Oct 18, 2001 (CIDRAP News) – Macrolide antibiotics, the mainstay of treatment for community-acquired pneumonia, are encountering increasing resistance from Streptococcus pneumoniae, the most common cause of the disease, according to a report in the Oct 17 issue of the Journal of the American Medical Association.
An analysis of thousands of S pneumoniae isolates from seven states shows that the organism's rate of resistance to macrolides nearly doubled, from 10.6% to 20.4%, between 1995 and 1999, states the report by Terri B. Hyde of the Centers for Disease control and Prevention and a large group of colleagues. Use of macrolides increased 13% overall during the interval and jumped 320% among children under 5 years old, the report says.
"In the setting of increasing macrolide use, pneumococcal resistance has become common," the authors state. However, they say it is not clear whether the current level of resistance threatens the effectiveness of newer macrolides such as clarithromycin and azithromycin.
The authors explain that pneumococcal resistance to macrolides is associated with two phenotypes, M and MLSB. Isolates of the M phenotype typically show moderate resistance, with a minimum inhibitory concentration (MIC) ranging from 1 to 32 mcg/mL, and are almost always susceptible to clindamycin. The MLSB phenotype, which uses a different resistance mechanism, has much greater resistance (MIC >64 mcg/mL) and is usually resistant to clindamycin.
Under auspices of the Active Bacterial Core surveillance (ABCs) system, the authors tested isolates of invasive S pneumoniae from 30 counties in Georgia, California, Minnesota, Oregon, Tennessee, Maryland, and Connecticut, with a total popoulation of 15.4 million. Isolates were classified as resistant, intermediate, or susceptible by standard criteria. Isolates found to be resistant to erythromycin (MIC >0.5 mcg/mL) were tested for clindamycin resistance; clindamycin-susceptible isolates were classified as M phenotype, and clindamycin-resistant specimens were classified as MLSB.
Testing was done on 15, 481 isolates, of which 2,273 (14.7%) showed decreased susceptibility to macrolides. Eighteen of these (0.1%) had intermediate resistance and the rest were fully resistant. With the near doubling of resistance rates over the period, increases in resistance were significant in all states except California. "The proportion of isolates with M phenotype increased from 7.4% in 1995 to 16.5% in 1999 (P<.01) and accounted for the overall increase seen in macrolide resistance," the report states. The median erythromycin MIC of the M phenotype increased from 4 to 8 mcg/mL. The proportion of MLSB isolates stayed about the same (3.4% in 1995 and 3.7% in 1999).
While prescriptions for all antibiotics decreased 15% between 1993 and 1999, the number of macrolide prescriptions per 1,000 people per year swelled 13% in the same period, from 69 to 78, the article says. For children under age 5, the number of macrolide prescriptions soared from 37 to 164 per 1,000. Macrolide prescriptions for people aged 5 and older stayed the same at 71 per 1,000.
"It is unclear whether pneumococci with M phenotype are clinically significant, especially since newer macrolides (eg, clarithromycin and azithromycin) achieve higher concentrations intracellularly in tissue and in the epithelial lining fluid of the lung than concentrations achieved in blood," the report states. "We found, however, that most M phenotype isolates have erythromycin MICs of at least 8 mcg/mL, an MIC at which treatment failures with clarithromycin and azithromycin have been reported." Consequently, further careful surveillance of the effect of macrolide resistance on clinical outcomes is important, the authors add.
Hyde TB, Gay K, Stephens DS, et al. Macrolide resistance among invasive Streptococcus pneumoniae isolates. JAMA 2001;286(15):1857-62