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Distribution and antibacterial susceptibility of macrolide resistance genotypes in Streptococcus pneumoniae: PROTEKT Year 5 (2003–2004)

https://doi.org/10.1016/j.ijantimicag.2007.10.022Get rights and content

Abstract

The distribution and antibacterial susceptibility of macrolide resistance genotypes among 7083 Streptococcus pneumoniae isolates collected worldwide during 2003–2004 from patients with community-acquired respiratory tract infections, including patients within 48 h of admission to hospital, were analysed. The overall rate of erythromycin resistance was 37.2% (intercountry range <10% to >50%). The most common resistance mechanism globally was erm(B) (55.0% of erythromycin-resistant S. pneumoniae (ERSP)), followed by mef(A) (30.6%) and erm(B) + mef(A) (12.0%). Genotype distribution varied by age group (P < 0.0001); erm(B) + mef(A) was more prevalent (21.8% of isolates) among patients 0–2 years of age than among other age groups (P < 0.001). The prevalence of tetracycline resistance among mef(A) isolates varied between different countries. Of the erm(B) + mef(A) strains, 43.5% were resistant to amoxicillin/clavulanic acid. Most ERSP isolates were susceptible to levofloxacin (98.3%) and telithromycin (99.4%).

Introduction

Among the antibacterials available for treating community-acquired respiratory tract infections (RTIs), macrolides remain one of the most commonly prescribed. However, the number of pneumococcal strains showing in vitro resistance to this class of antibacterials has increased dramatically across the world in the last decade [1], [2]. Although the link between resistance measured in the laboratory and adverse clinical outcome has not been fully substantiated to date, an increasing number of reports of treatment failure associated with macrolide-resistant pneumococcal infections [3], [4] have raised concern over the continued clinical utility of the macrolides. It has been suggested that the importance of macrolide resistance for clinical outcomes may depend on the strength of macrolide resistance in the strain causing infection. There are a number of macrolide resistance mechanisms, which differ in the level of resistance conferred. Determining the epidemiology of resistance mechanisms may therefore be important for predicting the efficacy of macrolide use in different countries.

Pneumococcal macrolide resistance is usually mediated via one of two major mechanisms [5]. The first involves modification of ribosomal macrolide target sites by methylases encoded by erm(B). The erm(B) genotype is the most common mechanism globally and is associated with high-level erythromycin resistance (minimum inhibitory concentrations (MICs) ≥256 μg/mL). The second major form of resistance, prevalent in North America and some other countries, involves drug efflux encoded by the mef(A) gene.

Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin (PROTEKT) is a global, longitudinal, international surveillance study designed primarily to compare the antibacterial activity of the ketolide telithromycin with other antibacterials. The study focuses on antibacterial resistance among common respiratory tract pathogens, including Streptococcus pneumoniae, and has successfully tracked temporal changes in resistance epidemiology using genotyping and other methodology [2], [6], [7], [8]. The current analysis, covering isolates collected during the 2003–2004 respiratory season (Year 5 of PROTEKT), provides an update of geographic and demographic patterns in the distribution and antibacterial susceptibility of pneumococcal macrolide resistance genotypes.

Section snippets

Bacterial isolates

S. pneumoniae isolates, deemed pathogenic on isolation, were collected in 38 countries and 122 centres during PROTEKT Year 5 (2003–2004). The isolates were collected from adult and paediatric outpatients with the following community-acquired RTIs: bacterial sinusitis; acute otitis media; pharyngitis; community-acquired pneumonia; acute bacterial exacerbations of chronic bronchitis; and acute exacerbations of chronic obstructive pulmonary disease. Isolates collected from hospitalised patients

Results and discussion

A total of 7083 S. pneumoniae isolates were collected in 38 countries during Year 5 of PROTEKT. Overall, 37.2% (2638/7083) of the isolates were erythromycin-resistant S. pneumoniae (ERSP). The rate of erythromycin resistance showed considerable geographic variability (Table 1), ranging from <10% in Brazil, Colombia, Czech Republic, Portugal, Russia and Sweden to >50% in France, South Africa and countries in the Far East.

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