Elsevier

Journal of Infection

Volume 55, Issue 2, August 2007, Pages 111-118
Journal of Infection

Regional trends in β-lactam, macrolide, fluoroquinolone and telithromycin resistance among Streptococcus pneumoniae isolates 2001–2004

https://doi.org/10.1016/j.jinf.2007.04.006Get rights and content

Summary

Objectives

To determine global antibacterial resistance rates among community-acquired isolates of Streptococcus pneumoniae.

Methods

Between 2001 and 2004, 20,142 S. pneumoniae isolates from 151 centres in 40 countries were collected and tested for susceptibility to common antibacterials in the PROTEKT surveillance study.

Results

The prevalence of β-lactam and macrolide resistance did not change, but there was marked geographic variability. The most common macrolide resistance mechanism was ribosomal methylation mediated by erm(B), except in Canada, Greece and the USA where drug efflux mediated by mef(A) was predominant. The erythromycin minimum inhibitory concentration for mef(A) isolates increased significantly (P < 0.001; χ2 test). The global prevalence of macrolide-resistant isolates positive for both erm(B) and mef(A) was 12.0% in 2003–2004; erm(B)+mef(A) strains were particularly common in South Korea (40.8%), South Africa (46.4%) and the USA (29.6%). Telithromycin was the most active antibacterial tested. Over the studied period, ≥99.7% of all isolates and >99% of erythromycin-resistant isolates, irrespective of genotype, were susceptible to telithromycin.

Conclusions

These results confirm the high worldwide prevalence of resistance to commonly used antibacterial agents and multiple resistance phenotypes among clinical isolates of S. pneumoniae and suggest that high-level macrolide resistance is continuing to increase in most countries.

Introduction

Streptococcus pneumoniae remains the most common bacterial pathogen causative of community-acquired pneumonia,1 and is also a major aetiological agent implicated in episodes of acute bacterial exacerbations of chronic bronchitis2 and acute bacterial sinusitis.3

In recent years, a number of international and national surveillance studies4, 5, 6, 7, 8 have documented high levels of antibacterial resistance in S. pneumoniae, leading to concerns over the continued clinical utility of agents such as the macrolides for the empirical treatment of community-acquired respiratory tract infections (RTIs).9 For example, published studies and case reports (reviewed by Rzeszutek and colleagues10 and a recent report by Daneman et al.11) have suggested a link between pneumococcal macrolide resistance and treatment failure (resulting in hospitalization) in patients with community-acquired RTIs.

Two mechanisms account for the majority of cases of pneumococcal macrolide resistance: methylation of ribosomal macrolide target sites, typically encoded by erm(B), and drug efflux, encoded by mef(A),12, 13 with the erm(B)-mediated mechanism predominating in most parts of the world. S. pneumoniae isolates positive for both erm(B) and mef(A) have also been confirmed in the USA and elsewhere14, 15 and are predominantly multiresistant and clonal in nature.15 The prevalence of erm(B)+mef(A)-mediated resistance has risen in some countries, in particular the USA, in recent years.15, 16 Pneumococcal resistance to macrolides may also be conferred by ribosomal mutations, including mutations in domains II and V of the 23S ribosomal RNA and in genes encoding riboproteins L4 and L22.17 However, reports are rare to date of such ribosomal mutations among macrolide-resistant clinical isolates of S. pneumoniae.17

The PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin) study was initiated in 1999. This longitudinal, international surveillance study was designed to evaluate the activity of telithromycin, a new ketolide antibacterial, against S. pneumoniae and other common RTI pathogens and to compare its activity with that of other antibacterial agents.6 This report analyses temporal and geographical trends in the phenotypic susceptibility and genotypes of S. pneumoniae isolates collected during Years 3–5 of PROTEKT (2001–2004) with a focus on the most recent (Year 5) patterns of macrolide resistance.

Section snippets

Collection centres

Isolates of S. pneumoniae were collected from a total of 151 centres from 40 countries worldwide over the latest 3 years of the PROTEKT study (Year 3, 2001–2002; Year 4, 2002–2003; Year 5, 2003–2004).

Bacterial isolates

Respiratory tract isolates of S. pneumoniae, deemed pathogenic on isolation, were collected from adult and paediatric outpatients with clinically diagnosed community-acquired RTIs (bacterial sinusitis, acute otitis media, community-acquired pneumonia, acute bacterial exacerbations of chronic

Results

A total of 20,142 S. pneumoniae isolates were collected over the 3 years of this analysis: 6320 in Year 3, 6739 in Year 4 and 7083 in Year 5.

Discussion

The current analysis demonstrates that pneumococcal antibacterial resistance remains common across many regions of the world. Approximately one-third of S. pneumoniae isolates worldwide were nonsusceptible to penicillin with little substantial change between 2001 and 2004. Other studies have indicated that, in some individual countries with very high penicillin resistance levels, penicillin resistance may be decreasing.22 Macrolide resistance is also exhibited by approximately one-third of

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