Penetration of pefloxacin into bronchial secretions

Abstract

Twelve patients, intubated for acute exacerbation of chronic obstructive pulmonary disease, received six intravenous doses of 400 mg of pefloxacin at 12-h intervals. Samples of blood and bronchial secretions were taken simultaneously, before the injection and at 0.5, 3, 6, 9, and 12 h after the end of the sixth infusion. There was a large variation in pefloxacin levels in both serum and bronchial secretions. The mean concentrations of pefloxacin in bronchial secretions ranged from 6.51 to 11.1 ,ug/mI and were higher than the corresponding concentrations in serum at all times. Of 61 bronchial specimens, 48 (79%) contained more than 8 ,ug of the antibiotic per ml.Pefloxacin is a new synthetic antibiotic derived from quinolinecarboxylic acid. In vitro, this drug has excellent activity against a wide range of bacterial species, including especially most members of the family Enterobacteriaceae, staphylococci, and Pseudomonas spp. (3,5,11). Most strains of these organisms are susceptible to concentrations equal to or less than 2 ,ug of the antibiotic per ml, except for Pseudomonas spp. (4 to 8 ,ug/ml).Since these organisms are frequently isolated from tracheal cultures of patients who require endotracheal intubation and mechanical ventilation (13), we undertook a study of pefloxacin penetration into the bronchial secretions of intubated patients.Twelve patients who required endotracheal intubation and mechanical ventilation because of acute respiratory failure were enrolled in this study. All of the patients studied, nine men and three women, had an acute exacerbation of chronic obstructive pulmonary disease. Their ages ranged from 38 to 73 years (mean, 65.9 years), and body weights ranged from 46 to 104 kg (mean, 62 kg). The apparent cause of acute respiratory failure in all patients was purulent tracheobronchitis, evidenced by the production of purulent bronchial secretions without radiologic features of pneumonia. At the time of the study, all patients were clinically stable, with plasma creatinine and routine biochemical liver function tests within the normal limits. All patients received intensive physiotherapy and a mucolytic agent, bromhexine (4 mg three times a day). All patients gave their informed consent to inclusion in the study. The samples were collected after the administration of six doses of 400 mg of pefloxacin, when the steady state was probably reached. Each dose was given at 12-h intervals as a 1-h intravenous infusion. Venous blood and bronchial secretion samples were taken simultaneously, immediately before the injection and at 0.5, 3, 6, 9, and 12 h after the end of the sixth infusion. Bronchial secretions, obtained with a suction catheter inserted into the endotracheal tube, were homogenized with pancreatin. All of the samples were stored at -40°C until assayed.In all patients, pefloxacin concentrations were measured in plasma and bronchial secretions by using a microbiologi- Good correlation was observed between the values obtained in serum and bronchial secretions, by both highperformance l...

Pefloxacin Clinical Pharmacokinetics

“…The ratio of AVC for bronchial secretions to AVC for the serum averaged 1.7. [112] At all times the mean concentration of pefloxacin in bronchial secretions was similar to, or higher than, the corresponding concentration in serum. The mean Cmax in bronchial secretions was 15.3 mg/L, occurring 0.5 hours postdose.…”

Antimicrobial Therapy for the Elderly Patient

“…The pharmacokinetics of quinolones in aging persons, primarily ciprofloxacin but also enoxacin, ofloxacin, and pefloxacin, have been studied extensively 204–214 ; tissue penetration of these drugs in elderly patients has also been studied 215–217 . These numerous reports can be summarized, although the reported results do not always agree.…”

Respiratory Tract Penetration of Quinolone Antimicrobials: A Case in Study

“…Concentrations of antimicrobials with active metabolites may appear to be higher when measured by microbiologic assay than when measured by high-performance liquid chromatography (HPLC). 16 The common HPLC technique detects active parent compound yet ignores metabolites that possess antimicrobial activity.l8# l9 The microbiologic assay gives a sense of overall antimicrobial activity, but is not able to discern the different active components or the effect that the active metabolites VOLUME 11, NUMBER 1, 1991 may have on each other (i.e., synergy). Both techniques have advantages and disadvantages for tissue sample analysis.…”