Pharmacoepidemiological Analysis of Provincial Differences between Consumption of Macrolides and Rates of Erythromycin Resistance among Streptococcus pyogenes Isolates in Spain

Abstract

The M phenotype is by far the most common mechanism of erythromycin resistance among Streptococcus pyogenes isolates in Spain. A geographic analysis of the relationship between within-country differences in the prevalence of M-type resistance to erythromycin in S. pyogenes and the level of consumption of 14-and 15-membered macrolides within different provinces was carried out. From 1998 to 1999, a nationwide multicenter surveillance study yielded 2,039 consecutive pharyngeal isolates of S. pyogenes. Data on antibiotic consumption for the same period were gathered from IMS Health, and the corresponding daily defined doses per 1,000 inhabitants per day were calculated according to the Anatomic Therapeutic Classification index. Macrolide use was subdivided into dosages given three times a day (TID), twice a day (BID), or once a day (OD). Spearman nonparametric correlation coefficients (R) were calculated, and variables proving to be significantly associated (P < 0.1) were introduced into a linear regression model. The total consumption of macrolides presented a significant correlation with the prevalence of resistance (R ‫؍‬ 0.527; P ‫؍‬ 0.032). Neither TID nor BID macrolide consumption showed significant correlations. Only OD consumption had a significance below 0.1. These data are consistent with the hypothesis that only the total consumption of macrolides influences the local rates of M-type erythromycin resistance in S. pyogenes, and subgroups of macrolides seem to have an additive rather than a selective effect by contributing to increasing the final amount of macrolides used. Local variations in total consumption were associated only with BID consumption (R ‫؍‬ 0.849; P ‫؍‬ 0.004). The simple linear regression with total macrolide consumption showed a considerable determination coefficient (R 2 ‫؍‬ 0.678; P ‫؍‬ 0.006). The model explains up to 68% of the measured variation and is clearly better as a predictor of the prevalence of resistance than the mere mean is. By solving the regression equation, the resultant value of 2.2 defined doses per 1,000 inhabitants per day fits with the existence of a critical threshold of selective pressure.

Inducible Clindamycin Resistance and Molecular Epidemiologic Trends of Pediatric Community-Acquired Methicillin-Resistant Staphylococcus aureus in Dallas, Texas

“…Additionally, in these countries, erm-type resistance in Streptococcus pneumoniae is predominant, in contrast to the United States, where efflux-mediated resistance rates are high (27). Increased macrolide use among children may be the reason for the increased macrolide resistance of the CA-MRSA strains isolated from pediatric patients in the United States (11).…”

Blood, Tissue, and Intracellular Concentrations of Erythromycin and Its Metabolite Anhydroerythromycin during and after Therapy

“…Although in many countries erythromycin has been replaced by newer relatives like azithromycin and clarithromycin, prescription of erythromycin still has a substantial place in less developed countries but also certain regions within Europe (15, 40). However, bacterial resistance against macrolides dramatically escalated in many countries during the last decades (14,23,35). Total consumption of antimicrobials on the one hand and the presence of long periods of exposure of bacterial populations to subinhibitory concentrations of antibiotics on the other hand are considered critical factors for selecting bacterial resistance (2, 3, 16).…”

Evolution and Global Dissemination of Macrolide-Resistant Group A Streptococci

“…The three major resistance genes (R genes) found in GAS, erm(A), erm(B), and mef(A), are associated with mobile genetic elements (3, 18). Mutations in 23S rRNA and the L4 ribosomal protein also seem to confer macrolide resistance in at least some strains (11,33,44).Studies in Japan, Finland, and elsewhere show a strong correlation between national macrolide consumption and resistance in GAS (14,15,17,35,41,50). Between 1998 and 2001, a statistically significant increase in GAS resistant to erythromycin and azithromycin was observed in Spain (2).…”

“…Studies in Japan, Finland, and elsewhere show a strong correlation between national macrolide consumption and resistance in GAS (14,15,17,35,41,50). Between 1998 and 2001, a statistically significant increase in GAS resistant to erythromycin and azithromycin was observed in Spain (2).…”