Gh. Miller et al., THE MOST FREQUENTLY OCCURRING AMINOGLYCOSIDE RESISTANCE MECHANISMS - COMBINED RESULTS OF SURVEYS IN 8 REGIONS OF THE WORLD, Journal of chemotherapy, 7, 1995, pp. 17-30
Aminoglycoside-resistant isolates from different patients were collect
ed in 149 hospitals in eight regions of the world. Aminoglycoside resi
stance mechanisms(1) were determined in 11,079 of these isolates by th
e correlation of resistance phenotypes to 12 aminoglycosides and DNA h
ybridisation with up to 19 resistance genes. A very large diversity of
different resistance mechanisms was found. For example, in scherichia
-Morganella-Proteus-Salmonella-Shigella, a total of 53 different mecha
nisms was found among the 2080 isolates studied. Therefore, the most c
ommon resistance mechanisms in the seven different pathogen groups wer
e summarised. The seven pathogen groups were chosen so that each one h
ad a unique mixture of resistance mechanisms. Among Enterobacteriaceae
, the Citrobacter-Enterobacter-Klebsiella, Providencia and Serratia gr
oups had a particularly high incidence of combinations of resistance m
echanisms especially when compared with data from eight earlier survey
s.(2-9) These mechanisms often tended to be combinations of previously
common gentamicin-modifying enzymes with AAC(6')-I, an enzyme which c
an acetylate tobramycin, netilmicin and amikacin but which does not us
ually cause resistance to isepamicin. Resistance rates among the four
Enterobacteriaceae groups reflected the incidence of these combination
s; 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 ver
y large diversity of mechanisms was found in Pseudomonas. However, thr
ee mechanisms - permeability, AAC(6')-II and ANT(2'')-I - were very co
mmon, both alone as single mechanisms and in combination with each oth
er 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 Acinetabacter. The most common mechanisms
- APH(3')-VI and AAC(3)-? - were generally very rare in other genera
but found frequently in Acinetobacter in combination with a wide varie
ty of other mechanisms. The most frequent resistance mechanisms in Aci
netobacter varied by geographic region much more than did mechanisms i
n other genera. The resistance rates to all of the clinically useful a
minoglycosides were generally higher in Acinetobacter than in any othe
r 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(1) and four
combinations of these three mechanisms. Because the principal resistan
ce mechanism, APH(2'') + AAC(G'), confers high-level resistance to gen
tamicin and tobramycin and a lower level of resistance to amikacin, is
epamicin and netilmicin, the observed resistance rate to netilmicin (1
5.0%) was the lowest for any of the aminoglycosides.