Aminoglycoside Resistance Mechanisms in Gram-Negative Bacteria: Recent Developments and the Results of the Turkish Survey

Resistance mechanisms of gram-negative bacteria to aminoglycoside antibiotics differs by region and country. Aminoglycoside resistance mechanisms (Ag RMs) in gram-negative isolates resistant to either one of gentamicin (G), tobramycin (T), netilmicin (N) and amikacin (A) collected in different regions of Turkey were determined by both phenotyping and genotyping methods. Phenotyping was performed on the basis of relative resistance profiles of the isolates to 12 aminoglycoside antibiotics. Genotypically, Ag RMs of the isolates were determined by using hybridization assay including 22 common aminoglycoside resistance gene probes. Among 585 aminoglycoside-resistant gram-negative bacteria, resistance rates were highest for gentamicin (91.5%) followed by tobramycin (93.2%), netilmicin (62.1%), and amikacin (48.2%). Although isepamicin (I) was the most active aminoglycoside in-vitro against gram-negative bacteria, resistance rate (29.2%) for this drug was higher than in most of the other countries surveyed in earlier studies. The most common Ag RMs [AAC(3)-II (GTN), AAC(6’)-I (TNA), ANT(2”)-I (GT)] in earlier studies, were also present in this study. In addition to those mechanisms, two new mechanisms were observed. AAC(6’)-III (TNAI), occurred in both Enterobacteriaceae (11.9%) and Pseudomonas spp.(19.3%). Despite the high incidence of the other new mechanism, AAC(6’)-IV (GTNA) in Enterobacteriaceae (26.9%), it was not determined in Pseudomonas spp. All these mechanisms were mostly found in combination with each other or with less occurring resistance mechanisms except for AAC(6’)-IV which mostly occurred alone. The incidence of combinations of the most common resistance mechanisms were high in both Enterobacteriaceae (48%) and Pseudomonas spp. (58.7%). High incidence of combinations reflects the high resistance rates to clinically useful aminoglycosides (G, T, N, A, I) in gram-negative bacteria. Although enzymatic resistance mechanisms [AAC(3)-I (16.6%), AAC(6’)-II (29.3%), AAC(6’)-III (19.3%), ANT(2”)-I (40%)] were frequent in Pseudomonas spp., permeability resistance seems to be responsible for resistance to a wide range of clinically available aminoglycosides in this organism