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Does moderate renal impairment affect clinical outcomes in complicated intra-abdominal and complicated urinary tract infections? Analysis of two randomized controlled trials with ceftolozane/tazobactam.
J Antimicrob Chemother. 2017 03 01; 72(3):900-905.JA

Abstract

Objectives

For reasons not well understood, antibacterials can yield lower cure rates in renally impaired patients. We explored this subject for the novel antibacterial ceftolozane/tazobactam.

Methods

ASPECT-complicated intra-abdominal infections (cIAIs) and ASPECT-complicated urinary tract infections (cUTIs) were randomized, double-blinded clinical trials. Analyses in moderate [creatinine clearance (CL CR) 30-50 mL/min] and mild/no (CL CR > 50 mL/min) renal impairment (RI) patients were pre-specified as exploratory endpoints in the statistical analysis plans. We also explored variables potentially impacting outcomes in these subgroups. Clinicaltrials.gov NCT01445665/NCT01445678 and NCT01345929/NCT01345955.

Results

At baseline, 4.5% (36/806) of cIAI patients and 7.3% (58/795) of cUTI patients had moderate RI. Moderate RI patients were older, had more comorbid conditions and had higher APACHE-II scores. In the cIAI microbiological intent-to-treat population, response rates were 48% and 69% in moderate RI patients receiving ceftolozane/tazobactam and meropenem, respectively; among moderate RI cIAI patients considered treatment failures, indeterminate responses were more frequent with ceftolozane/tazobactam (39%; 9/23) than meropenem (8%; 1/13). In the cUTI microbiological modified intent-to-treat population, response rates were 81% and 78% in moderate RI patients receiving ceftolozane/tazobactam and levofloxacin, respectively. In both studies, response rates in moderate RI patients were similar between treatment arms in microbiologically evaluable populations, which excluded indeterminate responses due to missing data/protocol deviations (cIAI: 72.7% ceftolozane/tazobactam versus 71.4% meropenem; cUTI: 87% ceftolozane/tazobactam versus 80% levofloxacin).

Conclusions

Regardless of treatment, clinical cure rates in cIAI and cUTI were lower in moderate versus mild/no RI patients. In moderate RI cIAI patients, numerical differences in response rates between treatments were attributable to imbalances in the numerical patients deemed indeterminate.

Authors+Show Affiliations

Merck Research Laboratories, Merck & Co, Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA.Department of Urology, Pediatric Urology and Andrology, Justus Liebig University Gieβen, Rudolf-Buchheim Str. 7, 35392 Gieβen, Germany.Merck Research Laboratories, Merck & Co, Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA.Merck Research Laboratories, Merck & Co, Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA.Merck Research Laboratories, Merck & Co, Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA.David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Ave, Los Angeles, CA 90095, USA. R. M. Alden Research Laboratory, 6133 Bristol Pkway #175, Santa Monica, CA 90230, USA.

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

27999024

Citation

Kullar, Ravina, et al. "Does Moderate Renal Impairment Affect Clinical Outcomes in Complicated Intra-abdominal and Complicated Urinary Tract Infections? Analysis of Two Randomized Controlled Trials With Ceftolozane/tazobactam." The Journal of Antimicrobial Chemotherapy, vol. 72, no. 3, 2017, pp. 900-905.
Kullar R, Wagenlehner FM, Popejoy MW, et al. Does moderate renal impairment affect clinical outcomes in complicated intra-abdominal and complicated urinary tract infections? Analysis of two randomized controlled trials with ceftolozane/tazobactam. J Antimicrob Chemother. 2017;72(3):900-905.
Kullar, R., Wagenlehner, F. M., Popejoy, M. W., Long, J., Yu, B., & Goldstein, E. J. (2017). Does moderate renal impairment affect clinical outcomes in complicated intra-abdominal and complicated urinary tract infections? Analysis of two randomized controlled trials with ceftolozane/tazobactam. The Journal of Antimicrobial Chemotherapy, 72(3), 900-905. https://doi.org/10.1093/jac/dkw486
Kullar R, et al. Does Moderate Renal Impairment Affect Clinical Outcomes in Complicated Intra-abdominal and Complicated Urinary Tract Infections? Analysis of Two Randomized Controlled Trials With Ceftolozane/tazobactam. J Antimicrob Chemother. 2017 03 1;72(3):900-905. PubMed PMID: 27999024.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Does moderate renal impairment affect clinical outcomes in complicated intra-abdominal and complicated urinary tract infections? Analysis of two randomized controlled trials with ceftolozane/tazobactam. AU - Kullar,Ravina, AU - Wagenlehner,Florian M, AU - Popejoy,Myra W, AU - Long,Jianmin, AU - Yu,Brian, AU - Goldstein,Ellie J C, PY - 2016/08/03/received PY - 2016/10/10/accepted PY - 2016/12/22/pubmed PY - 2017/10/11/medline PY - 2016/12/22/entrez SP - 900 EP - 905 JF - The Journal of antimicrobial chemotherapy JO - J Antimicrob Chemother VL - 72 IS - 3 N2 - Objectives: For reasons not well understood, antibacterials can yield lower cure rates in renally impaired patients. We explored this subject for the novel antibacterial ceftolozane/tazobactam. Methods: ASPECT-complicated intra-abdominal infections (cIAIs) and ASPECT-complicated urinary tract infections (cUTIs) were randomized, double-blinded clinical trials. Analyses in moderate [creatinine clearance (CL CR) 30-50 mL/min] and mild/no (CL CR > 50 mL/min) renal impairment (RI) patients were pre-specified as exploratory endpoints in the statistical analysis plans. We also explored variables potentially impacting outcomes in these subgroups. Clinicaltrials.gov NCT01445665/NCT01445678 and NCT01345929/NCT01345955. Results: At baseline, 4.5% (36/806) of cIAI patients and 7.3% (58/795) of cUTI patients had moderate RI. Moderate RI patients were older, had more comorbid conditions and had higher APACHE-II scores. In the cIAI microbiological intent-to-treat population, response rates were 48% and 69% in moderate RI patients receiving ceftolozane/tazobactam and meropenem, respectively; among moderate RI cIAI patients considered treatment failures, indeterminate responses were more frequent with ceftolozane/tazobactam (39%; 9/23) than meropenem (8%; 1/13). In the cUTI microbiological modified intent-to-treat population, response rates were 81% and 78% in moderate RI patients receiving ceftolozane/tazobactam and levofloxacin, respectively. In both studies, response rates in moderate RI patients were similar between treatment arms in microbiologically evaluable populations, which excluded indeterminate responses due to missing data/protocol deviations (cIAI: 72.7% ceftolozane/tazobactam versus 71.4% meropenem; cUTI: 87% ceftolozane/tazobactam versus 80% levofloxacin). Conclusions: Regardless of treatment, clinical cure rates in cIAI and cUTI were lower in moderate versus mild/no RI patients. In moderate RI cIAI patients, numerical differences in response rates between treatments were attributable to imbalances in the numerical patients deemed indeterminate. SN - 1460-2091 UR - https://www.unboundmedicine.com/medline/citation/27999024/Does_moderate_renal_impairment_affect_clinical_outcomes_in_complicated_intra_abdominal_and_complicated_urinary_tract_infections_Analysis_of_two_randomized_controlled_trials_with_ceftolozane/tazobactam_ L2 - https://academic.oup.com/jac/article-lookup/doi/10.1093/jac/dkw486 DB - PRIME DP - Unbound Medicine ER -