In vitro effect of fosfomycin on multi-drug resistant gram-negative bacteria causing urinary tract infections

Infection and Drug Resistance Dovepress open access to scientific and medical research Infection and Drug Resistance downloaded from https://www.dovepress.com/ by 88.198.20.149 on 21-Aug-2019 For personal use only. Open Access Full Text Article ORIGINAL RESEARCH In vitro effect of fosfomycin on multi-drug resistant gram-negative bacteria causing urinary tract infections This article was published in the following Dove Press journal: Infection and Drug Resistance Pallam Gopichand 1 Girija Agarwal 2 Mailan Natarajan 1 Jharna Mandal 1 Surendran Deepanjali 3 Sreejith Parameswaran 4 LN Dorairajan 5 1 Department of Microbiology, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Pondicherry, India; 2Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Pondicherry, India; 3 Department of Medicine, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Pondicherry, India; 4Department of Nephrology, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Pondicherry, India; 5 Department of Urology, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Pondicherry, India Background: Rising rates of resistance to antimicrobial drugs among Enterobacteriaceae limit the choice of therapeutic agents to treat urinary tract infections. In this context we assessed the invitro effect of fosfomycin against extended-spectrum beta-lactamases, AmpC beta-lactamases and carbapenemase-producing strains of Escherichia coli, Klebsiella pneumoniae, Enterobacter spp, and Pseudomonas aeruginosa isolated from the patients with urinary tract infection (UTI) and also studied the effect of fosfomycin on their biofilm formation. Materials and methods: A total of 326 multidrug-resistant (MDR) isolates comprising of Escherichia coli, Klebsiella pneumoniae, Enterobacter spp, and Pseudomonas aeruginosa from the urine samples of the patients with a diagnosis of UTI were included in the study. MIC 50 and MIC 90 were detected by agar dilution method and the capacity to form biofilm in the presence of fosfomycin by these MDR isolates was assessed by the tissue culture plate method. Results: The MIC50 for meropenem (0.5 µgm/mL) and nitrofurantoin (32 µgm/mL) was within the susceptible range only for E. coli. Fosfomycin was the only antibiotic that inhibited 100% E.coli, 70% Klebsiella spp, and 50% Pseudomonas spp and 40% Enterobacter spp which included the extended-spectrum beta-lactamases producers. It showed a similar effect on carbapenemase producers and AmpC producers. Fosfomycin disrupted biofilm in 67% (n=141) E.coli, 74% (n=50) Klebsiella spp, 88% (n=27) Pseudomonas spp and 36% (n=23) Enterobacter spp at 24 hrs of incubation with a concentration of 2 fold dilution lower than that of the MIC. Conclusion : Fosfomycin showed a good inhibitory effect on the biofilms produced by the MDR organisms studied here. Keywords: fosfomycin, MDR, UTI, MIC, biofilm Introduction Correspondence: Jharna Mandal Department of Microbiology, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Pondicherry, India Tel +91 967 745 1239 Email 2005 submit your manuscript | www.dovepress.com Infection and Drug Resistance 2019:12 2005–2013 DovePress © 2019 Gopichand et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/ terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). http://doi.org/10.2147/IDR.S207569 Powered by TCPDF (www.tcpdf.org) The most common cause of all forms of UTIs is Escherichia coli (uropathogenic Escherichia coli), followed by other members of Enterobacteriaceae like Klebsiella, Proteus, Enterobacter spp and other gram positives like Enterococci and Staphylococcus spp.1 Urinary tract infections caused by drug-resistant Enterobacteriaceae have been on the rise.2 The emergence of the multidrug-resistant (MDR) strains with either inherited or transmissible resistance, is resistant to most of the commonly used antibiotics has become a concern for treating UTI, both in the community as well as the hospital.2 The most disconcerting events are the UTIs caused by Carbapenemase-producing Enterobacteriaceae which are difficult-to-treat and are usually characterized Dovepress Infection and Drug Resistance downloaded from https://www.dovepress.com/ by 88.198.20.149 on 21-Aug-2019 For personal use only. Gopichand et al by high mortality.3 Many MDR pathogens are also known to produce biofilms in catheterized patients which are extremely difficult to treat.4 In this era of increasing antimicrobial resistance, there is definitely a need for a newer drug that is orally active, has low levels of existing resistance and also has an effect on biofilms. Fosfomycin is a relatively old drug and the present study was conducted to determine the effect of fosfomycin on MDR pathogens as well as its effect on biofilm formation by these isolates. Oral single-dose fosfomycin is considerably effective for the treatment of uncomplicated urinary tract infection.5 Other traditional empirical antibiotic regimens which are commonly used for treating uncomplicated urinary tract infections, such as fluoroquinolones and co-trimoxazole, might be not active against these pathogens that produce ESBL and can lead to suboptimum outcomes and treatment failure.6 Apart from fosfomycin, nitrofurantoin, and coamoxiclav could be other options for oral antimicrobial treatment of ESBL-associated but otherwise uncomplicated urinary tract infections. Furthermore, because of its unique chemical structure and mechanism of action, fosfomycin seems to be spared from the effect of various mechanisms of resistance to antimicrobial drugs. Apart from the Enterobacteriaceae that produce ESBL, the very good antimicrobial effect of fosfomycin has also been reported in Enterobacteriaceae that are resistant to fluoroquinolones. Due to its improved pharmacokinetics, fosfomycin is increasingly used for UTIs and has been approved as an oral single-dose treatment for acute uncomplicated cystitis with mean peak urinary concentration of an oral single dose of 3 g fosfomycin tromethamine, while concentrations sufficient to inhibit the majority of the urinary pathogens can be maintained for 1 to 2 days. Though this easy dosage schedule ensures compliance but the chance of clinical cure may be compromised.7 Materials and methods Study design The study was conducted in Jawaharlal Institute of Postgraduate Medical Education & Research (...truncated)