Abstract

BackgroundThe increasing prevalence of resistance to established antibiotics among key bacterial respiratory tract pathogens, such as Streptococcus pneumoniae, is a major healthcare problem in the USA. The PROTEKT US study is a longitudinal surveillance study designed to monitor the susceptibility of key respiratory tract pathogens in the USA to a range of commonly used antimicrobials. Here, we assess the geographic and temporal trends in antibacterial resistance of S. pneumoniae isolates from patients with community-acquired respiratory tract infections collected between Year 1 (2000–2001) and Year 4 (2003–2004) of PROTEKT US.MethodsAntibacterial minimum inhibitory concentrations were determined centrally using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method; susceptibility was defined according to CLSI interpretive criteria. Macrolide resistance genotypes were determined by polymerase chain reaction.ResultsA total of 39,495 S. pneumoniae isolates were collected during 2000–2004. The percentage of isolates resistant to erythromycin, penicillin, levofloxacin, and telithromycin were 29.3%, 21.2%, 0.9%, and 0.02%, respectively, over the 4 years, with marked regional variability. The proportion of isolates exhibiting multidrug resistance (includes isolates known as penicillin-resistant S. pneumoniae and isolates resistant to ≥ 2 of the following antibiotics: penicillin; second-generation cephalosporins, e.g. cefuroxime; macrolides; tetracyclines; and trimethoprim-sulfamethoxazole) remained stable at ~30% over the study period. Overall mef(A) was the most common macrolide resistance mechanism. The proportion of mef(A) isolates decreased from 68.8% to 62.3% between Year 1 and Year 4, while the percentage of isolates carrying both erm(B) and mef(A) increased from 9.7% to 18.4%. Over 99% of the erm(B)+mef(A)-positive isolates collected over Years 1–4 exhibited multidrug resistance. Higher than previously reported levels of macrolide resistance were found for mef(A)-positive isolates.ConclusionOver the first 4 years of PROTEKT US, penicillin and erythromycin resistance among pneumococcal isolates has remained high. Although macrolide resistance rates have stabilized, the prevalence of clonal isolates, with a combined erm(B) and mef(A) genotype together with high-level macrolide and multidrug resistance, is increasing, and their spread may have serious health implications. Telithromycin and levofloxacin both showed potent in vitro activity against S. pneumoniae isolates irrespective of macrolide resistance genotype.

Highlights

  • The increasing prevalence of resistance to established antibiotics among key bacterial respiratory tract pathogens, such as Streptococcus pneumoniae, is a major healthcare problem in the USA

  • Surveillance data have shown that, among S. pneumoniae isolates obtained from pediatric patients, the proportion exhibiting nonsusceptibility to penicillin increased each year after 1994, reaching 45% in 2000 [19]

  • This paper reports on the phenotypic susceptibility and the distribution of macrolide resistance genotypes for S. pneumoniae isolates collected in Year 4 (2003–2004) of the PROTEKT US study; in addition, it provides an update on temporal and geographic trends in resistance patterns over the 4 years of the study

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Summary

Introduction

The increasing prevalence of resistance to established antibiotics among key bacterial respiratory tract pathogens, such as Streptococcus pneumoniae, is a major healthcare problem in the USA. We assess the geographic and temporal trends in antibacterial resistance of S. pneumoniae isolates from patients with community-acquired respiratory tract infections collected between Year 1 (2000–2001) and Year 4 (2003–2004) of PROTEKT US. Streptococcus pneumoniae is a common causative pathogen in community-acquired respiratory tract infections (RTIs), including acute otitis media [1], acute bacterial exacerbations of chronic bronchitis [2], acute bacterial sinusitis [3], and community-acquired pneumonia [4]. It is a major cause of bacteremia [5]. Several published studies and case reports (reviewed by Rzeszutek and colleagues [20]) have suggested a link between pneumococcal macrolide resistance and treatment failure (resulting in hospitalization) in patients with community-acquired RTIs

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