Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2023 Jul 1;42(7):557-563.
doi: 10.1097/INF.0000000000003911. Epub 2023 Mar 29.

Safety and Efficacy of Ceftolozane/Tazobactam Plus Metronidazole Versus Meropenem From a Phase 2, Randomized Clinical Trial in Pediatric Participants With Complicated Intra-abdominal Infection

Carl-Christian A Jackson  1 , Jason Newland  2 , Nataliia Dementieva  3 , Julia Lonchar  4 , Feng-Hsiu Su  4 , Jennifer A Huntington  4 , Mekki Bensaci  4 , Myra W Popejoy  4 , Matthew G Johnson  4 , Carisa De Anda  4 , Elizabeth G Rhee  4 , Christopher J Bruno  4
Affiliations
Clinical Trial

Safety and Efficacy of Ceftolozane/Tazobactam Plus Metronidazole Versus Meropenem From a Phase 2, Randomized Clinical Trial in Pediatric Participants With Complicated Intra-abdominal Infection

Carl-Christian A Jackson et al. Pediatr Infect Dis J. .

Abstract

Background: Ceftolozane/tazobactam, a cephalosporin-β-lactamase inhibitor combination, is approved for the treatment of complicated urinary tract infections and complicated intra-abdominal infections (cIAI). The safety and efficacy of ceftolozane/tazobactam in pediatric participants with cIAI were assessed.

Methods: This phase 2 study (NCT03217136) randomized participants to either ceftolozane/tazobactam+metronidazole or meropenem for treatment of cIAI in pediatric participants (<18 years). The primary objective was to assess the safety and tolerability of intravenous ceftolozane/tazobactam+metronidazole. Clinical cure at end of treatment (EOT) and test of cure (TOC) visits were secondary end points.

Results: The modified intent-to-treat (MITT) population included 91 participants (ceftolozane/tazobactam+metronidazole, n = 70; meropenem, n = 21). Complicated appendicitis was the most common diagnosis (93.4%); Escherichia coli was the most common pathogen (65.9%). Adverse events (AEs) occurred in 80.0% and 61.9% of participants receiving ceftolozane/tazobactam+metronidazole and meropenem, drug-related AEs occurred in 18.6% and 14.3% and serious AEs occurred in 11.4% and 0% of participants receiving ceftolozane/tazobactam+metronidazole and meropenem, respectively. No drug-related serious AEs or discontinuations due to drug-related AEs occurred. Rates of the clinical cure for ceftolozane/tazobactam+metronidazole and meropenem at EOT were 80.0% and 95.2% (difference: -14.3; 95% confidence interval: -26.67 to 4.93) and at TOC were 80.0% and 100.0% (difference: -19.1; 95% confidence interval: -30.18 to -2.89), respectively; 6 of the 14 clinical failures for ceftolozane/tazobactam+metronidazole at TOC were indeterminate responses imputed as failures per protocol.

Conclusion: Ceftolozane/tazobactam+metronidazole was well tolerated in pediatric participants with cIAI and had a safety profile similar to the established safety profile in adults. In this descriptive efficacy analysis, ceftolozane/tazobactam+metronidazole appeared efficacious.

PubMed Disclaimer

Conflict of interest statement

J.L., F.-H.S, J.A.H., M.B., M.G.J., C.D.A., E.G.R., and C.J.B. are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD), who may own stock and/or hold stock options in Merck & Co., Inc., Rahway, NJ, USA. M.W.P. was an employee of MSD at the time of the study conduct. C.-C.A.J. received consulting fees from MSD and holds stock in Merck & Co., Inc., Rahway, NJ, USA. J.N. reports funding to conduct the study from MSD to his institution. N.D. has no potential conflicts of interest to disclose.

Figures

FIGURE 1.
FIGURE 1.
Rates of clinical cure in the MITT and clinical evaluable populations at EOT and TOC. CE indicates clinically evaluable; C/T, ceftolozane/tazobactam; EOT, end of treatment; MEM, meropenem; MITT, modified intent-to-treat; MTZ, metronidazole; pbo, placebo; TOC, test of cure. aDifference in C/T + MTZ minus MEM. bThe percent difference was based on the Miettinen & Nurminen method stratified by age group with Cochran-Mantel-Haenszel weights. If there was a zero count in any class of the stratum, the groups with the lower count were pooled with the near age group stratum in the model. cSix of the 14 failures at the TOC visit in the C/T plus MTZ group were based on indeterminate or missing clinical responses and not on observed clinical failures.
See this image and copyright information in PMC

References

    1. Menichetti F, Sganga G. Definition and classification of intra-abdominal infections. J Chemother. 2009;21(suppl 1):3–4. - PubMed
    1. Newman N, Wattad E, Greenberg D, et al. . Community-acquired complicated intra-abdominal infections in children hospitalized during 1995-2004 at a paediatric surgery department. Scand J Infect Dis. 2009;41:720–726. - PubMed
    1. Sartelli M, Catena F, Ansaloni L, et al. . Complicated intra-abdominal infections in Europe: a comprehensive review of the CIAO study. World J Emerg Surg. 2012;7:36. - PMC - PubMed
    1. Lob SH, Badal RE, Hackel MA, et al. . Epidemiology and antimicrobial susceptibility of gram-negative pathogens causing intra-abdominal infections in pediatric patients in Europe-SMART 2011-2014. J Pediatric Infect Dis Soc. 2017;6:72–79. - PubMed
    1. Solomkin JS, Mazuski JE, Bradley JS, et al. . Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Clin Infect Dis. 2010;50:133–164. - PubMed

Publication types

Associated data