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Antibiotic resistance patterns during aminoglycoside restriction
Abstract:
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').
Insights
Restricting gentamicin use led to decreased resistance, while amikacin resistance remained stable. However, lifting restrictions increased resistance to both antibiotics, particularly in Pseudomonas aeruginosa, suggesting careful aminoglycoside stewardship is crucial.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Aminoglycoside antibiotics like gentamicin and amikacin are critical for treating Gram-negative bacterial infections.
- Emergence of antibiotic resistance necessitates strategies to preserve the efficacy of these agents.
- Initial use of amikacin was restricted to prevent resistance development against this new drug.
Purpose of the Study:
- To evaluate the impact of restricted versus unrestricted aminoglycoside use on bacterial resistance patterns.
- To assess changes in resistance to gentamicin and amikacin in Gram-negative bacilli over time.
- To investigate the mechanisms of amikacin resistance in Pseudomonas aeruginosa.
Main Methods:
- Retrospective analysis of bacterial resistance data during three distinct periods of aminoglycoside use.
- Monitoring of gentamicin and amikacin resistance incidence in Gram-negative bacilli.
- Characterization of resistance mechanisms in Pseudomonas aeruginosa strains.
Main Results:
- Restricting gentamicin use led to a significant decrease in gentamicin-resistant bacteria (14% to 9.2%) while amikacin resistance remained low (2.4% to 2.2%).
- Lifting aminoglycoside restrictions resulted in increased resistance to both gentamicin (15.3%) and amikacin (4.0%), primarily due to resistant Pseudomonas aeruginosa.
- Escherichia coli remained sensitive to both antibiotics, whereas Pseudomonas aeruginosa showed fluctuating resistance patterns correlating with gentamicin use; impaired uptake was a key resistance mechanism in P. aeruginosa.
Conclusions:
- Aminoglycoside stewardship, including restriction of specific agents, can effectively reduce resistance.
- Unrestricted use of aminoglycosides can lead to increased resistance, particularly in challenging pathogens like P. aeruginosa.
- Understanding resistance mechanisms is vital for guiding antibiotic therapy and preserving drug effectiveness.