Pharm. Class. third generation cephalosporins beta lactamase inhibitors
Indications
Complicated intra-abdominal infections (in combination with metronidazole).
Complicated urinary tract infections.
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, Providencia stuartii, Enterobacter cloacae, Klebsiella oxytoca, Pseudomonas aeruginosa, Citrobacter koserii, Enterobacter aerogenes, Citrobacter freundii, Serratia marcescens, and Proteus spp.
Pharmacokinetics
Absorption: IV administration results in complete bioavailability.
Distribution: Ceftazidime–Widely distributed, enters breast milk in low concentrations; avibactam–widely distributed
Metabolism and 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)
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);
Geri: Consider age-related impairment of renal function;
OB: Use during pregnancy only if clearly needed
Lactation: Use cautiously in breast-feeding women;
Pedi: Safety and effectiveness not established.
Adverse Reactions/Side Effects
CNS: SEIZURES (↑ IN RENAL IMPAIRMENT), anxiety, dizziness, headache
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) CCr >50 mL/min) 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-acquired/ventilator-associated bacterial pneumonia).
Renal Impairment (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 6–15 mL/min–0.94 g (0.75 g ceftazidime/0.19 g avibactam) every 48 hr: hemodialysis–Administer dose after or on day of hemodialysis.
Availability
Powder for IV 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 throughout 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.
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 hrs at room temperature or 24 hrs if refrigerated.
Rate:Infuse over 2 hrs.
Y-Site Compatibility
daptomycin
dexmedetomidine
dopamine
ertapenem
furosemide
gentamicin
heparin
imipenem/cilastatin
linezolid
magnesium sulfate
meropenem
norepinephrine
phenylephrine
potassium chloride
potassium phosphates
sodium bicarbonate
vasopressin
vecuronium
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 female patient to notify health care professional if pregnancy is planned or suspected or if breast feeding.
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.
ceftazidime/avibactam is a sample topic from the Davis's Drug Guide.
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