Helio Sader, MD, PhD, FIDSA
Senior Director
JMI Laboratories, Inc.
North Liberty, IA
Disclosure information not submitted.
Mariana Castanheira, PhD
CSO
JMI Laboratories
North Liberty, Iowa, United States
Disclosure information not submitted.
Rodrigo Mendes, PhD
Director
JMI Laboratories
North Liberty, Iowa, United States
Disclosure information not submitted.
Title: Ceftazidime-Avibactam Activity against Gram-Negative Bacteria from Bloodstream Infections
Background:
The most significant changes in the etiology of bloodstream infections (BSIs) in recent years has been the resistance patterns of Gram-negative bacteria (GNB). We evaluated the antimicrobial susceptibility of GNB causing BSI in United States (US) hospitals.
Methods:
3,951 GNB, including 3,529 Enterobacterales (ENT), 360 P. aeruginosa (PSA) and 62 A. baumannii (ACB) isolates, were consecutively collected (1/patient) from patients with BSI in 72 US medical centers in 2019-2020. Isolates were susceptibility tested by broth microdilution method in a monitoring laboratory. Beta-lactamase screening was performed by whole genome sequencing on ENT with decreased susceptibility to broad-spectrum cephalosporins.
Results:
The most active agents against ENT were ceftazidime-avibactam (CAZ-AVI; 99.9% susceptible [S]), meropenem-vaborbactam (MEM-VAB; 99.8%S), amikacin (AMK, 99.4%S) and MEM (99.1%S). CAZ-AVI retained potent activity against ESBL producers (n=364; 98.9%S) and multidrug-resistant (MDR) ENT (n=270; 98.1%S). ENT susceptibility to piperacillin-tazobactam (PIP-TAZ), ceftriaxone and levofloxacin were 92.2%, 83.5% and 79.1%, respectively. Ceftolozane-tazobactam (C-T) was active against 95.5% of ENT, but showed limited activity against ESBL producers (84.1%S), MDR ENT (68.9%S) and E. cloacae (n=318; 85.8%S). Only 5 ENT isolates (0.14%) were CAZ-AVI-R, 4 NDM producers and a K. pneumoniae isolate carrying blaKPC-2-like with a mutation in the Ω-loop region of the KPC protein. An ESBL gene was identified in 10.3% of ENT and 46.2% of them had >=2 ESBL genes. The most common ESBL was CTX-M-type (n=327; 89.8% of ESBL producers), mainly CTX-M-15 (n=250), followed by OXA-1/30 (n=163; 44.8% of ESBL producers). CAZ-AVI (96.4%S) and C-T (97.2%S) were the most active beta-lactams against PSA and retained activity against MEM-non-S PSA (77.6% and 79.6% S to CAZ-AVI and C-T, respectively). PSA susceptibility to PIP-TAZ, MEM and cefepime was 85.0%, 86.4% and 88.9%, respectively. Half of C-T-non-S PSA isolates were CAZ-AVI-S and 61.5% of CAZ-AVI-non-S PSA isolates were C-T-S. ACB susceptibility to PIP-TAZ, MEM and AMK were 67.2%, 85.5% and 91.9%, respectively.
Conclusions:
CAZ-AVI showed potent in vitro activity and broad spectrum against ENT (99.9%S) and PSA (96.4%) isolated from patients with BSI from US hospitals.