Antimicrobial Activity of Ceftolozane-Tazobactam Tested against Enterobacteriaceae and Pseudomonas aeruginosa with Various Resistance Patterns Isolated in U.S. Hospitals (2011-2012)

<jats:title>ABSTRACT</jats:title> <jats:p> Ceftolozane/tazobactam, a novel antimicrobial agent with activity against <jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Pseudomonas aeruginosa</jats:named-content> (including drug-resistant strains) and other common Gram-negative pathogens (including most extended-spectrum-β-lactamase [ESBL]-producing <jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Enterobacteriaceae</jats:named-content> strains), and comparator agents were susceptibility tested by a reference broth microdilution method against 7,071 <jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Enterobacteriaceae</jats:named-content> and 1,971 <jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. aeruginosa</jats:named-content> isolates. Isolates were collected consecutively from patients in 32 medical centers across the United States during 2011 to 2012. Overall, 15.7% and 8.9% of <jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. aeruginosa</jats:named-content> isolates were classified as multidrug resistant (MDR) and extensively drug resistant (XDR), and 8.4% and 1.2% of <jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Enterobacteriaceae</jats:named-content> were classified as MDR and XDR. No pandrug-resistant (PDR) <jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Enterobacteriaceae</jats:named-content> isolates and only one PDR <jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. aeruginosa</jats:named-content> isolate were detected. Ceftolozane/tazobactam was the most potent (MIC <jats:sub>50/90</jats:sub> , 0.5/2 μg/ml) agent tested against <jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. aeruginosa</jats:named-content> and demonstrated good activity against 310 MDR strains (MIC <jats:sub>50/90</jats:sub> , 2/8 μg/ml) and 175 XDR strains (MIC <jats:sub>50/90</jats:sub> , 4/16 μg/ml). Ceftolozane/tazobactam exhibited high overall activity (MIC <jats:sub>50/90</jats:sub> , 0.25/1 μg/ml) against <jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Enterobacteriaceae</jats:named-content> and retained activity (MIC <jats:sub>50/90</jats:sub> , 4/>32 μg/ml) against many 601 MDR strains but not against the 86 XDR strains (MIC <jats:sub>50</jats:sub> , >32 μg/ml). Ceftolozane/tazobactam was highly potent (MIC <jats:sub>50/90</jats:sub> , 0.25/0.5 μg/ml) against 2,691 <jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Escherichia coli</jats:named-content> isolates and retained good activity against most ESBL-phenotype <jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">E. coli</jats:named-content> isolates (MIC <jats:sub>50/90</jats:sub> , 0.5/4 μg/ml), but activity was low against ESBL-phenotype <jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Klebsiella pneumoniae</jats:named-content> isolates (MIC <jats:sub>50/90</jats:sub> , 32/>32 μg/ml), explained by the high rate (39.8%) of meropenem coresistance observed in this species phenotype. In summary, ceftolozane/tazobactam demonstrated high potency and broad-spectrum activity against many contemporary <jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Enterobacteriaceae</jats:named-content> and <jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. aeruginosa</jats:named-content> isolates collected in U.S. medical centers. Importantly, ceftolozane/tazobactam retained potency against many MDR and XDR strains. </jats:p>