title: Comparative in vitro evaluation of dirithromycin tested against recent clinical isolates of Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae, including effects of medium supplements and test conditions on MIC results.
abstract: The use of macrolides for treatment of respiratory complaints has been complicated by susceptibility test conditions that adversely effect the in vitro test results and perceived potencies of these compounds. Dirithromycin was studied as to its in vitro activity compared to other macrolides as well as the effects that environmental incubation variations and inoculum concentrations may have on susceptibility results. Dirithromycin was less active than other macrolides tested (azithromycin clarithromycin, erythromycin) against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis with MIC90 values of 16, 32, and 1 microgram/ml, respectively; an activity that was most similar to roxithromycin. This reduced activity may be compensated by the superior pharmacokinetic properties that dirithromycin possesses compared to other members in its class. Method variation studies show that incubation in CO2 environments increase the MIC values for all macrolide compounds and dirithromycin was most effected by pH changes in three in vitro methods tested (Etest [AB BIODISK, Solna, Sweden] broth microdilution, and disk diffusion). Variations in inoculum concentration had minimal effect on dirithromycin potency. In addition the variability (lack of reproducibility) of the test results with dirithromycin were not significant. Dirithromycin is an alternative therapeutic choice among macrolide compounds for treatment of community-acquired respiratory infections caused by various streptococci, Legionella pneumophilia, Mycoplasma pneumoniae and M. catarrhalis, and also possesses a modest in vitro potency versus H. influenzae coupled with excellent pharmacokinetic properties. In vitro tests with dirithromycin will continue to be problematic for H. influenzae because of the adverse effects of recommended CO2 incubation for some standardized methods or commercial products (Etest).
authors.affiliation: Department of Pathology, University of Iowa College of Medicine, Iowa City 52242, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Biedenbach
authors.forename: R N
authors.initials: RN
authors.lastname: Jones
authors.forename: M T
authors.initials: MT
authors.lastname: Lewis
authors.forename: M A
authors.initials: MA
authors.lastname: Croco
authors.forename: M S
authors.initials: MS
authors.lastname: Barrett
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D004917:Erythromycin / Q000031:analogs & derivatives / Q000494:pharmacology; D005069:Evaluation Studies as Topic; D006193:Haemophilus influenzae / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D018942:Macrolides; D008826:Microbial Sensitivity Tests; D001936:Moraxella catarrhalis / Q000187:drug effects* / Q000302:isolation & purification; D015203:Reproducibility of Results; D012141:Respiratory Tract Infections / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000302:isolation & purification
chemical_list: D000900:Anti-Bacterial Agents; D018942:Macrolides; C053853:dirithromycin; D004917:Erythromycin