Nosocomial Spread of ArmA-Mediated High-Level Aminoglycoside Resistance in Enterobacteriaceae Isolates Producing CTX-M-3 β-Lactamase in a Cancer Hospital in Bulgaria

1,310 Enterobacteriaceae, 242 Pseudomonas aeruginosa and 97 Acinetobacter baumannii clinical isolates collected at a cancer hospital in Bulgaria were screened for the presence of 16S rRNA methylases. The armA methylase gene was identified in 20 (1.5%) Enterobacteriaceae (7 Klebsiella pneumoniae, 3 Escherichia coli, 3 Serratia marcescens, 3 Citrobacter freundii, 3 Enterobacter cloacae and 1 Klebsiella oxytoca). ArmA-mediated aminoglycoside resistance was transferable by conjugation and carried by closely related IncL/M plasmids which also carried ant39, dfrXII, sul1, bla(TEM-1), and bla(CTX-M-3) genes encoding resistance to streptomycin-spectinomycin, trimethoprim, sulfonamides, and beta-lactams, respectively. Most of the isolates were genetically different according to PFGE but shared similar restriction patterns of the armA-encoding plasmids. Our findings highlight the strong association of armA and bla(CTX-M-3) extended-spectrum beta-lactamase genes across various species in the family Enterobacteriaceae. The spread of multiresistant isolates expressing 16S rRNA methylases and ESBLs is a worrisome development requiring continuous monitoring.