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Introduction: Urinary tract infections (UTI) are the most common bacterial infections affecting humans.. Fosfomycin has been approved for use in uncomplicated UTI caused by E. coli and Enterococcus. However, data regarding sensitivity of organisms causing hospital acquired or complicated UTI is scarce worldwide. We aimed to determine the in vitro sensitivity of drug resistant organisms causing hospital acquired and complicated UTI towards fosfomycin.
Materials and Methods: Over a 6 month period, urine samples were processed as per standard microbiological protocols. Bacterial isolates were identified by routine microbiological methods followed by automated methods. Antibiotic sensitivity tests were done for different antibiotics. Fosfomycin sensitivity was tested by disc diffusion assay and minimum inhibitory concentration (MIC) was determined by E test method.
Results: A total of 248` organisms causing hospital acquired and/or complicated UTI were isolated of which E. coli 88(35.48%) was most common followed by K. pneumoniae 78(31.45%) and P. aeruginosa 64(25.80%). Of 248, 92.74% (230/248) isolates were sensitive to fosfomycin. All the E. coli isolates were sensitive to fosfomycin with a low MIC (range 0.064-16 mg/L) while 97.43% (76/78) of the K. pneumoniae and 71.87% (46/64) P. aeruginosa of isolates were sensitive with a higher MIC (range 0.5-32 mg/L and 6-64mg/L respectively). Fosfomycin MIC geometric mean among E. coli, K. pneumoniae and P. aeruginosa was; 1.05, 7.19 and 19.61 mg/L respectively. K. pneumoniae and P. aeruginosa showed a significantly higher geometric mean MIC compare to E. coli (P <0.0001).
Conclusions: This study suggests that fosfomycin has the potential to replace the parenteral antibiotics for treating complicated or hospital acquired lower UTI especially in case of Enterobacteriaceae.
Bader MS, Hawboldt J, Brooks A. Management of complicated urinary tract infections in the era of antimicrobial resistance. Postgrad Med. 2010;122(6):7-15.
Seroy JT, Grim SA, Reid GE, Wellington T, Clark NM. Treatment of MDR urinary tract infections with oral fosfomycin: A retrospective analysis. J Antimicrob Chemother. 2016;71(9):2563-8.
Liu HY, Lin HC, Lin YC, Yu SH, Wu WH, Lee YJ. Antimicrobial susceptibilities of urinary extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae to fosfomycin and nitrofurantoin in a teaching hospital in Taiwan. J Microbiol Immunol Infect. 2011;44(5):364-8.
Gupta K. Emerging antibiotic resistance in urinary tract pathogens. Infect Dis Clin North Am. 2003;17:243e59.
Gupta K, Hooton TM, Naber KG, Wullt B, Colgan R, Miller LG, et al. 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. Clin Infect Dis. 2011;52:e103-20.
Falagas ME, Vouloumanou EK, Samonis G, Vardakas KZ. Fosfomycin. Clin Microbiol Rev. 2016;29(2):321-347
Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG Harbarth S, Hindler JF, Kahlmeter G, Olsson-Liljequist B, Paterson DL, Rice LB, Stelling J, Struelens MJ, Vatopoulos A, Weber JT, Monnet DL. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2012;18(3):268-81
Schaeffer AJ, Matulewicz RS, Klumpp DJ. Infections of the urinary tract. In: McDougall S, Wein AJ, Kavoussi LR, Partin AW, Peters CA. Campbell-Walsh Urology. 11th ed. USA: Elsevier. 2015;804-05
Hooton TM. Nosocomial urinary tract infections. In: Bennett JE, Dolin R, Blaser MJ, editors. Mandell, Douglas and Benett’s Principle and Practice of Infectious Diseases. 8th Ed. Philadelphia: Elsevier; 2015;3334-46.
Collee JG, Fraser AG, Marmion BP, Simmons A. Tests for the identification of bacteria. In: Collee JG, Miles RS, Watt B, editors. Mackey and McCartney Practical Medical Microbiology. 14th ed. New Delhi: Elsevier. 2006;131–49.
Baltimore, USA: Clinical and laboratory standards institute. Clinical and laboratory standards institute 2003. Performance standards for antimicrobial susceptibility testing: Eighteenth Informational Supplement: Approved Standards. 2008;M100S18.
European committee on antimicrobial susceptibility testing clinical breakpoints-bacteria, version 5.0; 2015.
Sastry S, Clarke LG, Alrwais H, Querry AM, Shutt KA, Doi Y. Clinical appraisal of fosfomycin in the era of antimicrobial resistance. Antimicrob Agents Chemother, 2015;59:7355–7361.
De Cueto M, Lo’pez L, Hern’andez JR, Morillo C, Pascual A. In vitro activity of fosfomycin against extended-spectrum- lactamase- producing Escherichia coli and Klebsiella pneumoniae: Comparison of Susceptibility Testing Procedures. Antimicrob Agents Chemother. 2006;50(1): 368-370.
Linsenmeyer K, Strymish J, Weir S, Berg, G, Brecher S, Gupta K. Acitvity of fosfomycin for ESBL uropathogens in community and hospitalized patients. Antimicrob Agents Chemother. 2015;60(2):1134-6. DOI:10.1128/AAC.02614-15
Demir T, Buyukguclu T. Evaluation of the in vitro activity of fosfomycin tromethamine against gram-negative bacterial strains recovered from community- and hospital-acquired urinary tract infections in Turkey, Int J Infect Dis. 2013;17(11):966-70.
Sultan A, Rizvi M, Khan F, Sami H, Shukla I, Khan HM. Increasing antimicrobial resistance among uropathogens: Is fosfomycin the answer? Urol Ann. 2015;7(1):26–30.
Qiao LD, Chen S, Yang Y, Zhang K, Zheng B, Guo HF, Yang B, Niu YJ, Wang Y, Shi BK, Yang WM, Zhao XK, Gao XF, Chen M, Tian Y. Characteristics of urinary tract infection pathogens and their in vitro susceptibility to antimicrobial agents in China: data from a multicenter study. BMJ Open. 2013;3(12):e004152.
Hirsch EB, Raux BR, Zucchi PC, Kim Y, McCoy C, Kirby JE, Wright SB, Eliopoulos GM. Activity of fosfomycin and comparison of several susceptibility testing methods against contemporary urine isolates. Int J Antimicrob Agents. 2015;46(6):642-7.
Kaase M, Szabados F, Anders A, Gatermann SG. Fosfomycin susceptibility in carbapenem-resistant Enterobacteriaceae from Germany. J Clin Microbiol. 2014;52:1893–7.
Verdakas KZ, Legakis NJ, Triarides N, Falagas ME. Susceptibility of contemporary isolates to fosfomycin: A systematic review of the literature. Int J Antimicrob Agents. 2016;47(4):269-85.
Perdigao-Neto LV, Oliveira MS, Rizek CF, Carrilho CM, Costa SF, Levin AS. Susceptibility of multiresistant gram-negative bacteria to fosfomycin and performance of different susceptibility testing methods. Antimicrob Agents Chemother. 2014;58(3):1763-7.
Livermore DM, Warner M, Mushtaq S, Doumith M, Zhang J, Woodford N. What remains against carbapenem-resistant Enterobacteriaceae? Evaluation of chloramphenicol, ciprofloxacin, colistin, fosfomycin, minocycline, nitrofu- rantoin, temocillin and tigecycline. Int J Antimicrob Agents. 2011;37:415–9.
Chitra C, Kumar DRN, Shakti L, Diana SR, Balaji V. Technical and interpretative issues of fosfomycin susceptibility testing. Ind J Med Microbiol. 2015;33(4):611-12.
Lu CL, Liu CY, Huang YT, Liao CH, Teng LJ, Turnidge JD, Hseueh PR. Antimicrobial susceptibilities of commonly encountered bacterial isolates to fosfomycin determined by agar dilution and disk diffusion methods. Antimicrob Agents Chemother. 2011;55(9):4295-301.
del Mar Casal M, Causse M, Rodríguez-López F, Casal M. Antimicrobial resistance in clinical patterns of Pseudomonas aeruginosa. Rev Esp Quimioter. 2012;25: 37–41 [In Spanish].
García-Rodríguez JA, Trujillano Martín I, Baquero F, Cisterna R, Gobernado M, Liñares F, Martín-Luengo F, Piédrola G. In vitro activity of fosfomycin trometamol against pathogens from urinary tract infections: A Spanish multicenter study. J Chemother. 1997;9:394–402.
Diez-Aguilar M, Morosini MI, del Campo R, Garcia-Castillo M, Zamora J, Canton R. In vitro activity of fosfomycin against a collection of clinical Pseudomonas aeruginosa isolates from 16 Spanish hospitals: establishing the validity of standard broth microdilution as susceptibility testing method. Antimicrob Agents Chemother. 2013;57:5701–5703.
Jacobson S, Junco Noa L, Ahmed S, Wallace MR. Efficacy and safety of oral fosfomycin for urinary tract infections in hospitalized patients. Antimicrob Agents Chemother. 2016;60:1952.
Pallett A, Hand K. Complicated urinary tract infections: Practical solutions for the treatment of multiresistant Gram-negative bacteria. J Antimicrob Chemother. 2010;65 (Suppl 3):25-33.