Trends in antibacterial resistance among Streptococcus pneumoniae isolated in the USA: update from PROTEKT US Years 1-4

Abstract

Background: 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. 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.

Methods: Antibacterial 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.

Results: A 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 > or = 2 of the following antibiotics: penicillin; second-generation cephalosporins, e.g. cefuroxime; macrolides; tetracyclines; and trimethoprim-sulfamethoxazole) remained stable at approximately 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.

Conclusion: Over 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.

Figure 1

Geographic distribution of rates of penicillin and erythromycin nonsusceptibility in Streptococcus pneumoniae isolates (n = 39 495) collected during the 4 years of the PROTEKT US study (2000–2004). North-central: Illinois, Iowa, Kansas, Minnesota, Missouri, Nebraska, North Dakota, South Dakota, Wisconsin; Northeast: Connecticut, Delaware, District of Columbia, Indiana, Maryland, Massachusetts, Michigan, New Jersey, New York, Ohio, Pennsylvania, Vermont; Northwest: Alaska, Idaho, Montana, Oregon, Washington, Wyoming; South-central: Alabama, Arkansas, Louisiana, Oklahoma, Tennessee, Texas; Southeast: Florida, Georgia, Kentucky, North Carolina, Puerto Rico, South Carolina, Virginia, West Virginia; Southwest: Arizona, California, Colorado, Nevada, New Mexico, Utah. Ery^I, erythromycin intermediate; Ery^R, erythromycin resistant; Pen^I, penicillin intermediate; Pen^R, penicillin resistant.

Figure 2

Prevalence of resistance to 1, 2, 3, 4, 5, or 6 antibacterial agents^a among Streptococcus pneumoniae isolates collected during the PROTEKT US study Years 1–4 (2000–2004). ^aPenicillin (MIC ≥ 2 μg/mL), erythromycin (MIC ≥ 1 μg/mL), cefuroxime (MIC ≥ 4 μg/mL), tetracycline (MIC ≥ 8 μg/mL), trimethoprim-sulfamethoxazole; MIC ≥ 4 μg/mL), and levofloxacin (MIC ≥ 8 μg/mL).

Figure 3

Distribution of resistance genes among macrolide-resistant Streptococcus pneumoniae isolates (n = 11 578) collected during the PROTEKT US study Years 1–4 (2000–2004).