Helio Sader, MD, PhD, FIDSA
Senior Director
JMI Laboratories, Inc.
North Liberty, IA
Disclosure information not submitted.
Cecilia Carvalhaes, MD, PhD
Associate Director
JMI Laboratories
North Liberty, Iowa, United States
Disclosure information not submitted.
Mariana Castanheira, PhD
CSO
JMI Laboratories
North Liberty, Iowa, United States
Disclosure information not submitted.
Title: Antimicrobial Susceptibility of Pseudomonas aeruginosa and Klebsiella pneumoniae Causing Pneumonia
Background:
Antimicrobial treatment for pneumonia caused by P. aeruginosa (PSA) and K. pneumoniae (KPN) are very limited in some geographic regions. We evaluated the in vitro activity of ceftazidime-avibactam (CAZ-AVI), ceftolozane-tazobactam (C-T), meropenem-vaborbactam (MEM-VAB), and comparator agents against a large collection of contemporary PSA and KPN isolates causing pneumonia in United States (US) medical centers.
Methods:
2,457 PSA and 1,078 KPN isolates were consecutively collected from patients hospitalized with pneumonia in 73 US medical centers (36 states) in 2018-2020. MICs were determined by the reference broth microdilution method. KPNs with an elevated MIC for broad-spectrum cephalosporins were screened for beta-lactamases by whole genome sequencing.
Results:
CAZ-AVI (96.5% susceptible [S]) and C-T (96.3%S) were the most active compounds against PSA and retained activity against MEM-nonsusceptible (MEM-NS; 86.0-86.3%S) and piperacillin-tazobactam-NS (PIP-TAZ-NS; 85.0-85.2%S) isolates; 40.4% of C-T-NS PSA were CAZ-AVI-S and 38.4% of CAZ-AVI-NS PSA were C-T-S. PSA S rates for MEM, PIP-TAZ, and tobramycin were 77.0%, 77.5%, and 93.7%, respectively. The most active agents against KPN were CAZ-AVI (99.7%S), MEM-VAB (99.6%S), amikacin (AMK; 97.9%S), and MEM (95.4%S). C-T was active against 91.2% of KPN and showed limited activity against ESBL- and carbapenemase (CPE)-producers (75.7%S and 2.6%S, respectively). Among KPN, 16.4% were ESBL-producers (excluding CPE co-producers) and 4.3% were CPE-producers. The most common ESBLs were CTX-M-type (88.7% of isolates; 93.0% of them were CTX-M-15) and OXA-1/30 (55.4%); 57.1% produced >1 ESBL, mainly CTX-M-15+OXA-1/30 (53.1% of ESBL-producers). The most common CPE among the KPNs were KPC-3 (52.2% of CPE-producers) and KPC-2 (37.0%). Only 1 MBL-producer was observed (NDM-5). The most active agents against ESBL producers were CAZ-AVI (100.0%S), MEM-VAB (99.3%S), MEM (96.0%S), and AMK (96.0%S). CAZ-AVI and MEM-VAB were active against 93.5% of CPE-producers.
Conclusions:
CAZ-AVI and C-T were the most active compounds against PSA (96.3-96.5%S). CAZ-AVI and MEM-VAB were the most active compounds against KPN (99.6-99.7%S). Recently approved beta-lactam inhibitor combinations markedly improved the armamentarium against MDR PSA and KPN causing pneumonia in US hospitals.