Performance of disk diffusion and broth microdilution for fosfomycin susceptibility testing of multidrug-resistant clinical isolates of Enterobacterales and Pseudomonas aeruginosa

Mojica, María F; Cadena, Elsa De La; Hernández-Gómez, Cristhian; Correa, Adriana; Appel, Tobías Manuel; Pallares, Christian; Villegas, María Virginia

doi:10.1016/j.jgar.2020.01.003

Cited by 24 publications

(25 citation statements)

References 15 publications

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“…Mojica et al recently reported 89% categorical agreement between BMD and AD with zero very major errors and 11 major errors. When applying the EUCAST epidemiological cutoff value of Յ128 g/ml, the categorical agreement increased to 98%, further supporting BMD as a reliable testing method compared with AD (22,39). Our results demonstrate that the calculated AD ECV for this international collection to be quite high at 256 g/ml.…”

Section: Discussionsupporting

confidence: 59%

“…Some limitations include our nonconsecutive collection of isolates, which resulted in a population skewed toward an MDR phenotype. The higher incidence of MDR isolates may contribute to the increased MIC and ECV values in relation to other studies (26,39). Furthermore, it is important to note that ECV calculation is dependent on the number of isolates used and should be considered when comparing ECVs between study collections, as our collection was relatively small yet still met the minimum requirement of 100 isolates per CLSI recommendations.…”

Section: Discussionmentioning

confidence: 95%

“…Strengths of our study include assessment of concordance between four susceptibility testing methods. Previous papers have compared AD, Etest, and DD; however, few have analyzed agreement rates between all four methods (23,24,26,29,39). Assessment of BMD is crucial, as it is both used in automated testing devices and provides quantitative MIC values.…”

Section: Discussionmentioning

confidence: 99%

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Performance of Four Fosfomycin Susceptibility Testing Methods against an International Collection of Clinical Pseudomonas aeruginosa Isolates

et al. 2020

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Fosfomycin has been shown to have a wide spectrum of activity against multidrug-resistant gram-negative bacteria; however, breakpoints have been established only for Escherichia coli or Enterobacterales per the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST), respectively. Lack of additional organism breakpoints limits clinical use of this agent and has prompted extrapolation of these interpretive categories to other organisms like Pseudomonas aeruginosa without supporting evidence. Further complicating the utility of fosfomycin is the specified method for minimal inhibitory concentration determination, namely agar dilution, which is not widely available and is both labor- and time-intensive. We therefore sought to determine the susceptibility of a large international collection of P. aeruginosa isolates (n = 198) to fosfomycin, and to compare testing agreement rates across four methods: agar dilution, broth microdilution, disk diffusion, and Etest. Results were interpreted according to CLSI E. coli breakpoints with 49.0-85.8% considered susceptible, dependent upon the testing method used. Epidemiological cutoff values were calculated and determined to be 256 μg/mL or 512 μg/mL for agar dilution and broth microdilution, respectively. Agreement rates were analyzed using both agar dilution and broth microdilution with a resulting high essential agreement rate of 91.3% between the two susceptibility testing methods. These results indicate that broth microdilution may be a reliable method for fosfomycin susceptibility testing against P. aeruginosa and stress the need for P. aeruginosa-specific breakpoints.

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Section: Discussionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

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Performance of Four Fosfomycin Susceptibility Testing Methods against an International Collection of Clinical Pseudomonas aeruginosa Isolates

et al. 2020

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“…Kasse et al [ 37 ] and Van den Bijllaardt et al [ 38 ] reported VME rates that varied between 16.7% and 12.9%, respectively, in Enterobacteriaceae isolates when comparing disk diffusion and agar dilution for fosfomycin using the breakpoints suggested by Pasteran et al (susceptible: ≥17) [ 39 ] and Epidemiological cut-off values (ECOFFs) of 64 mg/L, concluding that disk diffusion could be overestimating the real MIC value. In order to solve these discrepancies, Mojica et al suggests the interpretation of disk diffusion results in accordance with CLSI established breakpoint taking into account EUCAST recommendations for obtaining the inhibition zone diameter to reach the best performance of DD [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

“…Although the CLSI has determined breakpoints for Minimal Inhibitory Concentration (MIC) and Zone Diameter for urinary isolates of E. coli , the European Committee on Antimicrobial Susceptibility Testing (EUCAST) has recommended lower breakpoint values following agar dilution and disk diffusion supplemented with G6P for Enterobacteriaceae and Pseudomonas aeruginosa [ 21 ]. It is noteworthy to highlight that discrepancies between agar dilution and broth dilution MICs for fosfomycin have been reported [ 22 ], creating a conundrum for the use of microdilution as the standard method in clinical diagnostic labs.…”

Section: Introductionmentioning

confidence: 99%

Fosfomycin, Applying Known Methods and Remedies to A New Era

Mariño-Brito

Villavicencio

et al. 2020

Diseases

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The exponential increase in the numbers of isolates of Carbapenem-Resistant Enterobacteriaceae (CRE) creates the need for using novel therapeutic approaches to save the lives of patients. Fosfomycin has long been considered a rational option for the treatment of CRE to be used as part of a combined therapy scheme. However, the assessment of fosfomycin susceptibility in the laboratory presents a great challenge due to the discrepancies found between different methodologies. Thus, our goal was to evaluate fosfomycin susceptibility in a group of 150 Enterobacteriaceae bacterial isolates using agar dilution as the gold standard technique to compare the results with those obtained by disk diffusion. We found a fosfomycin susceptibility of 79.3% in general terms. By comparing both methodologies, we reported a categorical agreement of 96% without Very Major Errors (VMEs) or Major Errors (MEs) and 4% of minor Errors (mEs). Our results suggest that fosfomycin could provide a rational alternative treatment for those patients that are infected by a Multidrug-Resistant (MDR) microorganism that is currently untreatable and that the disk diffusion and classical agar dilution techniques are adequate to assess the resistance profile of CRE to fosfomycin.

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