Abstract
Background
Ceftolozane/tazobactam (C/T) is an antipseudomonal cephalosporin combined with a β-lactamase inhibitor approved by FDA and EMA for complicated urinary tract and intraabdominal infections, and hospital-acquired and ventilator-associated bacterial pneumonia. We evaluated the activity of C/T against isolates collected from patients ≥65 years old as part of the SMART surveillance program in Asia/Pacific.
Methods
In 2016-2018, 49 clinical laboratories in Australia, Hong Kong, Malaysia, New Zealand, Philippines, Singapore, Korea, Taiwan, Thailand, and Vietnam each collected up to 250 consecutive gram-negative pathogens per year. Susceptibility was determined using CLSI broth microdilution and breakpoints. C/T-nonsusceptible (NS) Enterobacterales (ENT) and P. aeruginosa (PA) isolates were screened by PCR and sequenced for genes encoding β-lactamases (except ENT from 1 site in Taiwan).
Results
2082 PA (68.3% lower respiratory tract, 12.7% intraabdominal, 15.1% urinary tract, and 3.0% bloodstream infection isolates) and 8181 ENT isolates (29.8%, 27.8%, 32.5%, and 9.2%, respectively) were collected from patients ≥65 years old. In vitro susceptibility of PA and ENT stratified by length of hospital stay at time of specimen collection (LOS) is shown (Table).
C/T maintained activity against 75.5% of 518 P/T-NS, 67.9% of 395 cefepime-NS, and 71.6% of 377 meropenem-NS PA isolates. Among 136 C/T-NS PA isolates, 44.9% carried metallo-β-lactamases (MBL), 0.7% KPC, 1.5% GES carbapenemases, 5.9% only ESBL, and in 47.1% no acquired β-lactamases were detected. Among 878 characterized C/T-NS ENT, 14.1% carried MBL, 5.2% KPC, 3.3% OXA-48-like carbapenemases, and 53.5% AmpC and/or ESBL; no acquired β-lactamases were detected in 23.8% of isolates, of which 89.5% were species with intrinsic AmpC.
Table
Conclusion
Susceptibility of PA and ENT to all studied agents was lower for isolates collected ≥48 than < 48 hours post-admission. C/T was active against >92% of PA in both strata, 7-29 percentage points higher than the studied comparators except amikacin, and against >84% of ENT, 4-30% higher than the comparators except meropenem and amikacin. C/T is a potential new treatment option for older patients with infections caused by ENT and PA in Asia/Pacific.
Disclosures
Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Wei-Ting Chen, MD, Merck, Sharp & Dohme, Taiwan (Employee) Yivonne Khoo, PhD, Merck, Sharp & Dohme, Malaysia (Employee) Kanchan Balwani, MBBS, MS, Merck, Sharp & Dohme, Hong Kong (Employee) Katherine Young, MS, Merck & Co., Inc. (Employee, Shareholder)Merck & Co., Inc. (Employee, Shareholder) Mary Motyl, PhD, Merck & Co, Inc (Employee, Shareholder) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)
Neisseria gonorrhoeae strains isolated in Hong Kong: in vitro susceptibility to 13 antibiotics.