The changing nature of aminoglycoside resistance mechanisms and prevalenceof newly recognized resistance mechanisms in Turkey

Objective, To determine the most frequently. occurring individual and combi ned resistance mechanisms, in Gram-negative bacteria resistant to any of th e clinically available aminoglycosides in Turkey, and to compare these mech anisms with those found in smaller, earlier studies. Methods Aminoglycoside resistance mechanisms in Gram-negative isolates, res istant to either gentamicin, tobramycin, netilmicin or amikacin collected i n different regions of Turkey were evaluated both phenotypically and genoty pically using 12 aminoglycosides, and up to 22 aminoglycoside resistance ge ne probes. Results Among 696 aminoglycoside-resistant Gram-negative bacteria, resistan ce rates were very high for gentamicin (94.5%), tobramycin (82.4%). netilmi cin (53.6%), and amikacin (49.7%). Although isepamicin was the most active aminoglycoside, against Gram-negative bacteria, increased resistance (29.7% ) was found and resistance rates were higher than those in most of the othe r countries surveyed in earlier studies. The most common aminoglycoside res istance mechanisms (AAC(3)-II (GTN), AAC(6)-I (TNA), and ANT(2")-I (GT)) in the earlier studies were also found in the present isolates of Klebsiella spp., Enterobacter spp. and Escherichia coli, with increased complexity. In addition to these old mechanisms, two new aminoglycoside resistance mechan isms, namely AAC(6)-III (TNAI) and AAC(6)-IV (GTNA), were also found at sig nificant frequencies (11.9% and 26.9%, respectively) in these isolates of E nterobacteriaceae (n = 435). Among the isolates of Pseudomonas spp. (n = 15 0), in addition to the increased complexity of enzymatic resistance mechani sms (AAC(3)-I (16.6%), AAC(6')-II (29.3%), AAC(6)-III (19.3%), ANT(2")-I (4 0%)), permeability resistance seemed to be responsible for the high rates o f resistance to, aminoglycosides. Conclusion The results of this. study indicated increased resistance to cli nically available aminoglycosides, including isepamicin, even though it was , the most active, as a result of both the presence of new aminoglycoside r esistance mechanisms and the increased, complexity of all mechanisms, inclu ding permeability resistance, particularly in Pseudomonas in Turkey.