Dataset Information

Activity of ceftolozane/tazobactam against Gram-negative isolates from patients with lower respiratory tract infections - SMART United States 2018-2019.

ABSTRACT:

Background

Ceftolozane/tazobactam (C/T) is approved in 70 countries, including the United States, for the treatment of patients with hospital-acquired and ventilator-associated bacterial pneumonia caused by susceptible Gram-negative pathogens. C/T is of particular importance as an agent for the treatment of multidrug-resistant (MDR) Pseudomonas aeruginosa infections. The current study summarizes 2018-2019 data from the United States on lower respiratory tract isolates of Gram-negative bacilli from the SMART global surveillance program. The CLSI reference broth microdilution method was used to determine in vitro susceptibility of C/T and comparators against isolates of P. aeruginosa and Enterobacterales.

Results

C/T inhibited 96.0% of P. aeruginosa (n = 1237) at its susceptible MIC breakpoint (≤4 μg/ml), including > 85% of meropenem-nonsusceptible and piperacillin/tazobactam (P/T)-nonsusceptible isolates and 76.2% of MDR isolates. Comparator agents demonstrated lower activity than C/T against P. aeruginosa: meropenem (74.8% susceptible), cefepime (79.2%), ceftazidime (78.5%), P/T (74.4%), and levofloxacin (63.1%). C/T was equally active against ICU (96.0% susceptible) and non-ICU (96.7%) isolates of P. aeruginosa. C/T inhibited 91.8% of Enterobacterales (n = 1938) at its susceptible MIC breakpoint (≤2 μg/ml); 89.5% of isolates were susceptible to cefepime and 88.0% susceptible to P/T. 67.1 and 86.5% of extended-spectrum β-lactamase (ESBL) screen-positive isolates of Klebsiella pneumoniae (n = 85) and Escherichia coli (n = 74) and 49.6% of MDR Enterobacterales were susceptible to C/T. C/T was equally active against ICU (91.3% susceptible) and non-ICU (92.6%) Enterobacterales isolates.

Conclusion

Data from the current study support the use of C/T as an important treatment option for lower respiratory tract infections including those caused by MDR P. aeruginosa.

SUBMITTER: Karlowsky JA

PROVIDER: S-EPMC7936229 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The activities of ceftolozane-tazobactam and comparator agents against organisms deemed to be the cause of pneumonia among patients hospitalized in the United States during 2013 to 2015 were evaluated. Organisms included 1,576 Pseudomonas aeruginosa and 2,362 Enterobacteriaceae isolates susceptibility tested using reference broth microdilution methods. Ceftolozane-tazobactam, cefepime, ceftazidime, meropenem, and piperacillin-tazobactam inhibited 96.3%, 84.8%, 83.5%, 80.0%, and 78.6%, respectively, of the P. aeruginosa isolates. Ceftolozane-tazobactam inhibited 77.5 to 85.1% of isolates nonsusceptible to antipseudomonal ?-lactams and 86.6% and 71.0% of the 372 (23.6% overall) multidrug- and 155 (9.8%) extensively drug-resistant isolates tested. The activity of this combination was greater than those of other ?-lactams evaluated against P. aeruginosa groups across all U.S. census divisions. Ceftolozane-tazobactam was active against 90.6% of the Enterobacteriaceae, being less active than only meropenem (95.6% susceptible) among the ?-lactams evaluated. Against 145 Escherichia coli and Klebsiella pneumoniae isolates carrying extended-spectrum-?-lactamase (ESBL)-encoding genes without carbapenemases, ceftolozane-tazobactam inhibited 82.8% of these isolates and was more active than cefepime and piperacillin-tazobactam (15.2% and 74.3% susceptible, respectively). ESBL genes included in this analysis were mainly blaCTX-M-15-like (89 isolates) and blaCTX-M-14-like (22) genes but also blaSHV (31) and blaTEM (3). Ceftolozane-tazobactam also displayed activity (84.6% susceptible) against 13 isolates harboring acquired AmpC genes. All ?-lactams displayed limited activity against blaKPC-carrying isolates. Ceftolozane-tazobactam was the most active ?-lactam tested against P. aeruginosa isolates from isolates that were the probable cause of pneumonia and displayed in vitro activity against Enterobacteriaceae, including isolates resistant to cephalosporins and carrying ESBL genes.

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