Abstract
BackgroundCeftolozane/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.ResultsC/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.ConclusionData 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.
Highlights
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
Against individual species of Enterobacterales, C/T was most active against Proteus mirabilis (99.2% susceptible), Klebsiella oxytoca (97.8%), and Escherichia coli (97.2%)
C/T was active against intensive care units (ICUs) and non-ICU isolates of P. aeruginosa (96.0 and 96.7% susceptible, respectively) and of Enterobacterales (91.3 and 92.6%, respectively)
Summary
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. Gram-negative bacilli, including Pseudomonas aeruginosa and Enterobacterales are frequent and important pathogens in patients with hospital-acquired and ventilator-associated pneumonia. C/T is approved in 70 countries, including the United States for the treatment of patients with hospital-acquired and ventilator-associated bacterial pneumonia (3 g every 8 h), and in 75 countries for the treatment of complicated intraabdominal infection (1.5 g every 8 h, used in combination with metronidazole), and complicated urinary tract infection (1.5 g every 8 h), including pyelonephritis [10]. C/T is an important agent for the treatment of patients with severe infections due to multidrug-resistant (MDR) P. aeruginosa [11], which is a common phenotype in this pathogen in many countries, including the United States [4, 6, 12,13,14]. C/T may provide an alternative to carbapenems for the treatment of infections caused by Gram-negative bacilli, including extendedspectrum β-lactamase (ESBL)-producing isolates [15,16,17]
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