Penetration of cefotaxime into respiratory secretions

Abstract

The objective of this study was to quantitate cefotaxime and its active metabolite, desacetyl cefotaxime, in the distal airways and to compare these levels to concentrations in plasma. Respiratory secretions were obtained from the subsegmental level in 17 adult patients undergoing fiber-optic bronchoscopy within 2 h after receiving four doses of cefotaxime (2 g intravenously every 6 h). In 11 patients, cefotaxime levels measured by high-pressure liquid chromatography in bronchial secretions were below detectable limits (<0.5 mg/liter); however, levels of desacetyl cefotaxime exceeded 1.5 mg/liter in 9 of these 11 patients (range, 1.6 to 10 mg/liter).Concentrations of desacetyl cefotaxime in lung secretions (6.9 + 0.85 [standard error] mg/liter) was 77% of mean levels of desacetyl cefotaxime in plasma (8.9 + 1.26 mg/liter). In summary, concentrations of desacetyl cefotaxime in bronchial secretions are markedly higher than those of cefotaxime.Gram-negative-bacillary pneumonias are commonly treated with aminoglycoside antibiotics because other equally effective and less toxic agents have not been available. These lung infections respond to therapy slowly, are subject to relapse, and still have a mortality rate of 50%, despite the use of seemingly appropriate antimicrobial therapy (8,9). It is a common practice to determine antibiotic concentrations in the blood and to extrapolate this information to other tissues and body fluids in which the antibiotic may be less accessible. Antibiotic concentrations in blood are compared with the MIC for the infecting organism in an attempt to determine whether the antibiotic will be available in sufficient concentration to be effective. However, it has been demonstrated that even though adequate concentrations of aminoglycoside antibiotics are achievable in the blood, levels in bronchial secretions may be substantially lower (1, 4). Such low antibiotic concentrations in bronchial secretions may contribute to the continuing high mortality rate for gram-negative-bacillary pneumonias. Therefore, the goal of this study was to quantitate the potent broadspectrum cephalosporin, cefotaxime (CFX), and its active metabolite, desacetyl cefotaxime (DCFX), in the secretions of the distal airway of human subjects and then to relate these levels in lung secretions to concentrations in serum.The study protocol was designed to compare concentrations of CFX The antibiotic (2 g) was administered by intravenous infusion over a 5-to 10-min period every 6 h.Whole blood specimens (10 ml) were obtained at the same time as bronchial secretions. Blood samples were immediately centrifuged, and plasma was removed and preserved at -70°C until analysis was performed. Bronchoscopy permitted collection of undiluted respiratory secretions from the 4th-to 8th-generation airways and was performed as previously described (5,12). The respiratory secretions collected by this means (1-to 4-ml samples) were stored at -70°C until they were assayed by high-pressure liquid chromatography for CFX and DCFX. Plasma sampl...

Antimicrobianos en neonatología. Parte I: Recomendaciones de dosificaciones basadas, en la más reciente evidencia en recién nacidos Comité Consultivo de Infecciones Neonatales, Sociedad Chilena de Infectología

“…Carece de actividad contra BGN no fermentadores (Pseudomonas aeruginosa, Acinetobacter baumannii), L. monocytogenes, Enterococcus spp y anaerobios estrictos. Dentro de sus características FC destacan: una mínima metabolización hepática cuyo metabolito activo es la des-acetil-cefotaxima, una amplia distribución en distintos fluidos corporales (logrando Antimicrobianos Documento concentraciones bactericidas en LCR y secreciones bronquiales), un aclaramiento renal variable (dependiendo del peso y EG) y una vida media en promedio de 3,6 h [14][15][16] . A pesar de todas las características mencionadas, su utilidad en neonatología es limitada, debido a que su uso en este tipo de pacientes se ha asociado con mayor mortalidad, como lo demostró el estudio realizado por Clark y cols., en el cual, los pacientes que recibieron la combinación ampicilina-cefotaxima versus ampicilina-gentamicina dentro de los primeros tres días de vida, tuvieron 1,5 más probabilidades de morir 17 .…”

Desacetylcefotaxime

“…A recent review by Todd and Brogden (1990) reported that desacetylcefotaxime penetrated into cerebrospinal fluid (CSF), sputum, bronchial secretions, bile, ascitic fluid and peritoneal fluid. There are also data suggesting that during treatment with cefotaxime, high concentrations of desacetylcefotaxime occur in sputum and bronchial secretions (Fick et al 1987;Matsuoka et al 1986;Petrikkos et al 1987). Whether this apparent accumulation occurs because of an innate physicochemical property of desacetylcefotaxime or differences in the pharmacokinetics of the parent drug and/or active metabolite remains to be determined.…”

Bronchopulmonary Infectious Complications of Cystic Fibrosis

“…That is, the level in the airways will be only 20 to 30% of a simultaneously obtained serum concentration. 15,88 Additionally, Levy and coworkers 89 demonstrated biologic antagonism of gentamicin in CF purulent sputum caused by protein binding and antagonism by ions reducing antibiotic bioactivity. For these reasons, nebulized delivery has been more frequently resorted to in an attempt to attain suprapharmacologic levels of bactericidal antibiotics in these chronically infected airway fluids.…”