Ceftolozane/tazobactam activity tested against aerobic Gram-negative organisms isolated from intra-abdominal and urinary tract infections in European and United States hospitals (2012)
Introduction
Ceftolozane is a novel cephalospirin that is currently under clinical development in combination with the β-lactamase inhibitor tazobactam for treatment of complicated intra-abdominal infections (IAI; http://clinicaltrials.gov, identifiers NCT01147640, NCT01445665 and NCT01445678), complicated urinary tract infections (UTI; NCT01345955, NCT01345929 and NCT00921024) and ventilator-associated pneumonia (VAP; NCT01853982). This compound has shown remarkable stability against various resistance mechanisms employed by Pseudomonas aeruginosa to other β-lactam compounds, and has demonstrated activity against ceftazidime-resistant, as well as meropenem-resistant strains.1, 2, 3
Ceftolozane has also demonstrated good activity against members of the Enterobacteriaceae, but similar to other established oxyimino-cephalosporins, its activity can be compromised by production of extended-spectrum β-lactamases (ESBLs), carbapenemases and, to some degree, hyperproduction of AmpC β-lactamases. Thus, the addition of tazobactam, a well-established β-lactamase inhibitor, broadens the spectrum of ceftolozane activity to include many ESBL-producing organisms as well as some anaerobes, such as Bacteroides spp.4, 5, 6
In this study, we evaluated the activity of ceftolozane/tazobactam and comparator agents tested against Gram-negative aerobic bacteria causing IAI and healthcare-associated UTI (HCA-UTI) in United States (USA) and European hospitals during 2012.
Section snippets
Bacterial isolates
The organism collection included only aerobic Gram-negative bacilli collected from hospitalized patients with a diagnosis of IAI or HCA-UTI. The organisms were consecutively collected from January to December 2012 from 28 medical centers located in the USA and 31 medical centers in 15 European countries by the Program to Assess Ceftolozane/Tazobactam Susceptibility (PACTS). A total of 809 organisms from IAI and 2474 organisms from UTI were included in this investigation. Species identification
Intra-abdominal infections
The aerobic Gram-negative bacilli most frequently isolated from IAI were E. coli (42.2%), K. pneumoniae (15.6%) and P. aeruginosa (14.2%). Ceftolozane/tazobactam was very active (MIC50/90, 0.25/0.5 mg/L) against 341 E. coli isolates and retained activity against many of the 16 (4.7%) MDR isolates (MIC50/90, 0.5/>32 mg/L; 75.0% of isolates inhibited at an MIC of ≤8 mg/L) and 38 (11.1%) ESBL-phenotype strains (MIC50/90, 0.5/32 mg/L; 86.8% of isolates inhibited at an MIC of ≤8 mg/L; Table 1).
Discussion
Most complicated IAI are polymicrobial, and enteric Gram-negative bacilli, Gram-positive cocci and anaerobic organisms are the predominant pathogens.11, 12 E. coli is the most common organism, but other Enterobacteriaceae, such as Klebsiella spp. and Enterobacter spp., and P. aeruginosa are also frequently isolated from patients with complicated IAI. Obligate anaerobic organisms are important components of most IAI, even though microbiology laboratories may not recover or report these
Acknowledgments
This study was funded by research grants from Cubist Pharmaceuticals (Lexington, MA, USA).
References (19)
- et al.
Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance
Clin Microbiol Infect
(2012) - et al.
Intra-abdominal infections
Surg Clin North Am
(2009) - et al.
Diagnosis and management of urinary tract infection and pyelonephritis
Emerg Med Clin North Am
(2011) - et al.
Risk factors for multidrug resistance in nosocomial bacteremia caused by extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae
Microb Drug Resist
(2012) - et al.
In vitro potency of CXA-101, a novel cephalosporin, against Pseudomonas aeruginosa displaying various resistance phenotypes, including multidrug resistance
Antimicrob Agents Chemother
(2010) - et al.
Antimicrobial activity of ceftolozane/tazobactam tested against Enterobacteriaceae and Pseudomonas aeruginosa with various resistance patterns isolated in U.S. hospitals (2011–2012)
Antimicrob Agents Chemother
(2013) - et al.
Antimicrobial activity of CXA-101, a novel cephalosporin tested in combination with tazobactam against Enterobacteriaceae, Pseudomonas aeruginosa, and Bacteroides fragilis strains having various resistance phenotypes
Antimicrob Agents Chemother
(2011) - et al.
In vivo activities of ceftolozane, a new cephalosporin, with and without tazobactam against Pseudomonas aeruginosa and Enterobacteriaceae, including strains with extended-spectrum beta-lactamases, in the thighs of neutropenic mice
Antimicrob Agents Chemother
(2013) - et al.
Pharmacological basis of β-lactamase inhibitor therapeutics: tazobactam in combination with ceftolozane
Antimicrob Agents Chemother
(2013)