Trends in anti-bacterial resistance among Streptococcus pneumoniae isolated in the USA, 2000–2003: PROTEKT US years 1–3

Abstract

Objectives

To determine geographic and temporal trends in anti-bacterial resistance among Streptococcus pneumoniae isolated from patients with respiratory tract infections as part of the PROTEKT US surveillance study (2000–2003).

Methods

From 2000 to 2003, 31 001 isolates of S. pneumoniae were collected. Anti-bacterial minimum inhibitory concentrations were determined at a central laboratory using the CLSI broth microdilution method. Macrolide resistance genotypes were determined by PCR.

Results

Overall, 29.4, 22.5, 0.9, and 0.02% of S. pneumoniae isolates were resistant to erythromycin, penicillin, levofloxacin, and telithromycin, respectively, with considerable regional variability. Multidrug resistance was stable at approx. 31%. Among macrolide-resistant isolates, mef(A) was the most prevalent resistance gene identified; however, the percentage of isolates with this gene decreased from 68.8% (2000) to 63.9% (2003), while the prevalence of isolates containing both the erm(B) and mef(A) genes increased (2000, 9.7%; 2003, 16.4%). Over 90% of these erm(B)+mef(A)-positive isolates were also resistant to penicillin, tetracycline, or trimethoprim-sulfamethoxazole, while 98.6% were susceptible to levofloxacin and 99.1% were susceptible to telithromycin.

Conclusions

Penicillin and erythromycin resistance among isolates of S. pneumoniae from the U.S.A. remained high over the 3 years of the study. Telithromycin demonstrated potent in vitro activity against pneumococcal strains.

Introduction

Streptococcus pneumoniae is a key pathogen implicated in community-acquired respiratory tract infections (RTIs), including community-acquired pneumonia,¹ acute bacterial exacerbations of chronic bronchitis,² and acute bacterial sinusitis,³ as well as a major cause of bacteraemia.⁴

Numerous surveillance studies performed both internationally5, 6, 7 and in the U.S.A.8, 9, 10, 11, 12 have documented an increased prevalence of anti-microbial resistance among strains of S. pneumoniae during the last decade. Longitudinal national surveillance across the U.S.A. showed that resistance to the penicillins and other major classes of anti-bacterials—including the tetracyclines, sulfonamides (trimethoprim-sulfamethoxazole) and chloramphenicol—increased between 1994–1995 and 1999–2000. However, the largest rise was observed for the macrolides (erythromycin), with resistance rates increasing from ∼9 to ∼25% between these dates.⁹

There are two main mechanisms of macrolide resistance among S. pneumoniae: methylation of ribosomal macrolide target sites, typically encoded by erm(B), and drug efflux, encoded by mef(A).13, 14, 15 erm(B)-mediated resistance predominates in most parts of the world; however, in some countries—including the U.S.A.—the majority of macrolide-resistant S. pneumoniae express mef(A).¹⁵ S. pneumoniae isolates positive for both erm(B) and mef(A) have also been recorded in the U.S.A.,15, 16 and are predominantly multiresistant and clonal in nature.17, 18 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 L22.¹⁹ However, reports to date of such ribosomal mutations among macrolide-resistant clinical isolates of S. pneumoniae are rare.¹⁹

PROTEKT US (prospective resistant organism tracking and epidemiology for the ketolide telithromycin in the US) is a longitudinal surveillance study initiated in 2000 to monitor anti-microbial resistance patterns in S. pneumoniae and other common RTI pathogens in the U.S.A.⁷ A major aim of the program is to evaluate the activity of telithromycin—the first in a new class of anti-bacterial agents (the ketolides)—and to compare its activity with that of other anti-microbials. In 2000–2001, PROTEKT US revealed a national prevalence of pneumococcal erythromycin resistance of 31%, with rates approximating 40% in some Southern regions of the country.12, 20

This paper analyses phenotypic susceptibility and genotyping data for S. pneumoniae from years 1–3 of PROTEKT US (2000–2003) in order to identify temporal and geographic trends in resistance patterns, and to evaluate the activity of telithromycin during this period.