Available online 4 May 2024

Author links open overlay panel, , , , , ABSTRACTBackground

Specific data concerning the efficacy of alternative antibiotics for carbapenems against complicated urinary tract infections (cUTIs) attributed to antimicrobial-resistant (AMR) uropathogens are lacking.

Objectives

This study aimed to assess the efficacy of carbapenems and non-carbapenem antibiotics in the clinical outcomes of cUTIs caused by AMR uropathogens.

Methods

In this systematic review and meta-analysis, databases, including MEDLINE/PubMed, the Cochrane Library, Embase and ClinicalTrials.gov, were searched. The study eligibility criteria were research articles conducted as randomised controlled trials that evaluated the composite outcomes of cUTIs. Participants were adult patients with cUTIs caused by gram-negative uropathogens resistant to third-generation cephalosporins. The intervention involved a non-carbapenem class of antimicrobial agents with in vitro activities against gram-negative uropathogens resistant to third-generation cephalosporins. Two independent researchers assessed the risk-of-bias using the second version of the Cochrane risk-of-bias tool for randomised trials. The treatment effects on each outcome were estimated as a risk ratio (RR) with a 95% confidence interval (CI) using the random-effects model. Heterogeneity was assessed using the Cochrane Q-test and I2 statistics.

Results

Through database searches, 955 articles were retrieved. After screening the titles and abstracts, 52 articles were screened in full text. Finally, 12 studies met the inclusion criteria. No significant differences in efficacy were observed between alternative antibiotics and carbapenems (composite outcome, RR, 0.96; 95% CI, 0.63―1.49; I2 = 21%; low certainty of evidence).

Conclusions

Alternative antibiotics had clinical efficacy similar to that of carbapenems for treating patients with cUTI caused by gram-negative uropathogens resistant to third-generation cephalosporins.

Section snippetsINTRODUCTION

Complicated urinary tract infections (cUTIs) are associated with morbidity, mortality, hospitalisation and substantial healthcare expenditures 1, 2, 3, 4. The treatment guidelines for cUTIs advocate empirical therapy for gram-negative uropathogens, including Escherichia coli, Klebsiella pneumoniae and non-Enterobacterales [5]. Consequently, broad-spectrum antibiotics are frequently selected as empirical therapy for cUTIs [6].

Recently, the spread of gram-negative bacteria resistant to multiple

Methods

This systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) guidelines [15]. The PRISMA checklist is shown in Appendix S1 [15]. The review protocol was registered with PROSPERO, the International Prospective Register of Systematic Reviews (registration number CRD42022356064) and has already been published in a peer-reviewed journal [16].

Results

Through database searches, 955 articles were retrieved, of which 168 were removed for automation duplicate checking by Rayyan. After screening the titles and abstracts, 52 articles were screened in full text. Finally, 12 studies met the inclusion criteria. The overall identification process of studies through databases is shown in Figure 1 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34. The study ‘EUCTR2011-005722-21-BG’ obtained data from the results posted on ClinicalTrials.gov. (NCT01595438).

Discussion

This systematic review demonstrated that carbapenem and alternative antibiotics have similar efficacy in both clinical and microbiological responses to cUTIs caused by AMR uropathogens. The results of this study strongly support the notion that alternative antibiotics with in vitro activity for third-generation resistant gram-negative uropathogens are available for targeted therapy and de-escalation strategy once antimicrobial susceptible data were available. Siderophore cephalosporin,

Patient consent for publication

Not applicable

Transparency declaration

HN has received a research grant from GlaxoSmithKline for the outside theme of this work. The other authors have no conflicts of interest to declare.

Funding

None.

Contributions

Conception of the study: MM. Construction of search strategy: MM. Review activities; MM, TS and MTS. Quality assessment; MM, TS, MTS, TH and EO. Data analysis and interpretation; MM, HN and EO. Guarantor of the review: MM. Drafting manuscript: MM. Review and finalisation: TS, MTS, TH, HN and EO. All authors reviewed and approved the final version of the manuscript.

Data availability statement

All data generated and analysed during this study were included in this article.

Acknowledgments

None.

References (43)NealD.E. Complicated urinary tract infections

Urol Clin North Am

(2008)

Ten DoesschateT. et al.Carbapenem-alternative strategies for complicated urinary tract infections: A systematic review of randomized controlled trials

J Infect

(2020)

DerSimonianR. et al.Meta-analysis in clinical trials

Control Clin Trials

(1986)

CarmeliY. et al.Ceftazidime-avibactam or best available therapy in patients with ceftazidime-resistant Enterobacteriaceae and Pseudomonas aeruginosa complicated urinary tract infections or complicated intra-abdominal infections (REPRISE): a randomised, pathogen-directed, phase 3 study

Lancet Infect Dis

(2016)

MalaisriC. et al.A randomized controlled trial of sitafloxacin vs. ertapenem as a switch therapy after treatment for acute pyelonephritis caused by extended-spectrum β-lactamase-producing Escherichia coli: A pilot study

J Infect Chemother

(2017)

PortsmouthS. et al.Cefiderocol versus imipenem-cilastatin for the treatment of complicated urinary tract infections caused by Gram-negative uropathogens: a phase 2, randomised, double-blind, non-inferiority trial

Lancet Infect Dis

(2018)

HungK.C. et al.Clinical efficacy and safety of novel antibiotics for complicated urinary tract infection: A systematic review and meta-analysis of randomized controlled trials

Int J Antimicrob Agents

(2023)

BassettiM. et al.Efficacy and safety of cefiderocol or best available therapy for the treatment of serious infections caused by carbapenem-resistant Gram-negative bacteria (CREDIBLE-CR): a randomised, open-label, multicentre, pathogen-focused, descriptive, phase 3 trial

Lancet Infect Dis

(2021)

NicolleL.E. Complicated urinary tract infection in adults

Can J Infect Dis Med Microbiol

(2005)

WagenlehnerF.M.E. et al.Epidemiology, definition and treatment of complicated urinary tract infections

Nat Rev Urol

(2020)

BrownP. et al.Acute pyelonephritis among adults: cost of illness and considerations for the economic evaluation of therapy

Pharmacoeconomics

(2005)

HootonT.M. et al.Diagnosis, prevention, and treatment of catheter-associated urinary tract infection in adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America

Clin Infect Dis

(2010)

TammaP.D. et al.Infectious Diseases Society of America 2023 Guidance on the Treatment of Antimicrobial Resistant Gram-Negative Infections

Clin Infect Dis

(2023 Jul)

World Health Organization. Antimicrobial resistance. Available from:...BezabihY.M. et al.Comparison of the global prevalence and trend of human intestinal carriage of ESBL-producing Escherichia coli between healthcare and community settings: a systematic review and meta-analysis

JAC Antimicrob Resist

(2022)

PatersonD.L. et al.Current evidence for therapy of ceftriaxone-resistant Gram-negative bacteremia

Curr Opin Infect Dis

(2020)

European Centre for Disease Prevention and Control. Carbapenem-resistant Enterobacteriaceae (CRE). Available from:...WilsonA.P.R. Sparing carbapenem usage

J Antimicrob Chemother.

(2017)

SinghK.P. et al.Systematic review and meta-analysis of antimicrobial treatment effect estimation in complicated urinary tract infection

Antimicrob Agents Chemother

(2013)

EzureY. et al.Efficacy and safety of carbapenems vs new antibiotics for treatment of adult patients with complicated urinary tract infections: A systematic review and meta-analysis

Open Forum Infect Dis

(2022)

PageM.J. et al.The PRISMA 2020 statement: an updated guideline for reporting systematic reviews

BMJ

(2021)

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