ceftazidime/avibactam

Ceftazidime: Binds to the bacterial cell wall membrane, causing cell death.
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.

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

Distribution: Ceftazidime: Widely distributed, enters breast milk in low concentrations; avibactam: widely distributed

Metabolism/Excretion: ceftazidime: minimally metabolized, 80–90% excreted unchanged in urine; avibactam: minimally metabolized, mainly excreted unchanged in urine.

Half-Life: Ceftazidime: 2.8–3.3 hr (↑ in renal impairment); avibactam: 2.2–2.7 hr.

Time/Action Profile ⬆ ⬇

(blood levels)

ROUTE	ONSET	PEAK	DURATION
IV	rapid	end of infusion	8 hr (↑ in renal impairment)

Contraind./Precautions ⬆ ⬇

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;
Pedi: Children 3 mo (safety and effectiveness not established);
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.

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 urinary tract infections 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 urinary tract infections 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 urinary tract infections 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 urinary tract infections 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.

Availability ⬆ ⬇

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

Assessment ⬆ ⬇

Assess for infection (vital signs; appearance of wound, sputum, urine, and stool; WBC) at beginning of and during therapy.
Before initiating therapy, obtain a history to determine previous use of and reactions to penicillins, cephalosporins, or carbapenems. Persons with a negative history of sensitivity may still have an allergic response.
Obtain specimens for culture and sensitivity before initiating therapy. First dose may be given before receiving results.
Observe patient for signs and symptoms of anaphylaxis (rash, pruritus, laryngeal edema, wheezing). Discontinue the drug and notify health care professional immediately if these symptoms occur. Keep epinephrine, an antihistamine, and resuscitation equipment close by in the event of an anaphylactic reaction.
Monitor bowel function. Diarrhea, abdominal cramping, fever, and bloody stools should be reported to health care professional promptly as a sign of CDAD. May begin up to several mo following cessation of therapy.
Monitor for signs and symptoms of encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor, coma), myoclonus, and seizures during and following therapy. May require immediate treatment, dose adjustment, or discontinuation of therapy.

Lab Test Considerations:

May cause seroconversion from a negative to a positive direct Coombs' test. If anemia develops during or after therapy, perform a direct Coombs' test.
- May cause a false-positive reaction for glucose in urine with certain methods; use enzymatic glucose oxidase reactions.

Implementation ⬆ ⬇

IV Administration:

Intermittent Infusion: Reconstitution: Reconstitute with 10 mL of sterile water for injection. 0.9% NaCl, D5W, D5/0.9% NaCl, D5/0.45% NaCl, D2.5/0.9% NaCl, D2.5/0.45% NaCl, or LR. Mix gently.Diluent: Use same diluent used for reconstitution for a volume between 50 mL and 250 mL.Concentration: 40 and 10 mg/mL of ceftazidime and avibactam, respectively to 8 and 2 mg/mL of ceftazidime and avibactam, respectively. Solution ranges from clear to light yellow; do not administer solutions that are discolored or contain particulate matter. Solution is stable for 12 hr at room temperature or 24 hr if refrigerated.
Rate: Infuse over 2 hr.

Patient/Family Teaching ⬆ ⬇

Explain the purpose of ceftazidime/avibactam to patient.
Instruct patient to notify health care professional if fever and diarrhea develop, especially if stool contains blood, pus, or mucus. Advise patient not to treat diarrhea without consulting health care professional.
Advise patient to notify health care professional immediately if signs and symptoms of allergic reactions or nervous system reactions occur.
Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇