Abstract
Background
Ceftolozane is a cephalosporin specifically developed to have enhanced antibacterial activity against P. aeruginosa. Combined with tazobactam, it was approved by FDA and EMA for complicated urinary tract and intraabdominal infections, as well as hospital-acquired/ventilator-associated bacterial pneumonia. We evaluated the activity of ceftolozane/tazobactam (C/T) against P. aeruginosa isolates collected as part of the global SMART surveillance program in 10 countries in Latin America.
Methods
In 2017-2019, 41 clinical labs each collected up to 250 consecutive gram-negative pathogens per year from various infection sources. A total of 21,864 isolates were collected, of which 3,335 (15.3%) were P. aeruginosa. MICs were determined using CLSI broth microdilution and breakpoints. C/T-nonsusceptible (NS) P. aeruginosa isolates were screened for genes encoding β-lactamases.
Results
The table shows the antimicrobial susceptibility of P. aeruginosa and β-lactam-NS subsets.
C/T was active against 85.9% of all collected P. aeruginosa, with lowest activity against isolates collected in Chile and Venezuela, where 28.0% and 23.2% of isolates, respectively, carried carbapenemases, and highest activity against isolates from Ecuador and Guatemala, where 2.2% and 4.2%, respectively, were carbapenemase-positive. Substantial variability in the activity of C/T and comparators was observed among β-lactam-NS subsets. In aggregate, however, C/T remained active against 59.9% of all meropenem-NS P. aeruginosa isolates from Latin America (n=1,101), 57.3% of piperacillin/tazobactam-NS isolates (n=1054), 48.9% of cefepime-NS isolates (n=895), and 50.3% of ceftazidime-NS isolates (n=937). Conversely, other common β-lactams (meropenem, cefepime, ceftazidime, and piperacillin/tazobactam) remained active against 8-38% of these resistant isolates.
Results Table
Conclusion
C/T showed the highest activity against P. aeruginosa among the tested β-lactam antibiotics. While amikacin showed similar or better activity in vitro, its toxicities severely limit its clinical use. Given the desirability of β-lactams among clinicians, C/T represents an important option in the treatment of infections caused by P. aeruginosa in Latin America.
Disclosures
Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Meredith Hackel, PhD MPH, IHMA (Employee)Pfizer, Inc. (Independent Contractor) C. Andrew DeRyke, PharmD, Merck & Co., Inc. (Employee, Shareholder) Jacquleine Pavía, MSc, Merck & Co, Inc (Employee) Fakhar Siddiqui, PhD, Merck & Co, Inc (Employee) Katherine Young, MS, Merck (Employee) Mary Motyl, PhD, Merck & Co., Inc. (Employee, Shareholder) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)