Antimicrobial susceptibility of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Enterobacteriaceae isolates to fosfomycin

Falagas, Matthew E.; Maraki, Sofia; Karageorgopoulos, Drosos E.; Kastoris, Antonia C.; Mavromanolakis, E.; Samonis, George

doi:10.1016/j.ijantimicag.2009.10.019

Cited by 157 publications

(129 citation statements)

References 17 publications

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“…In a strain collection comprising mainly KPC-producing Enterobacteriaceae, MICs of Յ32 mg/liter for fosfomycin were found in 86.7% of the isolates (18). In our study, E. coli strains had significantly lower fosfomycin MICs than K. pneumoniae and E. cloacae strains, which is in accordance with previous reports (17,(23)(24)(25). As the treatment options for infections due to carbapenemase-producing Enterobacteriaceae are severely limited, fosfomycin therapy has been considered for infections caused by multidrug-resistant Enterobacteriaceae (4,26,27).…”

Section: Discussionsupporting

confidence: 92%

Fosfomycin Susceptibility in Carbapenem-Resistant Enterobacteriaceae from Germany

Kaase

Szabados²,

Anders

et al. 2014

J Clin Microbiol

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bDue to the increase in multidrug-resistant Enterobacteriaceae, the interest in older antimicrobial agents, like fosfomycin, has increased. In this study, we used agar dilution for testing susceptibilities to fosfomycin in a collection of 107 carbapenem-nonsusceptible Enterobacteriaceae isolates, of which 80 produced various types of carbapenemases, including KPC, VIM, NDM, and OXA-48. Overall, 78% of the strains had fosfomycin MICs of <32 mg/liter and were thus considered to be susceptible according to the current EUCAST breakpoint. The MIC 50 and MIC 90 were 8 mg/liter and 512 mg/liter, respectively. Escherichia coli strains had significantly lower fosfomycin MICs than the Klebsiella pneumoniae and Enterobacter cloacae strains. Furthermore, comparisons of the susceptibility testing methods, like Etest and disk diffusion, were performed against agar dilution as the reference method. Essential agreement between Etest and agar dilution was 78.9%, and categorical agreement between the two methods was 92.5%, with 20% very major errors and 2.6% major errors. Disk diffusion was studied with 50-g and 200-g fosfomycin disks, but no inhibition zone breakpoint that reduced very major and major errors to an acceptable level was found. Etest and disk diffusion showed poor agreement with fosfomycin agar dilution.

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Section: Discussionsupporting

confidence: 92%

Fosfomycin Susceptibility in Carbapenem-Resistant Enterobacteriaceae from Germany

Kaase

Szabados²,

Anders

et al. 2014

J Clin Microbiol

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“…The laboratory methods that have been used for the determination of in vitro susceptibility of Gram-positive and Gram-negative pathogens to fosfomycin include agar (Mueller-Hinton agar) dilution, broth dilution, disk diffusion, and Etest techniques (22,40,(56)(57)(58)(59). Supplementation of agar or broth with G-6-P enhances fosfomycin activity.…”

Section: Susceptibility Testing Methodologymentioning

confidence: 99%

Fosfomycin

et al. 2016

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SUMMARYThe treatment of bacterial infections suffers from two major problems: spread of multidrug-resistant (MDR) or extensively drug-resistant (XDR) pathogens and lack of development of new antibiotics active against such MDR and XDR bacteria. As a result, physicians have turned to older antibiotics, such as polymyxins, tetracyclines, and aminoglycosides. Lately, due to development of resistance to these agents, fosfomycin has gained attention, as it has remained active against both Gram-positive and Gram-negative MDR and XDR bacteria. New data of higher quality have become available, and several issues were clarified further. In this review, we summarize the available fosfomycin data regarding pharmacokinetic and pharmacodynamic properties, thein vitroactivity against susceptible and antibiotic-resistant bacteria, mechanisms of resistance and development of resistance during treatment, synergy and antagonism with other antibiotics, clinical effectiveness, and adverse events. Issues that need to be studied further are also discussed.

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“…It exhibits broad-spectrum activity and importantly remains highly active in vitro against multidrug-resistant (MDR) and extremely drug-resistant (XDR) Enterobacteriaceae and P. aeruginosa strains, including those with ESBL and CR phenotypes (6,7). Thus, there is increasing interest in exploring the utility of fosfomycin to treat these drug-resistant pathogens due to this retained activity, the noted epidemic rise in antimicrobial resistance, and the diminishing number of novel therapies coming through traditional drug-discovery programs.…”

mentioning

confidence: 99%

In Vivo Pharmacokinetics and Pharmacodynamics of ZTI-01 (Fosfomycin for Injection) in the Neutropenic Murine Thigh Infection Model against Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa

Lepak

Zhao

VanScoy

et al. 2017

Antimicrob Agents Chemother

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Fosfomycin is a broad-spectrum agent with activity against Gram-positive and Gram-negative bacteria, including drug-resistant strains, such as extended-spectrumbeta-lactamase (ESBL)-producing and carbapenem-resistant (CR) Gram-negative rods. In the present study, the pharmacokinetic/pharmacodynamic (PK/PD) activity of ZTI-01 (fosfomycin for injection) was evaluated in the neutropenic murine thigh infection model against 5 Escherichia coli, 3 Klebsiella pneumoniae, and 2 Pseudomonas aeruginosa strains, including a subset with ESBL and CR phenotypes. The pharmacokinetics of ZTI-01 were examined in mice after subcutaneous administration of 3.125, 12.5, 50, 200, 400, and 800 mg/kg of body weight. The half-life ranged from 0.51 to 1.1 h, area under the concentration-time curve (AUC 0 -∞ ) ranged from 1.4 to 87 mg · h/liter, and maximum concentrations ranged from 0.6 to 42.4 mg/liter. Dose fractionation demonstrated the AUC/MIC ratio to be the PK/PD index most closely linked to efficacy (R 2 ϭ 0.70). Net stasis and bactericidal activity were observed against all strains. Net stasis was observed at 24-h AUC/MIC ratio values of 24, 21, and 15 for E. coli, K., pneumoniae and P. aeruginosa, respectively. For the Enterobacteriaceae group, stasis was noted at mean 24-h AUC/MIC ratio targets of 23 and 1-log kill at 83. Survival in mice infected with E. coli 145 was maximal at 24-h AUC/MIC ratio exposures of 9 to 43, which is comparable to the stasis exposures identified in the PK/PD studies. These results should prove useful for the design of clinical dosing regimens for ZTI-01 in the treatment of serious infections due to Enterobacteriaceae and Pseudomonas.

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Antimicrobial susceptibility of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Enterobacteriaceae isolates to fosfomycin

Cited by 157 publications

References 17 publications

Fosfomycin Susceptibility in Carbapenem-Resistant Enterobacteriaceae from Germany

Fosfomycin Susceptibility in Carbapenem-Resistant Enterobacteriaceae from Germany

Fosfomycin

In Vivo Pharmacokinetics and Pharmacodynamics of ZTI-01 (Fosfomycin for Injection) in the Neutropenic Murine Thigh Infection Model against Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa

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