In vitro Activity of Fosfomycin Alone and in Combination with Ceftriaxone or Azithromycin Against Clinical Neisseria gonorrhoeae Isolates.

Hauser, Christoph; Hirzberger, Lea; Unemo, Magnus; Furrer, Hansjakob; Endimiani, Andrea (2014). In vitro Activity of Fosfomycin Alone and in Combination with Ceftriaxone or Azithromycin Against Clinical Neisseria gonorrhoeae Isolates. Antimicrobial agents and chemotherapy, 59(3), pp. 1605-1611. American Society for Microbiology 10.1128/AAC.04536-14

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New therapeutic strategies are needed to combat the emergence of infections due to multidrug-resistant Neisseria gonorrhoeae (Ng). In this study, fosfomycin (FOS) was tested against 89 Ng using the Etest method and showing MIC50/90s of only 8/16 μg/ml (range ≤ 1-32 μg/ml). FOS in combination with ceftriaxone (CRO) or azithromycin (AZT) was then evaluated using the checkerboard method for eight strains, including F89 (CRO-resistant) and AZT-HLR (high-level AZT-resistant). All combinations including FOS gave indifferent effects (fractional inhibitory concentration [FIC] index values between 1.2-2.3 for FOS plus CRO and between 1.8-3.2 for FOS plus AZT). Time-kill experiments for FOS, CRO, AZT and their combinations (at concentrations of 0.5×, 1×, 2× and 4× MIC) were performed against ATCC 49226, one Ng of NG-MAST ST1407, F89 and AZT-HLR. For all strains, at 24 hours results indicated that: i) FOS was bactericidal at 2× MIC concentrations but after >24 hours there was re-growth of bacteria; ii) CRO was bactericidal at 0.5× MIC; iii) AZT was bactericidal at 4× MIC; iv) CRO plus AZT was less bactericidal than CRO alone; v) FOS plus AZT was bactericidal at 2× MIC; vi) CRO plus AZT and FOS plus CRO were both bactericidal at 0.5× MIC, but the latter had more rapid effects. FOS is appealing for the management of Ng infections because of its single and oral formulation. However, our results suggest its use in combination with CRO. This strategy could, after appropriate clinical trials, be implemented for the treatment of infections due to isolates possessing resistance to CRO and/or AZT.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Infectiology

UniBE Contributor:

Hauser, Christoph; Hirzberger, Lea; Furrer, Hansjakob and Endimiani, Andrea

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0066-4804

Publisher:

American Society for Microbiology

Language:

English

Submitter:

Annelies Luginbühl

Date Deposited:

10 Feb 2015 10:58

Last Modified:

10 Sep 2017 16:26

Publisher DOI:

10.1128/AAC.04536-14

PubMed ID:

25547354

BORIS DOI:

10.7892/boris.61583

URI:

https://boris.unibe.ch/id/eprint/61583

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