{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T16:29:54Z","timestamp":1791649794687,"version":"4.3.4"},"reference-count":53,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,5]]},"abstract":"<jats:title>ABSTRACT.<\/jats:title>\n<jats:p>The likelihood of antimicrobial failure in COVID-19 patients with bacterial superinfection arises from both phenotypic (biofilms) and genotypic mechanisms. This cross-sectional study aimed to determine the inhibitory concentrations of quinolones\u2014nalidixic acid, norfloxacin, ciprofloxacin, ofloxacin, and levofloxacin\u2014in biofilm formers (minimum biofilm inhibitory concentration [MBIC]) and nonformers (minimum inhibitory concentration [MIC]) and correlate inhibitory concentrations with plasmid-mediated quinolone resistance (PMQR) genes in quinolone-resistant bacteria isolated from COVID-19 inpatients. Quinolone-resistant bacteria (<jats:italic>n<\/jats:italic> = 193), verified through disc diffusion, were tested for quinolone inhibitory concentrations using broth microdilution and biofilm formation using microtiter plate methods. The polymerase chain reaction was used to detect PMQR genes. Study variables were analyzed using SPSS v.17.0, with a significance level set at <jats:italic>P<\/jats:italic> &lt;0.05. MIC-to-MBIC median fold increases for ciprofloxacin, ofloxacin, and levofloxacin were 128 (2\u20138,192), 64 (4\u20131,024), and 32 (4\u2013512) in gram-positive cocci (GPC, <jats:italic>n<\/jats:italic> = 43), respectively, whereas they were 32 (4\u20138,192), 32 (4\u20132,048), and 16 (2\u20131,024) in fermentative gram-negative bacilli (F-GNB, <jats:italic>n<\/jats:italic> = 126) and 16 (4\u20134,096), 64 (2\u201364), and 16 (8\u2013512) in nonfermentative gram-negative bacilli (NF-GNB, <jats:italic>n<\/jats:italic> = 24). In biofilm-forming F-GNB and NF-GNB, <jats:italic>qnrB<\/jats:italic> (10\/32 versus 3\/10), <jats:italic>aac(6\u2032)-Ib-cr<\/jats:italic> (10\/32 versus 4\/10), and <jats:italic>qnrS<\/jats:italic> (9\/32 versus 0\/10) genes were detected. A 32-fold median increase in the MIC-to-MBIC of ciprofloxacin was significantly (<jats:italic>P<\/jats:italic> &lt;0.05) associated with <jats:italic>qnrA<\/jats:italic> in F-GNB and <jats:italic>qnrS<\/jats:italic> in NF-GNB. Biofilms formed by F-GNB and NF-GNB were significantly associated with the <jats:italic>aac(6\u2032)-Ib-cr and qnrS<\/jats:italic> genes, respectively. Nearly one-third of the superinfecting bacteria in COVID-19 patients formed biofilms and had at least one PMQR gene, thus increasing the need for quinolones at higher inhibitory concentrations.<\/jats:p>","DOI":"10.4269\/ajtmh.24-0276","type":"journal-article","created":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T15:51:06Z","timestamp":1732031466000},"page":"346-354","source":"Crossref","is-referenced-by-count":4,"title":["Biofilm Formation and Plasmid-Mediated Quinolone Resistance Genes at Varying Quinolone Inhibitory Concentrations in Quinolone-Resistant Bacteria Superinfecting COVID-19 Inpatients"],"prefix":"10.4269","volume":"112","author":[{"given":"Ajaya","family":"Basnet","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology, Shi-Gan International College of Science and Technology, Tribhuvan University, Kathmandu, Nepal;"},{"name":"Department of Microbiology, Nepal Armed Police Force Hospital, Kathmandu, Nepal;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun Bahadur","family":"Chand","sequence":"additional","affiliation":[{"name":"Department of Microbiology, KIST Medical College and Teaching Hospital, Lalitpur, Nepal;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sohani","family":"Bajracharya","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Kanti Children\u2019s Hospital, Kathmandu, Nepal;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahendra Raj","family":"Shrestha","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Nepal Armed Police Force Hospital, Kathmandu, Nepal;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shila","family":"Shrestha","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Shi-Gan International College of Science and Technology, Tribhuvan University, Kathmandu, Nepal;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basanta","family":"Tamang","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Nepal Armed Police Force Hospital, Kathmandu, Nepal;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maina","family":"Dulal","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Shi-Gan International College of Science and Technology, Tribhuvan University, Kathmandu, Nepal;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nayanum","family":"Pokhrel","sequence":"additional","affiliation":[{"name":"Research Section, Nepal Health Research Council, Kathmandu, Nepal;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lok Bahadur","family":"Shrestha","sequence":"additional","affiliation":[{"name":"School of Medical Sciences and The Kirby Institute, University of New South Wales, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2795","reference":[{"key":"b1","series-title":"Respir Res","article-title":"From SARS and MERS to COVID-19: A brief summary and comparison of severe acute respiratory infections caused by three highly pathogenic human coronaviruses","volume":"21","author":"Zhu","year":"2020"},{"key":"b2","series-title":"Eur J Epidemiol","first-page":"1099","article-title":"The potential impact of previous exposure to SARS or MERS on control of the COVID-19 pandemic","volume":"35","author":"Huang","year":"2020"},{"key":"b3","series-title":"Pneumonia (Nathan)","first-page":"5","article-title":"The role of co-infections and secondary infections in patients with COVID-19","volume":"13","author":"Feldman","year":"2021"},{"key":"b4","series-title":"New Microbes New Infect","first-page":"100910","article-title":"Bacterial coinfection among coronavirus disease 2019 patient groups: An updated systematic review and meta-analysis","volume":"43","author":"Soltani","year":"2021"},{"key":"b5","series-title":"Trends Microbiol","first-page":"930","article-title":"Bacterial coinfections in coronavirus disease 2019","volume":"29","author":"Westblade","year":"2021"},{"key":"b6","series-title":"Clin Microbiol Infect","first-page":"1622","article-title":"Bacterial co-infection and secondary infection in patients with COVID-19: A living rapid review and meta-analysis","volume":"26","author":"Langford","year":"2020"},{"key":"b7","series-title":"AIMS Microbiol","first-page":"482","article-title":"An overview of the antimicrobial resistance mechanisms of bacteria","volume":"4","author":"Reygaert","year":"2018"},{"key":"b8","series-title":"Trends Microbiol","first-page":"438","article-title":"Fluoroquinolone resistance: Mechanisms, impact on bacteria, and role in evolutionary success","volume":"22","author":"Redgrave","year":"2014"},{"key":"b9","series-title":"BMC Infect Dis","article-title":"Association between the rate of fluoroquinolones-resistant gram-negative bacteria and antibiotic consumption from China based on 145 tertiary hospitals data in 2014","volume":"20","author":"Yang","year":"2020"},{"key":"b10","series-title":"Antimicrob Resist Infect Control","first-page":"76","article-title":"Antibiotics versus biofilm: An emerging battleground in microbial communities","volume":"8","author":"Sharma","year":"2019"},{"key":"b11","series-title":"Egypt J Basic Appl Sci","first-page":"64","article-title":"Bacterial biofilm dependent catheter associated urinary tract infections: Characterization, antibiotic resistance pattern and risk factors","volume":"8","author":"Ramadan","year":"2021"},{"key":"b12","series-title":"Australas Med J","first-page":"344","article-title":"Antiobiotic resistance pattern of biofilm-forming uropathogens isolated from catheterised patients in Pondicherry","volume":"5","author":"Subramanian","year":"2012"},{"key":"b13","series-title":"Clin Microbiol Infect","first-page":"981","article-title":"Antimicrobial susceptibility testing in biofilm-growing bacteria","volume":"20","author":"Macia","year":"2014"},{"key":"b14","series-title":"Biol Proced Online","first-page":"18","article-title":"MBEC versus MBIC: The lack of differentiation between biofilm reducing and inhibitory effects as a current problem in biofilm methodology","volume":"21","author":"Thieme","year":"2019"},{"key":"b15","series-title":"Koneman\u2019s Color Atlas and Textbook of Diagnostic Microbiology","author":"Procop","year":"2020"},{"key":"b16","series-title":"Lancet Microbe","first-page":"e354","article-title":"Co-infections, secondary infections, and antimicrobial use in patients hospitalised with COVID-19 during the first pandemic wave from the ISARIC WHO CCP-UK study: A multicentre, prospective cohort study","volume":"2","author":"Russell","year":"2021"},{"key":"b17","series-title":"J Clin Microbiol","first-page":"e0021321","article-title":"Overview of changes to the Clinical and Laboratory Standards Institute performance standards for antimicrobial susceptibility testing, M100","volume":"59","author":"Humphries","year":"2021"},{"key":"b18","series-title":"J Clin Microbiol","first-page":"996","article-title":"Adherence of coagulase-negative staphylococci to plastic tissue culture plates: A quantitative model for the adherence of staphylococci to medical devices","volume":"22","author":"Christensen","year":"1985"},{"key":"b19","series-title":"Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically","author":"Waitz","year":"1990"},{"key":"b20","series-title":"Int J Curr Microbiol Appl Sci","first-page":"198","article-title":"Biofilm quantification and comparative analysis of MIC (minimum inhibitory concentration) & MBIC (minimum biofilm inhibitory concentration) value for different antibiotics against E. coli.","volume":"4","author":"Ankit","year":"2015"},{"key":"b21","series-title":"Cold Spring Harb Protoc","article-title":"Preparation of plasmid DNA by alkaline lysis with sodium dodecyl sulfate: Minipreps","volume":"2016:","author":"Green","year":"2016"},{"key":"b22","series-title":"medRxiv","article-title":"Precautions are needed for COVID-19 patients with coinfection of common respiratory pathogens","author":"Xing","year":"2020"},{"key":"b23","series-title":"Biology (Basel)","first-page":"822","article-title":"Profile of bacterial infections in COVID-19 patients: Antimicrobial resistance in the time of SARS-CoV-2","volume":"10","author":"Stefanini","year":"2021"},{"key":"b24","series-title":"BMC Infect Dis","first-page":"108","article-title":"Bacterial co-infections in community-acquired pneumonia caused by SARS-CoV-2, influenza virus and respiratory syncytial virus","volume":"22","author":"Hedberg","year":"2022"},{"key":"b25","series-title":"Front Microbiol","first-page":"1176","article-title":"Enhanced bacterial fitness under residual fluoroquinolone concentrations is associated with increased gene expression in wastewater-derived qnr plasmid-harboring strains","volume":"9","author":"Kaplan","year":"2018"},{"key":"b26","series-title":"Lancet","first-page":"1054","article-title":"Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study","volume":"395","author":"Zhou","year":"2020"},{"key":"b27","series-title":"Lancet","first-page":"497","article-title":"Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China","volume":"395","author":"Huang","year":"2020"},{"key":"b28","series-title":"Infect Control Hosp Epidemiol","first-page":"1228","article-title":"Coinfections with SARS-CoV-2 and other respiratory pathogens","volume":"41","author":"Hazra","year":"2020"},{"key":"b29","series-title":"JAMA","first-page":"275","article-title":"Bacterial coinfection in influenza: A grand rounds review","volume":"309","author":"Chertow","year":"2013"},{"key":"b30","series-title":"JNMA J Nepal Med Assoc","first-page":"294","article-title":"Co-infection of uropathogenic Escherichia coli among COVID-19 patients admitted to a tertiary care centre: A descriptive cross-sectional study","volume":"60","author":"Basnet","year":"2022"},{"key":"b31","series-title":"J Infect","first-page":"266","article-title":"Co-infections in people with COVID-19: A systematic review and meta-analysis","volume":"81","author":"Lansbury","year":"2020"},{"key":"b32","series-title":"GMS Hyg Infect Control","first-page":"Doc29","article-title":"Random effects meta-analysis of COVID-19\/S. aureus partnership in co-infection","volume":"15","author":"Adeiza","year":"2020"},{"key":"b33","series-title":"Lancet Respir Med","first-page":"251","article-title":"Comparison of the characteristics, morbidity, and mortality of COVID-19 and seasonal influenza: A nationwide, population-based retrospective cohort study","volume":"9","author":"Piroth","year":"2021"},{"key":"b34","series-title":"J Infect Dev Ctries","first-page":"818","article-title":"Detection of plasmid-mediated qnr genes among the quinolone-resistant Escherichia coli isolates in Iran","volume":"8","author":"Firoozeh","year":"2014"},{"key":"b35","series-title":"Braz J Microbiol","first-page":"462","article-title":"Prevalence of antimicrobial resistance and integrons in Escherichia coli from Punjab, Pakistan","volume":"42","author":"Muhammad","year":"2011"},{"key":"b36","series-title":"Braz J Biol","first-page":"239868","article-title":"Phenotypic and molecular characterization of fluoroquinolone resistant Pseudomonas aeruginosa isolates in Palestine","volume":"82","author":"Adwan","year":"2022"},{"key":"b37","series-title":"Infect Drug Resist","first-page":"915","article-title":"Investigation of six plasmid-mediated quinolone resistance genes among clinical isolates of pseudomonas: A genotypic study in Saudi Arabia","volume":"12","author":"El-Badawy","year":"2019"},{"key":"b38","series-title":"Sci Rep","first-page":"2296","article-title":"Occurrence of plasmid-mediated quinolone resistance genes in Pseudomonas aeruginosa strains isolated from clinical specimens in southwest Iran: A multicentral study","volume":"12","author":"Saki","year":"2022"},{"key":"b39","series-title":"Osong Public Health Res Perspect","first-page":"307","article-title":"Plasmid-mediated quinolone-resistance (qnr) genes in clinical isolates of Escherichia coli collected from several hospitals of Qazvin and Zanjan Provinces, Iran","volume":"7","author":"Rezazadeh","year":"2016"},{"key":"b40","series-title":"J Nepal Health Res Counc","first-page":"173","article-title":"Bacteriological profile and antimicrobial susceptibility pattern among isolates obtained from body fluids","volume":"17","author":"Shrestha","year":"2019"},{"key":"b41","series-title":"Antimicrob Resist Infect Control","first-page":"5","article-title":"Correlation between biofilm formation and resistance toward different commonly used antibiotics along with extended spectrum beta lactamase production in uropathogenic Escherichia coli isolated from the patients suspected of urinary tract infections visiting Shree Birendra Hospital, Chhauni, Kathmandu, Nepal","volume":"5","author":"Neupane","year":"2016"},{"key":"b42","series-title":"Indian J Nephrol","first-page":"30","article-title":"Clinico-microbiological profile of urinary tract infection in south India","volume":"21","author":"Eshwarappa","year":"2011"},{"key":"b43","series-title":"J Med Microbiol","first-page":"471","article-title":"Propensity for biofilm formation by clinical isolates from urinary tract infections: Developing a multifactorial predictive model to improve antibiotherapy","volume":"63","author":"Alves","year":"2014"},{"key":"b44","series-title":"Can J Infect Dis Med Microbiol","first-page":"e60","article-title":"Mechanisms of reduced susceptibility to ciprofloxacin in Escherichia coli isolates from Canadian hospitals","volume":"23","author":"Baudry-Simner","year":"2012"},{"key":"b45","series-title":"Antimicrob Agents Chemother","first-page":"2031","article-title":"Use of a broad-host-range gyrA plasmid for genetic characterization of fluoroquinolone-resistant gram-negative bacteria","volume":"35","author":"Heisig","year":"1991"},{"key":"b46","series-title":"Antimicrob Agents Chemother","first-page":"229","article-title":"Relationships among ciprofloxacin, gatifloxacin, levofloxacin, and norfloxacin MICs for fluoroquinolone-resistant Escherichia coli clinical isolates","volume":"53","author":"Becnel Boyd","year":"2009"},{"key":"b47","series-title":"Curr Res Bacteriol","first-page":"24","article-title":"Molecular detection of qnrA, qnrB and qnrS resistance genes among Salmonella spp. in Iran","volume":"5","author":"Saboohi","year":"2011"},{"key":"b48","series-title":"Ann Acad Med Singap","first-page":"1070","article-title":"Plasmid-mediated quinolone resistance determinants in urinary isolates of Escherichia coli and Klebsiella pneumoniae in a large Singapore hospital","volume":"38","author":"Deepak","year":"2009"},{"key":"b49","series-title":"J Antimicrob Chemother","first-page":"804","article-title":"First detection of plasmid-mediated quinolone resistance (qnrA and qnrS) in Escherichia coli strains isolated from humans in Scandinavia","volume":"59","author":"Cavaco","year":"2007"},{"key":"b50","series-title":"Clin Infect Dis","first-page":"1736","article-title":"Population-based laboratory surveillance for Escherichia coli-producing extended-spectrum \u03b2-lactamases: Importance of community isolates with blaCTX-M genes","volume":"38","author":"Pitout","year":"2004"},{"key":"b51","series-title":"Iran J Med Microbiol","first-page":"10","article-title":"Frequency of plasmid-mediated quinolone resistance genes among clinical isolates of Pseudomonas aeruginosa in Kerman, Iran","volume":"11","author":"Rajaei","year":"2017"},{"key":"b52","series-title":"Infect Disord Drug Targets","first-page":"49","article-title":"Plasmid-mediated quinolone resistance in Pseudomonas aeruginosa isolated from burn patients in Tehran, Iran","volume":"20","author":"Molapour","year":"2020"},{"key":"b53","series-title":"J Antimicrob Chemother","first-page":"795","article-title":"Dose-related selection of fluoroquinolone-resistant Escherichia coli","volume":"60","author":"Olofsson","year":"2007"}],"container-title":["The American Journal of Tropical Medicine and Hygiene"],"original-title":[],"link":[{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/112\/2\/article-p346.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.ajtmh.org\/downloadpdf\/journals\/tpmd\/112\/2\/article-p346.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/www.ajtmh.org\/downloadpdf\/journals\/tpmd\/112\/2\/article-p346.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T18:43:31Z","timestamp":1738781011000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/112\/2\/article-p346.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,5]]},"references-count":53,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.4269\/ajtmh.24-0276","relation":{},"ISSN":["0002-9637","1476-1645"],"issn-type":[{"value":"0002-9637","type":"print"},{"value":"1476-1645","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,5]]}}}