Investigation of phosphomycin sensitivity and phosphomycin resistance genes in carbapenem-resistant enterobacteriacea strains in the blood culture of liver transplant patients

Objective: Liver transplantation is the only effective and current treatment option in end-stage liver disease or acute liver failure. In this patient group, the risk of infection is higher due to the use of immunosuppressive agents, and it is known that especially bacteremia and sepsis are complications with high mortality. Fosfomycin, an old antibiotic previously used as an oral treatment, has come to the fore in recent years to be used in resistant infections with the introduction of its intravenous formulation. There are very few studies on fosfomycin susceptibility and resistance genes in our country. In our study, it was aimed to determine the susceptibility of fosfomycin in CRE strains yielded in blood cultures by agar dilution method and to detect fosA, fosA3, fosC2 resistance genes, which cause enzymatic resistance to fosfomycin, by PCR method. Materials and Methods: Adult liver transplant patients aged 18 years and over, who were hospitalized at İnönü University Liver Transplant Institute Hospital and, between January 1, 2017 and December 31, 2019, with bacterial growth of at least one CRE in their blood culture were evaluated. Antibiotic susceptibility profiles were determined by agar dilution method for fosfomycin and by disk diffusion method for other antibiotics. fosA, fosA3 and fosC2 genes were investigated by PCR. Results: Twenty-four (72.7%) of the patients were male and nine (26.5%) were female; median age was 55 (Min:30, Max:70). When the 34 isolates included in the study were evaluated, 14 (41.2%) were Escherichia coli and 20 (58.8%) were Klebsiella pneumoniae. All isolates were ertapenem resistant, and meropenem resistance was 14.3% in E. coli, 75% in K. pneumoniae. Imipenem resistance was 14.3% and 45% in E. coli and K. pneumoniae, respectively. While fosfomycin susceptibility was detected as 64.3% in Escherichia coli isolates, no susceptible isolates were detected in K. pneumoniae isolates. In a total of 34 isolates, the fosfomycin resistance rate was 73.5%, and the fosA gene was found at a rate of 5.9%. The fosA gene was present in only two K. pneumoniae isolates. fosA3 and fosC2 genes were not detected in any of the isolates. Conclusions: This is a cross-sectional study evaluating the fosfomycin resistance profile of CRE isolates at the Liver Transplant Institute of our hospital. This is the first study in our country to investigate fosfomycin resistance genes in blood culture isolates in a group of patients with special characteristics such as liver transplantation. The data of our study reveal that the rates of carbapenem resistance are high in CRE, and that forfomycin, which should be considered in alternative or rescue therapy, is the size of the resistance problem due to other resistance mechanisms, even though only two resistance genes were detected in the study group. Keywords: Bacteremia, Enterobacteriaceae, fosA, fosA3, fosC2, fosfomycin resistance, liver transplantation