2062. Evaluation of Susceptibility Testing Methods for Fosfomycin Against Enterobacteriaceae and Pseudomonas aeruginosa

Abstract

BackgroundFosfomycin (FOS) is a broad-spectrum bactericidal agent that has been suggested as an alternative treatment option for infections caused by multi-drug resistant Gram-negatives. The approved in vitro antimicrobial susceptibility testing method for FOS is agar dilution (AD) and disk diffusion (DD); however, broth microdilution (BMD) is the basis of automated systems used in clinical microbiology laboratories. Herein we evaluated the accuracy of BMD and DD vs. the gold standard AD test for FOS susceptibility assessment using clinical isolates.MethodsSusceptibility to FOS of 140 isolates, comprising 39 E. coli (Eco), 33 K. pneumoniae (Kpn), 9 Enterobacter spp., (Ent); and 59 P. aeruginosa (Pae), were determined by BMD, DD and AD. Mueller–Hinton supplemented with 25 mg/L glucose 6-phosphate (G6P) was used for BMD and AD; results were interpreted according to CLSI and EUCAST guidelines. For DD screening, 50 μg FOS discs supplemented with 50 μg G6P were used and interpretation was performed following the FMS. For Pae, the EUCAST epidemiological cutoff was used. Concordance of BMD and DD with AD is reported in terms of categorical agreement (CA), defined as results between the two methods that matched based on the interpretative breakpoint proposed; false-resistant results to be major errors (ME); and false-susceptible results to be very major errors (VME).ResultsAccording to AD, the susceptibility to FOS of Eco, Kpn, Ent, and Pae was 97.4, 72.7, 100, and 98.3% respectively. Concordance analysis between BMD and DD with the gold standard AD is shown in Table 1.ConclusionThe high proportion of ME found with BMD, which is used in the automated systems may cause an overestimation of the FOS resistance, especially in Kpn and Ent. Thus, we suggest that microbiology laboratories confirm resistant strains by AD. DD may be useful for Eco and Ent, when scattered colonies within inhibition zones are ignored. Results also show high rates of FOS susceptibility among clinical isolates.Table 1.Agreement Between BMD and DD with AD for FOS Susceptibility TestsEcoKpnEntPaeBMDDDBMDDDBMDDDBMDDDCA87.20%97.40%60.60%72.70%66.70%100%64.40%ND*ME12.80%2.60%21.20%18.20%33.30%—11.90%NDVME———27.20%———ND*ND, not determined.Disclosures C. Hernandez, MSD: Consultant, Consulting fee and Speaker honorarium; Pfizer: Consultant, Consulting fee and Speaker honorarium. C. Pallares, Pfizer: Consultant, Consulting fee and Speaker honorarium. M. V. Villegas, MSD: Grant Investigator, Grant recipient and Speaker honorarium; Pfizer: Grant Investigator, Grant recipient and Speaker honorarium; Zambon: Grant Investigator, Grant recipient; West: Consultant, Consulting fee and Speaker honorarium; Merck S.A.: Grant Investigator, Grant recipient.