Effect of CO2 on susceptibilities of anaerobes to erythromycin, azithromycin, clarithromycin, and roxithromycin.

The Oxyrase agar dilution method (Oxyrase, Inc., Mansfield, Ohio), which provides an anaerobic environment without added CO2, was compared with the reference agar dilution method recommended by the National Committee for Clinical Laboratory Standards (anaerobic chamber with 10% CO2) to test the susceptibilities of 302 gram-negative and gram-positive anaerobes to erythromycin, azithromycin, clarithromycin, and roxithromycin. For erythromycin, the overall MIC for 50% of isolates tested (MIC50) was 0.5 micrograms/ml and the MIC90 was 8.0 micrograms/ml by the Oxyrase method, whereas they were 4.0 and 64.0 micrograms/ml, respectively, under standard anaerobic conditions with CO2. At a breakpoint of 4.0 micrograms/ml, 88% of strains were susceptible to erythromycin by the Oxyrase method, whereas 63% were susceptible in the chamber. The corresponding MIC50s and MIC90s of azithromycin, clarithromycin, and roxithromycin by the Oxyrase method were 0.5 and 8.0, 0.25 and 4.0, and 0.5 and 16.0 micrograms/ml, respectively, whereas in the chamber they were 4.0 and > 64.0, 2.0 and 64.0, and 2.0 and 64.0 micrograms/ml, respectively. At a breakpoint of 8.0 micrograms/ml for these three drugs, 89, 92, and 85% of the isolates, respectively, were susceptible by the Oxyrase method, whereas 67%, 72, and 68% of the isolates, respectively, were susceptible in the chamber. Most strains resistant to all four compounds by both methods were Bacteroides distasonis, Fusobacterium mortiferum, Fusobacterium varium and non-Clostridium perfringens Clostridium species. Results of the study may lead to a reappraisal of the role played by macrolides and azalides in the treatment of anaerobic infections.