An Insight into Genes Responsible for Fosfomycin Resistance Among Uropathogens of Asymptomatic Bacteriuria during Pregnancy: A North Indian Study

Purpose: Asymptomatic bacteriuria (ASB) is a common finding during pregnancy. Effective antibiotic treatment could reduce its adverse effects on both mother and fetus. However, emerging antimicrobial resistance limits the treatment options. Fosfomycin might be a promising drug in this regard, as its resistance is still low. The aim of the study was to determine the antimicrobial susceptibility pattern of fosfomycin in isolates causing ASB by disc diffusion and agar dilution (in selected isolates), determine minimum inhibitory concentration (MIC) by agar dilution in isolates resistant by disc diffusion and detect the genes responsible for fosfomycin resistance. Material and Methods: This was a 2-year study carried in the Department of Microbiology, Jawaharlal Nehru Medical College and Hospital (JNMCH), Aligarh Muslim University (AMU), Aligarh. Total 10252 urine samples from asymptomatic pregnant females (18-45 years) attending the antenatal care (ANC) outpatient department (OPD) were submitted. Identification of pathogen and antimicrobial susceptibility testing (AST) done as per standard methods of CLSI. There was phenotypic detection of methicillin resistant Staphylococcus aureus (MRSA) and Other Staphylococcusspecies (MRSS), high level aminoglycoside resistance (HLAR), vancomycin resistant Enterococci (VRE) and S. aureus (VRSA), extended spectrum β-lactamase (ESBL) and carbapenem resistant Enterobacterales (CRE). All the fosfomycin resistant isolates (by disk diffusion) were tested by agar dilution. Conventional PCR was performed for murA, fosA, uhpT and glpT genes on all resistant isolates. Result: In this study, the prevalence of ASB among pregnant females was 1173(11.4%), in which Escherichia coli 495(42%) being the predominant organism. The overall sensitivity of fosfomycin among Gram-positive cocci (GPC) and Gram-negative bacilli (GNB) was 99% and 97.6% respectively. MRSA and MRSS accounted for 50 (66.6%) and 71 (76%) respectively. Highest rate of MIC >2048 µg/ml were shown by most isolates (mainly E. coli) on agar dilution. PCR studies revealed four E. coli strains possessed both murA (also present in 1 K. pneumoniae strain) and glpT genes. While only one isolate (E. faecalis) was positive for fosA gene. But none of the strain possessed uhpT gene. Conclusion: According to this study, murA and glpT genes were more frequent than fosA. We cannot comment on the prevalence and regional distribution of fosfomycin resistant genes based on this preliminary study. Therefore, more Indian studies should be carried out to create awareness about the presence of genes in a particular area.