title: Susceptibility of aerobic gram-negative bacilli to aminoglycosides. Effects of 45 months of amikacin as first-line aminoglycoside therapy.
abstract: Amikacin was instituted as the primary empiric aminoglycoside at the San Juan Veterans Administration Medical Center in January 1982; at that time, 16 percent of the strains at the hospital were gentamicin-resistant. A prospective surveillance study was designed to correlate detection of bacterial resistance with aminoglycoside use. In the current report, the baseline period, during which gentamicin was the first-line aminoglycoside, accounting for 61 percent of overall aminoglycoside use, is compared with the period from January 1982 to September 1985, during which the first-line aminoglycoside was amikacin, accounting for 85 percent of overall use. This study is ongoing. During the two periods, the patient population did not differ with regard to aminoglycoside therapy, indications, or overall aminoglycoside use (541 versus 680 patient days per month). Among the gram-negative bacilli isolated, the percent of strains resistant to amikacin was as follows: pre-baseline period/baseline period, 0.8/0.2 percent; amikacin-usage period, 3.6 percent. Resistance to gentamicin and tobramycin during the period of amikacin use decreased from 16 to 11 percent for gentamicin and from 17 to 11 percent for tobramycin. The decrease in resistance of the gram-negative bacilli to gentamicin varied among strains: the resistance of Escherichia coli decreased from 8 to 4 percent; that of Proteus mirabilis, from 12 to 5 percent; that of indole-positive Proteus, from 19 to 12 percent; that of Acinetobacter, from 57 to 23 percent; that of Citrobacter, from 15 to 7 percent; and that of Pseudomonas aeruginosa, from 24 to 16 percent. During the amikacin-usage period, amikacin resistance was unchanged for most strains, with the exception of P. aeruginosa, the resistance of which increased from 4.5 to 7.8 percent. Of the 4,795 strains isolated, 174 were resistant to amikacin; of these, 29 Pseudomonas strains were studied for all mechanisms of resistance. Changes in permeability were exhibited by 11 of the 29 strains; 14 strains exhibited the AAC(6')-I enzyme, 10 strains exhibited the APH(3')-II enzyme, and two strains exhibited ANT(2") in addition to some other unidentified mechanism. Multiple enzyme production was found in 15 of the strains. The use of amikacin as a first-line aminoglycoside is associated with a decrease in resistance to other aminoglycosides and a slight increase in overall resistance to amikacin among aerobic gram-negative bacilli. The usefulness of amikacin has not been affected at our institution.
mesh_terms: D000123:Acetyltransferases / Q000378:metabolism; D000583:Amikacin / Q000494:pharmacology / Q000627:therapeutic use*; D000617:Aminoglycosides / Q000494:pharmacology / Q000627:therapeutic use; D001424:Bacterial Infections / Q000188:drug therapy*; D004352:Drug Resistance, Microbial; D005839:Gentamicins / Q000494:pharmacology; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D007612:Kanamycin / Q000031:analogs & derivatives* / Q000494:pharmacology; D019868:Kanamycin Kinase; D009428:Netilmicin / Q000494:pharmacology; D009713:Nucleotidyltransferases / Q000378:metabolism; D010770:Phosphotransferases / Q000378:metabolism; D011159:Population Surveillance; D011446:Prospective Studies; D014031:Tobramycin / Q000494:pharmacology
chemical_list: D000617:Aminoglycosides; D005839:Gentamicins; D009428:Netilmicin; D007612:Kanamycin; D000583:Amikacin; D000123:Acetyltransferases; C019681:aminoglycoside acetyltransferase; D010770:Phosphotransferases; D019868:Kanamycin Kinase; D009713:Nucleotidyltransferases; C020565:gentamicin 2''-nucleotidyltransferase; D014031:Tobramycin