Chest
Volume 117, Issue 6, June 2000, Pages 1734-1739
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Laboratory and Animal Investigations
Antibiotic Levels in Empyemic Pleural Fluid

https://doi.org/10.1378/chest.117.6.1734Get rights and content

Objective

To determine the degree to which bioactive penicillin, metronidazole, ceftriaxone, clindamycin, vancomycin, and gentamicin penetrate into empyemic pleural fluid using our new rabbit model of empyema.

Methods

An empyema was created via the intrapleural injection of 108 Pasteurella multocida bacteria into the pleural space of New Zealand white rabbits. After an empyema was verified by thoracentesis and pleural fluid analysis, penicillin, 24,000 U/kg; metronidazole, 37 mg/kg; ceftriaxone, 30 mg/kg; clindamycin, 9 mg/kg; vancomycin, 15 mg/kg; or gentamicin, 1 mg/kg, were administered IV. Antibiotic levels in samples of pleural fluid and serum, collected serially for up to 480 min, were then determined using a bioassay.

Results

The degree to which the different antibiotics penetrated into the infected pleural space was highly variable. Penicillin penetrated most easily, followed by metronidazole, ceftriaxone, clindamycin, vancomycin, and gentamicin. Of the antibiotics tested, penicillin and metronidazole equilibrated the most rapidly with the infected pleural fluid. Penicillin levels remained elevated in pleural fluid even after serum levels had decreased.

Conclusions

Using this rabbit model of empyema, there was marked variation in the penetration of antibiotics into the empyemic fluid. Although there are species differences between rabbit and human pleura, the variance in degree of penetration of antibiotics into the pleural space should be considered when antibiotics are selected for the treatment of patients with empyema.

Section snippets

Materials and Methods

This project was approved by the Animal Subjects Committee of the Veterans Affairs Medical Center, Long Beach, prior to the start of the study. Twelve New Zealand male white rabbits weighing from 2.0 to 3.0 kg were utilized for this study. Two rabbits each were used to study the pleural fluid antibiotic levels after the administration of each of the following six antibiotics: penicillin, metronidazole, ceftriaxone, clindamycin, vancomycin, and gentamicin.

Results

All rabbits developed empyema after the intrapleural injection of 108P multocida bacteria (Table 1). The pleural fluid was thick and grossly opaque. The pleural fluid pH was < 7.10 and the pleural fluid glucose level was < 20 mg/dL in all rabbits. The pleural fluid culture results were positive in all rabbits.

The relationships between the pleural fluid antibiotic levels and the serum antibiotic levels varied from one antibiotic to another (Fig 1). These relationships were primarily evaluated in

Discussion

The present study shows that penetration of antibiotics into infected pleural fluid and equilibration between the serum and pleural fluid varies from one antibiotic to another, using this experimental model of empyema in the rabbit.

Penicillin was the most effective agent in penetrating into the pleural space, followed by metronidazole. The antibiotics ceftriaxone, vancomycin, and clindamycin were of similar effectiveness, with gentamicin being the least effective penetrator.

Equilibration of

ACKNOWLEDGMENT

The authors would like to acknowledge the assistance of Dr. Dong-Sheng Cheng in preparing Figure 1, Ms. Sheila Rupp in preparing and editing the manuscript, and Patrick Chan (from Microbiological Reference Laboratories).

References (21)

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Dr. Teixeira is supported by Fundacao De Amparo a Pesquisa Do Estado de Sao Paulo, Brazil.

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