RESISTANCE TO AMIKACIN AND ISEPAMICIN IN RABBITS WITH EXPERIMENTAL ENDOCARDITIS OF AN AAC(6')-IB-BEARING STRAIN OF KLEBSIELLA-PNEUMONIAE SUSCEPTIBLE IN-VITRO

The effect of production of the aminoglycoside 6'-N-acetyltransferase [AAC(6')-Ib] in Klebsiella pneumoniae on the outcome of amikacin and i sepamicin treatment of rabbits with experimental endocarditis was asse ssed, Isogenic high-level (Hi) and low-level (Lo) AAC(6')-Ib-producing transconjugants (T) were constructed from clinical isolates with plas mid-borne resistance determinants. The MICs of amikacin and isepamicin , their bactericidal effects, and AAC(6')-Ib production appeared to be well correlated among the clinical isolates and the transconjugants, The susceptibility data determined in vitro, with MICs (in micrograms per milliliter) of amikacin and isepamicin for LoT and HiT of 4 and 0. 5 and 32 and 8, respectively, were, however, not predictive of the in vivo efficacies of the drugs, While amikacin and isepamicin caused red uctions in bacterial densities (log(10) CFU per gram of cardiac vegeta tion) of 5.1 and 4.8 of the fully susceptible recipient strain (MICs o f amikacin and isepamicin, 0.5 and 0.25, respectively), the reductions in density of both LoT and HiT caused by the two drugs (2.7 and 2.4 a nd 2.9 and 2.2, respectively) were only marginally significant, if at all, There was no significant difference (P > 0.05) when the reduction s in density of LoT and HIT by either drug were compared or when the e fficacies of the two drugs in reducing the density of any strain [non- AAC(6')-producing, LoT, or HiT] were compared (P > 0.5), It is conclud ed that AAC(6')-Ib in K. pneumoniae, even when produced at a low level and not conferring resistance to amikacin and isepamicin in vitro, co mpromises the efficacies of both drugs in vivo and possibly does so be yond the experimental model studied here.