiotics, including cephalosporins, may increase the INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Additionally, certain cephalosporins (cefotetan, cefoperazone, cefamandole) are associated with prolongation of the prothrombin time due to the methylthiotetrazole (MTT) side chain at the R2 position, which disturbs the synthesis of vitamin K-dependent clotting factors in the liver. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary.
Ceftazidime, a beta-lactam antibiotic, is mainly bactericidal. It inhibits the third and final stage of bacterial cell wall synthesis by preferentially binding to specific penicillin-binding proteins (PBPs) that are located inside the bacterial cell wall. PBPs are responsible for several steps in cell wall synthesis and are found in quantities of several hundred to several thousand molecules per bacterial cell. PBPs vary among different bacterial species. Thus, the intrinsic activity of ceftazidime and other beta-lactams against a particular organism depends on their ability to gain access to and bind with the necessary PBP. In particular, ceftazidime preferentially binds to PBP-3 of gram-negative rods. Since PBP-3 is responsible for formation of the septum during cell division, ceftazidime's inhibition of these proteins causes elongation of the bacteria, inhibition of bacterial cell division, and breakage of the cell wall resulting in cell lysis and death. Lysis is mediated by bacterial cell wall autolytic enzymes (i.e., autolysins). The relationship between PBPs and autolysins is unclear, but it is possible that the beta-lactam antibiotic interferes with an autolysin inhibitor. Prevention of the autolysin response to beta-lactam antibiotic exposure through loss of autolytic activity (mutation) or inactivation of autolysin (low-medium pH) by the microorganism can lead to tolerance to the beta-lactam antibiotic resulting in bacteriostatic activity.
Beta-lactams, including ceftazidime, exhibit concentration-independent or time-dependent killing. In vitro and in vivo animal studies have demonstrated that the major pharmacodynamic parameter that determines efficacy for beta-lactams is the amount of time free (non-protein bound) drug concentrations exceed the minimum inhibitory concentration (MIC) of the organism (free T above the MIC). This microbiological killing pattern is due to the mechanism of action, which is acylation of PBPs. There is a maximum proportion of PBPs that can be acylated; therefore, once maximum acylation has occurred, killing rates cannot increase. Free beta-lactam concentrations do not have to remain above the MIC for the entire dosing interval. The percentage of time required for both bacteriostatic and maximal bactericidal activity is different for the various classes of beta-lactams. Cephalosporins require free drug concentrations to be above the MIC for 35% to 40% of the dosing interval for bacteriostatic activity and 60% to 70% of the dosing interval for bactericidal activity.
Due to the presence of an aminothiazolyl side chain, third-generation cephalosporins display enhanced activity against gram-negative bacteria, particularly the Enterobacterales. Also, because ceftazidime contains a 2-carboxy-2-oxypropane imino group, it shows increased activity against P. aeruginosa, which gives it an important advantage over other cephalosporins. However, the presence of the 2-carboxy-2-oxypropane imino group limits ceftazidime's activity against most gram-positive bacteria.
The susceptibility interpretive criteria for ceftazidime are delineated by pathogen. The Clinical and Laboratory Standards Institute (CLSI) and the FDA differ on MIC interpretation for P. aeurginosa. The MICs are defined for P. aeurginosa by the FDA as susceptible at 8 mcg/mL or less and resistant at 16 mcg/mL or more (based on a dosage of 2 g IV every 8 hours); however, the MICs are defined by CLSI as susceptible at 8 mcg/mL or less, intermediate at 16 mcg/mL, and resistant at 32 mcg/mL or more (based on a dosage of 1 g IV every 6 hours or 2 g IV every 8 hours). The MICs are defined for Enterobacterales, Vibrio sp., and Aeromonas sp. as susceptible at 4 mcg/mL or less, intermediate at 8 mcg/mL, and resistant at 16 mcg/mL or more (based on a dosage of 1 g IV every 8 hours). The MICs are defined for Acinetobacter sp., other non-Enterobacterales, S. maltophilia, B. cepacia complex, B. mallei, and B. pseudomallei as susceptible at 8 mcg/mL or less, intermediate at 16 mcg/mL, and resistant at 32 mcg/mL or more. The MICs are defined for H. influenzae, H. parainfluenzae, and M. catarrhalis as susceptible at 2 mcg/mL or less.
Resistance to cephalosporins occurs as a result of decreased permeability, alterations of PBPs, and hydrolysis by beta-lactamases.
Ceftazidime is administered intravenously or intramuscularly. Approximately 10% of the circulating drug is protein-bound. Ceftazidime is distributed into most body tissues and fluids, including urine, bile, peritoneal fluid, sputum, bone, skin, muscle, and cerebrospinal fluid (CSF). Average ceftazidime concentrations in the CSF and CSF with inflamed meninges after a 2 g IV dose were 9.8 mcg/mL and 9.4 mcg/mL, respectively. The drug is excreted into the urine primarily via glomerular filtration and achieves high therapeutic concentrations in the urine (2100 mcg/mL after a 500 mg IM dose and 12,000 mcg/mL after a 2 g IV dose). Approximately 80% to 90% is excreted unchanged by the kidneys over 24 hours. In patients with normal renal function, the elimination half-life of ceftazidime is approximately 1.4 to 2 hours, but half-life increases as renal function declines.
Affected cytochrome P450 isoenzymes and drug transporters: none
-Route-Specific Pharmacokinetics
Intravenous Route
Peak concentrations are reached approximately 30 minutes after IV administration.
Intramuscular Route
Peak concentrations are reached approximately 1 hour after IM administration.
-Special Populations
Hepatic Impairment
In adults with hepatic impairment, the pharmacokinetics of ceftazidime are unaltered. Pharmacokinetic data are unavailable in children with hepatic impairment.
Renal Impairment
Ceftazidime is substantially excreted in the kidneys and elimination half-life is significantly increased in patients with renal dysfunction. Ceftazidime is removed by hemodialysis and peritoneal dialysis. Dosage adjustments are recommended. Pharmacokinetic data in children with renal impairment are not available.
Pediatrics
Infants and Children
Pharmacokinetics of ceftazidime in children are similar as in adults. The elimination half-life in infants and children is approximately 1.4 to 2 hours.
Neonates
Postnatal age is significantly correlated with clearance and elimination half-life in neonates, with clearance increasing rapidly in the first 2 weeks of life. In a study in preterm neonates (n = 136; 24 to 37 weeks gestational age) who received IV ceftazidime (25 or 50 mg/kg/dose every 12 hours), mean values for clearance, volume of distribution (Vd), and elimination half-life were 37.3 mL/kg/hour, 350 mL/kg, and 6.95 hours, respectively. In term neonates (38 weeks gestational age or older), mean values for clearance, Vd, and elimination half-life after multiple doses of ceftazidime (50 mg/kg/dose every 8 to 12 hours) were approximately 108 mL/kg/hour, 546 mL/kg, and 3.5 hours, respectively. Infants who are receiving concomitant indomethacin have lower ceftazidime clearance rates.
Cystic Fibrosis
Clearance is higher in patients with cystic fibrosis (CF). An elimination half-life of approximately 1 hour was reported in a study (n = 8) in children with CF.
Other
Plasmapheresis
Less than 10% of an administered ceftazidime dose is removed during plasmapheresis.