title: The most frequently occurring aminoglycoside resistance mechanisms--combined results of surveys in eight regions of the world. The Aminoglycoside Resistance Study Groups.
abstract: Aminoglycoside-resistant isolates from different patients were collected in 149 hospitals in eight regions of the world. Aminoglycoside resistance mechanisms were determined in 11,079 of these isolates by the correlation of resistance phenotypes to 12 aminoglycosides and DNA hybridisation with up to 19 resistance genes. A very large diversity of different resistance mechanisms was found. For example, in Escherichia-Morganella-Proteus-Salmonella-Shigella, at total of 53 different mechanisms was found among the 2080 isolates studied. Therefore, the most common resistance mechanisms in the seven different pathogen groups were summarised. The seven pathogen groups were chosen so that each one had a unique mixture of resistance mechanisms. Among Enterobacteriaceae, the Citrobacter-Enterobacter-Klebsiella, Providencia and Serratia groups had a particularly high incidence of combinations of resistance mechanisms especially when compared with data from eight early surveys. These mechanisms often tended to be combinations of previously common gentamicin-modifying enzymes with AAC(6')-I, an enzyme which can acetylate tobramycin, netilmicin and amikacin but which does not usually cause resistance to isepamicin. Resistance rates among the four Enterobacteriaceae groups reflected the incidence of these combinations; that is, amikacin resistance was 43.1%, 21.7%, 4.2% and 37.6% while that to isepamicin was 9.9%, 9.7% 2.7% and 7.6%, respectively. A very large diversity of mechanisms was found in Pseudomonas. However, three mechanism - permeability, ACC(6')-II and ANT(2")-I - were very common, both alone as single mechanisms and in combination with each other or other mechanisms. Because of the high incidence of permeability resistance in Pseudomonas, resistance to all aminoglycosides was quite high and the difference between amikacin (41.7%) and isepamicin (36.8%) was smaller. The greatest diversity of resistance mechanisms (67 in 1189 isolates) was found in Acinetobacter. The most common mechanisms - APH(3')-VI and AAC(3)-? - were generally very rare in other genera but found frequently in Acinetobacter in combinations with a wide variety of other mechanisms. The most frequent resistance mechanisms in Acinetobacter varied by geographic region much more than did mechanisms in other genera. The resistance rates to all of the clinically useful aminoglycosides were generally higher in Acinetobacter than in any other pathogen group. In contrast to the other pathogen groups, only seven resistance mechanisms were found in the 898 resistant Staphylococcus. These were composed of the three known single mechanisms and four combinations of these three mechanisms. Because the principal resistance mechanism, (APH(2") + ACC(6'), confers high-level resistance to gentamicin and tobramycin and a lower level of resistance to amikacin, isepamicin and netilmicin, the observed resistance rate to netilmicin (15.0%) was the lowest for any of the aminoglycosides.
mesh_terms: D000123:Acetyltransferases / Q000378:metabolism; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002240:Carbohydrate Sequence; D004352:Drug Resistance, Microbial; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006801:Humans; D008969:Molecular Sequence Data
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000123:Acetyltransferases; C019681:aminoglycoside acetyltransferase