Resistance of bacteria to the newer aminoglycoside antibiotics: An epidemiological and enzymatic study.

Abstract

There were 435 Staphylococcus aureus strains and 395 strains of gram-negative bacteria tested for susceptibility to gentamicin, sisomicin, tobramycin, netilmicin and amikacin. None of the staphylococcal strains were resistant to the 5 drugs, except 2 strains that were resistant to amikacin. Eighteen percent of the gram-negative bacteria were resistant to gentamicin, 16% to tobramycin, 14% to sisomicin, 7% to netilmicin and 2% to amikacin. Tests from representative strains showed that these differences were mainly due to the production of aminoglycoside-modifying enzymes. The lower incidence of strains resistant to sisomicin compared to gentamicin was due to a slightly better antimicrobial activity of sisomicin. Results of experiments on the efficiency of enzymatic phosphorylation, acetylation and adenylylation and the inactivation of aminoglycoside antibiotics were not always in concurrence with the degree of phenotypic expression of resistance. Thus, the aminoglycoside 3''-phosphotransferase of staphylococci modified amikacin, but the strains were susceptible to the drug. Similarly, the aminoglycoside 2"-nucleotidyltransferase from members of Enterobacteriaceae and Pseudomonas efficiently adenylylated and inactivated netilmicin, but the strains were susceptible to netilmicin. There can be factors, intrinsically inherent in some strains, contributing to their phenotypic expression of resistance level. The contribution of enzymes to the degree of resistance to aminoglycoside antibiotics in a given strain can be evaluated only by comparative examination of resistance in the wild type strain and its corresponding enzyme-negative variant.