|Year : 2017 | Volume
| Issue : 3 | Page : 437-438
In vitro fosfomycin susceptibility against carbapenem-resistant or extended-spectrum beta–lactamase-producing gram-negative fosfomycin-naive uropathogens: An alluring option or an illusion
Manisa Sahu1, Sanjith Saseedharan2, Pallavi Bhalekar1
1 Department of Microbiology, S. L. Raheja - Fortis Associate Hospital, Mumbai, Maharashtra, India
2 Department of Critical Care, S. L. Raheja - Fortis Associate Hospital, Mumbai, Maharashtra, India
|Date of Web Publication||12-Oct-2017|
Department of Critical Care, S. L. Raheja - Fortis Associate Hospital, Mumbai, Maharashtra
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Sahu M, Saseedharan S, Bhalekar P. In vitro fosfomycin susceptibility against carbapenem-resistant or extended-spectrum beta–lactamase-producing gram-negative fosfomycin-naive uropathogens: An alluring option or an illusion. Indian J Med Microbiol 2017;35:437-8
|How to cite this URL:|
Sahu M, Saseedharan S, Bhalekar P. In vitro fosfomycin susceptibility against carbapenem-resistant or extended-spectrum beta–lactamase-producing gram-negative fosfomycin-naive uropathogens: An alluring option or an illusion. Indian J Med Microbiol [serial online] 2017 [cited 2020 Feb 28];35:437-8. Available from: http://www.ijmm.org/text.asp?2017/35/3/437/216612
Treating infections caused by carbapenem-resistant Gram-negative pathogens presents major problems, in hospital as well as community setup. Treatment options are limited. When looking for alternate treatment options, fosfomycin, an old but broad-spectrum antibiotic, comes into mind. Fosfomycin coverage includes a wide spectrum of the Gram-negative bacteria as well as Gram-positive bacteria such as Staphylococcus and Enterococcus., Fosfomycin is a small molecule that inhibits the first step in peptidoglycan (cell wall) synthesis by acting as an analogue of phosphoenolpyruvate. The activity of fosfomycin was evaluated against 68 KPC-producing Klebsiella pneumoniae isolates, 23 of which were non-susceptible to tigecycline and/or colistin. The susceptibility rates were 93% for the overall group, 87% for the group non-susceptible to tigecycline and/or colistin and 83% (5 of 6 isolates) for the extremely drug-resistant subgroup that was non-susceptible to tigecycline and colistin. In a study, the activity of antibiotics was evaluated against 81 carbapenem-resistant Enterobacteriaceae (CRE) isolates from the UK. Colistin was active against 75/81 isolates (92.6%). Colistin resistance was seen in 3/52 Klebsiella spp. Fosfomycin was active against 49/81 isolates (60.5%), including 25/52 Klebsiella, 7/7 Escherichia More Details coli, 16/20 Enterobacter and Citrobacter spp. Tigecycline was active against 38/81 isolates (46.9%) including 21/52 Klebsiella spp. There are few data available from India on the susceptibility of fosfomycin.
We did a prospective, non-randomised study of all laboratory-certified extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae and CRE isolates in a period of 3 months between July and September 2014, in a tertiary care hospital in Mumbai. The ESBL and CRE isolates were verified by the Clinical and Laboratory Standards Institute (CLSI) guidelines using VITEK 2 automated system.
Specimens were processed using enriched Mueller-Hinton medium supplemented with 25 mg/L of glucose-6-phosphate with CLSI-approved fosfomycin E-test methods, with fosfomycin gradient concentrations ranging from 0.04 to 1024 μg/ml. Minimum inhibitory concentration (MIC) of ≤64 μg was considered sensitive, 128 μg as intermediate and ≥256 μg as resistant to fosfomycin as per the CLSI 2013 guideline for E. coli and other Enterobacteriaceae urinary isolates.
A total of 24 ESBL only and 55 CRE plus ESBL urinary isolates were tested. The baseline characteristic of the isolates is illustrated in [Table 1]. The susceptibilities of Enterobacteriaceae to fosfomycin are illustrated in [Table 2]. Five isolates had a MIC range in the intermediate susceptibility range.
The MIC distribution of fosfomycin ranged from 0.25 to 1024 for the CRE isolates, with a median MIC of 16 μg/ml. Maximum susceptibility was for colistin, with only two isolates, one E. coli and one K. pneumoniae isolate being resistant to colistin as well, followed by amikacin. CR-Klebsiella showed lower level of susceptibility (23.6%) to fosfomycin.
Our results are not very promising as compared to the various studies from India and abroad. Fosfomycin showed excellent effectiveness to most of the common ESBL-producing bacteria such as E. coli (93%) and Klebsiella (64%) in a study by Khan et al.
Noin vitro resistance was seen for fosfomycin among the ESBL- and AmpC-producing E. coli uropathogens in another study by Gupta et al., suggesting it as a newer choice of drug (although not new) in future. Our study is comparable to Chitra et al., showing high susceptibility of CR-E. coli to fosfomycin, 95.1%. However, CR-Klebsiella will still be a concern, with much lower sensitivity to fosfomycin, as was in the study by Chitra et al.
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Conflicts of interest
There are no conflicts of interest.
| ~ References|| |
Baylan O. Fosfomycin: Past, present and future. Mikrobiyol Bul 2010;44:311-21.
Allerberger F, Klare I. In-vitro
activity of fosfomycin against vancomycin-resistant enterococci. J Antimicrob Chemother 1999;43:211-7.
Endimiani A, Patel G, Hujer KM, Swaminathan M, Perez F, Rice LB, 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;54:526-9.
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, nitrofurantoin, temocillin and tigecycline. Int J Antimicrob Agents 2011;37:415-9.
Clinical and Laboratory Standards Institute. Performance Standards for Anti-Microbial Susceptibility Testing; Twenty-Second Informational Supplement. Document M100-S22. Wayne, PA: CLSI; 2013.
Khan IU, Mirza IA, Ikram A, Ali S, Hussain A, Ghafoor T.In vitro
activity of fosfomycin tromethamine against extended spectrum beta-lactamase producing urinary tract bacteria. J Coll Physicians Surg Pak 2014;24:914-7.
Gupta V, Rani H, Singla N, Kaistha N, Chander J. Determination of extended-spectrum β-lactamases and ampc production in uropathogenic isolates of Escherichia coli and susceptibility to fosfomycin. J Lab Physicians 2013;5:90-3.
] [Full text]
Chitra C, Kumar D, Shakti L, Diana S R, Balaji V. Technical and interpretative issues of fosfomycin susceptibility testing. Indian J Med Microbiol 2015;33:611-2.
] [Full text]
[Table 1], [Table 2]