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Efficacy of ceftolozane/tazobactam against urinary tract and intra-abdominal infections caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae: a pooled analysis of Phase 3 clinical trials.
J Antimicrob Chemother. 2017 01; 72(1):268-272.JA

Abstract

OBJECTIVES

The increase in infections caused by drug-resistant ESBL-producing Enterobacteriaceae (ESBL-ENT) is a global concern. The characteristics and outcomes of patients infected with ESBL-ENT were examined in a pooled analysis of Phase 3 clinical trials of ceftolozane/tazobactam in patients with complicated urinary tract infections (ASPECT-cUTI) and complicated intra-abdominal infections (ASPECT-cIAI).

METHODS

Trials were randomized and double blind. The ASPECT-cUTI regimen was 7 days of either intravenous ceftolozane/tazobactam (1.5 g) every 8 h or levofloxacin (750 mg) once daily. The ASPECT-cIAI regimen was 4-14 days of either intravenous ceftolozane/tazobactam (1.5 g) plus metronidazole (500 mg) or meropenem (1 g) every 8 h. Baseline cultures were obtained in both indications. Enterobacteriaceae were selected for ESBL characterization based on predefined criteria and were verified genotypically. Outcomes were assessed at the test-of-cure visit 5-9 days post-therapy in ASPECT-cUTI and 24-32 days post-randomization in ASPECT-cIAI among microbiologically evaluable (ME) patients.

RESULTS

Of 2076 patients randomized, 1346 were included in the pooled ME population and 150 of 1346 (11.1%) had ESBL-ENT at baseline. At US FDA/EUCAST breakpoints of ≤2/≤1 mg/L, 81.8%/72.3% of ESBL-ENT (ESBL-Escherichia coli, 95%/88.1%; ESBL-Klebsiella pneumoniae, 56.7%/36.7%) were susceptible to ceftolozane/tazobactam versus 25.3%/24.1% susceptible to levofloxacin and 98.3%/98.3% susceptible to meropenem at CLSI/EUCAST breakpoints. Clinical cure rates for ME patients with ESBL-ENT were 97.4% (76/78) for ceftolozane/tazobactam [ESBL-E. coli, 98.0% (49 of 50); ESBL-K. pneumoniae, 94.4% (17 of 18)], 82.6% (38 of 46) for levofloxacin and 88.5% (23 of 26) for meropenem.

CONCLUSIONS

Randomized trial data demonstrated high clinical cure rates with ceftolozane/tazobactam treatment of cIAI and cUTI caused by ESBL-ENT.

Authors+Show Affiliations

Merck & Co., Inc., Kenilworth, NJ, USA myra.popejoy@merck.com.Center for Clinical Research, University of Queensland, Brisbane, Australia.Merck & Co., Inc., Kenilworth, NJ, USA.Merck & Co., Inc., Kenilworth, NJ, USA.Merck & Co., Inc., Kenilworth, NJ, USA.Merck & Co., Inc., Kenilworth, NJ, USA.Merck & Co., Inc., Kenilworth, NJ, USA.Merck & Co., Inc., Kenilworth, NJ, USA.Merck & Co., Inc., Kenilworth, NJ, USA.Detroit Medical Center and Department of Medicine, Wayne State University, Detroit, MI, USA.

Pub Type(s)

Clinical Trial, Phase III
Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

27707990

Citation

Popejoy, Myra W., et al. "Efficacy of Ceftolozane/tazobactam Against Urinary Tract and Intra-abdominal Infections Caused By ESBL-producing Escherichia Coli and Klebsiella Pneumoniae: a Pooled Analysis of Phase 3 Clinical Trials." The Journal of Antimicrobial Chemotherapy, vol. 72, no. 1, 2017, pp. 268-272.
Popejoy MW, Paterson DL, Cloutier D, et al. Efficacy of ceftolozane/tazobactam against urinary tract and intra-abdominal infections caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae: a pooled analysis of Phase 3 clinical trials. J Antimicrob Chemother. 2017;72(1):268-272.
Popejoy, M. W., Paterson, D. L., Cloutier, D., Huntington, J. A., Miller, B., Bliss, C. A., Steenbergen, J. N., Hershberger, E., Umeh, O., & Kaye, K. S. (2017). Efficacy of ceftolozane/tazobactam against urinary tract and intra-abdominal infections caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae: a pooled analysis of Phase 3 clinical trials. The Journal of Antimicrobial Chemotherapy, 72(1), 268-272.
Popejoy MW, et al. Efficacy of Ceftolozane/tazobactam Against Urinary Tract and Intra-abdominal Infections Caused By ESBL-producing Escherichia Coli and Klebsiella Pneumoniae: a Pooled Analysis of Phase 3 Clinical Trials. J Antimicrob Chemother. 2017;72(1):268-272. PubMed PMID: 27707990.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Efficacy of ceftolozane/tazobactam against urinary tract and intra-abdominal infections caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae: a pooled analysis of Phase 3 clinical trials. AU - Popejoy,Myra W, AU - Paterson,David L, AU - Cloutier,Daniel, AU - Huntington,Jennifer A, AU - Miller,Benjamin, AU - Bliss,Caleb A, AU - Steenbergen,Judith N, AU - Hershberger,Ellie, AU - Umeh,Obiamiwe, AU - Kaye,Keith S, Y1 - 2016/10/05/ PY - 2016/04/19/received PY - 2016/08/05/revised PY - 2016/08/10/accepted PY - 2016/10/7/pubmed PY - 2017/8/15/medline PY - 2016/10/7/entrez SP - 268 EP - 272 JF - The Journal of antimicrobial chemotherapy JO - J Antimicrob Chemother VL - 72 IS - 1 N2 - OBJECTIVES: The increase in infections caused by drug-resistant ESBL-producing Enterobacteriaceae (ESBL-ENT) is a global concern. The characteristics and outcomes of patients infected with ESBL-ENT were examined in a pooled analysis of Phase 3 clinical trials of ceftolozane/tazobactam in patients with complicated urinary tract infections (ASPECT-cUTI) and complicated intra-abdominal infections (ASPECT-cIAI). METHODS: Trials were randomized and double blind. The ASPECT-cUTI regimen was 7 days of either intravenous ceftolozane/tazobactam (1.5 g) every 8 h or levofloxacin (750 mg) once daily. The ASPECT-cIAI regimen was 4-14 days of either intravenous ceftolozane/tazobactam (1.5 g) plus metronidazole (500 mg) or meropenem (1 g) every 8 h. Baseline cultures were obtained in both indications. Enterobacteriaceae were selected for ESBL characterization based on predefined criteria and were verified genotypically. Outcomes were assessed at the test-of-cure visit 5-9 days post-therapy in ASPECT-cUTI and 24-32 days post-randomization in ASPECT-cIAI among microbiologically evaluable (ME) patients. RESULTS: Of 2076 patients randomized, 1346 were included in the pooled ME population and 150 of 1346 (11.1%) had ESBL-ENT at baseline. At US FDA/EUCAST breakpoints of ≤2/≤1 mg/L, 81.8%/72.3% of ESBL-ENT (ESBL-Escherichia coli, 95%/88.1%; ESBL-Klebsiella pneumoniae, 56.7%/36.7%) were susceptible to ceftolozane/tazobactam versus 25.3%/24.1% susceptible to levofloxacin and 98.3%/98.3% susceptible to meropenem at CLSI/EUCAST breakpoints. Clinical cure rates for ME patients with ESBL-ENT were 97.4% (76/78) for ceftolozane/tazobactam [ESBL-E. coli, 98.0% (49 of 50); ESBL-K. pneumoniae, 94.4% (17 of 18)], 82.6% (38 of 46) for levofloxacin and 88.5% (23 of 26) for meropenem. CONCLUSIONS: Randomized trial data demonstrated high clinical cure rates with ceftolozane/tazobactam treatment of cIAI and cUTI caused by ESBL-ENT. SN - 1460-2091 UR - https://www.unboundmedicine.com/medline/citation/27707990/Efficacy_of_ceftolozane/tazobactam_against_urinary_tract_and_intra_abdominal_infections_caused_by_ESBL_producing_Escherichia_coli_and_Klebsiella_pneumoniae:_a_pooled_analysis_of_Phase_3_clinical_trials_ L2 - https://academic.oup.com/jac/article-lookup/doi/10.1093/jac/dkw374 DB - PRIME DP - Unbound Medicine ER -