{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:35:39Z","timestamp":1792002939379,"version":"4.4.0"},"reference-count":43,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,11]],"date-time":"2021-02-11T00:00:00Z","timestamp":1613001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UNIVERSITY OF MALAYA RESEARCH FUND","award":["RU008-2018"],"award-info":[{"award-number":["RU008-2018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>The increasing prevalence of extended-spectrum \u03b2-lactamase (ESBL)-producing Enterobacteriaceae has greatly affected the clinical efficacy of \u03b2-lactam antibiotics in the management of urinary tract infections (UTIs). The limited treatment options have resulted in the increased use of carbapenem. However, flomoxef could be a potential carbapenem-sparing strategy for UTIs caused by ESBL-producers. Here, we compared the in vitro susceptibility of UTI-associated ESBL-producers to flomoxef and established \u03b2-lactam antibiotics. Fifty Escherichia coli and Klebsiella pneumoniae strains isolated from urine samples were subjected to broth microdilution assay, and the presence of ESBL genes was detected by polymerase chain reactions. High rates of resistance to amoxicillin-clavulanate (76\u201380%), ticarcillin-clavulanate (58\u201376%), and piperacillin-tazobactam (48\u201350%) were observed, indicated by high minimum inhibitory concentration (MIC) values (32 \u00b5g\/mL to 128 \u00b5g\/mL) for both species. The ESBL genes blaCTX-M and blaTEM were detected in both E. coli (58% and 54%, respectively) and K. pneumoniae (88% and 74%, respectively), whereas blaSHV was found only in K. pneumoniae (94%). Carbapenems remained as the most effective antibiotics against ESBL-producing E. coli and K. pneumoniae associated with UTIs, followed by flomoxef and cephamycins. In conclusion, flomoxef may be a potential alternative to carbapenem for UTIs caused by ESBL-producers in Malaysia.<\/jats:p>","DOI":"10.3390\/antibiotics10020181","type":"journal-article","created":{"date-parts":[[2021,2,12]],"date-time":"2021-02-12T17:20:38Z","timestamp":1613150438000},"page":"181","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["In Vitro Efficacy of Flomoxef against Extended-Spectrum Beta-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae Associated with Urinary Tract Infections in Malaysia"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8332-4833","authenticated-orcid":false,"given":"Soo Tein","family":"Ngoi","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy Shuan Ju","family":"Teh","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun Wie","family":"Chong","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Monash University Malaysia, Bandar Sunway 47500, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8716-4416","authenticated-orcid":false,"given":"Kartini","family":"Abdul Jabar","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiang Chiet","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lean Huat","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kin Chong","family":"Leong","sequence":"additional","affiliation":[{"name":"Shionogi Singapore Pte Ltd., 10, Anson Road, #34-14 International Plaza, Singapore 079903, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loong Hua","family":"Tee","sequence":"additional","affiliation":[{"name":"Shionogi Singapore Pte Ltd., 10, Anson Road, #34-14 International Plaza, Singapore 079903, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sazaly","family":"AbuBakar","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia"},{"name":"Tropical Infectious Diseases Research and Education Centre (TIDREC), University of Malaya, Kuala Lumpur 50603, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,11]]},"reference":[{"key":"ref_1","unstructured":"Goldman, M.B., Troisi, R., and Rexrode, K.M. (2013). Urinary Tract Infection. Women and Health, Academic Press. [2nd ed.]."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.idc.2013.09.003","article-title":"Urinary tract infection syndromes: Occurrence, recurrence, bacteriology, risk factors, and disease burden","volume":"28","author":"Foxman","year":"2014","journal-title":"Infect. Dis Clin. N. Am."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e103","DOI":"10.1093\/cid\/ciq257","article-title":"International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases","volume":"52","author":"Gupta","year":"2011","journal-title":"Clin. Infect. Dis."},{"key":"ref_4","unstructured":"Ministry of Health (MOH) Malaysia (2019). National Antimicrobial Guideline 2019."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/S0002-9343(02)01055-0","article-title":"The etiology of urinary tract infection: Traditional and emerging pathogens","volume":"113","author":"Ronald","year":"2002","journal-title":"Am. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/nrmicro3432","article-title":"Urinary tract infections: Epidemiology, mechanisms of infection and treatment options","volume":"13","author":"Walker","year":"2015","journal-title":"Nat. Rev. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1016\/j.molmed.2016.09.003","article-title":"Urinary Tract Infection: Pathogenesis and Outlook","volume":"22","author":"McLellan","year":"2016","journal-title":"Trends Mol. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.ajog.2017.12.231","article-title":"Diagnosis and treatment of urinary tract infections across age groups","volume":"219","author":"Chu","year":"2018","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"S44","DOI":"10.1093\/jtm\/taw102","article-title":"The ecology of extended-spectrum \u03b2-lactamases (ESBLs) in the developed world","volume":"24","author":"Doi","year":"2017","journal-title":"J. Travel Med."},{"key":"ref_10","unstructured":"(2020, September 22). National Surveillance of Antimicrobial Resistance, Malaysia, Available online: https:\/\/www.imr.gov.my\/MyOHAR\/index.php\/site\/archive_rpt."},{"key":"ref_11","first-page":"270","article-title":"A clinical update on antibiotic resistance Gram-negative bacteria in Malaysia\u2013A review","volume":"45","author":"Fazlul","year":"2019","journal-title":"J. Int. Pharm. Res."},{"key":"ref_12","unstructured":"Kawamoto, I. (1992). \u03b2-Lactams and Other Antimicrobial Agents. Antibiotics, CRC Press."},{"key":"ref_13","first-page":"1349","article-title":"The study of flomoxef in the pediatric field","volume":"40","author":"Sato","year":"1987","journal-title":"Jpn. J. Antibiot."},{"key":"ref_14","first-page":"1809","article-title":"Studies on antibacterial activity of flomoxef and its distribution to serum and intraperitoneal exudate in surgery","volume":"40","author":"Yokoyama","year":"1987","journal-title":"Jpn. J. Antibiot."},{"key":"ref_15","first-page":"1803","article-title":"Clinical studies on flomoxef in respiratory tract infections","volume":"40","author":"Kanegae","year":"1987","journal-title":"Jpn. J. Antibiot."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5107","DOI":"10.1128\/AAC.00701-15","article-title":"Multicenter retrospective study of cefmetazole and flomoxef for treatment of extended-spectrum-\u03b2-lactamase-producing Escherichia coli bacteremia","volume":"59","author":"Matsumura","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"635","DOI":"10.14740\/jocmr3928","article-title":"Change in the antimicrobial resistance profile of extended-spectrum \u03b2-lactamase-producing Escherichia coli","volume":"11","author":"Miyazaki","year":"2019","journal-title":"J. Clin. Med. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.jiac.2018.02.011","article-title":"Antimicrobial susceptibility of common pathogens isolated from postoperative intra-abdominal infections in Japan","volume":"24","author":"Takesue","year":"2018","journal-title":"J. Infect. Chemother."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.diagmicrobio.2018.11.017","article-title":"In vitro activity of flomoxef against extended-spectrum \u03b2-lactamase\u2013producing Escherichia coli and Klebsiella pneumoniae in Korea","volume":"94","author":"Jung","year":"2019","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1093\/jac\/dkl381","article-title":"Treatment of ESBL-producing Klebsiella pneumoniae bacteraemia with carbapenems or flomoxef: A retrospective study and laboratory analysis of the isolates","volume":"58","author":"Lee","year":"2006","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.ijantimicag.2014.11.012","article-title":"In vitro activity of flomoxef and comparators against Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis producing extended-spectrum \u03b2-lactamases in China","volume":"45","author":"Yang","year":"2015","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1007\/s10157-019-01775-w","article-title":"Increased community-acquired upper urinary tract infections caused by extended-spectrum beta-lactamase-producing Escherichia coli in children and the efficacy of flomoxef and cefmetazole","volume":"23","author":"Horie","year":"2019","journal-title":"Clin. Exp. Nephrol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.jiac.2017.04.006","article-title":"Efficacy of non-carbapenem antibiotics for pediatric patients with first febrile urinary tract infection due to extended-spectrum beta-lactamase-producing Escherichia coli","volume":"23","author":"Abe","year":"2017","journal-title":"J. Infect. Chemother."},{"key":"ref_24","first-page":"325","article-title":"Antibiotics for URTI and UTI\u2013prescribing in Malaysian primary care settings","volume":"40","author":"Teng","year":"2011","journal-title":"Aust. Fam. Physician"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Ab Rahman, N., Teng, C.L., and Sivasampu, S. (2016). Antibiotic prescribing in public and private practice: A cross-sectional study in primary care clinics in Malaysia. BMC Infect. Dis., 16.","DOI":"10.1186\/s12879-016-1530-2"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Karaiskos, I., and Giamarellou, H. (2020). Carbapenem-sparing strategies for ESBL producers: When and how. Antibiotics, 9.","DOI":"10.3390\/antibiotics9020061"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.ijantimicag.2015.07.020","article-title":"Comparative effectiveness of flomoxef versus car-bapenems in the treatment of bacteraemia due to extended-spectrum \u03b2-lactamase-producing Escherichia coli or Klebsiella pneumoniae with emphasis on minimum inhibitory concentration of flomoxef: A retrospective study","volume":"46","author":"Lee","year":"2015","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Yang, C.C., Li, S.H., Chuang, F.R., Chen, C.H., Lee, C.H., Chen, J.B., Wu, C.H., and Lee, C.T. (2012). Discrepancy between effects of carbapenems and flomoxef in treating nosocomial hemodialysis access-related bacteremia secondary to extended spectrum beta-lactamase producing Klebsiella pneumoniae in patients on maintenance hemodialysis. BMC Infect. Dis., 12.","DOI":"10.1186\/1471-2334-12-206"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1128\/AAC.01009-09","article-title":"Updated functional classification of beta-lactamases","volume":"54","author":"Bush","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_30","first-page":"14","article-title":"Antimicrobial susceptibility of Klebsiella pneumoniae and Escherichia coli with extended-spectrum \u03b2-lactamase associated genes in Hospital Tengku Ampuan Afzan, Kuantan, Pahang","volume":"23","author":"Mohsen","year":"2016","journal-title":"Malays. J. Med Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1089\/mdr.2011.0222","article-title":"Prevalence and characterization of multi-drug-resistant and extended-spectrum beta-lactamase-producing Escherichia coli from pediatric wards of a Malaysian hospital","volume":"18","author":"Ho","year":"2012","journal-title":"Microb. Drug Resist."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/s42770-019-00208-w","article-title":"Molecular characterization of extended-spectrum \u03b2-lactamase-producing Klebsiella pneumoniae from a Malaysian hospital","volume":"51","author":"Mobasseri","year":"2019","journal-title":"Braz. J. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.jgar.2018.12.015","article-title":"The emergence of colistin-resistant Klebsiella pneumoniae strains from swine in Malaysia","volume":"17","author":"Mobasseri","year":"2019","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1128\/AAC.35.9.1697","article-title":"More extended-spectrum beta-lactamases","volume":"35","author":"Jacoby","year":"1991","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.sjbs.2014.08.002","article-title":"Antibiotic resistance and extended spectrum beta-lactamases: Types, epidemiology and treatment","volume":"22","author":"Shaikh","year":"2015","journal-title":"Saudi J. Biol. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"326","DOI":"10.21037\/atm.2016.09.14","article-title":"Resistance mechanisms","volume":"4","author":"Cag","year":"2016","journal-title":"Ann. Transl. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1128\/JCM.01544-09","article-title":"Positive extended-spectrum-\u03b2-lactamase (ESBL) screening results may be due to ampC \u03b2-lactamases more often than to ESBLs","volume":"48","author":"Munier","year":"2010","journal-title":"J. Clin. Microbiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1128\/JCM.01687-08","article-title":"Unreliable extended-spectrum \u03b2-lactamase detection in the presence of plasmid-mediated AmpC in Escherichia coli clinical isolates","volume":"47","author":"Robberts","year":"2009","journal-title":"J. Clin. Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4178","DOI":"10.1128\/JCM.43.8.4178-4182.2005","article-title":"Multilocus sequence typing of Klebsiella pneumoniae nosocomial isolates","volume":"43","author":"Diancourt","year":"2005","journal-title":"J. Clin. Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1016\/S0025-326X(99)00164-2","article-title":"A sensitive and versatile multiplex PCR system for the rapid detection of enter-otoxigenic (ETEC), enterohaemorrhagic (EHEC) and enteropathogenic (EPEC) strains of Escherichia coli. Mar","volume":"38","author":"Kong","year":"1999","journal-title":"Pollut. Bull."},{"key":"ref_41","unstructured":"Clinical and Laboratory Standards Institute (CLSI) (2020). Performance Standards for Antimicrobial Susceptibility Testing, Clinical and Laboratory Standards Institute (CLSI). [30th ed.]. CLSI Suppl. M100."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1093\/jac\/dkp498","article-title":"Development of a set of multiplex PCR assays for the detection of genes encoding important \u03b2-lactamases in Enterobacteriaceae","volume":"65","author":"Dallenne","year":"2010","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1128\/AAC.48.4.1249-1255.2004","article-title":"Dissemination of CTX-M-Type \u03b2-Lactamases among clinical isolates of Enterobacteriaceae in Paris, France","volume":"48","author":"Eckert","year":"2004","journal-title":"Antimicrob. Agents Chemother."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/10\/2\/181\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:22:54Z","timestamp":1760160174000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/10\/2\/181"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,11]]},"references-count":43,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["antibiotics10020181"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics10020181","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,11]]}}}