PMID- 25670823 OWN - NLM STAT- MEDLINE DCOM- 20160120 LR - 20220331 IS - 1537-6591 (Electronic) IS - 1058-4838 (Print) IS - 1058-4838 (Linking) VI - 60 IP - 10 DP - 2015 May 15 TI - Ceftolozane/Tazobactam Plus Metronidazole for Complicated Intra-abdominal Infections in an Era of Multidrug Resistance: Results From a Randomized, Double-Blind, Phase 3 Trial (ASPECT-cIAI). PG - 1462-71 LID - 10.1093/cid/civ097 [doi] AB - BACKGROUND: Increasing antimicrobial resistance among pathogens causing complicated intra-abdominal infections (cIAIs) supports the development of new antimicrobials. Ceftolozane/tazobactam, a novel antimicrobial therapy, is active against multidrug-resistant Pseudomonas aeruginosa and most extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. METHODS: ASPECT-cIAI (Assessment of the Safety Profile and Efficacy of Ceftolozane/Tazobactam in Complicated Intra-abdominal Infections) was a prospective, randomized, double-blind trial. Hospitalized patients with cIAI received either ceftolozane/tazobactam (1.5 g) plus metronidazole (500 mg) every 8 hours or meropenem (1 g) every 8 hours intravenously for 4-14 days. The prospectively defined objectives were to demonstrate statistical noninferiority in clinical cure rates at the test-of-cure visit (24-32 days from start of therapy) in the microbiological intent-to-treat (primary) and microbiologically evaluable (secondary) populations using a noninferiority margin of 10%. Microbiological outcomes and safety were also evaluated. RESULTS: Ceftolozane/tazobactam plus metronidazole was noninferior to meropenem in the primary (83.0% [323/389] vs 87.3% [364/417]; weighted difference, -4.2%; 95% confidence interval [CI], -8.91 to .54) and secondary (94.2% [259/275] vs 94.7% [304/321]; weighted difference, -1.0%; 95% CI, -4.52 to 2.59) endpoints, meeting the prespecified noninferiority margin. In patients with ESBL-producing Enterobacteriaceae, clinical cure rates were 95.8% (23/24) and 88.5% (23/26) in the ceftolozane/tazobactam plus metronidazole and meropenem groups, respectively, and 100% (13/13) and 72.7% (8/11) in patients with CTX-M-14/15 ESBLs. The frequency of adverse events (AEs) was similar in both treatment groups (44.0% vs 42.7%); the most common AEs in either group were nausea and diarrhea. CONCLUSIONS: Treatment with ceftolozane/tazobactam plus metronidazole was noninferior to meropenem in adult patients with cIAI, including infections caused by multidrug-resistant pathogens. CLINICAL TRIALS REGISTRATION: NCT01445665 and NCT01445678. CI - (c) The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. FAU - Solomkin, Joseph AU - Solomkin J AD - Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio. FAU - Hershberger, Ellie AU - Hershberger E AD - Cubist Pharmaceuticals, Lexington, Massachusetts. FAU - Miller, Benjamin AU - Miller B AD - Cubist Pharmaceuticals, Lexington, Massachusetts. FAU - Popejoy, Myra AU - Popejoy M AD - Cubist Pharmaceuticals, Lexington, Massachusetts. FAU - Friedland, Ian AU - Friedland I AD - Cubist Pharmaceuticals, Lexington, Massachusetts. FAU - Steenbergen, Judith AU - Steenbergen J AD - Cubist Pharmaceuticals, Lexington, Massachusetts. FAU - Yoon, Minjung AU - Yoon M AD - Cubist Pharmaceuticals, Lexington, Massachusetts. FAU - Collins, Sylva AU - Collins S AD - Cubist Pharmaceuticals, Lexington, Massachusetts. FAU - Yuan, Guojun AU - Yuan G AD - Cubist Pharmaceuticals, Lexington, Massachusetts. FAU - Barie, Philip S AU - Barie PS AD - Departments of Surgery and Medicine, Weill Cornell Medical College, New York, New York. FAU - Eckmann, Christian AU - Eckmann C AD - Department of General, Visceral and Thoracic Surgery, Academic Hospital of Medical University Hannover, Peine, Germany. LA - eng SI - ClinicalTrials.gov/NCT01445665 SI - ClinicalTrials.gov/NCT01445678 PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20150210 PL - United States TA - Clin Infect Dis JT - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America JID - 9203213 RN - 0 (Anti-Bacterial Agents) RN - 0 (Cephalosporins) RN - 0 (ceftolozane, tazobactam drug combination) RN - 140QMO216E (Metronidazole) RN - 87-53-6 (Penicillanic Acid) RN - SE10G96M8W (Tazobactam) SB - IM CIN - Clin Infect Dis. 2016 Feb 15;62(4):525-6. PMID: 26486703 CIN - Clin Infect Dis. 2016 Feb 15;62(4):526. PMID: 26486708 MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - Anti-Bacterial Agents/*administration & dosage MH - Bacterial Infections/*drug therapy/microbiology MH - Cephalosporins/*administration & dosage MH - Double-Blind Method MH - *Drug Resistance, Multiple, Bacterial MH - Drug Therapy, Combination/methods MH - Female MH - Humans MH - Intraabdominal Infections/*drug therapy/microbiology MH - Male MH - Metronidazole/*administration & dosage MH - Middle Aged MH - Penicillanic Acid/administration & dosage/*analogs & derivatives MH - Prospective Studies MH - Tazobactam MH - Treatment Outcome MH - Young Adult PMC - PMC4412191 OTO - NOTNLM OT - Enterobacteriaceae OT - ceftolozane/tazobactam OT - complicated intra-abdominal infection OT - gram-negative bacteria OT - multidrug resistance EDAT- 2015/02/12 06:00 MHDA- 2016/01/21 06:00 PMCR- 2015/02/10 CRDT- 2015/02/12 06:00 PHST- 2014/10/02 00:00 [received] PHST- 2015/02/01 00:00 [accepted] PHST- 2015/02/12 06:00 [entrez] PHST- 2015/02/12 06:00 [pubmed] PHST- 2016/01/21 06:00 [medline] PHST- 2015/02/10 00:00 [pmc-release] AID - civ097 [pii] AID - 10.1093/cid/civ097 [doi] PST - ppublish SO - Clin Infect Dis. 2015 May 15;60(10):1462-71. doi: 10.1093/cid/civ097. Epub 2015 Feb 10.