ceftazidime/avibactam

Contraindicated in:

Known hypersensitivity to ceftazidime, other cephalosporins, or avibactam-containing products; cross-sensitivity with other penicillins, carbapenems, and cephalosporins may occur.

Use Cautiously in:

CCr 30–50 mL/min (efficacy may be ↓, monitor renal function frequently and adjust dose if necessary);
OB: Use during pregnancy only if potential material benefit justifies potential fetal risk;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
Geri: Consider age-related impairment of renal function.

Adv. Reactions/Side Effects ⬆ ⬇

F and E: hypokalemia

GI: CLOSTRIDIOIDES DIFFICILE-ASSOCIATED DIARRHEA (CDAD), diarrhea, nausea, vomiting

Hemat: eosinophilia, thrombocytopenia

Neuro: anxiety, dizziness, headache, SEIZURES ( IN RENAL IMPAIRMENT)↑ in renal impairment)

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS AND SERIOUS SKIN REACTIONS)

Interactions ⬆ ⬇

Drug-drug:

Probenecid may ↓ renal excretion of avibactam; concurrent administration is not recommended.

Availability ⬆ ⬇

Powder for injection: ceftazidime 2 g/avibactam 0.5 g/vial

Route/Dosage ⬆ ⬇

IV (Adults ): 2.5 g (2 g ceftazidime/0.5 g avibactam) every 8 hr. Duration of therapy = 5–14 days (complicated intra-abdominal infections); 7–14 days (complicated UTIs or hospital-/ventilator-acquired bacterial pneumonia).
IV (Children ≥2 yr): 62.5 mg/kg (50 mg/kg ceftazidime/12.5 mg/kg avibactam) (max dose = 2.5 g [2 g ceftazidime/0.5 g avibactam]) every 8 hr. Duration of therapy = 5–14 days (complicated intra-abdominal infections); 7–14 days (complicated UTIs or hospital-/ventilator-acquired bacterial pneumonia).
IV (Children 6 mo–<2 yr): 62.5 mg/kg (50 mg/kg ceftazidime/12.5 mg/kg avibactam) every 8 hr. Duration of therapy = 5–14 days (complicated intra-abdominal infections); 7–14 days (complicated UTIs or hospital-/ventilator-acquired bacterial pneumonia).
IV (Children 3 mo–<6 mo): 50 mg/kg (40 mg/kg ceftazidime/10 mg/kg avibactam) every 8 hr. Duration of therapy = 5–14 days (complicated intra-abdominal infections); 7–14 days (complicated UTIs or hospital-/ventilator-acquired bacterial pneumonia).
IV (Children >28 days–<3 mo): 37.5 mg/kg (30 mg/kg ceftazidime/7.5 mg/kg avibactam) every 8 hr. Duration of therapy = 5–14 days (complicated intra-abdominal infections); 7–14 days (complicated UTIs or hospital-/ventilator-acquired bacterial pneumonia).
IV (Children ≤28 days with gestational age ≥31 wk): 25 mg/kg (20 mg/kg ceftazidime/5 mg/kg avibactam) every 8 hr. Duration of therapy = 5–14 days (complicated intra-abdominal infections); 7–14 days (complicated UTIs or hospital-/ventilator-acquired bacterial pneumonia).

Renal Impairment

IV (Adults ): CCr 31–50 mL/min: 1.25 g (1 g ceftazidime/0.25 g avibactam) every 8 hr; CCr 16–30 mL/min: 0.94 g (0.75 g ceftazidime/0.19 g avibactam) every 12 hr; CCr 6–15 mL/min: 0.94 g (0.75 g ceftazidime/0.19 g avibactam) every 24 hr; CCr ≤5 mL/min: 0.94 g (0.75 g ceftazidime/0.19 g avibactam) every 48 hr: Hemodialysis: Administer dose after hemodialysis on hemodialysis days.

Renal Impairment

IV (Children ≥2 yr): CCr 31–50 mL/min: 31.25 mg/kg (25 mg/kg ceftazidime/6.25 mg/kg avibactam) (max dose = 1.25 g [1 g ceftazidime/0.25 g avibactam]) every 8 hr; CCr 16–30 mL/min: 23.75 mg/kg (19 mg/kg ceftazidime/4.75 mg/kg avibactam) (max dose = 0.94 g [0.75 g ceftazidime/0.19 g avibactam]) every 12 hr; CCr 6–15 mL/min: 23.75 mg/kg (19 mg/kg ceftazidime/4.75 mg/kg avibactam) (max dose = 0.94 g [0.75 g ceftazidime/0.19 g avibactam]) every 24 hr; CCr ≤5 mL/min: 23.75 mg/kg (19 mg/kg ceftazidime/4.75 mg/kg avibactam) (max dose = 0.94 g [0.75 g ceftazidime/0.19 g avibactam]) every 48 hr; Hemodialysis: Administer dose after hemodialysis or on hemodialysis days.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Ceftazidime: Inhibits bacterial cell wall synthesis.
Avibactam: Inhibits beta-lactamase, an enzyme that destroys penicillins and cephalosporins.

Therapeutic effects:

Death of susceptible bacteria with resolution of infection.

Spectrum:

Active against Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Haemophilus influenzae, Enterobacter cloacae, Klebsiella oxytoca, Pseudomonas aeruginosa, Citrobacter freundii, and Serratia marcescens.

Classifications ⬆ ⬇

Therapeutic Classification: anti-infectives

Pharmacologic Classification: third generation cephalosporins, beta lactamase inhibitors

Pharmacokinetics ⬆ ⬇

Ceftazidime

Absorption: IV administration results in complete bioavailability.

Distribution: Widely distributed to tissues.

Metabolism/Excretion: Minimally metabolized; 80–90% excreted unchanged in urine.

Half-Life: 2.8–3.3 hr (↑ in renal impairment).

Avibactam

Absorption: IV administration results in complete bioavailability.

Distribution: Widely distributed to tissues.

Metabolism/Excretion: Minimally metabolized, mainly excreted unchanged in urine.

Half-Life: 2.2–2.7 hr.

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Indications ⬇

Contraind./Precautions ⬆ ⬇