Penetration of newer quinolones in the empyema fluid

Abstract

The degree of penetration of newer quinolones into the pleural fluid has not been studied. The objective of the present study was to determine the degree to which moxifloxacin and levofloxacin penetrate into empyemic pleural fluid using a new rabbit model of empyema.An empyema was created via the intrapleural injection of turpentine (1 mL), followed 24 h later by instillation of 2 mL (1610 10 ) Escherichia coli bacteria (ATCC 35218) into the pleural space of New Zealand white rabbits. After an empyema was verified by thoracentesis and pleural fluid analysis, moxifloxacin and levofloxacin (25 mg?kg -1 for both, i.v.) were administered. Antibiotic levels were determined in samples of pleural fluid and in blood collected serially over 12 h. Antibiotic levels were measured using HPLC.Each of the antibiotics penetrated well into the empyemic pleural fluid. Antibiotic penetration was the greatest for moxifloxacin (area under the curve (AUC) for pleural fluid/blood (AUCPF/AUCblood) ratio=1.37) followed by levofloxacin (ratio=1.13). The time to equilibration between the pleural fluid and blood antibiotic levels was more rapid for moxifloxacin (3.9 h) than for levofloxacin (4.4 h). With moxifloxacin, the peak pleural fluid concentration (Cmax,PF) was 2.77 mg?mL -1 and occurred at a time to maximum pleural fluid concentration (Tmax,PF) of 6 h after infusion and decreased thereafter. The peak blood concentration (Cmax,blood) was 4.81 mg?mL -1 at 1 h after administration. With levofloxacin, the peak pleural fluid level (Cmax,PF=1.39 mg?mL -1 ) occurred at 6 h (Tmax,PF=6 h) after infusion. The Cmax,blood was 1.88 mg?mL -1 at 1 h after administration.In conclusion, differences were found in the degree of penetration of the two quinolones into infected pleural fluid in rabbits. The clinical significance of these differences is unknown. More studies are needed to evaluate the pharmacokinetic parameters in the pleural space in humans.

Antimicrobial resistance development following surgical site infections

“…The 52.40% resistance to ciprofloxacin is important in treating the pleural infections, as ciprofloxacin penetrates well in the pleural space (11). …”

Management of pleural infection in adults: British Thoracic Society pleural disease guideline 2010

“…Clindamycin achieves good penetration of the infected pleural space126 133 134 and offers adequate antimicrobial cover for these patients. Patients with a penicillin allergy can therefore be treated by clindamycin alone7 129 or in combination with ciprofloxacin or a cephalosporin 135.…”

Experimental pleural empyema model in rabbits: Why, how and what are the next steps

“…This model was used for research of pharmacological characteristics and therapeutic efficacy of gentamicin 15 . Turpentine rabbit experimental empyema model with 10 10 /mL Escherichia coli was applied for the research of clarithromycin efficacy, newer quinolones and azithromycin penetration in the empyema fluid 9,26,27 . This model was also used to study linezolid and ertapenem pharmacokinetics in parapneumonic effusions 28 .…”