ceftazidime/avibactam

General

Pronunciation:
sef-tay-zi-deem/a-vi-bak-tam

Trade Name(s)

• Avycaz

Ther. Class.

anti-infectives

Pharm. Class.

third generation cephalosporins

beta lactamase inhibitors

Indications

• Complicated intra-abdominal infections (in combination with metronidazole).
• Complicated urinary tract infections (UTIs) (including pyelonephritis).
• Hospital-acquired and ventilator-associated bacterial pneumonia.

Action

• Ceftazidime:  Binds to the bacterial cell wall membrane, causing cell death.
• Avibactam:  Inhibits beta-lactamase, an enzyme that destroys penicillins and cephalosporins.

Therapeutic Effect(s):

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

Ceftazidime

Absorption: IV administration results in complete bioavailability.

Distribution: Widely distributed to tissues.

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

Half-life: 2.2–2.7 hr.

TIME/ACTION PROFILE (plasma concentrations)

Contraindication/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;
• Geri:  Consider age-related impairment of renal function.

Adverse 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)

Misc: HYPERSENSITIVITY REACTIONS (including anaphylaxis and serious skin reactions)

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

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 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.

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

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.
• Rep:  Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

Evaluation/Desired Outcomes

Resolution of the signs and symptoms of infection. Length of time for complete resolution depends on the organism and site of infection.