Penetration of cefaclor into bronchial mucosa.

Abstract

Bronchial mucosal biopsy specimens were obtained during fibreoptic bronchoscopy in 30 patients receiving a new oral cephalosporin antibiotic, cefaclor (10 had 250 mg, 10 had 500 mg, and 10 had 1000 mg every eight hours). In 10 patients (from all dosage groups) cefaclor was undetectable in the bronchial mucosa but in every case the serum concentration was low, suggesting incomplete absorption. The mean (SD) bronchial mucosal concentration after 250 mg was 3-78 (1-77) ,ug/g (range 2-1-5-8 pug/g, n = 4), after 500 mg 4-43 (2.04) ug/g (range 2-0-7-1 ,ug/g, n = 8), and after 1000 mg 7*73 (2.76) ug/g (range 5-012-7 ,ug/g, n = 6). A significantly higher concentration in the bronchial mucosa was achieved with 1000 mg than with 250 mg (p < 0.05) or 500 mg (p < 0-025). These concentrations should be effective against Streptococcus pneumoniae, most strains being inhibited below 10 ,ug/ml. The concentrations were within one dilution of the minimal inhibitory concentration for Haemophilus infuenzae, most strains being inhibited below 4 0 Zg/ml. Some strains of H injflenzae will not be inhibited by the concentrations of cefaclor found in the bronchial mucosa, particularly those that are ampicillin resistant.

Pulmonary disposition of antimicrobial agents: methodological considerations

“…The relative proportion of drug in the intracellular and extracellular components is important, because a major determinant of the total drug concentration in a tissue is the degree of intracellular penetration and accumulation. Thus, the fluoroquinolones and macrolides, which accumulate in the intracellular environment, have higher concentrations in bronchial biopsy specimens than in serum, whereas 3-lactams which do not penetrate cell membranes to any significant degree have lower concentrations in bronchial biopsy specimens than in serum (25,(39)(40)(41). Despite these facts, there are few published data on the constituents of bronchial biopsy specimens in terms of tissue types, and there are no data on the relative amounts of intra-and extracellular water.…”

“…AMs reside in this microenviron- (7,47). This sputum pooling invalidates measurements of antimicrobial agent concentrations with respect to the time of dosing and allows time for the degradation of antimicrobial agents, e.g., by P-lactamases (58 (25,39,40). However, the major criticism is that the most relevant information is the relative amount of drug in the interstitial fluid and cellular fluid (49).…”

Pulmonary disposition of antimicrobial agents: in vivo observations and clinical relevance

“…The fluoroquinolones have different ratios. Ciprofloxacin, temafloxacin, and lomefloxacin have mean ratios of between 1.7 and 1.9 (4, 5, 26), while enoxacin has been reported to achieved ratios of over 100 (34), although the latter observation is not readily explicable and requires confirmation. Similarly, for the macrolides a ratio of over 50 is found for azithromycin (2) which is greatly in excess of the ratios found for erythromycin.…”

“…Clear differences can be demonstrated between classes of antimicrobial agents, and the similarity of the ratios, particularly for the 3-lactams, is probably sufficient to allow prediction of levels of drug in biopsy specimens from the concentrations in serum. This is somewhat surprising, since one might expect differences in half-lives of drug in tissue and serum to influence the ratio when, in single-dose studies, the time from the dose is varied (2,7,37). This is not the case for P-lactams; whether they are administered as single or multiple doses, the BB/S ratio is between 0.35 and 0.55.…”

Lewofloksacyna i moksyfloksacyna w leczeniu zakażeń bakteryjnych

“…Z tego powodu coraz częściej przeprowadza się określanie stężeń antybiotyku, uwzględniając wpływ wielu różnych czynników na jego przechodzenie do tkanek i płynów [47]. Od dawna stężenie antybiotyku w błonie śluzowej oskrzeli w odniesieniu do stężenia leku w surowicy jest uznawane za wskaźnik penetracji do płuc [48]. Artyku jest dost pny na zasadzie dozwolonego u ytku osobistego.…”