FOSFOMYCIN AGAINST CARBAPENEM-RESISTANT KLEBSIELLA PNEUMONIAE BLOODSTREAM INFECTION: IN VITRO ACTIVITY, CORRELATION OF SUSCEPTIBILITY TESTING METHODS AND TREATMENT CHARACTERISTICS

Abstract

Fosfomycin is an adjunctive therapy for carbapenem-resistant Klebsiella pneumoniae (CRKP) infection, despite the lack of defined breakpoints.  Treatment decisions rely on pharmacokinetics/pharmacodynamics (PK/PD) targets.  The study evaluated fosfomycin efficacy against CRKP isolates harboring various carbapenemase genotypes, the association between disc diffusion zone diameters and Etest MIC values, and treatment regimens of patients ≥20 years of age with CRKP bloodstream infection from four hospitals across Thailand.  The most prevalent carbapenemase genotype identified by PCR was blaOXA-48-like (62%).  Of the CRKP isolates (n = 133), 19 and 34% demonstrated fosfomycin MIC values ≤32 and ≥128 μg/ml, respectively.  A categorical agreement of 99% (1% error rate) between the two sensitivity assay methods was achieved for isolates with MIC ≤ 128 μg/ml and zone diameter ≥16 mm.  Over half of the patients received a combination therapy of fosfomycin plus colistin and the most prevalent comorbidity was chronic kidney disease (56%). The 14-day all-cause mortality rate was 32%.  Fosfomycin is still considered necessary in situations where alternative effective drugs are not available, highlighting the need for standardized susceptibility testing methods.