Antimicrobial Activities and Postantibiotic Effects of Clarithromycin, 14-Hydroxy-Clarithromycin, and Azithromycin in Epithelial Cell Lining Fluid against Clinical Isolates ofHaemophilus influenzaeandStreptococcus pneumoniae

Abstract

The antimicrobial activity of concentrations of selected macrolides found in epithelial cell lining fluid was investigated. Clarithromycin demonstrated greater potency and a significantly longer postantibiotic effect (PAE) than azithromycin againstStreptococcus pneumoniae. Azithromycin displayed greater potency, faster killing, and a longer PAE than clarithromycin againstHaemophilus influenzae. Drug concentrations in epithelial cell lining fluid similar to those found in tissue did not improve the synergistic potential of 14-hydroxy-clarithromycin and indicate that a maximal PAE may exist despite increasing concentrations of drug.

Pharmacokinetics/pharmacodynamics of macrolides

“…The metabolite has demonstrated greater in vitro potency against H. injluenzae than the parent compound alone and additive or synergistic properties when combined with the parent compound [13,37]. In sera of human volunteers, the concentrations of clarithromycin and its metabolite were equally active in vitro against pathogens implicated in community acquired pneumonia, with the metabolite having twofold more activity than clarithromycin against H. injluenzae [37].…”

“…The pharmacokinetic profiles of these newer drugs differ in many aspects from each other, as well as from erythromycin, however, both are excellent at reaching high concentrations intracellularly. Azithromycin is unique because of 1) its long serum half-life, enabling it to function effectively in oncedaily dosing, and 2) its extensive tissue distribution, reaching high concentrations in alveolar macrophages while low levels remain in the plasma [13][14][15]. Table 1 provides a summary of the pharmacokinetics of several macrolides.…”

“…Clarithromycin has greater acid stability, improved pharmacokinetics, better gastrointenstinal tolerance, and a broader spectrum of activity than erythromycin [13,14]. Hepatic metabolism of an oral dose results in its principal metabolite, 14hydroxyclarithromycin.…”

“…Clarithromycin's activity against this pathogen is due to the activity of the parent compound and its active metabolite 14-hydroxyclarithromycin [13,37].…”

“…Much of clarithromycin's antimicrobial effect is believed to be due to its active metabolite, 14-hydroxyclarithromycin [13,21,37,38]. The metabolite has demonstrated greater in vitro potency against H. injluenzae than the parent compound alone and additive or synergistic properties when combined with the parent compound [13,37].…”