Evaluating the Activity of Fosfomycin and Frequency of Inner Colony Mutants

In the absence of interpretive criteria, Fosfomycin has been used to treat Psuedomonas aeruginosa infections, but new research suggests that this option should be evaluated further.

According to the authors of an abstract presented at IDWeek 2019, a recent study identified a low frequency of nonsusceptible inner colony mutants during disk diffusion (DD) testing of Escherichia coli.

Little is known about the frequency of the occurrence in P aeruginosa isolates, therefore the investigators set out to evaluate the activity of Fosfomycin against an international collection of isolates while also observing the frequency of inner colony mutants observed during Etest and DD testing.

For the study, the investigators determined minimal inhibitory concentration (MIC) values for a collection of 109 P aeruginosa ([70/94] 64.2% multidrug-resistant) isolates from the United States and Australia.

The team followed the Clinical and Laboratory Standards Institute (CLSI) recommendations and conducted MIC testing in duplicate on separate days via agar dilution (AD), broth microdilution (BMD), DD, and ETest. MIC interpretations CLSI E coli interpretive criteria (≤ 64 mg/L susceptible) was also used.

DD and Etest were used to determine the isolates containing inner colonies and the mutants were subcultured and retested using BMC with comparison to the parents isolate MICs.

The authors write that the Fosfomycin MICs “varied widely and ranged from 1024 mg/L with MIC₅₀/MIC₉₀ values of 64/256 (AD), 64/512 (Etest), and 64/256 (BMD) mg/L. Using E coli criteria, susceptible/resistant rates were: 60.5/17.4% for AD; 60.5/22.0% for Etest; 86.2/7.3% for DD; and 53.2/17.4% for BMD.”

Furthermore, inner colonies were frequently observed in 38.5% and 35.8% of DD and Etest inhibition zones, respectively. Following repeat testing, the mutant MIC values ranged from 64 to > 1024 mg/L and 85.9% had MIC values ≥ 512 mg/L.

The investigators summarize their findings by noting that the observed values of the collection varied widely with MIC values at or above the E coli susceptibility breakpoint. Additionally, inner colony mutants were frequently observed and highly resistant.

“Whole genome sequencing is currently underway for a subset of parent/mutant pairs to determine whether specific genetic alterations are attributed to the increased MICs,” the authors note. “Based on these results, caution should be warranted in extrapolating E coli breakpoints to other organisms, and treatment of PA with Fosfomycin should be further evaluated.

The abstract, Activity of Fosfomycin (FOF) and Frequency of Nonsusceptible Inner Colonies During Susceptibility Testing of an International Collection of Clinical Pseudomonas aeruginosa (PA) Isolates, was presented in a poster session at IDWeek 2019 in Washington DC.