Concentrations of levofloxacin (HR 355) in the respiratory tract following a single oral dose in patients undergoing fibre-optic bronchoscopy

Abstract

Concentrations of levofloxacin were measured in bronchial biopsies, alveolar macrophages (AM), epithelial lining fluid (ELF) and serum following a single oral dose. Concentrations were measured by a microbiological assay method. A total of 35 patients undergoing fibre-optic bronchoscopy were studied. Mean serum, AM, ELF and biopsy concentrations were as follows. 0.5 h: 4.73 mg/L, 19.1 mg/L, 4.74 mg/L and 4.3 mg/kg; 1 h: 6.6 mg/L, 32.5 mg/L, 10.8 mg/L and 8.3 mg/kg; 2 h: 4.9 mg/L, 41.9 mg/L, 9.0 mg/L and 6.5 mg/kg; 4 h: 4.1 mg/L, 27.7 mg/L, 10.9 mg/L and 6.0 mg/kg; and 6-8 h: 4.0 mg/L, 38.4 mg/L, 9.6 mg/L and 4.0 mg/kg respectively. Mean serum and AM concentrations at 12-24 h were 1.2 and 13.9 mg/L respectively (concentrations in biopsy and ELF were only measurable in three of the six patients). These concentrations exceed the MIC90s of the common respiratory pathogens, Haemophilus influenzae (0.015 mg/L), Moraxella catarrhalis (0.06 mg/L) and Streptococcus pneumoniae (1 mg/L) and suggest that levofloxacin should be efficacious in the treatment of community- and hospital-acquired respiratory infection.

Bronchoscopic Microsampling Method for Measuring Drug Concentration in Epithelial Lining Fluid

“…It is of note that levofloxacin concentrations in ELF never exceeded those in serum at any time point examined. These findings do not agree with previous studies using BAL, in which the concentrations of the levofloxacin in BAL fluid were approximately twice as high as those of plasma for at least 12 hours (13,14). Although BAL has been considered to be only way of obtaining ELF from humans, this method includes a substantial methodologic problem (24).…”

“…The calculation of ELF volume and levofloxacin concentrations in ELF sampled by BAL was performed, as previously reported (13,14,20).…”

“…Thus, direct measurement of antimicrobial concentrations in bronchoalveolar space fluid may lead to a critical reappraisal of current antimicrobial dosing guidelines (9). To date, drug concentrations at the site of infection in the respiratory tracts of humans have been estimated by assaying whole-lung tissue, collecting sputum or sampling bronchoalveolar lavage (BAL) fluid (10)(11)(12)(13)(14). However, at least two methodologic problems hamper a correct interpretation of data derived from these techniques: (1 ) the concentration in the collected samples might not necessarily reflect the concentration at the anatomic target site, and (2 ) it would be impossible to obtain samples easily and repeatedly from the same subject.…”

Efficacy and safety of levofloxacin in the context of other contemporary fluoroquinolones: a review

“…Fluoroquinolones are concentrated in various tissues and, for example, after a standard 500-mg dose, levofloxacin clearly achieves effective therapeutic concentrations in bronchial mucosa (∼6 mg/L), epithelial lining fluid (∼9 mg/L), and alveolar macrophages (Ͼ40 mg/L). 30 Thus, although they do not entirely explain the undoubted activity of levofloxacin, existing PD parameters certainly indicate that a high dose is required to ensure efficacy (and probably to avoid resistance emergence) and that, should an upward shift in MIC distribution in S pneumoniae be encountered, assessment of higher-than-currently-used doses should be investigated. The safety profile at the presently recommended dose 31 of levofloxacin encourages this possibility.…”

In Vitro Activities of Garenoxacin and Levofloxacin against Chlamydia pneumoniae Are Not Affected by Presence of Mycoplasma DNA

“…To our knowledge, garenoxacin has not been studied in a similar system. However, results from two studies with these drugs in which comparable methods were used suggest that garenoxacin penetrates human phagocytic cells to a slightly greater extent than levofloxacin (2,3). Second, garenoxacin also has greater activity than levofloxacin in an in vitro assay of inhibition of C. pneumoniae DNA gyrase activity (1).…”