Penetration of ciprofloxacin into bronchial secretions from mechanically ventilated patients with nosocomial bronchopneumonia

Abstract

The aim of the study was to evaluate the penetration of ciprofloxacin into bronchial secretions from mechanically ventilated patients with nosocomial bronchopneumonia. For this purpose, in each patient studied, simultaneous serial blood and bronchial secretion samples were obtained over a 12-h period on days 2 and 4. Eight patients were included in the study. Ciprofloxacin was given at a dose of 200 mg over 30 min by using an automatic pump. Ciprofloxacin was measured by high-performance liquid chromatography. Peak levels of drug in serum were 2.95 ± 1 mg/liter on day 2 and 2.43 ± 0.7 mg/liter on day 4. Peak and trough levels in bronchial secretions were 0.95 ± 0.51 and 0.21 ± 0.12 mg/liter, respectively, on day 2 and 0.76 ± 0.17 and 0.18 ± 0.14 mg/liter, respectively, on day 4. The ratios of peak concentrations in bronchial secretions/serum were 0.32 ± 0.11 and 0.33 ± 0.06 on days 2 and 4, respectively. The ratios of the area under the concentration-time curve from 0 to 12 h (AUC1_12) for bronchial secretions/those for serum were 0.66 ± 0.40 and 0.55 ± 0.30 on days 2 and 4, respectively. A significant positive correlation was found on day 4 between the AUCO_12 for serum and the AUCo_12 for bronchial secretions. No significant correlations were found between peak values in serum and bronchial secretions.Ciprofloxacin is a fluoroquinolone with a broad spectrum of activity, including activity against staphylococci and gramnegative bacteria, including most members of the family Enterobacteriaceae and Pseudomonas aeruginosa (1,22). Weaker activity against gram-positive cocci other than staphylococci has also been reported. These bacteriological aspects make this antibiotic of interest for the treatment of nosocomial bronchopneumonia (23). Bronchial tree colonization by pathogens coming from the patient's oropharynx and secondary bronchial tree infection are the main pathogenic mechanisms of nosocomial bronchopneumonia acquired by intubated patients under mechanical ventilation (16,19). Therefore, it is of interest to determine the degree of penetration of ciprofloxacin into bronchial secretions when this drug is used to treat nosocomial pulmonary infections. Penetration of ciprofloxacin has been studied in patients with cystic fibrosis or acute exacerbation of chronic bronchitis (5,6,8,10,12,17,24 following diagnostic criteria: purulent sputum; body temperature, .38.50C; leukocyte count, .12,000/mm3; new or progressive infiltrate on chest X ray; hypoxia which required the use of positive end-expiratory pressure or an increase in fraction inspiratory oxygen concentration; no other site of infection; and growth of a pathogenic bacterium on a protected specimen brush or bronchoalveolar lavage specimens. The pathogens that were isolated were P. aeruginosa (six patients), Enterobacter aerogenes (one patient), and Klebsiella pneumoniae (1 patient). Five patients had a mild impairment of their renal function, with a creatinine clearances of between 60 and 70 ml/min/1.74 M2. The other three patients had creatinine clearance...

Pharmacokinetics of Ciprofloxacin and Its Penetration into Bronchial Secretions of Mechanically Ventilated Patients with Chronic Obstructive Pulmonary Disease

“…A study done in mechanically ventilated patients with nosocomial bronchopneumonia, who were being treated with 200 mg of ciprofloxacin q12h, showed that its penetration was 55 to 60% (27). This ratio ranged from 0.79 to 1.11, much closer to the value that we observed in a previous study (4).…”

Assessment of antibiotic levels in lung tissue with erosion-controlled dosage forms

“…The pharmacokinetic parameters of various fluoroquinolones have been established in a mouse model of infected lung (6), and it was determined that infection did not affect the tissue distribution of these drugs. The aim of other studies was to evaluate the penetration of ciprofloxacin in the bronchial tissue (7,8) and, more specifically, in the bronchial mucosa (9,12) or in the pleural fluid (13). Transcapillary exchange of antibiotics is carried out by diffusion and occurs in the capillary beds of the tissues.…”

Suboptimal Ciprofloxacin Dosing as a Potential Cause of Decreased Pseudomonas aeruginosa Susceptibility in Children with Cystic Fibrosis

“…This diffusion was found to be 46% in patients with cystic fibrosis and approximately 60% in patients without cystic fibrosis. 23,24 Although the difference in these percentages does not appear to be that much, the lower diffusion of ciprofloxacin into the respiratory secretions of patients with cystic fibrosis would need to be balanced by higher plasma exposure in order to achieve a similar concentration at the site of infection. This, however, may not be sufficient, as a direct influence of cystic fibrosis on the pharmacokinetics and pharmacodynamics of ciprofloxacin cannot be excluded.…”