Clinical and Microbiologic Efficacy and Safety of Imipenem/Cilastatin/Relebactam in Complicated Infections: A Meta-analysis
2
조회
0
다운로드
4
인용
0
참고문헌
키워드
초록
Background: Antimicrobial resistance is on the rise. The use of redundant and inappropriate antibiotics is contributing to recurrent infections and resistance. Newer antibiotics with more robust coverage for Gram-negative bacteria are in great demand for complicated urinary tract infections (cUTIs), complicated intra-abdominal infections (cIAIs), hospital-acquired bacterial pneumonia (HABP), and ventilator-associated bacterial pneumonia (VABP). Materials and Methods: We performed this meta-analysis to evaluate the efficacy and safety profile of a new antibiotic, Imipenem/cilastatin/relebactam, compared to other broad-spectrum antibiotics for complicated infections. We conducted a systemic review search on PubMed, Embase, and Central Cochrane Registry. We included randomized clinical trials-with the standard of care as comparator arm with Imipenem/cilastatin/relebactam as intervention arm. For continuous variables, the mean difference was used. For discrete variables, we used the odds ratio. For effect sizes, we used a confidence interval of 95%. A P-value of less than 0.05 was used for statistical significance. Analysis was done using a random-effects model irrespective of heterogeneity. Heterogeneity was evaluated using the I2 statistic. Results: The authors observed similar efficacy at clinical and microbiologic response levels on early follow-up and late follow-up compared to the established standard of care. The incidence of drug-related adverse events, serious adverse events, and drug discontinuation due to adverse events were comparable across both groups. Conclusion: Imipenem/cilastatin/relebactam has a non-inferior safety and efficacy profile compared to peer antibiotics to treat severe bacterial infections (cUTIs, cIAIs, HABP, VABP).
Abstract
Background: Antimicrobial resistance is on the rise. The use of redundant and inappropriate antibiotics is contributing to recurrent infections and resistance. Newer antibiotics with more robust coverage for Gram-negative bacteria are in great demand for complicated urinary tract infections (cUTIs), complicated intra-abdominal infections (cIAIs), hospital-acquired bacterial pneumonia (HABP), and ventilator-associated bacterial pneumonia (VABP). Materials and Methods: We performed this meta-analysis to evaluate the efficacy and safety profile of a new antibiotic, Imipenem/cilastatin/relebactam, compared to other broad-spectrum antibiotics for complicated infections. We conducted a systemic review search on PubMed, Embase, and Central Cochrane Registry. We included randomized clinical trials-with the standard of care as comparator arm with Imipenem/cilastatin/relebactam as intervention arm. For continuous variables, the mean difference was used. For discrete variables, we used the odds ratio. For effect sizes, we used a confidence interval of 95%. A P-value of less than 0.05 was used for statistical significance. Analysis was done using a random-effects model irrespective of heterogeneity. Heterogeneity was evaluated using the I2 statistic. Results: The authors observed similar efficacy at clinical and microbiologic response levels on early follow-up and late follow-up compared to the established standard of care. The incidence of drug-related adverse events, serious adverse events, and drug discontinuation due to adverse events were comparable across both groups. Conclusion: Imipenem/cilastatin/relebactam has a non-inferior safety and efficacy profile compared to peer antibiotics to treat severe bacterial infections (cUTIs, cIAIs, HABP, VABP).
참고문헌 (40)
- Bassetti M, "Systematic review of the impact of appropriate versus inappropriate initial antibiotic therapy on outcomes of patients with severe bacterial infections", Int J Antimicrob Agents, 56, pp.106184~ (2020)
- Badia JM, "Impact of surgical site infection on healthcare costs and patient outcomes: a systematic review in six European countries", J Hosp Infect, 96, pp.1~15 (2017)
- Paul M, "Systematic review and meta-analysis of the efficacy of appropriate empiric antibiotic therapy for sepsis", Antimicrob Agents Chemother, 54, pp.4851~4863 (2010)
- Tagini F, "Bacterial genome sequencing in clinical microbiology: a pathogen-oriented review", Eur J Clin Microbiol Infect Dis, 36, pp.2007~2020 (2017)
- Olesen SW, "The distribution of antibiotic use and its association with antibiotic resistance", ELife, 7, pp.e39435~ (2018)
- Jernigan JA, "Multidrug-resistant bacterial infections in U.S. hospitalized patients, 2012-2017", N Engl J Med, 382, pp.309~319 (2020)
- Peyrani P, "The burden of community-acquired bacterial pneumonia in the era of antibiotic resistance", Expert Rev Respir Med, 13, pp.139~152 (2019)
- Arzanlou M, "ntrinsic, adaptive and acquired antimicrobial resistance in Gramnegative bacteria", Essays Biochem, 61, pp.49~59 (2017)
- Mukerji S, "Development and transmission of antimicrobial resistance among Gram-negative bacteria in animals and their public health impact", Essays Biochem, 61, pp.23~35 (2017)
- Boucher HW, "Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America", Clin Infect Dis, 48, pp.1~12 (2009)
- Rice LB, "Federal funding for the study of antimicrobial resistance in nosocomial pathogens: no ESKAPE", J Infect Dis, 197, pp.1079~1081 (2008)
- Spera AM, "Emerging antibiotic resistance: carbapenemase-producing enterobacteria. Bad new bugs, still no new drugs", Infez Med, 27, pp.357~364 (2019)
- Khan MA, "Antimicrobial resistance patterns of Pseudomonas aeruginosa in tertiary care hospitals of Makkah and Jeddah", Ann Saudi Med, 36, pp.23~28 (2016)
- Yayan J, "Antibiotic resistance of Pseudomonas aeruginosa in pneumonia at a Single University Hospital Center in Germany over a 10-year period", PLoS One, 10, pp.e0139836~ (2015)
- Xu JJ, "Analysis of antibiotic treatment of children in a Shanghai tertiary hospital based on point prevalence surveys", BMC Infect Dis, 20, pp.804~ (2020)
- Mayor S, "First WHO antimicrobial surveillance data reveal high levels of resistance globally", BMJ, 360, pp.k462~ (2018)
- acconelli E, "Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis", Lancet Infect Dis, 18, pp.318~327 (2018)
- Nordmann P, ". The real threat of Klebsiella pneumoniae carbapenemase-producing bacteria", Lancet Infect Dis, 9, pp.228~236 (2009)
- Tehrani KHME, "β-lactam", β-lactamase inhibitor combinations: an update, 2018, pp.9, 1439~1456
- Fiore M, "Ceftolozanetazobactam combination therapy compared to ceftolozane-tazobactam monotherapy for the treatment of severe infections: a systematic review and meta-analysis", Antibiotics (Basel), 10, pp.79~ (2021)
- Tzouvelekis LS, "Treating infections caused by carbapenemase-producing Enterobacteriaceae", Clin Microbiol Infect, 20, pp.862~872 (2014)
- Hashizume T, "Studies on the mechanism of action of imipenem (N-formimidoylthienamycin) in vitro: binding to the penicillin-binding proteins (PBPs) in Escherichia coli and Pseudomonas aeruginosa, and inhibition of enzyme activities due to the PBPs in E. coli", J Antibiot (Tokyo), 37, pp.394~400 (1984)
- Williams RJ, "Mechanisms by which imipenem may overcome resistance in gramnegative bacilli", J Antimicrob Chemother, 18(Suppl E), pp.9~13 (1986)
- Buckley MM, "Imipenem", cilastatin. A reappraisal of its antibacterial activity, pharmacokinetic properties and therapeutic efficacy, 1992, pp.44, 408~444
- Shayan M, "Cilastatin as a protective agent against drug-induced nephrotoxicity: a literature review", Expert Opin Drug Saf, 19, pp.999~1010 (2020)
- Tooke CL, "Molecular basis of class A β-lactamase inhibition by relebactam", Antimicrob Agents Chemother, 63, pp.e00564~e00519 (2019)
- Crass RL, "Pharmacokinetics and pharmacodynamics of β-lactamase inhibitors", Pharmacotherapy, 39, pp.182~195 (2019)
- Lucasti C, "Phase 2, dose-ranging study of relebactam with imipenem-cilastatin in subjects with complicated intra-abdominal infection", Antimicrob Agents Chemother, 60, pp.6234~6243 (2016)
- Sims M, "Prospective, randomized, double-blind, Phase 2 dose-ranging study comparing efficacy and safety of imipenem", cilastatin plus relebactam with imipenem, J Antimicrob Chemother, pp.2017, 72[DOI]
- Knapp KM, "Carbapenems", Semin Pediatr Infect Dis, 12, pp.175~185 (2001)
- David M. Livermore, "Current Epidemiology and Growing Resistance of Gram- Negative Pathogens", The Korean Journal of Internal Medicine, 27(2), pp.128~142 (2012), 대한내과학회[DOI]
- Meletis G, "Carbapenem resistance: overview of the problem and future perspectives", Ther Adv Infect Dis, 3, pp.15~21 (2016)
- Codjoe FS, "Carbapenem resistance: a review", Med Sci (Basel), 6, pp.1~ (2017)
- Dyar OJ, "What is antimicrobial stewardship?", Clin Microbiol Infect, 23, pp.793~798 (2017)
- White AR, "BSAC Working Party on The Urgent Need: Regenerating Antibacterial Drug Discovery and Development. Effective antibacterials: at what cost? The economics of antibacterial resistance and its control", J Antimicrob Chemother, 66, pp.1948~1953 (2011)
- Zasowski EJ, "The β-lactams strike back: ceftazidime-avibactam", Pharmacotherapy, 35, pp.755~770 (2015)
- Karlowsky JA, "In-vitro activity of imipenem", relebactam and key β-lactam agents against Gram-negative bacilli isolated from lower respiratory tract infection samples of intensive care unit patients - SMART Surveillance United States 2015-2017, 2020, pp.55, 105841~
- Titov I, "A Randomized, double-blind, multicenter trial comparing efficacy and safety of imipenem", cilastatin, tazobactam in adults with hospital-acquired or ventilatorassociated bacterial pneumonia (RESTORE-IMI 2 Study), pp.Clin Infect Dis, 2020
- Cannon JP, "The risk of seizures among the carbapenems: a metaanalysis", J Antimicrob Chemother, 69, pp.2043~2055 (2014)
- Motsch J, "RESTORE-IMI 1: A multicenter, randomized, double-blind trial comparing efficacy and safety of imipenem", relebactam vs colistin plus imipenem in patients with imipenem-nonsusceptible bacterial infections, 2020, pp.70, 1799~1808