Determination of fosfomycin susceptibility in carbapenemaseproducing K. pneumoniae strains isolated prior to clinical use of the intravenous formulation in Turkey

Year 2021, , 127 - 131, 31.05.2021

Gülsen Altınkanat Gelmez Barış Can Buket Erturk Sengel Volkan Korten Güner Soyletır

https://doi.org/10.5472/marumj.942784

Abstract

Objectives: The incidence of infections caused by carbapenem-resistant Enterobacteriaceae has increased worldwide. Limitations
in the development of new antimicrobial agents have led clinicians to reconsider the clinical efficiency of old antibiotics, such as
intravenous formulation of fosfomycin, in the treatment of multidrug-resistant Gram-negative bacterial infections. We investigated
the fosfomycin susceptibility of carbapenemase-producing Klebsiella pneumoniae strains isolated prior to the clinical use of the
intravenous formulation of fosfomycin in Turkey.
Materials and Methods: A total of the 155 K. pneumoniae isolates which previously characterized at the molecular level for their
carbapenemase were included in this study. The minimum inhibitory concentration of fosfomycin was determined by the agar
dilution method.
Results: Overall, 65.1% of the isolates were susceptible to fosfomycin. The MIC50 and MIC90 values were 32 and 256 mg/L, respectively.
According to our results, at least two-third of carbapenemase-positive K. pneumoniae are susceptible to fosfomycin.
Conclusions: Although, the susceptibility of fosfomycin, which has just been put into the clinical use of intravenous formulation in
Turkey, is not very high, it can be considered as an alternative

Keywords

Fosfomycin susceptibility, Carbapenemase-producing, Klebsiella pneumoniae

References

• Tzouvelekis LS, Markogiannakis A, Psichogiou M, Tassios PT, Daikos GL. Carbapenemases in Klebsiella pneumoniae and other Enterobacteriaceae: an evolving crisis of global dimensions. Clin Microbiol Rev 2012; 25:682–707. doi: 10.1128/CMR.05035-11
• Queenan AM, Bush K. Carbapenemases: the versatile betalactamases. Clin Microbiol Rev 2007; 20(3):440–458. doi: 10.1128/CMR.00001-07
• Walsh TR. Emerging carbapenemases: a global perspective. Int J Antimicrob Agents 2010; 36 Suppl 3: 8–14. doi: 10.1016/ S0924-8579(10)70004-2
• Sheu CC, Chang YT, Lin SY, Chen YH, Hsueh PR. Infections caused by carbapenem-resistant Enterobacteriaceae: An update on therapeutic options. Front Microbiol 2019; 10:80. doi: 10.3389/fmicb.2019.00080
• Raz R. Fosfomycin: an old-new antibiotic. Clin Microbiol Infect 2012;18(1):4–7. doi: 10.1111/j.1469-0691.2011.03636.x
• Grabein B, Graninger W, Rodríguez Baño J, et al. Intravenous fosfomycin–back to the future. Systemic review and metaanalysis of the clinical literature. Clin Microbiol Infect 2017; 23(6): 363–372. doi: 10.1016/j.cmi.2016.12.005
• Michalopoulos A, Virtzili S, Rafailidis P, et al. Intravenous fosfomycin for the treatment of nosocomial infections caused by carbapenem-resistant Klebsiella pneumoniae in critically ill patients: a prospective evaluation. Clin Microbiol Infect 2010; 16(2):184–186. doi: 10.1111/j.1469-0691.2009.02921.x
• European Committee on Antimicrobial Susceptibility Testing (EUCAST): Clinical breakpoints version 9.0. In: European Committee on Antimicrobial Susceptibility Testing. Vaxjo: EUCAST 2019. Available from: http://www.eucast.org
• Aktaş Z, Kayacan CB, Schneider I, et al. Carbapenem hydrolyzing oxacillinase, OXA-48, persists in Klebsiella pneumoniae in Istanbul, Turkey. Chemotherapy 2018; 54(2):101–106. doi: 10.1159/000118661.
• Perry JD, Naqvi SH, Mirza IA, et al. Prevalence of faecal carriage of Enterobacteriaceae with NDM-1 carbapenemase at military hospitals in Pakistan, and evaluation of two chromogenic media. J Antimicrob Chemother 2011; 66(10):2288–2294. doi: 10.1093/jac/dkr299
• Pitout JD, Gregson DB, Poirel L, et al. Detection of Pseudomonas aeruginosa producing metallo-beta-lactamases in a large centralized laboratory. J Clin Microbiol 2005; 43(7):3129–35. doi: 10.1128/JCM.43.7.3129-3135.2005.
• Cole JM, Schuetz AN, Hill CE, Nolte FS. Development and evaluation of a real-time PCR assay for detection of Klebsiella pneumoniae carbapenemase genes. J Clin Microbiol 2009; 47(2):322–326. doi: 10.1128/JCM.01550-08
• Roussos N, Karageorgopoulos DE, Samonis G, Falagas ME. Clinical significance of the pharmacokinetic and pharmacodynamic characteristics of fosfomycin for the treatment of patients with systemic infections. Int J Antimicrob Agents 2009; 34(6):506–515. doi: 10.1016/j. ijantimicag.2009.08.013
• Evren E, Azap KO, Çolakoğlu Ş, Arslan H. In vitro activity of fosfomycin in combination with imipenem, meropenem, colistin and tigecycline against OXA 48-positive Klebsiella pneumoniae strains. Diagn Microbiol Infect Dis 2013;76(3):335-8. doi: 10.1016/j.diagmicrobio.2013.04.004
• Yıldız SS, Kaşkatepe B, Şimşek H, Sarıgüzel FM. High rate of colistin and fosfomycin resistance among carbapenemaseproducing Enterobacteriaceae in Turkey. Acta Microbiol Immunol Hung, 2019 Mar 1;66(1):103-112. doi: 10.1556/030.65.2018.042.
• Livermore DM, Warner M, Mushtaq S, et al. What remains against carbapenem-resistant Enterobacteriaceae? Evaluation of chloramphenicol, ciprofloxacin, colistin, fosfomycin, minocycline, nitrofurantoin, temocillin, and tigecycline. Int J Antimicrob Agents 2011; 37:415–419. doi: 10.1016/j. ijantimicag.2011.01.012.
• Bielen L, Likić R, Erdeljić V, et al. Activity of fosfomycin against nosocomial multiresistant bacterial pathogens from Croatia: a multicentric study. Croat Med J 2018;59(2):56–64. doi: 10.3325/cmj.2018.59.56
• Kaase M, Szabados F, Anders A, Gatermann SG. Fosfomycin susceptibility in carbapenem-resistant Enterobacteriaceae from Germany. J Clin Microbiol 2014; 52:1893–1897. doi: 10.1128/JCM.03484-13
• Camarlinghi G, Parisio EM, Antonelli A, et al. Discrepancies in fosfomycin susceptibility testing of KPC-producing Klebsiella pneumoniae with various commercial methods. Diagn Microbiol Infect Dis 2019; 93(1):74–76. doi: 10.1016/j. diagmicrobio.2018.07.014
• Tuon FF, Rocha JL, Formighieri MS, et al. Fosfomycin susceptibility of isolates with blaKPC-2 from Brazil. J Infect 2013; 67:247–249. doi: 10.1016/j.jinf.2013.04.017
• Kopacz J, Mariano N, Colon-Urban R, et al. Identification of extended-spectrum-beta-lactamase-positive Klebsiella pneumoniae urinary tract isolates harboring KPC and CTX-M beta-lactamases in nonhospitalized patients. Antimicrob Agents Chemother 2013; 57:5166–5169. doi: 10.1128/ AAC.00043-13
• Endimiani A, Patel G, Hujer KM, et al. In vitro activity of fosfomycin against blaKPC-containing Klebsiella pneumoniae isolates, including those nonsusceptible to tigecycline and/ or colistin. Antimicrob Agents Chemother 2010; 54:526–529. doi: 10.1128/AAC.01235-09
• Souli M, Galani I, Antoniadou A, et al. An outbreak of infection due to beta-lactamase Klebsiella pneumoniae carbapenemase- 2-producing K. pneumoniae in a Greek university hospital: molecular characterization, epidemiology, and outcomes. Clin Infect Dis 2010; 50:364–373. doi: 10.1086/649865
• Paño-Pardo JR, Ruiz-Carrascoso G, Navarro-San Francisco C, et al. Infections caused by OXA-48-producing Klebsiella pneumoniae in a tertiary hospital in Spain in the setting of a prolonged, hospital-wide outbreak. J Antimicrob Chemother 2013; 68:89–96. doi: 10.1093/jac/dks364
• Choudhury S, Yeng JL, Krishnan PU. In vitro susceptibilities of clinical isolates of carbapenemase-producing Enterobacteriaceae to fosfomycin and tigecycline. Clin Microbiol Infect 2015; 21(10): e75–6. doi: 10.1016/j. cmi.2015.06.005
• Karageorgopoulos DE, Miriagou V, Tzouvelekis LS, et al. Emergence of resistance to fosfomycin used as adjunct therapy in KPC Klebsiella pneumoniae bacteremia: report of three cases. J Antimicrob Chemother 2012; 67(11):2777–2779. doi: 10.1093/jac/dks270.
• Souli M, Galani I, Boukovalas S, et al. In-vitro interactions of antimicrobial combinations with fosfomycin against KPC-2 producing Klebsiella pneumoniae and protection of resistance development. Antimicrobial Agents Chemother 2011;55(5):2395–2397. doi: 10.1128/AAC.01086-10
• Karageorgopoulos DE, Wang R, Yu XH, Falagas ME. Fosfomycin: evaluation of the published evidence on the emergence of antimicrobial resistance in Gram-negative pathogens. J Antimicrob Chemother 2012;67(2):255–268. doi: 10.1093/jac/dkr466.
• Falagas ME, Giannopoulou KP, Kokolakis GN, Rafailidis PI. Fosfomycin: use beyond urinary tract and gastrointestinal infections. Clin Infect Dis 2008; 46(7):1069–1077. doi: 10.1086/527442.
• Falagas ME, Kastoris AC, Karageorgopoulos DE Rafailidis PI. Fosfomycin for the treatment of infections caused by multidrug-resistant non-fermenting Gram-negative bacilli: a systemic review of microbiological, animal and clinical studies. Int J Antimicrob Agents 2009;34(2): 111–120. doi: 10.1016/j.ijantimicag.2009.03.009.
• Falagas ME, Vouloumanou EK, Samonis G, Vardakas KZ. Fosfomycin. Clin Microbiol Rev 2016; 29 (2):21–347. doi: 10.1128/CMR.00068-15