Ceftazidime-Avibactam: Prescription Guidelines and Clinical Applications
Ceftazidime-avibactam is strongly recommended for treating infections caused by carbapenem-resistant Enterobacterales (CRE) producing serine carbapenemases (KPC and OXA-48), with a standard dosage of 2.5 g IV (2 g ceftazidime + 0.5 g avibactam) administered as a 2-hour infusion every 8 hours for patients with normal renal function. 1, 2, 3
Approved Indications and Dosing
- For complicated intra-abdominal infections (cIAI), administer ceftazidime-avibactam 2.5 g IV every 8 hours concurrently with metronidazole 500 mg IV every 6-8 hours, with treatment duration of 5-14 days 3
- For complicated urinary tract infections (cUTI) including pyelonephritis, administer 2.5 g IV every 8 hours for 7-14 days 3, 4
- For hospital-acquired and ventilator-associated bacterial pneumonia, administer 2.5 g IV every 8 hours for 7-14 days 3
- All doses should be administered as 2-hour intravenous infusions 5, 6
Renal Dosage Adjustments
- For creatinine clearance (CrCL) ≤50 mL/min, dose adjustment is required 7, 8
- The standard dose of 2.5 g IV every 8 hours is appropriate for patients with CrCL >50 mL/min 7, 8
- Dosage should be determined based on renal function before initiating therapy and adjusted if significant changes in renal function occur during treatment 5
Antimicrobial Spectrum and Clinical Applications
Ceftazidime-avibactam is active against:
Ceftazidime-avibactam is NOT active against:
Efficacy Data
- For CRE infections, ceftazidime-avibactam may be associated with 182 fewer deaths per 1000 patients treated compared to other antimicrobial therapies 1
- Clinical cure rates for cUTI are comparable to carbapenems (91% for ceftazidime-avibactam vs 91% for best available therapy) 9
- Microbiological cure rates for ceftazidime-resistant pathogens in cUTI were 71.5% for ceftazidime-avibactam vs 56.9% for best available therapy 4
- For complicated intra-abdominal infections, clinical cure rates were similar to meropenem (91.2% vs 93.4%) 6
Important Considerations and Monitoring
- Determine carbapenemase type and/or ceftazidime-avibactam susceptibility of CRE isolates before initiating treatment when possible 1
- Resistance to ceftazidime-avibactam in KPC-producing organisms has been reported, particularly with prior ceftazidime-avibactam exposure 2, 3
- Consider combination therapy with ceftazidime-avibactam plus a carbapenem or colistin when treating KPC-3 producers due to potential resistance development 3
- For infections caused by metallo-beta-lactamase (MBL)-producing pathogens, consider adding aztreonam to ceftazidime-avibactam 2
- Most common adverse events are gastrointestinal disorders (13-18% of patients) 9, 6
Special Populations
- High target attainment (>95%) against MICs ≤8 mg/L is achieved regardless of older age, obesity, augmented renal clearance, or severity of infection 7
- For patients with bacteremia, microbiological cure rates of 81.6% have been reported with ceftazidime-avibactam 4
Treatment Algorithm for CRE Infections
- Confirm or suspect CRE infection based on clinical presentation and local epidemiology 1, 2
- Determine carbapenemase type if possible (KPC, OXA-48, NDM, etc.) 1
- For KPC or OXA-48 producing CRE: Use ceftazidime-avibactam 2.5 g IV every 8 hours 1, 2
- For MBL-producing CRE (e.g., NDM): Consider ceftazidime-avibactam plus aztreonam 2
- For unknown carbapenemase type: Initiate ceftazidime-avibactam empirically if local epidemiology suggests KPC or OXA-48 predominance 1, 2
- Adjust therapy based on susceptibility testing and clinical response 1, 3
- Monitor for development of resistance, especially in patients with prior ceftazidime-avibactam exposure 2, 3