Treatment Options for New Delhi Metallo-Beta-Lactamase-Harboring Enterobacteriaceae

The New Delhi metallo-beta-lactamase gene (bla(NDM-1)) has emerged as a worldwide concern among isolates of Enterobacteriaceae. Its epidemiology is been strongly associated with travel and healthcare on the Indian Subcontinent. We report two cases of urinary tract infection with Enterobacteriaceae harboring a bla(NDM-1). Both cases presented as infection in community-dwelling individuals in Australia and were associated with travel to the Indian Subcontinent. One isolate of Escherichia coli harbored the previously undescribed enzyme variant bla(NDM-3), differing from bla(NDM-1) by a single nonsynonymous SNP conferring a putative peptide sequence change at the 95th position (ASP -> ASN). The second was an Enterobacter cloacae harboring bla(NDM-1). Further genetic characterization included identification of additional beta-lactamase and aminoglycoside resistance genes. Legacy antimicrobials were used for treatment. Oral therapy with nitrofurantoin was successful in one case, while combination of colistin and rifampicin was required in the second patient. Such infection, due to extensively drug-resistant pathogens, poses significant challenges in balancing the efficacy and toxicity of potential antimicrobial therapies.