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Multicenter, double-blind, randomized, phase II trial to assess the safety and efficacy of ceftolozane-tazobactam plus metronidazole compared with meropenem in adult patients with complicated intra-abdominal infections.
Antimicrob Agents Chemother. 2014 Sep; 58(9):5350-7.AA

Abstract

Ceftolozane-tazobactam (TOL-TAZ) is a novel antibacterial with activity against Pseudomonas aeruginosa and other common Gram-negative pathogens, including extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, that are associated with complicated intra-abdominal infections (cIAIs). This prospective, double-blind, randomized, multicenter, phase II trial assessed patient clinical and microbiological responses to and the safety of TOL-TAZ plus metronidazole compared with those of meropenem. Hospitalized adults with cIAIs that required surgical intervention were randomized (2:1) to receive intravenous (i.v.) TOL-TAZ (1.5 g [containing 1,000 mg TOL and 500 mg TAZ] every 8 h [q8h]) with or without i.v. metronidazole (500 mg q8h) or i.v. meropenem (1 g q8h) for 4 to 7 days. The primary endpoint was the clinical response at the test-of-cure visit in the microbiologically modified intent-to-treat (mMITT) and microbiologically evaluable (ME) populations. Secondary measures included the patients' microbiological response and safety. In total, 82 patients received TOL-TAZ (90.2% with metronidazole), and 39 received meropenem. For the mMITT population, clinical cure was seen in 83.6% of the patients (51/61; 95% confidence interval [CI], 71.9 to 91.8) who received TOL-TAZ and 96.0% of the patients (24/25; 95% CI, 79.6 to 99.9) who received meropenem (difference, -12.4%; 95% CI, -34.9% to 11.1%); in the ME population, clinical cure was seen in 88.7% and 95.8% of the patients (difference, -7.1%; 95% CI, -30.7% to 16.9%) who received TOL-TAZ and meropenem, respectively. TOL-TAZ demonstrated microbiological success against Escherichia coli (89.5%), Klebsiella pneumoniae (100%), and P. aeruginosa (100%). The adverse event rates were similar in the groups (50.0% with TOL-TAZ and 48.8% with meropenem). TOL-TAZ in combination with metronidazole was well tolerated and resulted in clinical and microbiological success rates supportive of further clinical development in patients with cIAIs. (This study has been registered at ClinicalTrials.gov under registration no. NCT01147640.).

Authors+Show Affiliations

South Jersey Infectious Disease, Somers Point, New Jersey, USA infect123@aol.com.Cubist Pharmaceuticals, Lexington, Massachusetts, USA.Cubist Pharmaceuticals, Lexington, Massachusetts, USA.Cubist Pharmaceuticals, Lexington, Massachusetts, USA.Cubist Pharmaceuticals, Lexington, Massachusetts, USA.Cubist Pharmaceuticals, Lexington, Massachusetts, USA.University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.

Pub Type(s)

Clinical Trial, Phase II
Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24982069

Citation

Lucasti, Christopher, et al. "Multicenter, Double-blind, Randomized, Phase II Trial to Assess the Safety and Efficacy of Ceftolozane-tazobactam Plus Metronidazole Compared With Meropenem in Adult Patients With Complicated Intra-abdominal Infections." Antimicrobial Agents and Chemotherapy, vol. 58, no. 9, 2014, pp. 5350-7.
Lucasti C, Hershberger E, Miller B, et al. Multicenter, double-blind, randomized, phase II trial to assess the safety and efficacy of ceftolozane-tazobactam plus metronidazole compared with meropenem in adult patients with complicated intra-abdominal infections. Antimicrob Agents Chemother. 2014;58(9):5350-7.
Lucasti, C., Hershberger, E., Miller, B., Yankelev, S., Steenbergen, J., Friedland, I., & Solomkin, J. (2014). Multicenter, double-blind, randomized, phase II trial to assess the safety and efficacy of ceftolozane-tazobactam plus metronidazole compared with meropenem in adult patients with complicated intra-abdominal infections. Antimicrobial Agents and Chemotherapy, 58(9), 5350-7. https://doi.org/10.1128/AAC.00049-14
Lucasti C, et al. Multicenter, Double-blind, Randomized, Phase II Trial to Assess the Safety and Efficacy of Ceftolozane-tazobactam Plus Metronidazole Compared With Meropenem in Adult Patients With Complicated Intra-abdominal Infections. Antimicrob Agents Chemother. 2014;58(9):5350-7. PubMed PMID: 24982069.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Multicenter, double-blind, randomized, phase II trial to assess the safety and efficacy of ceftolozane-tazobactam plus metronidazole compared with meropenem in adult patients with complicated intra-abdominal infections. AU - Lucasti,Christopher, AU - Hershberger,Ellie, AU - Miller,Benjamin, AU - Yankelev,Sara, AU - Steenbergen,Judith, AU - Friedland,Ian, AU - Solomkin,Joseph, Y1 - 2014/06/30/ PY - 2014/7/2/entrez PY - 2014/7/2/pubmed PY - 2015/9/22/medline SP - 5350 EP - 7 JF - Antimicrobial agents and chemotherapy JO - Antimicrob Agents Chemother VL - 58 IS - 9 N2 - Ceftolozane-tazobactam (TOL-TAZ) is a novel antibacterial with activity against Pseudomonas aeruginosa and other common Gram-negative pathogens, including extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, that are associated with complicated intra-abdominal infections (cIAIs). This prospective, double-blind, randomized, multicenter, phase II trial assessed patient clinical and microbiological responses to and the safety of TOL-TAZ plus metronidazole compared with those of meropenem. Hospitalized adults with cIAIs that required surgical intervention were randomized (2:1) to receive intravenous (i.v.) TOL-TAZ (1.5 g [containing 1,000 mg TOL and 500 mg TAZ] every 8 h [q8h]) with or without i.v. metronidazole (500 mg q8h) or i.v. meropenem (1 g q8h) for 4 to 7 days. The primary endpoint was the clinical response at the test-of-cure visit in the microbiologically modified intent-to-treat (mMITT) and microbiologically evaluable (ME) populations. Secondary measures included the patients' microbiological response and safety. In total, 82 patients received TOL-TAZ (90.2% with metronidazole), and 39 received meropenem. For the mMITT population, clinical cure was seen in 83.6% of the patients (51/61; 95% confidence interval [CI], 71.9 to 91.8) who received TOL-TAZ and 96.0% of the patients (24/25; 95% CI, 79.6 to 99.9) who received meropenem (difference, -12.4%; 95% CI, -34.9% to 11.1%); in the ME population, clinical cure was seen in 88.7% and 95.8% of the patients (difference, -7.1%; 95% CI, -30.7% to 16.9%) who received TOL-TAZ and meropenem, respectively. TOL-TAZ demonstrated microbiological success against Escherichia coli (89.5%), Klebsiella pneumoniae (100%), and P. aeruginosa (100%). The adverse event rates were similar in the groups (50.0% with TOL-TAZ and 48.8% with meropenem). TOL-TAZ in combination with metronidazole was well tolerated and resulted in clinical and microbiological success rates supportive of further clinical development in patients with cIAIs. (This study has been registered at ClinicalTrials.gov under registration no. NCT01147640.). SN - 1098-6596 UR - https://www.unboundmedicine.com/medline/citation/24982069/Multicenter_double_blind_randomized_phase_II_trial_to_assess_the_safety_and_efficacy_of_ceftolozane_tazobactam_plus_metronidazole_compared_with_meropenem_in_adult_patients_with_complicated_intra_abdominal_infections_ L2 - http://aac.asm.org/cgi/pmidlookup?view=long&pmid=24982069 DB - PRIME DP - Unbound Medicine ER -