title: Efficacy of clarithromycin against Streptococcus pneumoniae expressing mef(A)-mediated resistance.
abstract: As a result of macrolide resistance rates of 25% for pneumococci in the US, the clinical use of this class as empirical therapy has been questioned. However, macrolides continue to be used with clinical success. Using an immunocompromised murine pneumonia model, this study evaluated in vivo efficacy of human simulated exposures of clarithromycin for 62 isolates of Streptococcus pneumoniae considered resistant by current methods of breakpoint determinations. Changes in bacterial density were compared between treated animals and untreated controls. Inhibition of bacterial growth was consistently observed for the majority of isolates tested with mean (S.D.) reductions in logCFU per lung of -0.88 (0.69), -1.02 (0.87), -0.47 (0.79), -0.84 (0.66), -0.25 (0.26), -0.80 (0.72) and -0.58 (0.47) for MICs of 1, 2, 4, 8, 16, 32 and 64 mg/l, respectively. A beneficial treatment effect was clearly noted for isolates with clarithromycin MICs <==8 mg/l. However, the sample size of isolates tested beyond the MIC of 8 mg/l was diminished due to mortality in both treated and untreated animals. Consistent suppression of bacterial growth observed in this neutropenic model provides support for the in vivo efficacy of clarithromycin with low-level macrolide-resistant S. pneumoniae.
authors.affiliation: Center for Anti-Infective Research and Development, Hartford Hospital, 80 Seymour Street, Hartford, CT 06102, USA.
authors.forename: Dana
authors.initials: D
authors.lastname: Maglio
authors.forename: Blair
authors.initials: B
authors.lastname: Capitano
authors.forename: Mary Anne
authors.initials: MA
authors.lastname: Banevicius
authors.forename: Pamela R
authors.initials: PR
authors.lastname: Tessier
authors.forename: Charles H
authors.initials: CH
authors.lastname: Nightingale
authors.forename: David P
authors.initials: DP
authors.lastname: Nicolau
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000235:genetics*; D017291:Clarithromycin / Q000494:pharmacology* / Q000627:therapeutic use*; D015169:Colony Count, Microbial; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D016867:Immunocompromised Host; D008168:Lung / Q000382:microbiology; D008565:Membrane Proteins / Q000235:genetics*; D008780:Methyltransferases / Q000235:genetics; D051379:Mice; D008826:Microbial Sensitivity Tests; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy* / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C117866:MefA protein, Streptococcus; D008565:Membrane Proteins; D008780:Methyltransferases; C035181:rRNA (adenosine-O-2'-)methyltransferase; D017291:Clarithromycin