Evaluation of in vitro activity of ceftolozane-tazobactam against recent clinical bacterial isolates from Brazil - the EM200 study

Abstract

Background: The emergence of antibiotic resistance is increasing and there are few effective antibiotics to treat infections caused by resistant and multidrug resistant bacterial pathogens. This study aimed to evaluate the in vitro activity of ceftolozane-tazobactam against clinical bacterial isolates from Brazil.

Methods: A total of 673 Gram-negative bacterial isolates including Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and other Enterobacterales collected from 2016 to 2017 were tested, most of them isolated from patients in intensive care units. Minimum inhibitory concentrations (MIC_50/90) were determined by broth microdilution for amikacin, aztreonam, cefepime, cefotaxime, cefoxitin, ceftolozane-tazobactam, ceftazidime, ceftriaxone, ciprofloxacin, colistin, ertapenem, imipenem, levofloxacin, meropenem, and piperacillin-tazobactam using dried panels. Antimicrobial susceptibility results were interpreted according to Clinical and Laboratory Standards Institute criteria.

Results: Susceptibility rates to ceftolozane-tazobactam ranged from 40.4% to 94.9%. P. aeruginosa susceptibility rate to ceftolozane-tazobactam was 84.9% (MIC_50/90, 1/16μg/mL) and 99.2% to colistin. For E. coli, ceftolozane-tazobactam inhibited 94.9% (MIC_50/90, 0.25/1μg/mL) of the microorganisms. The susceptibility rate of K. pneumoniae to ceftolozane-tazobactam was 40.4% (MIC_50/90, 16/>32μg/mL). Other Enterobacterales have shown susceptibility rates of 81.1% (MIC_50/90, 0.5/16μg/mL) to ceftolozane-tazobactam, 93.9% to meropenem, 90.9% to amikacin (90.9%), and 88.6% to ertapenem. In non-carbapenemase producing isolates, AmpC mutations were found three isolates.

Conclusions: Ceftolozane-tazobactam has shown relevant activity against a large variety of the analyzed microorganisms collected from multiple centers in Brazil, showing promising results even in multidrug resistant strains.

Keywords: Antimicrobial Resistance; Antimicrobial Susceptibility Test; Ceftolozane; Drug Resistance; Enterobacterales; Pseudomonas aeruginosa; tazobactam.

Fig. 1

Frequency distribution (n) of ceftolozane–tazobactam at each MIC (μg/mL) for 132 Pseudomonas aeruginosa from Brazil.

Fig. 2

Frequency distribution (n) of ceftolozane–tazobactam at each MIC (μg/mL) for 216 Escherichia coli from Brazil.

Fig. 3

Frequency distribution (n) of ceftolozane–tazobactam at each MIC (μg/mL) for 193 Klebsiella pneumoniae from Brazil.

Fig. 4

Frequency distribution (n) of ceftolozane–tazobactam at each MIC (μg/mL) for 132 other* Enterobacterales from Brazil. * Other Enterobacterales consist of (n): Klebsiella aerogenes (3); E. asburiae (1); E. cloacae (38); Klebsiella oxytoca (11); K. variicola (4); Morganella morganii (1); Proteus mirabilis (72); P. vulgaris (1); Providencia rettgeri (1).