1619 - Meta-analysis of Randomized Control Trials Evaluating New Beta-Lactamase Combination Antibiotics

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Presenting Author(s)

Geneva M. Wilson

Research Health Scientist Specialist
Hines VA
Hines, Illinois
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.

Co-Author(s)

MF

Margaret A. Fitzpatrick

Infectious Diseases Physician
Rocky Mountain Regional VA Medical Center
Aurora, Colorado
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
KW

Kyle Walding

General Resident Physician
Loyola University Medical Center
Hines, Illinois
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
BG

Beverly Gonzalez

Mathematical Statistician
Department of Veterans Affairs
Hines, IL
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Katie J. Suda

Research Health Scientist and Professor
Center for Health Equity Research and Promotion and University of Pittsburgh
Pittsburgh, Pennsylvania
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Charlesnika T. Evans

Associate Professor and Research Health Scientist
Northwestern University and VA
Hines, Illinois
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.

Background:

Background: Ceftolozane/ Tazobactam (C/T), Ceftazidime/ Avibactam (C/A), Meropenem/ Vaborbactam (M/V) and Imipenem/ Relebactam (I/R) are new combination beta-lactam/ beta-lactamase inhibitor antibiotics primarily used to treat multidrug-resistant (MDR) Gram-negative infections. This study synthesized outcomes of comparative observational studies and randomized control trials (RCTs) that evaluated clinical success of these antibiotics compared to other therapies.

Methods:

Methods: PubMed, EMBASE, and Google Scholar were searched from January 1^st, 2013 through October 1^st, 2019 for comparative observational studies and RCTs of C/T, C/A, M/V and I/R in patients with pneumonia, complicated intra-abdominal and urinary tract infections. Study and patient demographics were collected along with clinical and microbiological success rates. Meta-regression analysis was used to determine the pooled effectiveness of C/T, C/A, M/V, and I/R. Heterogeneity and publication bias were assessed via I² values and funnel plots, respectively.

Results:

Results: Literature search returned 1,645 results. After exclusion criteria, 21 publications representing 6,246 patients were retained: 16 RCTs (8 C/A, 3 C/T, 3 I/R, 2 M/V) and 5 comparative observational studies (3 C/A, 2 C/T). Pooled risk ratios for clinical success showed that all four antibiotics were non-inferior to comparator antibiotics (0.99 (95% CI (0.97-1.01)). Eleven of the sixteen RCTs evaluated microbiological success; pooled risk ratio was 1.08 (95% CI 1.04-1.13), indicating that older therapies were more successful at microbiological eradication than newer antibiotics. Only 6 of the included studies (3 RCTs and 2 observational studies) focused on patients with MDR infections. Limiting the analysis to MDR RCTs did not change the overall conclusions.

Conclusion:

Conclusions: Although older therapies had slightly higher microbiologic clearance, pooled clinical success rates for C/A, C/T, M/V, and I/R were non-inferior to older therapies, including in studies focused on patients with MDR infections. Additional studies are needed to further evaluate these drugs’ effectiveness for treatment of MDR infections.