The relationship between trends in macrolide use and resistance to macrolides of common respiratory pathogens

Čižman, Milan; Pokorn, Marko; Seme, Katja; Orazem, A; Paragi, Metka

doi:10.1093/jac/47.4.475

Cited by 59 publications

(41 citation statements)

References 8 publications

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“…In the absence of such data, the use of macrolides for the treatment of GAS infections may be associated with an increased risk of both bacteriologic failure and the sequelae of GAS pharyngitis, including acute rheumatic fever. Previous studies have documented a correlation between increased rates of use of macrolides and increased rates of resistance to this class of antibiotics among GAS (10,28). Recent national and local pharmacy data substantiate impressive increases in the rates of prescription of azithromycin (22).…”

Section: Discussionmentioning

confidence: 96%

Reemergence of Macrolide Resistance in Pharyngeal Isolates of Group A Streptococci in Southwestern Pennsylvania

Green

Martin

Barbadora

et al. 2004

Antimicrob Agents Chemother

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We previously reported on the emergence of macrolide-resistant pharyngeal isolates of group A streptococci (GAS) in our community. The purpose of the present study was to track longitudinal trends in macrolide resistance in these isolates in southwestern Pennsylvania. Testing for susceptibility to erythromycin and clindamycin was performed for all pharyngeal GAS isolates recovered at the Children's Hospital of Pittsburgh and a local pediatric practice between September 2001 and May 2002. Macrolide resistance phenotypes and genotypes were determined by double-disk diffusion and PCR, respectively. Strain relatedness was determined by field inversion gel electrophoresis and emm gene sequence typing. A total of 708 isolates of GAS were recovered during the study period; 68 (9.6%) were macrolide resistant, while all isolates were sensitive to clindamycin. The monthly prevalence of macrolide resistance ranged from 0 to 41%. and streptogramin B antibiotics); these isolates were confirmed to be mef(A) and erm(A), respectively. Three unique mef(A) clones and four unique erm(A) clones were identified among the resistant isolates. The MIC at which 50% of isolates are inhibited (MIC 50 ) for the mef(A) strains was 16 g/ml, while the MIC 50 for erm(A) strains was 8 g/ml. The finding of high levels of macrolide resistance among pharyngeal isolates of GAS for a second successive year in our community raises the concern that this problem may be more common in the United States than was previously appreciated. Longitudinal surveillance of isolates from multiple centers is needed to define the prevalence of antimicrobial agent-resistant GAS in the United States.Sore throat is the most common complaint for which older children and adolescents seek acute medical care (9). Group A streptococci (GAS) are the most frequent and important cause of bacterial pharyngitis in children and adults (7). Penicillin V remains the treatment of choice for GAS pharyngitis (2, 8), and macrolides are recommended only for patients who are allergic to penicillin. Nonetheless, azithromycin is increasingly prescribed because its short course of dosing and single daily dosing are attractive to both parents and practitioners.A high prevalence of macrolide resistance among GAS has been recognized in Europe and Japan for many years. However, the rates of macrolide resistance among GAS in the United States have remained low (4,12,16,19,20). In the spring of 2001 we documented the emergence of a high level of macrolide resistance in pharyngeal isolates of GAS in Pittsburgh, Pa., as part of a longitudinal surveillance study of schoolchildren (22). A 38% incidence of macrolide resistance was also found in community isolates of GAS during the same time period. The purpose of this study was to investigate trends in macrolide resistance in pharyngeal GAS over time in our region. MATERIALS AND METHODS GAS isolates. Beginning in September 2001, testing for susceptibility to erythromycin and clindamycin was performed for all pharyngeal GAS isolates recovered from the ...

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Section: Discussionmentioning

confidence: 96%

Reemergence of Macrolide Resistance in Pharyngeal Isolates of Group A Streptococci in Southwestern Pennsylvania

Green

Martin

Barbadora

et al. 2004

Antimicrob Agents Chemother

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“…In the case of S. pyogenes, published results appear conflicting, since sometimes they attribute a role to antibiotic use in the level of resistance (4,11,25,29,30), but sometimes they do not (26,34). The fact that only a few clones seem to drive resistance to erythromycin makes clonal spread a variable worth considering (M12 in Japan and M4 and M75 in Spain and Finland).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2002

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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.

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“…Results of these studies overall revealed a remarkable variability of resistance rates at different times and in different epidemiological settings (for examples, see references 1, 8, 9, 11, 25, 31, 37, and 41). A clear relationship between resistance rates and the extent of macrolide usage in community medicine was also demonstrated, with relatively rapid variations of the former in response to modifications of prescription policies (6,11,30,31).Recently, increased macrolide resistance rates in clinical isolates of S. pyogenes have been reported in several countries (1,6,8,25). This phenomenon, which likely reflects the vast popularity of the last generation of macrolides (such as azithromycin, clarithromycin, and roxithromycin) in community medicine, is a cause of considerable concern for antimicrobial chemotherapy.…”

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confidence: 90%

Resistance Determinants and Clonal Diversity in Group A Streptococci Collected during a Period of Increasing Macrolide Resistance

Cresti

Lattanzi²,

Zanchi³

et al. 2002

Antimicrob Agents Chemother

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Susceptibility to macrolides and lincosamides was investigated with 299 consecutive nonduplicate Streptococcus pyogenes clinical isolates collected over a 6-year period (1992 to 1997) from an area of central Italy. During this period, macrolide resistance rates steadily increased (from 9% in 1992 to 53% in 1997; P < 0.001). The increase was caused by isolates with a macrolide-lincosamide-streptogramin B resistance phenotype, carrying mostly erm(B) but also erm(TR) genes, that were not detected in the first 2 years and were detected with increasing prevalence (8, 5, 26, and 37%, respectively) during the following 4 years. During the same period, the prevalence of isolates with a macrolide resistance phenotype, carrying mef(A) determinants, did not vary significantly; on average it was 13%, with modest rate fluctuations in different years and no definite trend. Molecular typing revealed a remarkable clonal diversity among susceptible and resistant isolates and a notable heterogeneity of the genetic environment of the resistance genes. The analysis of clonal diversity in relation with resistance phenotypes and genotypes revealed that increased macrolide resistance rates were due to a complex interplay of different mechanisms, with a relevant contribution played by an "epidemic" spread of genetic elements carrying the erm(B) gene among the circulating streptococcal population.Streptococcus pyogenes (group A streptococcus) remains one of the leading bacterial pathogens worldwide. Superficial infections caused by group A streptococci, such as pharyngitis and impetigo, are usually mild and self-limiting but ubiquitous and extremely common. On the other hand, the occurrence of severe invasive infections and of nonsuppurative sequelae, although less common, make of S. pyogenes a major public health concern (see reference 3 and references therein).Macrolide antibiotics are among the preferred drugs for the treatment of group A streptococcal pharyngitis and are largely used in community medicine for empirical chemotherapy of respiratory tract infections, due to their clinical efficacy, good compliance, and low toxicity (34). Resistance to macrolides in S. pyogenes can be caused by two different mechanisms: (i) active drug efflux via a transmembrane pump encoded by horizontally acquired mef genes (7, 35) and (ii) modification of the 23S rRNA target by rRNA adenine methylases encoded by horizontally acquired erm genes (see references 19 and 38 and references therein). The Mef efflux system operates only with 14-and 15-membered ring macrolides (M resistance phenotype) (7), while ribosomal modification by Erm methylases prevents the binding of macrolides, lincosamides, and streptogramins B, leading to resistance to all these compounds (MLS resistance phenotype) (19 (19,38,39).Since the first report in the 1950s (20), a large number of epidemiological surveys on macrolide resistance in S. pyogenes have been carried out. Results of these studies overall revealed a remarkable variability of resistance rates at different times and...

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The relationship between trends in macrolide use and resistance to macrolides of common respiratory pathogens

Cited by 59 publications

References 8 publications

Reemergence of Macrolide Resistance in Pharyngeal Isolates of Group A Streptococci in Southwestern Pennsylvania

Reemergence of Macrolide Resistance in Pharyngeal Isolates of Group A Streptococci in Southwestern Pennsylvania

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

Resistance Determinants and Clonal Diversity in Group A Streptococci Collected during a Period of Increasing Macrolide Resistance

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