{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T17:36:06Z","timestamp":1791048966412,"version":"4.1.0"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,11,30]],"date-time":"2023-11-30T00:00:00Z","timestamp":1701302400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Antimicrobial resistance poses a grave global threat, particularly with the emergence of multidrug-resistant gram-negative bacterial infections, which severely limit treatment options. The increasing global threat of antimicrobial resistance demands rigorous investigation, particularly concerning multidrug-resistant gram-negative bacterial infections that present limited therapeutic options. This study employed a network meta-analysis, a powerful tool for comparative effectiveness assessment of diverse antibiotics. The primary aim of this study was to comprehensively evaluate and compare resistance patterns among widely used antibiotic classes, namely carbapenems, fluoroquinolones, and aminoglycosides, for combating gram-negative pathogens.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We searched PubMed, Web of Sciences, Scopus, Scholarly, Medline, Embase, and Cochrane databases up to August 27, 2023. Studies showing antibiotic resistance in clinical isolates of Enterobacteriaceae, <jats:italic>Pseudomonas aeruginosa<\/jats:italic>, and <jats:italic>Acinetobacter baumannii<\/jats:italic> exposed to carbapenems, fluoroquinolones, and aminoglycosides were included. This study determined treatment-specific resistance percentages and ranked these treatments based on resistance using a random-effects network meta-analysis technique. To investigate the impact of the study and pathogen features, subgroup and meta-regression analyses were performed. Risk ratios and 95% confidence intervals (CIs) were calculated using a network meta-analysis (NMA) incorporating both direct and indirect evidence. Clinical improvement, cure, microbiological eradication, and death from any cause were the primary outcomes. Nephrotoxicity was a secondary result.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The analysis included 202 publications and 365,782 gram-negative isolates. The NMA included data from 20 studies and 4,835 patients. Carbapenems had the lowest resistance rates throughout the pathogen spectrum, with resistance percentages of 17.1, 22.4, and 33.5% for Enterobacteriaceae, <jats:italic>P. aeruginosa<\/jats:italic>, and <jats:italic>A. baumannii<\/jats:italic>, respectively. For the same infections, aminoglycosides showed resistance rates of 28.2, 39.1, and 50.2%, respectively. Fluoroquinolones had the highest resistance rates at 43.1, 57.3, and 65.7%, respectively. Unexpectedly, resistance to all three antibiotic classes has increased over time, with multidrug resistance being the most prevalent.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This extensive network meta-analysis provides an overview of the patterns of resistance throughout the world and how they are changing. The most effective choice is still carbapenems, but the increasing resistance highlights the critical need for multimodal therapies to protect antibiotic effectiveness against these powerful gram-negative infections.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2023.1304011","type":"journal-article","created":{"date-parts":[[2023,11,30]],"date-time":"2023-11-30T08:56:31Z","timestamp":1701334591000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Network meta-analysis of antibiotic resistance patterns in gram-negative bacterial infections: a comparative study of carbapenems, fluoroquinolones, and aminoglycosides"],"prefix":"10.3389","volume":"14","author":[{"given":"Ghazala","family":"Muteeb","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,11,30]]},"reference":[{"key":"ref1","first-page":"447","volume-title":"Management of Antimicrobial use in the intensive care unit","author":"\u00c1lvarez-Lerma","year":"2012"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"8331","DOI":"10.1073\/pnas.1400352111","article-title":"Exploring the collaboration between antibiotics and the immune response in the treatment of acute, self-limiting infections","volume":"111","author":"Ankomah","year":"2014","journal-title":"Proc. Natl. Acad. Sci. U S A."},{"key":"ref9012","doi-asserted-by":"publisher","first-page":"100563","DOI":"10.1016\/j.lanepe.2022.100563","article-title":"EPI-Net One Health consensus working group. EPI-Net One Health reporting guideline for antimicrobial consumption and resistance surveillance data: a Delphi approach","volume":"26","author":"Babu Rajendran","year":"2022","journal-title":"Lancet. Reg. Health Eur."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/1471-2334-14-13","article-title":"systematic review and meta-analysis of the effects of antibiotic consumption on antibiotic resistance","volume":"14","author":"Bell","year":"2014","journal-title":"BMC Infect Dis."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"e46803","DOI":"10.1371\/journal.pone.0046803","article-title":"Upper Airways Microbiota in Antibiotic-Naive Wheezing and Healthy Infants from the Tropics of Rural Ecuador","volume":"7","author":"Cardenas","year":"2012","journal-title":"PLOS ONE."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"2949","DOI":"10.1111\/j.1469-0691.2011.03527.x","article-title":"Epidemiological characterization of IMP-type metallo-\u03b2-lactamase-producing Acinetobacter baumannii in Italy","volume":"51","author":"Carretto","year":"2013","journal-title":"J. Clin. Microbiol."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1155\/2017\/3925868","article-title":"New metallo-\u03b2-lactamase NMC-A from Acinetobacter baumannii clinical isolates collected in a Malaysian hospital","volume":"56","author":"Chai","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref9","article-title":"Advice on the designation of antimicrobials or groups of antimicrobials reserved for treatment of certain infections in humans - in relation to implementing measures under Article 37(5) of Regulation (EU) 2019\/6 on veterinary medicinal products EMA\/CVMP\/678496\/2021-rev.","year":"2022"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1111\/j.1365-2125.2008.03306.x","article-title":"Effectiveness and safety of short vs. long duration of antibiotic therapy for acute bacterial sinusitis: a meta-analysis of randomized trials","volume":"67","author":"Falagas","year":"2009","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"12","DOI":"10.3389\/fonc.2022.998346","article-title":"Pomegranate juice anthocyanidins induce cell death in human cancer cells by mobilizing intracellular copper ions and producing reactive oxygen species","volume":"12","author":"Farhan","year":"2022","journal-title":"Front. Oncol."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"959","DOI":"10.2147\/IJGM.S214305","article-title":"Carbapenem-resistant Enterobacteriaceae strains of Klebsiella pneumoniae ST147 and Escherichia coli ST131 as causes of bacteraemia in a German university hospital","volume":"59","author":"Fischer","year":"2010","journal-title":"J. Med. Microbiol."},{"key":"ref12","volume-title":"Canadian antimicrobial resistance surveillance system report","year":"2022"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"84","DOI":"10.3390\/antibiotics8020084","article-title":"Qualitative Analysis of Primary Care Provider Prescribing Decisions for Urinary Tract Infections","volume":"8","author":"Grigoryan","year":"2019","journal-title":"Antibiotics"},{"key":"ref9007","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.3389\/fmicb.2016.01021","article-title":"Phenotypic and Molecular Characterization of Antimicrobial Resistance in Klebsiella spp. Isolates from Companion Animals in Japan: Clonal Dissemination of Multidrug-Resistant Extended-Spectrum \u03b2-Lactamase-Producing Klebsiella pneumoniae","volume":"7","author":"Harada","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref9008","doi-asserted-by":"publisher","first-page":"h6420","DOI":"10.1136\/bmj.h6420","article-title":"Antibiotic resistance in Enterobacteriaceae: mechanisms and clinical implications","volume":"352","author":"Iredell","year":"2016","journal-title":"BMJ."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"263e1","DOI":"10.1016\/j.ijantimicag.2020.106126","article-title":"Clinical presentation and risk factors for mortality in patients infected with metallo-\u03b2-lactamase-producing Enterobacteriaceae in a university hospital in Poland","volume":"21","author":"Izdebski","year":"2015","journal-title":"Clin. Microbiol. Infect."},{"key":"ref9009","doi-asserted-by":"publisher","first-page":"745862","DOI":"10.3389\/fgwh.2022.745862","article-title":"Gender and Antimicrobial Resistance: What Can We Learn From Applying a Gendered Lens to Data Analysis Using a Participatory Arts Case Study?","volume":"3","author":"Jones","year":"2022","journal-title":"Front. Glob. Womens Health"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"250","DOI":"10.4065\/mcp.2010.0674","article-title":"Current Concepts in Antimicrobial Therapy Against Resistant Gram-Negative Organisms: Extended-Spectrum \u03b2-Lactamase\u2013Producing Enterobacteriaceae, Carbapenem-Resistant Enterobacteriaceae, and Multidrug-Resistant Pseudomonas aeruginosa","volume":"86","author":"Kanj","year":"2011","journal-title":"Mayo. Clin. Proc"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/j.jegh.2014.07.003","article-title":"Epidemiology, clinical manifestations, and molecular typing of salmonella typhi isolated from patients with typhoid fever in Lebanon","volume":"5","author":"Kanj","year":"2015","journal-title":"J. Epidemiol. Glob. Health."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1016\/S1473-3099(09)70054-4","article-title":"Klebsiella pneumoniae carbapenemase-producing bacterial infections at a university hospital in the United States","volume":"30","author":"Keller","year":"2009","journal-title":"Infect. Control Hosp. Epidemiol."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1016\/S1473-3099(10)70143-2","article-title":"Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study","volume":"10","author":"Kumarasamy","year":"2010","journal-title":"Lancet Infect. Dis."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1443","DOI":"10.1093\/cid\/ciu213","article-title":"Evaluation of colistin and polymyxin B in combination with carbapenems for the treatment of extensively drug-resistant Acinetobacter baumannii infections","volume":"65","author":"Lee","year":"2010","journal-title":"J. Antimicrob. Chemother."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1016\/j.cmi.2016.01.023","article-title":"Incidence and prognostic factors of severe infections and dysglycemia in hospitalized patients with carbapenem-resistant Klebsiella pneumoniae","volume":"32","author":"Leport","year":"2013","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref9014","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1007\/s11908-022-00785-2","article-title":"No Crystal Ball? Using Risk Factors and Scoring Systems to Predict Extended-Spectrum Beta-Lactamase Producing Enterobacterales (ESBL-E) and Carbapenem-Resistant Enterobacterales (CRE) Infections","volume":"24","author":"Li","year":"2022","journal-title":"Curr. Infect. Dis. Rep."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1099\/jmm.0.001655","article-title":"Carbapenem resistance among Acinetobacter baumannii clinical isolates from Xi\u2019an, China: emergence of NDM-1","volume":"19","author":"Liu","year":"2013","journal-title":"Microb. Drug Resist."},{"key":"ref9015","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.envpol.2018.12.005","article-title":"Occurrence and fate of antibiotics and antibiotic resistance genes in typical urban water of Beijing, China","volume":"246","author":"Liu","year":"2019","journal-title":"Environmental Pollution"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"237","DOI":"10.3390\/antibiotics10030237","article-title":"Antibiotic Resistance in Shiga Toxigenic Escherichia coli Isolates from Surface Waters and Sediments in a Mixed Use Urban Agricultural Landscape","volume":"10","author":"Ma","year":"2021","journal-title":"Antibiotics (Basel)."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"341","DOI":"10.7416\/ai.2018.2224","article-title":"Metallo-beta-lactamase-producing acinetobacter infections in intensive care units in Australia over 5 years","volume":"39","author":"McIntyre","year":"2012","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref9010","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.jiph.2014.07.010","article-title":"Assessing the Lebanese population for their knowledge, attitudes and practices of antibiotic usage","volume":"8","author":"Mouhieddine","year":"2015","journal-title":"J. Infect. Public. Health."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"1489","DOI":"10.3390\/microorganisms11061489","article-title":"Nanotechnology \u2013 A light of Hope for combating antibiotic resistance","volume":"11","author":"Muteeb","year":"2023","journal-title":"Microorganisms"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"5930","DOI":"10.3390\/molecules27185930","article-title":"Identification of a potential inhibitor (MCULE-8777613195-0-12) of New Delhi Metallo-beta; -Lactamase-1 (NDM-1) using in silico and in vitro approaches","volume":"27","author":"Muteeb","year":"2022","journal-title":"Molecules"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"90","DOI":"10.2174\/1389200217666160727100434","article-title":"Phage display technique: a novel medicinal approach to overcome an tibiotic resistance by using peptide-based inhibitors against \u03b2-lactamases","volume":"18","author":"Muteeb","year":"2017","journal-title":"Curr. Drug Metab."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1186\/s13756-018-0444-8","article-title":"Alarming levels of antimicrobial resistance among sepsis patients admitted to ICU in a tertiary care hospital in India - a case control retrospective study","volume":"7","author":"Nagarjuna","year":"2018","journal-title":"Antimicrob. Resist. Infect. Control"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"82","DOI":"10.3947\/ic.2015.47.2.81","article-title":"Clinical features of metallo-beta-lactamase-producing Pseudomonas aeruginosa isolates in Japanese hospitals","volume":"14","author":"Ogawa","year":"2008","journal-title":"J. Infect. Chemother."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.drup.2011.02.002","article-title":"Diagnostics as essential tools for containing antibiotic resistance","volume":"14","author":"Okeke","year":"2011","journal-title":"Drug Resist. Updat."},{"key":"ref30","doi-asserted-by":"crossref","DOI":"10.5772\/intechopen.99546","volume-title":"Bactericidal and Bacteriostatic Antibiotics","author":"Patil","year":"2021"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"680","DOI":"10.3390\/antibiotics10060680","article-title":"Prevalence and Risk Factors for Multidrug-Resistant Organisms Colonization in Long-Term Care Facilities Around the World: A Review","volume":"10","author":"Rodr\u00edguez-Villodres","year":"2021","journal-title":"Antibiotics (Basel)."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"15290","DOI":"10.1038\/s41598-019-51711-x","article-title":"Monotherapy versus combination therapy for multidrug-resistant Gram-negative infections: Systematic Review and Meta-Analysis","volume":"9","author":"Schmid","year":"2019","journal-title":"Sci. Rep."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"106344","DOI":"10.1016\/j.ijantimicag.2021.106344","article-title":"Systematic review and meta-analysis of in vitro efficacy of antibiotics against carbapenem-resistant gram-negative bacilli","volume":"57","author":"Scudeller","year":"2021","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref9023","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciad222","article-title":"Colonization With Antibiotic-Resistant Bacteria in a Hospital and Associated Communities in Guatemala: An Antibiotic Resistance in Communities and Hospitals (ARCH) Study","author":"Smith","year":"2023","journal-title":"OUP Academic"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1086\/649554","article-title":"Diagnosis and Management of Complicated Intra-abdominal Infections: evidence-based guidelines","volume":"50","author":"Solomkin","year":"2010","journal-title":"Clin. Infect. Dis."},{"key":"ref9024","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1164\/rccm.201809-1739OC","article-title":"Long-Term Azithromycin Reduces Haemophilus influenzae and Increases Antibiotic Resistance in Severe Asthma","volume":"200","author":"Taylor","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref9025","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1016\/j.bjid.2017.08.002","article-title":"Mobile health application to assist doctors in antibiotic prescription \u2013 an approach for antibiotic stewardship","volume":"21","author":"Tuon","year":"2017","journal-title":"Mobile Health Application to Assist Doctors in Antibiotic Prescription \u2013 an Approach for Antibiotic Stewardship"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.bjid.2020.04.004","article-title":"Evaluation of in vitro activity of ceftolozane-tazobactam against recent clinical bacterial isolates from Brazil - the EM200 study","volume":"24","author":"Tuon","year":"2020","journal-title":"Braz. J. Infect. Dis."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"43","DOI":"10.3201\/eid2811.220415","article-title":"Spread of carbapenemase-producing enterobacteriaceae in Latin America: need for enhanced surveillance and regional cooperation","volume":"11","author":"Villar","year":"2014","journal-title":"J. Antimicrob. Chemother."},{"key":"ref9020","doi-asserted-by":"publisher","first-page":"478","DOI":"10.3390\/antibiotics10050478","article-title":"Antibiotic Resistance in Wastewater Treatment Plants and Transmission Risks for Employees and Residents: The Concept of the AWARE Study","volume":"10","author":"Wengenroth","year":"2021","journal-title":"Antibiotics (Basel)."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"e728","DOI":"10.4161\/viru.19700","article-title":"Characteristics and mortality of patients with community-onset pneumonia due to Acinetobacter baumannii across Thailand","volume":"15","author":"Wongchotigul","year":"2011","journal-title":"Int. J. Infect. Dis."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1038\/s41598-019-40420-0","article-title":"Antimicrobial resistance in UK NPMRS data analysis and data capture: surveillance for carbapenemase-producing Enterobacteriaceae (CPE) in the UK, 2011-2013","volume":"70","author":"Woodford","year":"2015","journal-title":"J. Antimicrob. Chemother."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"990","DOI":"10.4103\/0974-2727.86841","article-title":"New Delhi metallo-beta-lactamase-producing Enterobacteriaceae, United Kingdom","volume":"19","author":"Woodward","year":"2013","journal-title":"Emerg. Infect. Dis."},{"key":"ref40","volume-title":"Antimicrobial resistance: Health care-associated infections caused by antibiotic-resistant gram-negative Bacteria. WHO.","year":"2023"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1007\/s42399-020-00395-w","article-title":"Clinical outcomes of multidrug-resistant Pseudomonas aeruginosa pneumonia treated with carbapenems vs tigecycline","volume":"123","author":"Zhang","year":"2010","journal-title":"Chinese Med J."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2023.1304011\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,30]],"date-time":"2023-11-30T08:56:37Z","timestamp":1701334597000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2023.1304011\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,30]]},"references-count":51,"alternative-id":["10.3389\/fmicb.2023.1304011"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2023.1304011","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,30]]},"article-number":"1304011"}}