Antibiotic resistance patterns during aminoglycoside restriction.
When amikacin first became available its use was restricted to prevent the emergence of resistant strains of gram-negative bacilli to this new agent. Gentamicin was the aminoglycoside most widely used at this time, and the incidence of gentamicin-resistant bacteria was 14%, while only 2.4% were resistant to amikacin. For a period of 15 months gentamicin use was restricted, and amikacin was used almost exclusively. Amikacin use was associated with a fall in the incidence of gentamicin-resistant bacteria to 9.2% (p less than .00005), while amikacin resistance remained unchanged at 2.2% (NS). During a period of 21 months after all aminoglycoside restrictions were lifted, gentamicin use again increased, and was accompanied by a return of gentamicin resistance to the baseline level of 15.3%. During this period, amikacin resistance also increased to 4.0% (p less than .0000001) but was due primarily to an increase in resistant Pseudomonas aeruginosa. Escherichia coli was the most frequently isolated gram-negative bacillus during all three periods, and it remained sensitive to both antibiotics regardless of the drug in use. In contrast, P. aeruginosa showed a high level of resistance to gentamicin, which fell when this antibiotic was restricted, only to return to a high level with reinstitution of gentamicin. While there was also an increase in amikacin resistant strains of P. aeruginosa with unrestricted aminoglycoside use, there was no apparent shift in the pattern of aminoglycoside modifying enzymes among a small random selection of amikacin-resistant bacteria. Impaired uptake of antibiotic was the predominant mechanism responsible for P. aeruginosa resistance among strains that did not produce aminoglycoside acetyltransferase (AAC)(6').