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    3rd Generation Cephalosporin Antibiotics

    DEA CLASS

    Rx

    DESCRIPTION

    Parenteral third-generation cephalosporin
    Extremely active against Pseudomonas aeruginosa; used for lower respiratory tract infections, skin and soft-tissue infections, UTIs, bone and joint infections, and meningitis
    Limited use for empiric monotherapy for neutropenic fever due to emergence of resistant pathogens and poor gram-positive activity

    COMMON BRAND NAMES

    Fortaz, Tazicef, Tazidime

    HOW SUPPLIED

    Ceftazidime/Ceftazidime Pentahydrate/Fortaz/Tazicef/Tazidime Intramuscular Inj Pwd F/Sol: 1g, 2g, 6g, 500mg
    Ceftazidime/Ceftazidime Pentahydrate/Fortaz/Tazicef/Tazidime Intravenous Inj Pwd F/Sol: 1g, 2g, 6g, 500mg
    Fortaz Intravenous Inj Sol: 1mL, 20mg, 40mg

    DOSAGE & INDICATIONS

    For the treatment of bone and joint infections, including osteomyelitis.
    Intravenous or Intramuscular dosage
    Adults

    2 g IV every 12 hours. For severe or life-threatening infections, 2 g IV every 8 hours.[29916] Guidelines suggest 2 g IV every 8 hours for P. aeruginosa vertebral osteomyelitis or prosthetic joint infection. Treat for 6 weeks (with or without ciprofloxacin or an aminoglycoside) for vertebral osteomyelitis and for 4 to 6 weeks (with or without an aminoglycoside) for prosthetic joint infections.[61051] [61052]

    Adolescents

    2 g IV every 12 hours. For severe or life-threatening infections, 2 g IV every 8 hours.

    Infants and Children

    30 to 50 mg/kg/dose IV or IM every 8 hours (Max: 2 g/dose).[29916] [63245] Higher doses (e.g., 50 mg/kg/dose IV every 8 hours) are recommended for immunocompromised patients.[29916] 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.[63245]

    Neonates 32 weeks gestation and older and 8 days and older

    50 mg/kg/dose IV or IM every 8 hours is recommended by the American Academy of Pediatrics (AAP). The FDA-approved labeling recommends 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 is recommended by the American Academy of Pediatrics (AAP). The FDA-approved labeling recommends 30 mg/kg/dose IV every 12 hours.

    Neonates younger than 32 weeks gestation and 14 days and older

    50 mg/kg/dose IV or IM every 8 hours is recommended by the American Academy of Pediatrics (AAP). The FDA-approved labeling recommends 30 mg/kg/dose IV every 12 hours.

    Neonates younger than 32 weeks gestation and 0 to 13 days

    50 mg/kg/dose IV or IM every 12 hours is recommended by the American Academy of Pediatrics (AAP). The FDA-approved labeling recommends 30 mg/kg/dose IV every 12 hours.

    For the treatment of lower respiratory tract infections (LRTIs), including pneumonia, community-acquired pneumonia (CAP), and nosocomial pneumonia.
    For the treatment of nonspecific lower respiratory tract infections (LRTIs), including pneumonia.
    Intravenous or Intramuscular dosage
    Adults

    2 g IV every 8 hours for severe or life-threatening infections, especially in immunocompromised patients. For uncomplicated pneumonia, 500 mg to 1 g IV or IM every 8 hours.[29916]

    Adolescents

    2 g IV every 8 hours for severe or life-threatening infections, especially in immunocompromised patients. For uncomplicated pneumonia, 500 mg to 1 g IV or IM every 8 hours.[29916]

    Infants and Children

    30 to 50 mg/kg/dose (Max: 2 g/dose) IV or IM every 8 hours.  50 mg/kg/dose IV every 8 hours is recommended for immunocompromised patients. For serious P. aeruginosa infections, 200 to 300 mg/kg/day IV divided every 8 hours (Max: 12 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 14 days and older

    50 mg/kg/dose IV or IM every 8 hours.[63245] The FDA-approved dose is 30 mg/kg/dose IV every 12 hours.[29916]

    Neonates younger than 32 weeks gestation and 0 to 13 days

    50 mg/kg/dose IV or IM every 12 hours.[63245] The FDA-approved dose is 30 mg/kg/dose IV every 12 hours.[29916]

    For the treatment of community-acquired pneumonia (CAP).
    Intravenous dosage
    Adults

    2 g IV every 8 hours for at least 7 days as part of combination therapy for hospitalized patients with prior respiratory isolation of P. aeruginosa or risk factors for P. aeruginosa and recent hospitalization with parenteral antibiotic use.[64669]

    For the treatment of nosocomial pneumonia.
    Intravenous dosage
    Adults

    2 g IV every 8 hours for 7 days. For patients with risk factors for gram-negative resistance or with a high mortality risk, add a second non-beta-lactam agent with antipseudomonal activity (i.e., quinolone, aminoglycoside, polymyxin).[61215]

    For the treatment of urinary tract infection (UTI).
    Intravenous or Intramuscular dosage
    Adults

    1 g IV or IM every 8 to 12 hours is the usual dosage. FDA-labeling suggests 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.

    Adolescents

    1 g IV or IM every 8 to 12 hours is the usual dosage. FDA-labeling suggests 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. 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.

    Infants and Children

    30 to 50 mg/kg/dose IV or IM every 8 hours (Max: 2 g/dose). Higher doses (e.g., 50 mg/kg/dose every 8 hours) are recommended for immunocompromised patients. 100 to 150 mg/kg/day IV divided every 8 hours for 7 to 14 days is recommended by the American Academy of Pediatrics (AAP) for the treatment of initial UTI in febrile infants and young children (2 months to 2 years). 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.

    Neonates 32 weeks gestation and older and 8 days and older

    50 mg/kg/dose IV or IM every 8 hours is recommended by the American Academy of Pediatrics (AAP).The FDA-approved labeling recommends 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 is recommended by the American Academy of Pediatrics (AAP). The FDA-approved labeling recommends 30 mg/kg/dose IV every 12 hours.

    Neonates younger than 32 weeks gestation and 14 days and older

    50 mg/kg/dose IV or IM every 8 hours is recommended by the American Academy of Pediatrics (AAP).The FDA-approved labeling recommends 30 mg/kg/dose IV every 12 hours.

    Neonates younger than 32 weeks gestation and 0 to 13 days

    50 mg/kg/dose IV or IM every 12 hours is recommended by the American Academy of Pediatrics (AAP). The FDA-approved labeling recommends 30 mg/kg/dose IV every 12 hours.

    For the treatment of very severe life-threatening infections, such as bacteremia and sepsis.
    Intravenous dosage
    Adults

    2 g IV every 8 hours. Start within 1 hour of recognition as part of empiric multi-drug therapy. Duration of therapy is generally 7 to 10 days, but may be shorter or longer depending upon patient response, site of infection, and pathogen(s) isolated. Treatment may be narrowed with pathogen identification and/or adequate clinical response.

    Adolescents

    2 g IV every 8 hours.[29916] 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. [64985]

    Infants and Children

    30 to 50 mg/kg/dose IV every 8 hours (Max: 2 g/dose).[29916] [63245] Higher doses (e.g., 50 mg/kg/dose IV every 8 hours) are recommended for immunocompromised patients.[29916] 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.[63245] 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. [64985]

    Neonates 32 weeks gestation and older and 8 days and older

    50 mg/kg/dose IV every 8 hours is recommended by the American Academy of Pediatrics (AAP).[63245] The FDA-approved labeling recommends 30 mg/kg/dose IV every 12 hours.[29916] 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 younger than 37 weeks gestational age were excluded from the scope of the Surviving Sepsis Campaign guidelines.[64985]

    Neonates 32 weeks gestation and older and 0 to 7 days

    50 mg/kg/dose IV every 12 hours is recommended by the American Academy of Pediatrics (AAP).[63245] The FDA-approved labeling recommends 30 mg/kg/dose IV every 12 hours.[29916] 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 younger than 37 weeks gestational age were excluded from the scope of the Surviving Sepsis Campaign guidelines.[64985]

    Neonates younger than 32 weeks gestation and 14 days and older

    50 mg/kg/dose IV every 8 hours is recommended by the American Academy of Pediatrics (AAP). The FDA-approved labeling recommends 30 mg/kg/dose IV every 12 hours.

    Neonates younger than 32 weeks gestation and 0 to 13 days

    50 mg/kg/dose IV every 12 hours is recommended by the American Academy of Pediatrics (AAP). The FDA-approved labeling recommends 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 is the usual 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 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. Treat for 21 days.

    Infants and Children

    150 to 200 mg/kg/day IV divided every 8 hours (Max: 6 g/day) is the usual 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 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. Treat for 21 days.

    Neonates 8 days and older

    50 mg/kg/dose IV every 8 hours is recommended by guidelines. The FDA-approved labeling recommends 30 mg/kg/dose IV every 12 hours. Treat for at least 21 days.

    Neonates 0 to 7 days

    50 mg/kg/dose IV every 8 to 12 hours is recommended by guidelines, with every 12 hour frequency used for neonates weighing less than 2 kg. The FDA-approved labeling recommends 30 mg/kg/dose IV every 12 hours. Treat for at least 21 days.

    For the treatment of skin and skin structure infections, including 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 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 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 IV divided every 8 hours (Max: 6 g/day).  200 to 300 mg/kg/day IV divided every 8 hours (Max: 6 g/day) 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/dose 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 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 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 every 12 hours. The FDA-approved dose 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 IV divided every 6 to 8 hours (Max: 8 to 12 g/day) is recommended by guidelines and supported by study data. The FDA-approved labeling recommends 150 mg/kg/day IV divided every 8 hours (Max: 6 g/day); 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 IV divided every 6 to 8 hours (Max: 8 to 12 g/day) is recommended by guidelines and supported by study data. The FDA-approved labeling recommends 150 mg/kg/day IV divided every 8 hours (Max: 6 g/day); however, pharmacokinetic/pharmacodynamic data have suggested this dose to be suboptimal in treating Pseudomonas infections in acute pulmonary exacerbations.

    For the treatment of intraabdominal infections, including peritonitis, appendicitis, intraabdominal abscess, and peritoneal dialysis-related peritonitis†.
    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 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 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 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 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.

    †Indicates off-label use

    MAXIMUM DOSAGE

    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 IV/IM (Max: 6 g/day) 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, and doses up to 150 mg/kg/day have been used for meningitis in those weighing 2 kg or more.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No dosage adjustment needed.

    Renal Impairment

    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).

    ADMINISTRATION

    For storage information, see specific product information within the How Supplied section.

    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.[29916] [52276]
    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.[29916] [52276]
     
    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.[52276] [63003]
    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.[52276] [63003]
     
    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.[62605]
     
    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.[59725]
     
    Intermittent IV Infusion
    Infuse IV over 30 minutes.
    Do not use plastic containers in series connections.[29916] [59725]
     
    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.[29916]
     
    Plasmapheresis
    Administer IV doses at least 2 hours before plasmapheresis.[33359]

    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.[29916] [52276]
     
    Intramuscular Injection
    Inject deeply into a large muscle (e.g., anterolateral thigh or deltoid).[29916]
    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.[53249]
     
    Plasmapheresis
    Administer IM doses at least 3 hours before plasmapheresis.[33359]

    STORAGE

    Fortaz:
    - Protect from light
    - Store reconstituted product in accordance with package insert instructions
    - Store unreconstituted product at 59 to 86 degrees F
    Tazicef:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion 4 hours after initial entry of container
    - Discard unused portion 4 hours after initial puncture of container
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    - Store in carton until time of use
    Tazidime:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion 4 hours after initial entry of container
    - Discard unused portion 4 hours after initial puncture of container
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    - Store in carton until time of use

    CONTRAINDICATIONS / PRECAUTIONS

    Carbapenem hypersensitivity, cephalosporin hypersensitivity, penicillin hypersensitivity

    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.

    C. difficile-associated diarrhea, diarrhea, pseudomembranous colitis

    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.

    Hepatic disease, malnutrition, renal failure, renal impairment

    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.

    Laboratory test interference

    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.

    Geriatric

    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.

    Pregnancy

    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).

    Breast-feeding

    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. 

    Reproductive risk

    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.

    ADVERSE REACTIONS

    Severe

    agranulocytosis / Delayed / 0-1.0
    hemolytic anemia / Delayed / 0-1.0
    bronchospasm / Rapid / 0-1.0
    interstitial nephritis / Delayed / 0-1.0
    angioedema / Rapid / 0-1.0
    pancytopenia / Delayed / Incidence not known
    aplastic anemia / Delayed / Incidence not known
    coma / Early / Incidence not known
    seizures / Delayed / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    erythema multiforme / Delayed / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known
    C. difficile-associated diarrhea / Delayed / Incidence not known

    Moderate

    eosinophilia / Delayed / 7.7-7.7
    thrombocytosis / Delayed / 2.2-2.2
    phlebitis / Rapid / 0-2.0
    thrombocytopenia / Delayed / 0-1.0
    neutropenia / Delayed / 0-1.0
    lymphocytosis / Delayed / 0-1.0
    leukopenia / Delayed / 0-1.0
    hypotension / Rapid / 0-1.0
    jaundice / Delayed / 0-1.0
    hyperbilirubinemia / Delayed / 0-1.0
    cholestasis / Delayed / 0-1.0
    vaginitis / Delayed / 0-1.0
    candidiasis / Delayed / 0-1.0
    hypoprothrombinemia / Delayed / Incidence not known
    encephalopathy / Delayed / Incidence not known
    myoclonia / Delayed / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    pseudomembranous colitis / Delayed / Incidence not known
    superinfection / Delayed / Incidence not known

    Mild

    injection site reaction / Rapid / 0-2.0
    maculopapular rash / Early / 2.0-2.0
    fever / Early / 2.0-2.0
    pruritus / Rapid / 2.0-2.0
    nausea / Early / Incidence not known
    abdominal pain / Early / Incidence not known
    diarrhea / Early / Incidence not known
    vomiting / Early / Incidence not known
    headache / Early / Incidence not known
    asterixis / Delayed / Incidence not known
    paresthesias / Delayed / Incidence not known
    dizziness / Early / Incidence not known
    urticaria / Rapid / Incidence not known

    DRUG INTERACTIONS

    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.
    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.
    Kanamycin: (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.
    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.
    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.
    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.
    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.

    PREGNANCY AND LACTATION

    Pregnancy

    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. 

    MECHANISM OF ACTION

    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.[44649] [51464] [51465] [58909] 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.[51465]
     
    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).[34145] [34143] [35436] [35437] [35438] [35439] 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.[35439] 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.[35436] [35437] [35438]
     
    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.[44649] [58909]
     
    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 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, and B. cepacia complex as susceptible at 8 mcg/mL or less, intermediate at 16 mcg/mL, and resistant at 32 mcg/mL or more. For H. influenzae and H. parainfluenzae, an MIC of 2 mcg/mL or less is considered susceptible.[63320] [63321]
     
    Resistance to cephalosporins occurs as a result of decreased permeability, alterations of PBPs, and hydrolysis by beta-lactamases.[44649] [58909]

    PHARMACOKINETICS

    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

    Intravenous Route

    Peak concentrations are reached approximately 30 minutes after IV administration.

    Intramuscular Route

    Peak concentrations are reached approximately 1 hour after IM administration.