Is Avycaz Effective for E. coli Bacteremia?
Yes, Avycaz (ceftazidime-avibactam) is highly effective for E. coli bacteremia, achieving 100% susceptibility in clinical studies, with particular strength against multidrug-resistant strains including ESBL-producers. 1, 2
FDA-Approved Indication
- Ceftazidime-avibactam is FDA-approved for bacterial septicemia caused by E. coli, among other organisms, making it a legitimate first-line option for E. coli bloodstream infections. 1
Clinical Efficacy Data
All E. coli isolates (100%) from intra-abdominal infections were susceptible to ceftazidime-avibactam in a large U.S. surveillance study of 1,540 isolates from 57 hospitals (2012-2014), compared to 99.8% susceptibility to meropenem and only 93.6% to piperacillin-tazobactam. 2
Among ESBL-producing E. coli (15.8% of isolates), ceftazidime-avibactam rendered all ceftazidime-resistant strains susceptible, demonstrating complete restoration of activity. 2, 3
Mechanism Supporting Efficacy
Avibactam inhibits Ambler class A β-lactamases (including ESBLs like CTX-M, TEM, SHV, and KPC), class C (AmpC), and some class D enzymes (OXA-48), which are the primary resistance mechanisms in E. coli. 4, 2
At a fixed concentration of 4 mg/L avibactam, all ceftazidime-resistant Enterobacteriaceae became susceptible with MICs ≤4 mg/L in checkerboard assays. 5
Ceftazidime-avibactam maintained activity even against E. coli strains with combined resistance mechanisms (ESBLs plus acquired AmpC β-lactamases). 3
When to Use Ceftazidime-Avibactam for E. coli Bacteremia
Use as first-line therapy when:
- Multidrug-resistant E. coli is suspected or confirmed (ESBL-producer, carbapenem-resistant). 6
- Local epidemiology shows high rates of ESBL-producing E. coli (>10-15%). 6
- Patient has healthcare-associated bacteremia or prior antibiotic exposure selecting for resistant organisms. 6
Use as monotherapy:
- For carbapenem-resistant E. coli (CRE) susceptible to ceftazidime-avibactam, monotherapy is recommended—combination therapy is NOT needed. 6
Critical Exception: Metallo-β-lactamase Producers
If E. coli produces NDM or other metallo-β-lactamases (MBL), ceftazidime-avibactam MUST be combined with aztreonam (ceftazidime-avibactam 2.5g IV q8h PLUS aztreonam 2g IV q8h). 7
Avibactam has NO activity against MBLs, and ceftazidime-avibactam monotherapy will fail against NDM-producing strains. 7, 8
If local epidemiology suggests MBL prevalence or rapid molecular testing indicates NDM, initiate combination therapy immediately without waiting for complete carbapenemase typing. 7
Dosing for Bacteremia
Standard dose: Ceftazidime-avibactam 2.5g IV every 8 hours (adjust for renal function). 7
For severe infections or high-inoculum bacteremia, maintain full dosing without reduction. 6
Comparative Advantage
Ceftazidime-avibactam coverage (98.7% inhibited at ≤8 mg/L) of Enterobacteriaceae exceeded meropenem (95.7% susceptible) and piperacillin-tazobactam (88.4% susceptible) in surveillance data. 2
For CRE infections, observational studies showed 64% probability of better outcomes with ceftazidime-avibactam versus colistin (95% CI 57%-71%). 6
Resistance Monitoring
Resistance to ceftazidime-avibactam in KPC-producing E. coli can emerge during treatment (3.7%-8.1% of treated patients) through KPC Ω-loop mutations. 6, 9
Certain KPC-2 variants with single amino acid substitutions at positions 164 or 179 demonstrated MICs >8 mg/L despite avibactam presence. 9
Monitor clinical response and repeat cultures if bacteremia persists beyond 48-72 hours. 6