Effects of environmental factors on the in vitro potency of azithromycin.
The effects of media, pH, cations, serum, CO2 or anaerobic atmosphere, inoculum size and time of incubation on the in vitro potency of azithromycin were determined. The potency of azithromycin against all genera was particularly sensitive to changes in pH. The MIC for Staphylococcus aureus strains ranged from 50 micrograms/ml at pH 6 to less than or equal to 0.025 micrograms/ml at pH 8; for erythromycin the MIC change was less (1.6 to 0.05 micrograms/ml). Incubation for 18 h in 5% CO2 or an anaerobic atmosphere (10% CO2, 10% H2, 80% N2) lowered the pH by approximately 0.8 units with gram-negative organisms and 0.4 units with gram-positive organisms. This resulted in an MIC eight times greater than the aerobic MIC. In addition, the MIC100 for azithromycin and erythromycin against Bacteroides strains growing in Wilkins-Chalgren broth fell from 3.1 micrograms/ml in the anaerobic atmosphere to 0.2 and 0.4 micrograms/ml, respectively, when using the Oxyrase enzyme system to remove oxygen. With the Oxyrase system, the pH of the medium at the MIC remained at 7.2, while it fell to 6.7 in the anaerobic gas mixture. An increase in potency for both agents was also observed with other anaerobic species when using the Oxyrase system. The addition of serum produced an increase in potency of azithromycin and erythromycin that correlated with an increase in pH during incubation, despite the use of buffered media. Adding cations to Mueller-Hinton broth resulted in increased MICs for gram-negative organisms; the highest increases observed were four-fold for Escherichia coli.(ABSTRACT TRUNCATED AT 250 WORDS)
Retsema
J A
JA
Central Research Division, Pfizer Inc., Groton, CT 06340.
Brennan
L A
LA
Girard
A E
AE
D000693:Anaerobiosis; D017963:Azithromycin; D001421:Bacteria, Anaerobic / Q000187:drug effects; D002245:Carbon Dioxide / Q000494:pharmacology; D003470:Culture Media / Q000494:pharmacology; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D008826:Microbial Sensitivity Tests; D013997:Time Factors
D003470:Culture Media; D002245:Carbon Dioxide; D004917:Erythromycin; D017963:Azithromycin