Penetration of Aminoglycosides in Uninfected Pleural Exudates and in Pleural Empyemas

doi:10.1378/chest.93.3.530

Chest

Volume 93, Issue 3, March 1988, Pages 530-532

https://doi.org/10.1378/chest.93.3.530 Get rights and content

The concentrations of gentamicin, netilmicin, and amikacin were determined after one single intravenous injection in uninfected pleural fluid after thoracotomy and in purulent pleural empyemas. The mean peak concentrations in the pleural fluid after the injection of gentamicin (1.5 mg/kg), netilmicin (2.0 mg/kg), and amikacin (7.5 mg/kg) were 2.9 ± 0.3 mg/L, 3.7±0.8 mg/L, and 11.0 ±3.1 mg/L, respectively. The pleural penetration of the drugs was very high (from 80.0 to 99.1 percent). By contrast, gentamicin and netilmicin were not detectable in empyema pus; in this exudate the mean peak level of amikacin was 5.7 ± 2.2 mg/L, with the penetration of this drug being 31.0 percent. The concentrations of parenterally administered aminoglycosides are substantially lower in empyema pus than in sterile pleural fluid. The possibility of poor pleural penetration of some aminoglycosides, as well as the presence of local conditions in pleural empyema unfavorable to the bioactivity of these drugs, must be kept in mind when treating pleural infections.

Section snippets

Uninfected Pleural Exudates

Patients and Experiment. The 19 patients underwent a lobectomy (17 cases) or a pneumomectomy (two cases) two to seven days (mean, 3.1 days) before investigation. Pulmonary resections were performed for bronchial carcinoma (16 cases), emphysematous bullae (one case), tuberculosis (one case), and bronchiectasis (one case). Renal function of all of the patients was normal (serum creatinine level, ≤1 mg/dl). All had postoperative pleural drainage with a chest tube and continuous suction. A single

Uninfected Pleural Exudates

Tables 1 to 3 present the concentrations of gentamicin, netilmicin, and amikacin observed in serum and uninfected pleural exudates. For gentamicin the mean peak and trough concentrations in the pleural fluid were 2.4 ± 0.3 and 1.1 ± 0.2 mg/L, respectively; the ratio of the pleural fluid and serum mean peak concentrations was 56.9 percent. The half-life of the drug in the pleural fluid was significantly longer than that of the drug in the serum (3.95 ± 0.42 vs 2.86 ± 0.14 hours; p<0.025). The

DISCUSSION

The pharmacokinetics of aminoglycosides in the pleural space after systemic administration has not been extensively investigated. Most of the studies report pleural antibiotic levels in samples taken at various intervals after the injection of the drug in different patients, which does not provide kinetic information about the pleural diffusion of the drugs. In a sterile effusion, a pleural fluid/serum concentration ratio of streptomycin, gentamicin, tobramycin, amikacin, and sisomicin ranging

ACKNOWLEDGMENTS

We thank the medical and nursing staff of the Thoracic Surgery Department at the Erasme Hospital for their help during the study. The expert laboratory assistance of Ms. M. Vanderlinden was greatly appreciated. We are grateful to Ms. L. Zech and Ms. M. Onrubia tor their competent secretarial work.

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Pleural diffusion of amoxicillin 1 and vancomycin in patients treated fro post-surgical empyema
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Le traitement des empyèmes après chirurgie d’exérèse pulmonaire comporte, le drainage pleural, une antibiothérapie, une kinésithérapie adaptée et parfois une reprise chirurgicale pour un lavage des cavités infectées. Il existe peu de données chez l’homme sur la pénétration des antibiotiques en situation d’empyème post-chirurgicaux. Le but de notre travail était d’étudier prospectivement la diffusion pleurale de 2 antibiotiques fréquemment utilisés : l’amoxicilline et la vancomycine chez des patients présentant un empyème après chirurgie d’exérèse pulmonaire.
Des dosages plasmatiques et pleuraux d’antibiotiques ont été effectués chez 9 patients ayant un empyème après exérèse pulmonaire majeure (pneumonectomie n = 6) après plusieurs jours de traitement (3-12 Jours), correspondant au plateau de la concentration pleurale.
La présence d’antibiotiques a été détectée dans le liquide pleural de tous les patients. Chez 5 patients sur 9, les concentrations résiduelles pleurales étaient supérieures aux concentrations résiduelles plasmatiques. Le ratio moyen concentration pleurale/plasmatique était de 1,96 (extrêmes : 0,6-4,9). L’évolution infectieuse a été favorable dans 8 cas.
Cette étude démontre que l’amoxicilline et la vancomycine diffusent correctement dans la plèvre en situation pathologique chez l’homme, atteignant le plus souvent des concentrations pleurales supérieures aux concentrations plasmatiques.
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The ratio pleural/plasma antibiotic concentration was 1.96 (range: 0.6-4.9). The pleural infection was cured for 8 on 9 patients. The last patients required thoracostomy, and the outcome was favorable after this procedure.
That the penetration of amoxicillin and vancomycin in pleural space after post surgical empyema is good. Pleural antibiotics concentrations are in the majority of cases higher than plasmatic concentrations.
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Synthèse des données : Les résultats étaient relativement similaires pour les différents types de prélèvements. Il existait des différences en fonction des études, liées en particulier aux difficultés méthodologiques de dosage tissulaire des antibiotiques.
Conclusion : Dˈautres études plus standardisées, en particulier en effectuant le dosage des antibiotiques dans le film alvéolaire et dans les macrophages alvéolaires, seraient souhaitables pour obtenir des résultats plus fiables en terme de quotient inhibiteur. Enfin, seules des études cliniques correctement menées, à la lumière peut-être de ces différentes données, permettraient dˈétablir lˈefficacité réelle des antibiotiques dans le cadre des infections pulmonaires.
Objectives: Collect exhaustive data from the literature concerning the diffusion of antibiotics into lung tissue and calculate their inhibitory quotient towards the germs most frequently encountered in pulmonary infections.
Data sources: Review of the literature. Data collected from the Medline database with the key words : lung, diffusion, disposition, antibiotics. Inhibitory quotients calculated from these data.
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Supported by a grant from Schering-Essex Brussels and from Bristol Benelux, Brussels, which also, respectively, provided gentamicin and netilmicin, and amikacin.

Presented in part at the 23rd International Conference on Antimicrobial Agents and Chemotherapy, Las Vegas, October 1983.

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Chest

Penetration of Aminoglycosides in Uninfected Pleural Exudates and in Pleural Empyemas

Section snippets

Uninfected Pleural Exudates

Uninfected Pleural Exudates

DISCUSSION

ACKNOWLEDGMENTS

J Infection

Chest

Interaction of purulent material with antibiotics used to treat Pseudomonas infections.

Antimicrob Agents Chemother

Gentamicin inactivation in purulent exudates: the role of the cell lysis.

J Infect Dis

Simplified, accurate method for antibiotic assay of clinical specimens.

Appl Microbiol