Zavicefta (Ceftazidime-Avibactam): Recommended Use and Dosage
Zavicefta is indicated for treating complicated urinary tract infections (including pyelonephritis), complicated intra-abdominal infections (with metronidazole), and hospital-acquired/ventilator-associated pneumonia caused by susceptible Gram-negative organisms, with particular value against carbapenem-resistant Enterobacterales (CRE) and difficult-to-treat Pseudomonas aeruginosa. 1
FDA-Approved Indications
Adult Dosing (≥18 years)
Standard dose: 2.5 grams (ceftazidime 2 g + avibactam 0.5 g) IV every 8 hours, infused over 2 hours in patients with creatinine clearance >50 mL/min 1
Complicated intra-abdominal infections (cIAI): Must be administered concurrently with metronidazole 500 mg IV every 6-8 hours; treatment duration 5-14 days 1
Complicated urinary tract infections (cUTI) including pyelonephritis: Treatment duration 7-14 days 1
Hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP): Treatment duration 7-14 days 1
Pediatric Dosing (≥31 weeks gestational age)
Ages 2 to <18 years: 62.5 mg/kg (maximum 2.5 grams) IV every 8 hours over 2 hours 1
Ages 6 months to <2 years: 62.5 mg/kg IV every 8 hours 1
Ages 3 to <6 months: 50 mg/kg (ceftazidime 40 mg/kg + avibactam 10 mg/kg) IV every 8 hours 1
Ages >28 days to <3 months: 37.5 mg/kg (ceftazidime 30 mg/kg + avibactam 7.5 mg/kg) IV every 8 hours 1
Ages ≤28 days (≥31 weeks gestational age): 25 mg/kg (ceftazidime 20 mg/kg + avibactam 5 mg/kg) IV every 8 hours 1
Antimicrobial Spectrum and Clinical Applications
Carbapenem-Resistant Enterobacterales (CRE)
Ceftazidime-avibactam 2.5 g IV every 8 hours is recommended for CRE infections, particularly those caused by KPC-producing organisms and OXA-48-producing Enterobacterales 2, 3
Active against extended-spectrum β-lactamase (ESBL)-producing organisms, AmpC β-lactamases, and Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacterales 4
Not active against metallo-β-lactamase (MBL)-producing strains; aztreonam should be considered for MBL-producing pathogens 3, 4
Difficult-to-Treat Pseudomonas aeruginosa (DTR-PA)
Recommended dosage: 2.5 g IV every 8 hours for DTR-PA infections 2, 3
Treatment duration: 5-10 days for complicated UTI and complicated intra-abdominal infections; 10-14 days for HABP/VABP and bloodstream infections 2
Critical Resistance Considerations
Emergence of Resistance
Resistance to ceftazidime-avibactam in KPC-producing organisms has been reported, particularly with prior ceftazidime-avibactam exposure 2, 3
A "see-saw effect" has been observed where mutations in bla KPC-3 gene result in decreased ceftazidime-avibactam susceptibility but restored meropenem susceptibility (4-fold reduction in meropenem MICs to susceptible range) 2
Combination Therapy Considerations
Combination therapy with ceftazidime-avibactam plus a carbapenem or colistin may be considered when treating KPC-3 producers due to potential resistance development 2, 3
For most infections, monotherapy is appropriate except for complicated intra-abdominal infections requiring anaerobic coverage with metronidazole 5
Network meta-analysis showed no mortality difference between combination therapy versus monotherapy for CRE bloodstream infections (OR: 0.96,95% CI: 0.65-1.41) 6
Clinical Efficacy Evidence
Comparative Effectiveness
Phase III REPRISE trial demonstrated 91% clinical cure rates with ceftazidime-avibactam versus 91% with best available therapy (mostly carbapenems) in patients with ceftazidime-resistant Enterobacterales and Pseudomonas aeruginosa 7
Microbiological response rates were superior with ceftazidime-avibactam (81.8%) compared to best available therapy (63.5%) 7
High target attainment (>95%) achieved against MICs ≤8 mg/liter regardless of older age, obesity, augmented renal clearance, or severity of infection 8
Safety and Tolerability
Generally well tolerated with a safety profile consistent with ceftazidime alone 4
Adverse events occurred in 31% of ceftazidime-avibactam patients versus 39% with best available therapy, mostly mild-to-moderate in intensity 7
Gastrointestinal disorders were the most common treatment-emergent adverse events (13% with ceftazidime-avibactam) 7
Important Clinical Caveats
Dosage adjustments required for patients with creatinine clearance ≤50 mL/min 1
For urosepsis management, early antimicrobial therapy must be initiated immediately after microbiological sampling, with source control measures including alleviating urinary obstruction and removing/replacing indwelling catheters 3
Use should be limited to patients with documented multidrug-resistant Gram-negative organisms or those with limited treatment options to preserve effectiveness and prevent resistance development 9