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Bronchial secretion levels of amikacin
Abstract:
Amikacin was given to 14 noninfected men as three consecutive intramuscular injections (7.5 mg/kg) at 12-h intervals. Serum and bronchial secretion specimens were obtained at various times during flexible fiberoptic bronchoscopy after the final dose. Serum and bronchial secretion concentrations obtained between 1.5 and 2.0 h after the final dose ranged from 17 to 40 mug/ml and 2.3 to 8.4 mug/ml with a mean of 23.7 +/- 2.9 and 5.23 +/- 1.5 mug/ml, +/-1 standard error of the mean, respectively. The highest bronchial secretion concentration in each subject correlated with the highest serum concentration (r = 0.83, P < 0.001), and all concurrent serum and bronchial secretion concentrations demonstrated a significant correlation (r = 0.82, P < 0.001). Clearance occurred at the same rate (half-life serum = 2.84 h; half-life of bronchial secretion = 2.60 h, P > 0.5). The mean bronchial secretion concentration of the 15 specimens obtained more than 7 h after the final dose was less than 1.0 mug/ml, with a range from 0.3 to 1.6 mug/ml. It is concluded that amikacin may achieve minimal inhibitory concentrations for many gram-negative bacteria in the bronchial secretions of noninfected patients 1 to 2 h after the final dose. However, levels fall below the reported minimal inhibitory concentrations against negative bacteria 6 to 7 h after the final dose. Furthermore, bronchial secretion levels may never reach the minimal inhibitory concentration against Pseudomonas aeruginosa.
Insights
Amikacin reaches therapeutic levels in bronchial secretions within 2 hours but declines rapidly, potentially falling below effective concentrations for some bacteria within 7 hours.
Area of Science:
- Pharmacology
- Pulmonology
- Infectious Diseases
Background:
- Amikacin is an aminoglycoside antibiotic used for serious bacterial infections.
- Understanding amikacin penetration into bronchial secretions is crucial for treating respiratory infections.
Purpose of the Study:
- To determine amikacin concentrations in serum and bronchial secretions.
- To assess the correlation between serum and bronchial secretion levels.
- To evaluate the duration of amikacin presence in bronchial secretions.
Main Methods:
- 14 noninfected men received intramuscular amikacin (7.5 mg/kg) every 12 hours.
- Serum and bronchial secretion samples were collected via bronchoscopy after the final dose.
- Concentrations were measured at various time points, with analysis of correlation and elimination half-life.
Main Results:
- Peak serum amikacin levels (1.5-2.0 h post-dose) averaged 23.7 µg/ml, while bronchial secretion levels averaged 5.23 µg/ml.
- A strong positive correlation was observed between serum and bronchial secretion concentrations (r=0.82).
- Elimination half-lives were similar in serum (2.84 h) and bronchial secretions (2.60 h).
- After 7 hours, bronchial secretion levels dropped below 1.0 µg/ml.
Conclusions:
- Amikacin can achieve concentrations potentially effective against some gram-negative bacteria in bronchial secretions 1-2 hours after dosing.
- However, levels may not be sufficient against Pseudomonas aeruginosa.
- Rapid decline necessitates careful consideration of dosing intervals for effective treatment.