Bacteriology
Community- and health care-associated methicillin-resistant Staphylococcus aureus: a comparison of molecular epidemiology and antimicrobial activities of various agents

https://doi.org/10.1016/j.diagmicrobio.2006.10.021Get rights and content

Abstract

The epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) is changing. We determined the inhibitory and bactericidal activity of select antimicrobial agents utilizing a well-characterized group of 200 staphylococcal cassette chromosome mec (SCCmec) type IV community-associated MRSA (CAMRSA) and 50 SCCmec type II health care-associated MRSA (HAMRSA). Differences in carriage of the Panton-Valentine leukocidin (PVL) genes, agr group, and agr function in CAMRSA and HAMRSA were also examined. Pulsed-field gel electrophoresis (PFGE) patterns were determined for a subset of study strains. CAMRSA typically belonged to the USA 300 PFGE profile, were associated with high rates of PVL carriage (78%), and primarily were agr group I. Susceptibility to daptomycin, linezolid, teicoplanin, and vancomycin was 100%. In contrast, HAMRSA isolates typically belonged to the USA 100 PFGE profile, were associated with low rates of PVL carriage (8%), and primarily were agr group II. Comparing susceptibilities between the 2 types of MRSA strains, there was a 2-fold increase in MIC for daptomycin, doxycycline, teicoplanin, trimethoprim–sulfamethoxazole (TMP/SMX), and vancomycin in HAMRSA versus CAMRSA. Levofloxacin and clindamycin susceptibly decreased dramatically by 66% and 54%, respectively, against HAMRSA versus CAMRSA. With respect to agr function, 3.5% of CAMRSA and 48% of HAMRSA displayed a down-regulated agr gene cluster. The comparative bactericidal activities of daptomycin were similar to those of vancomycin and clindamycin, but were significantly greater than those of linezolid, teicoplanin, and TMP/SMX against CAMRSA at 24-h terminal end points. Further studies are warranted against a larger number of molecularly defined, geographically diverse CAMRSA to confirm these findings.

Introduction

The epidemiology of Staphylococcus aureus is changing (Carleton et al., 2004, Chambers, 2005, Eguia and Chambers, 2003). Although methicillin-resistant S. aureus (MRSA) traditionally has been confined to nosocomial settings, the prevalence of MRSA arising from the community is increasing (Naimi et al., 2003, Tacconelli et al., 2003). A plethora of recent outbreaks of community-associated MRSA (CAMRSA) have been well described in both children and healthy adults worldwide (Baggett et al., 2004, Miller et al., 2005, Naimi et al., 2001). It is estimated that 8–20% of all MRSA isolates are reported to be community-associated (Fridkin et al., 2005).

Distinguishing CAMRSA from health care-associated MRSA (HAMRSA) is becoming increasingly challenging (Folden et al., 2005, Lesens et al., 2005). Although CAMRSA are frequently defined clinically, these isolates possess unique molecular features, which distinguish them from health care-associated strains in the United States. In the United States, CAMRSA typically possess staphylococcal cassette chromosome mec (SCCmec) type IV, whereas HAMRSA mainly possess SCCmec type II (Baba et al., 2002). In addition, 97% of CAMRSA may contain lukS-PV and lukF-PV genes encoding Panton-Valentine leukocidin (PVL), a bicomponent cytotoxin associated with severe necrotizing pneumonia, necrotizing skin lesions, and deep-seated follicular infections (Baggett et al., 2004, Gillet et al., 2002, Lina et al., 1999, Miller et al., 2005). Finally, most CAMRSA isolates in the United States belong to accessory gene regulator (agr) group I or III, whereas HAMRSA typically belongs to agr group II (Dufour et al., 2002, Sakoulas et al., 2003). In health care-associated strains in the United States a down-regulated agr locus has been associated with the development of heterogeneous vancomycin intermediate resistance and persistent bacteremia (Fowler et al., 2004, Sakoulas et al., 2003). However, this phenomenon has not been studied in community-associated isolates.

In addition, SCCmec type IV CAMRSA are generally susceptible to non–β-lactam antibiotics including clindamycin, trimethoprim–sulfamethoxazole (TMP/SMX), and glycopeptides. However, limited data exist on the effectiveness of these and newer agents for treatment of infections due to CAMRSA. In contrast, SCCmec type II HAMRSA possess multiple antimicrobial resistance determinants and are typically multidrug resistant.

The objectives of the current study were to compare the molecular characteristics in SCCmec type IV CAMRSA and SCCmec type II HAMRSA by evaluating carriage of the PVL genes, the presence of inducible macrolide–lincosamide–type B streptogramin (iMLSB) resistance, agr group, and agr function, and to determine the inhibitory and bactericidal activities of several antimicrobial agents against these strain types.

Section snippets

Bacterial isolates

Two hundred isolates of CAMRSA (SCCmec type IV) and 50 HAMRSA (SCCmec type II) were evaluated. All isolates were of clinical origin and were obtained from infected patients at the Detroit Receiving Hospital, a 340-bed hospital in the Detroit Medical Center, Detroit, MI. This study was approved by the Wayne State University Human Investigation Committee. A community-associated isolate was defined as one which was both SCCmec type IV and met the Centers for Disease Control and Prevention (CDC)

Molecular characteristics and sources of CAMRSA and HAMRSA

The most common strain among CAMRSA was USA 300, with 66% of the 92 isolates tested having this PFGE profile. Sixteen percent displayed the USA 800 PFGE profile, and the remaining strains had a variety of different PFGE profiles. Of the 12 HAMRSA tested, USA 100 (75%) was most common. The PVL genes were present in 78% of CAMRSA versus 8% of HAMRSA. The distribution of agr group types among CAMRSA and HAMRSA is shown in Fig. 1. The majority of CAMRSA belong to agr group I versus group II in

Discussion

CAMRSA are emerging pathogens worldwide. Recent reports of infections with this organism in both children and young healthy adults are of importance as significant morbidity and in some cases mortality have been noted (Folden et al., 2005, Lesens et al., 2005, Naimi et al., 2003).

The CDC distinguishes CAMRSA from HAMRSA if the diagnosis of MRSA infection/colonization is made in the outpatient setting or by a culture positive for MRSA within 48 h of hospitalization in a patient with no prior

Acknowledgments

This project was supported in part by grants from Cubist Pharmaceuticals (Lexington, MA). We thank Susan Seo, Doina Plesoianu, Jillian Szczesiul, Julie Watt, and Kerri Lau for their contributions. We are grateful to Hermínia de Lencastre, The Rockefeller University, New York, NY, for providing SCCmec control strains.

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