Skip to main content

Advertisement

SpringerLink
Log in

In Vitro Activity of Fosfomycin on Multidrug-Resistant Strains of Klebsiella pneumoniae and Klebsiella oxytoca Causing Urinary Tract Infection

  • Short Communication
  • Published:
Current Microbiology Aims and scope Submit manuscript

Abstract

With the emergence of multi-drug resistant strains among Klebsiella isolates, the use of old drugs such as fosfomycin has been considered. In this context, we investigated the effect of fosfomycin on biofilm-producing Klebsiella pneumoniae and Klebsiella oxytoca strains isolated from ICU patients. A total of 90 isolates of Klebsiella pneumoniae and 30 isolates of Klebsiella oxytoca were collected from the ICU ward. All isolates were confirmed by biochemical and genotypic methods. Antibiotic susceptibility testing was performed by disc diffusion method and for fosfomycin and colistin, minimum inhibitory concentration (MIC) was done using micro broth dilution. The presence of the beta-lactamase encoding genes, biofilm-related genes, and fosfomycin resistance-related genes was detected by PCR. Finally, for fosfomycin-resistant isolates, we determined the sequence type by the MLST method. Sensitivity rate to fosfomycin in Klebsiella pneumoniae and Klebsiella oxytoca isolates was 92.2% and 100%, respectively. Fosfomycin was the most active antimicrobial agent with 96% sensitivity among all tested antibiotics. All tested isolates could produce biofilm. The frequency of biofilm-related genes for Klebsiella pneumoniae was as follows: 95.5% fimH, 86.6% mrkD, 77.7% mrkA, and 50% wcaG. The frequency of these genes for Klebsiella oxytoca was as follows: 56.6% fimA, 46.6% mrkA, 93.3% matB, and 90% pilQ. Only 4.4% of Klebsiella pneumoniae isolates showed resistance to fosfomycin, and the fosA gene was detected in all of them. Our results showed that fosfomycin effectively inhibits multidrug-resistant (MDR) strains of Klebsiella pneumoniae and Klebsiella oxytoca.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Data Availability

Datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Medina M, Castillo-Pino E (2019) An introduction to the epidemiology and burden of urinary tract infections. Ther Adv Urol 2(11):1756287219832172. https://doi.org/10.1177/1756287219832172

    Article  Google Scholar 

  2. Wyres KL, Lam MMC, Holt KE (2020) Population genomics of Klebsiella pneumoniae. Nat Rev Microbiol 18:344–359. https://doi.org/10.1038/s41579-019-0315-1

    Article  CAS  PubMed  Google Scholar 

  3. Elmekes A, Zahlane K, Aitsaid L et al (2020) The clinical and epidemiological risk factors of infections due to multi-drug resistant bacteria in an adult intensive care unit of University Hospital Center in Marrakesh-Morocco. J Infect Public Health 13:637–643. https://doi.org/10.1016/j.jiph.2019.08.012

    Article  Google Scholar 

  4. Imtiaz W, Syed Z, Rafaque Z, Andrews SC, Dasti JI (2021) Analysis of antibiotic resistance and virulence traits (genetic and phenotypic) in Klebsiella pneumoniae clinical isolates from Pakistan: identification of significant levels of carbapenem and colistin resistance. Infect Drug Resist 25(14):227–236. https://doi.org/10.2147/IDR.S293290

    Article  Google Scholar 

  5. Nirwati H, Sinanjung K, Fahrunissa F et al (2019) Biofilm formation and antibiotic resistance of Klebsiella pneumoniae isolated from clinical samples in a tertiary care hospital, Klaten, Indonesia. BMC Proc 13:20. https://doi.org/10.1186/s12919-019-0176-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Ghasemian A, Mohabati Mobarez A, Najar Peerayeh S et al (2019) Expression of adhesin genes and biofilm formation among Klebsiella oxytoca clinical isolates from patients with antibiotic-associated haemorrhagic colitis. J Med Microbiol 68:978–985. https://doi.org/10.1099/jmm.0.000965

    Article  CAS  PubMed  Google Scholar 

  7. Vuotto C, Longo F, Balice MP et al (2014) Antibiotic resistance related to biofilm formation in Klebsiella pneumoniae. Pathogens 3:743–758. https://doi.org/10.3390/pathogens3030743

    Article  PubMed  PubMed Central  Google Scholar 

  8. Gopichand P, Agarwal G, Natarajan M, Mandal J, Deepanjali S, Parameswaran S, Dorairajan LN (2019) In vitro effect of fosfomycin on multi-drug resistant gram-negative bacteria causing urinary tract infections. Infect Drug Resist 9(12):2005–2013. https://doi.org/10.2147/IDR.S207569

    Article  Google Scholar 

  9. Falagas ME, Vouloumanou EK, Samonis G, Vardakas KZ (2016) Fosfomycin. Clin Microbiol Rev 29:321–347. https://doi.org/10.1128/CMR.00068-15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Johnson JR (2004) Laboratory diagnosis of urinary tract infections in adult patients. Clin Infect Dis 39:873–873. https://doi.org/10.1086/423844

    Article  PubMed  Google Scholar 

  11. CLSI. Performance Standards for Antimicrobial Susceptibility Testing. 30th ed. CLSI supplement M100. Wayne, PA: Clinical and Laboratory Standards Institute; 2020.

  12. Azimi A, Aslanimehr M, Yaseri M et al (2020) Distribution of smf-1, rmlA, spgM and rpfF genes among Stenotrophomonas maltophilia isolates in relation to biofilm-forming capacity. J Glob Antimicrob Resist 23:321–326. https://doi.org/10.1016/j.jgar.2020.10.011

    Article  PubMed  Google Scholar 

  13. Diancourt L, Passet V, Verhoef J et al (2005) Multilocus sequence typing of Klebsiella pneumoniae nosocomial isolates. J Clin Microbiol 43:4178–4182. https://doi.org/10.1128/JCM.43.8.4178-4182.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Yang T-Y, Lu P-L, Tseng S-P (2019) Update on fosfomycin-modified genes in Enterobacteriaceae. J Microbiol Immunol Infect 52:9–21. https://doi.org/10.1016/j.jmii.2017.10.006

    Article  CAS  PubMed  Google Scholar 

  15. Liu P, Chen S, Wu Z et al (2020) Mechanisms of fosfomycin resistance in clinical isolates of carbapenem-resistant Klebsiella pneumoniae. J Glob Antimicrob Resist 22:238–243. https://doi.org/10.1016/j.jgar.2019.12.019

    Article  CAS  PubMed  Google Scholar 

  16. Fajfr M, Louda M, Paterová P et al (2017) The susceptibility to fosfomycin of Gram-negative bacteria isolates from urinary tract infection in the Czech Republic: data from a unicentric study. BMC Urol 17:33. https://doi.org/10.1186/s12894-017-0222-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Tulara N (2018) Nitrofurantoin and Fosfomycin for extended spectrum beta-lactamases producing Escherichia coli and Klebsiella pneumoniae. J Glob Infect Dis 10:19. https://doi.org/10.4103/jgid.jgid_72_17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Conejo MC (2021) Efficacy of Fosfomycin and its combination with aminoglycosides in an experimental sepsis model by Carbapenemase-producing Klebsiella pneumoniae clinical strains. Front Med (Lausanne). 8:615540. https://doi.org/10.3389/fmed.2021.615540

    Article  PubMed  PubMed Central  Google Scholar 

  19. Aris P, Boroumand MA, Rahbar M, Douraghi M (2018) The activity of fosfomycin against extended-spectrum beta-lactamase-producing isolates of enterobacteriaceae recovered from urinary tract infections: a single-center study over a period of 12 years. Microb Drug Resist 24:607–612. https://doi.org/10.1089/mdr.2017.0097

    Article  CAS  PubMed  Google Scholar 

  20. Cebrero-Cangueiro T, Labrador-Herrera G, Pascual Á et al (2021) Efficacy of Fosfomycin and its combination with aminoglycosides in an experimental sepsis model by carbapenemase-producing Klebsiella pneumoniae clinical strains. Front Med 8:615540. https://doi.org/10.3389/fmed.2021.615540

    Article  Google Scholar 

Download references

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Medical Microbiology Research Center, Qazvin University of Medical Sciences, Qazvin, Iran

    Fatemeh Ghayaz, Fatemeh Zeynali Kelishomi, Samira Amereh, Amir Peymani & Farhad Nikkhahi

  2. Social Determinants of Health Research Center, Research Institute for Prevention of Non-Communicable Diseases, Qazvin University of Medical Sciences, Qazvin, Iran

    Ehsan Aali

  3. Department of Community Medicine, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran

    Amir Javadi

Authors
  1. Fatemeh Ghayaz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fatemeh Zeynali Kelishomi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Samira Amereh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ehsan Aali
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Amir Javadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Amir Peymani
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Farhad Nikkhahi
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

The study was conceptualized by FN. The investigations were performed by FG, FZK, SA, and EA. The data analysis was done by AJ. The writing, editing, and reviewing of the manuscript were done by FG and FZK. All authors have also approved the manuscript.

Corresponding author

Correspondence to Farhad Nikkhahi.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical Approval and Consent to Participate

This study was approved by the Ethics Committee of Qazvin University of Medical Sciences, Iran [Approval No. IR.QUMS.REC.1400.035]. Patient information was anonymized.

Consent for Publication

Not applicable.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 20 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ghayaz, F., Kelishomi, F.Z., Amereh, S. et al. In Vitro Activity of Fosfomycin on Multidrug-Resistant Strains of Klebsiella pneumoniae and Klebsiella oxytoca Causing Urinary Tract Infection. Curr Microbiol 80, 115 (2023). https://doi.org/10.1007/s00284-023-03208-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00284-023-03208-0

Search

Navigation