Determination of Fosfomycin MIC values in multidrug-resistant Klebsiella pneumoniae isolates and a cost-effective method attempt for routine laboratory testing.

Intravenous fosfomycin has regained importance in recent years due to its effectiveness against difficult-to-treat pathogens. We aimed to determine the minimum inhibitory concentration (MIC) values of fosfomycin in multidrug-resistant (MDR) Klebsiella pneumoniae strains, to classify isolates using epidemiological cutoff values (ECOFF) and to evaluate a cost-effective method for fosfomycin MIC determination. Multidrug resistant K. pneumoniae isolates from blood cultures were included. Identification and susceptibility to antibiotics were determined. The carbapenemase genes were detected. Fosfomycin MICs were determined using the agar dilution method and isolates were classified based on ECOFF values as wild-type (WT) and non-wild-type (non-WT). The distribution of carbapenemase genes according to the fosfomycin MIC values were presented. Additionally, a modified agar dilution test was used to determine fosfomycin MICs more cost-effectively. Media containing various concentrations of fosfomycin were prepared in two-well plates. Five isolates (including E. coli ATCC 25922) selected through random sampling were tested weekly over a period of three weeks, followed by testing of all clinical isolates. The performance of this method was described using categorical agreement (CA), essential agreement (EA), major error (ME) and very major error (VME) rates. Between September 2022 and September 2023, 200 MDR K. pneumoniae isolates were included. Among carbapenemase types, OXA-48 was most frequent, followed by KPC and NDM, with no significant correlation observed between carbapenemase groups and fosfomycin MIC distributions. According to ECOFF values, 75% of isolates were WT and 25% were non-WT. With the modified agar dilution method, fosfomycin MICs did not vary by more than one dilution over three consecutive weeks. EA and CA were 95,5% and 93% with ME and VME rates of 4,5% and 2,5%, respectively. The modified agar dilution method serves as a reliable, cost-efficient alternative for fosfomycin susceptibility testing in routine clinical laboratories.