In vitro efficacy of fosfomycin against clinical strains

Abstract

Objectives: Fosfomycin is an alternative drug for treatment of uncomplicated urinary tract infections. This study aimed to investigate in vitro activity of fosfomycin against methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant coagulase negative staphylococci (MRCoNS), vancomycin-resistant Enterococcus faecium (VR E. faecium), Escherichia coli, Klebsiella pneumoniae, and Enterobacter isolates. Methods: Clinical isolates of MRSA, MRCoNS, E. coli, K. pneumoniae and Enterobacter spp. and VRE isolates which were isolated from rectal swaps were identified with Vitek 2 Compact (Biomeriux, France) and BD Phoenix (BD USA) automated systems. The Kirby-Bauer disc diffusion method was used to determine the susceptibility to fosfomycin. Results: All the MRSA (n=40), MRCoNS (n=40), and VR E. faecium (n=62) isolates were susceptible to fosfomycin. The fosfomycin susceptibility rates for E. coli, K. pneumoniae, and Enterobacter spp. were 97.5% (39 of 40), 97.3% (36 of 37), and 86.9% (20 of 23), respectively. One (2.7%) isolate of K. pneumoniae and three (13.1%) isolates of Enterobacter spp. showed intermediate susceptibility to fosfomycin. Resistance to fosfomycin was detected in only one (2.5%) isolate of E. coli. Conclusion: Based on the results of our study, fosfomycin is highly active against a collection of several gram-positive and gram-negative bacteria, including multidrug resistant isolates, and is an alternative drug in the treatment option.

Keywords

• Fosfomycin, gram-positive bacteria, gram-negative bacteria, antimicrobial agent

In vitro efficacy of fosfomycin against clinical strains

Öz

Amaç: Fosfomisin komplike olmayan üriner sistem enfeksiyonlarının tedavisinde alternative bir ilaçtır. Bu çalışmanın amacı fosfomisinin in vitro etkinliğini, metisiline dirençli Staphylococcus aureus (MRSA), metisiline dirençli koagülaz negatif stafilokoklar (MRKNS), vankomisine dirençli Enterococcus faecium (VR- E. faecium), Escherichia coli, Klebsiella pneumoniae ve Enterobacter izolatlarında araştırmaktır. Yöntemler: MRSA, MRKNS, E. coli, K. pneumoniae ve Enterobacter spp. klinik örnekleri ve rektal sürüntüden izole edilen VRE izolatlarının tanımlanması Vitek2 Compact (Biomeriux, Fransa) ve Phoenix (BD, ABD) otomatize sisteminlerinde yapıldı. Fosfomisin duyarlılığı belirlenmesinde Kirby-Bauer disk difüzyon yöntemi kullanıldı. Bulgular: Tüm MRSA (n=40), MRKNS (n=40) ve VR- E. faecium (n=62) suşları fosfomisine duyarlı olarak saptandı. E. coli, K. pneumoniae ve Enterobacter spp. için fosfomisin duyarlılık oranları sırasıyla; % 97,5 (40’da 39), % 97,3 (37’de 36), % 86,9 (23’te 20) olarak bulundu. Bir K. pneumoniae izolatı (% 2,7) ve üç Enterobacter spp. izolatı (% 13,1) fosfomisine ortaduyarlı olarak saptandı. Fosfomisine karşı direnç sadece bir E. coli izolatında (% 2,5) saptandı.Sonuçlar: Fosfomisin çoklu ilaç direncine sahip izolatlar dahil birçok Gram pozitif ve Gram negatif bakteriye karşı invitro yüksek etkinliğe sahiptir ve alternatif bir tedavi seçeneği olarak kullanılabilir

Anahtar Kelimeler

• Fosfomisin, gram pozitif bakteri, gram negatif bakteri, antimikrobiyal ajan

References

1. Popovic M, Steinart D, Pillai S, Jouchadar C. Fosfomycin: an old, new friend? Europe J Clin Microb Infect Dis, 2012;29:127-142.
2. Lu GL, Liu CY, Huang YT, et al. Antimicrobial susceptibilities of commonly encountered bacterial isolates to fosfomycin deter- mined by agar dilution and disc diffusion methods. Antimicrob Agents Chemother 2011;55:4295-4301.
3. Maraki S, Samonis G, Rafilidis PI, et al. Susceptibilities of uri- nary tract bacteria to fosfomycin. Antimicrob Agents Chemother 2009;53:4508-4510.
4. Souli M, Galani I, Boukovalos S, et al. In vitro interactions of an- timicrobial combinations with fosfomycin against KPC-2 produc- ing Klebsiella pneumoniae and protection of resistance develop- ment. Antimicrob Agents Chemother 2011;55:2395-2397.
5. Poeppl W, Tabudic S, Lingscheid T, et al. Efficacy of fosfomycin in experimental osteomyelitis due to methicillin resistant Staphylo- coccus aureus. Antimicrob Agents Chemother 2011;55:931-933.
6. Falagas ME, Kastoris AC, Kaposkelis AM, et al. Fosfomycin for the treatment of multidrug- resistant, including extended- spectrum β- lactamase producing Enterobacreiceae infections: a system- atic review. Lancet Infect Dis 2010;40:43-50.
7. Superti S, Gomes Dias CA, Azevedo PA. In vitro fosfomycin activity in vancomycin resistant Enterococcus faecalis. Brazil J Infect Dis 2008;13:123-124.
8. Klevens RM, Morrison MA, Nadle J. Invasive methicillin resistant Staphylococcus aureus infections in the United States. JAMA 2007;115:1763-1771.

9. Ponchon-Ibanez ME, Ribes S, Dominguez MA. Efficacy of fosfo- mycin and its combination with linezolid, vancomycin and imipe- nem in an experimental peritonitis model caused by a Staphylo- coccu aureus strain with reduced susceptibility to vancomycin. Eur J Clin Microbiol Infect Dis 2011;30:89-95.
10. Tiwani HK, Sen MR. Emergence of vancomycin resistant Staphy- lococcu aureus (VRSA) from tertiary care hospital from northern part of India. BMC Infect Dis 2006;6:26-32.
11. Falagas ME, Giannopoulou KP, Kakolakis GH, et al. Fosfomycin: use beyond urinary tract and gastrointestinal infections. Clin In- fect Dis 2008;46:1069-1077.
12. Clinical and Laboratory Standarts Instıtute. Performance stand- arts for Antimicrobial Susceptibility testing; Twenty- First Informa- tional Supplement, M100- S21 2011.
13. Yao JDC, Moellering JrRC. Antibacterial Agents.In: Murray PR, Baron EJ, Jorgensen JH, et al, eds. Manuel of Clinical Micribiol- ogy. Washington: ASM Press 2007.
14. Abdulla FE, Abdulla EM. Antibiotic options for Enterococcus fae- calis infections. Pak J Med Sci 2006;22:286-290.
15. Allerberger F, Klare I. In vitro activity of fosfomycin against vancomycin- resistant enterococci. J Antimicrob Chemother 1999;43:211-217.
16. Perri MB, Herschberger E, Ionescu M. In vitro susceptibility of vancomycin- resistant enterococci (VRE) to fosfomycin. Diag Mi- crob Infect Dis 2002;42:269-271.
17. Shresta NK, Amush D, Goldman MD. Treatment of a complicated vancomycin resistant entrococcal urinary tract infection with fos- fomycin. Infect Dis Clin Prac 2000;9:368-371.
18. Butcu M, Akcay SS, Inan AS, et al. In vitro susceptibility of entero- cocci strains isolated from urine samples to fosfomycin and other antibiotics. J Infect Chemother 2011;14:575-578.
19. Yu XH, Song XJ, Cai Y, et al. In vitro activity of two old antibiotics against clinical isolates of methicillin-resistant Staphylococcus aureus. J Antibiot 2010;63:657-659.
20. Falagas ME, Maraki S, Karageorgopoulos DE, et al. Antimicrobial susceptibility of gram positive non- urinary isolates of fosfomycin. Int J Antimicrob Agents 2010;35:497-499.
21. Oksuz L, Dupieux C, Tristan A, et al. The high diversity of MRSA clones detected in a university hospital in Istanbul. Int J Med Sci 2013;10:1740-1745.
22. Pullukcu H, Tasbakan M, Sipahi OR, et al. Fosfomycin in the treatment of extended- spectrum betalactamase producing Escherichiae coli related lower urinary tract infectious. Int J Anti- mirob Agents 2007;29:62-65.
23. Endimiani A, Patel G, Hujer KM, et al. In vitro activity of fosfomy- cin against blaKPC- containing Klebsiella pneumoniae isolates, including those nonsusceptible to tigecycline and/or colistin. An- timicrob Agents Chemother 2010;54:526-529.
24. Ho PL, Wong RC, Yip KS. Antimicrobial resistance in Esch- erichiae coli outpatient urinary isolates from women: emerg- ing multidrug resistance phenotypes. Diag Microbiol Infect Dis 2007;59:439-445.
25. Tharavichitkul P, Khantawa B, Bousoung V, et al. Activity of fos- fomycin against extended- spectrum β-lactamase producing Klebsiella pnumoniae and Escherichia coli in Mahoney Nakorn Chiang Mai hospital. J Infect Dis Antimicrob Agents 2005;22:125- 126.
26. Gouby A, Neuwinth C, Boung G. Epidemiological study by pulsed field gel electroforesis of an outbreak of extended- spectrum β- lactamase producing Klebsiella pneumoniae in a geriatric hospi- tal. J Clin Microbiol 1994;32:301-305.
27. Arpin C, Coze C, Rogues AM, et al. Epidemiological study of an outbreak due to multidrug resistant Enterobacter aerogenes in a medical intensive care unit. J Clin Microbiol 1996;34:2163-2169.
28. Demir T, Buyukguclu T. Evaluation of the in vitro activity of fos- fomysin tromethamine against Gram- negative bacterial strains recovered from community- and hospital-acquired urinary tract infections in Turkey. Int J Infect Dis 2013;17:966-970.