SUSCEPTIBILITY OF MYCOPLASMA PNEUMONIAE ISOLATES TO JOSAMYCIN

Abstract

We previously reported patients with Mycoplasma pneumoniae pneumonia in whom M.pneumoniae acquired resistance to erythromycin or josamycin during the treatment with erythromycin or josamycin. The resistance developed to a macrolide antibiotic was accompanied by the cross-resistance to other macrolides.The results indicated that the infection with M.pneumoniae resistant to macrolides is possibly encountered. We determined the susceptibility to erythromycin and josamycin in 237 isolates of M.pneumoniae recovered from 237 patients up to 1976 and concluded that the infection with M. pneumoniae resistant to erythromycin or josamycin was not observed.As josamycin recently has been widely used for the therapy of M. pneumoniae infections in Japan, the infection with M. pneumoniaeresistant to josamycin has become more possible.In the present study we determined the josamycin susceptibility of M.pneumoniae isolates recovered from 1980 to March, 1981.
Isolates served for the determination of the minimum inhibitory concentration (MIC) of josamycin were 137 isolates of M.pneumoniae recovered from 113 patients with M.pneumoniae infections.
The prelintinary experiment with the use of Mac strain of M.pneumoniae showed that the microtiter method gave the same value of the MIC as the tube method and so the microtiter method was used in the present study.The plates were observed every day during the incubation.As read on the day when the control wells without josamycin first changed in color to yellow (pH6.4), showing a rich growth, the minimum concentration of josamycin which inhibited the growth, showing no color change, was termed as MIC. The minimurn concentration of josamycin which inhibited the growth during a month's incubation was termed as the final minimum inhibitory concentration (FMIC).
For the M.pneumoniae isolates, the MIC of josamycin ranged from 0.0031 to 0.024 μg/ml and the FMIC from 0.0061 to 0.05 μg/ml. The MIC was 0.0031 μg/ml for 2 isolates (1.5%), 0.0061 μg/ml for 25 isolates (18, 2%), 0.0122 μg/ml for 76 isolates (55.5%), and 0.024 tiglinl for 34 isolates (24.8%), revealing that the MIC was 0.0122 μg/ml or less in more than a half of the isolates tested.The FMIC was 0.0061μg/ml for 9 isolates (6.6%), 0.0122μg/ml for 38 isolates (27.7%), 0.024μg/ml for 85 isolates (62.0%), and 0.05μg/ml for 5 isolates (3.6%), revealing that the FMIC was0.024μg/ml in more than a half of the isolates. The FMIC was similar or close to the MIC in values.All of the isolates were sensitive to josamycin.The results reveal that M.pneumoniae resistant to josamycin as well as other macrolides has not yet caused infections in man.
Of 21 patients from whom M.pneumoniae was isolated twice or more, 6 patients had received erythromycin more than 7 days.As we previously reported, the development of the resistance to erythromycin in M. pneumoniae is accompanied by the cross-resistance to josamycin as well as other macrolides. The MIC of josamycin for the isolates from the 6 patients was not different more than 3 times between the isolates before and after the erythromycin therapy, showing that all of the isolates were sensitive to josamycin.The results indicated that the resistance to macrolides did not develop in the 6 patients after the erythromycin therapy.