Prevalence of Aminoglycoside-Modifying Enzymes in Escherichia coli and Klebsiella pneumoniae Producing Extended Spectrum β-Lactamases Collected in Two Multicenter Studies in Spain

Abstract

The in vitro activity of amikacin, gentamicin, kanamycin, tobramycin, neomycin, and netilmicin against 420 Escherichia coli producing extended spectrum β-lactamases (Ec-ESBLs) and 139 Klebsiella pneumoniae producing extended spectrum β-lactamase (Kp-ESBL) collected in two multicenter studies performed in Spain in 2000 and 2006 was determined. The presence of genes encoding aminoglycoside-modifying enzymes (AMEs) and 16S ribosomal RNA (rRNA) methylases [aac(3)-Ia, aac(3)-IIa, aac(3)-IVa, aac(6′)-Ib, ant(2")-Ia, ant(4′)-IIa, aph(3′)-Ia, aph(3′)-IIa, armA, rmtB, and rmtC] was also investigated. The resistance to (one or more) aminoglycosides was significantly higher in Kp-ESBL (104/139, 74.8%) than in Ec-ESBL (171/420, 40.7%; p < 0.0001). The lowest resistance rates for both species in the two studies were observed for amikacin. The prevalence of AME genes was significantly different in Ec-ESBL (161/420, 38.3%) than in Kp-ESBL (115/139, 82.7%; p < 0.0001). The most prevalent AME genes in Ec-ESBL and Kp-ESBL were aac(6′)-Ib (16.2% and 44.6%) and aac(3)-IIa (14.7% and 43.1%), respectively. The expected phenotypic profile correlated with the found AMEs encoding genes in 59.6% Ec-ESBL and 26.1% Kp-ESBL. In Ec-ESBL, aac(6′)-Ib was usually associated in 2000 with bla_SHV (26.6%), but with bla_CTX-M-1 group (34.8%) in 2006, while aac(3)-IIa was coincident in 2000 with bla_TEM (14.6%) and with bla_CTX-M-1 group (16.3%) in 2006. Among Kp-ESBL, the aac(6′)-Ib and aac(3)-IIa genes were more frequent in strains with bla_TEM (22.0% and 44.0%) in 2000 and with bla_CTX-M-1 group (46.4% and 34.0%) in 2006. Resistance to aminoglycosides in Ec-ESBL and Kp-ESBL is frequent and related to production of AMEs; this limits the clinical use of aminoglycosides against these organisms.