Mark D. King, MD, MS; Bianca J. Humphrey, BS; Yun F. Wang, PhD; Ekaterina V. Kourbatova, MD, MPH; Susan M. Ray, MD; Henry M. Blumberg, MD
Acknowledgments: The authors thank Fred Tenover, Linda McDougal, Sigrid McAllister, and Gregory Foshiem at the Centers for Disease Control and Prevention for performing the Panton–Valentine leukocidin and SCCmec analyses and for providing images containing USA-type strains for comparison. They also thank John Boring for his assistance with calculating prevalence ratios and advice on other statistical considerations.
Grant Support: In part by the Emory Medical Care Foundation, the Emory Mentored Clinical Research Scholars Program (National Institutes of Health/National Center for Research Resources [K12 RR 017643]), and the National Institutes of Health/National Institute of Allergy and Infectious Diseases (K23 AI054371).
Potential Financial Conflicts of Interest: None disclosed.
Requests for Single Reprints: Henry M. Blumberg, MD, Division of Infectious Diseases, Emory University School of Medicine, 49 Jesse Hill Drive, Atlanta, GA 30303; e-mail, email@example.com.
Current Author Addresses: Dr. King: Beacon Clinic, 1136 Alpine Avenue, Suite 205, Boulder, CO 80304.
Drs. Ray and Blumberg and Ms. Humphrey: Division of Infectious Diseases, Emory University School of Medicine, 49 Jesse Hill Drive, Atlanta, GA 30303.
Dr. Wang: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Grady Memorial Hospital, P.O. Box 26248, 80 Jesse Hill Drive, Atlanta, GA 30303.
Dr. Kourbatova: Division of Tuberculosis and Lung Diseases, Samara State Medical University, Pionerskaya Street, 48, 443099 Samara, Russia.
Author Contributions: Conception and design: M.D. King, H.M. Blumberg.
Analysis and interpretation of the data: M.D. King, B.J. Humphrey, Y.F. Wang, E.V. Kourbatova, S.M. Ray, H.M. Blumberg.
Drafting of the article: M.D. King, S.M. Ray, H.M. Blumberg.
Critical revision of the article for important intellectual content: M.D. King, B.J. Humphrey, Y.F. Wang, E.V. Kourbatova, S.M. Ray, H.M. Blumberg.
Final approval of the article: M.D. King, B.J. Humphrey, Y.F. Wang, E.V. Kourbatova, S.M. Ray, H.M. Blumberg.
Statistical expertise: M.D. King, E.V. Kourbatova.
Obtaining of funding: M.D. King, H.M. Blumberg.
Administrative, technical, or logistic support: M.D. King, H.M. Blumberg.
Collection and assembly of data: M.D. King, B.J. Humphrey.
King M., Humphrey B., Wang Y., Kourbatova E., Ray S., Blumberg H.; Emergence of Community-Acquired Methicillin-Resistant Staphylococcus aureus USA 300 Clone as the Predominant Cause of Skin and Soft-Tissue Infections. Ann Intern Med. 2006;144:309-317. doi: 10.7326/0003-4819-144-5-200603070-00005
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Published: Ann Intern Med. 2006;144(5):309-317.
Methicillin-resistant Staphylococcus aureus (MRSA) infections have usually been associated with exposure to health care settings, but they have recently been recognized in persons without traditional risk factors. These infections have been called community-acquired or community-associated MRSA (1). Most cases have been associated with skin and soft-tissue infection and have been reported among selected populations, including correctional facility inmates, homosexual men, and sports teams (2-5). Molecular typing studies in the United States and Australia have demonstrated that most community-acquired MRSA infections are caused by one of several clones or pulsed-field types (6, 7). In the United States, 2 clones, designated as USA 300 and USA 400 by the Centers for Disease Control and Prevention (CDC), have been identified as the primary types that cause community-acquired MRSA infections (6). The outbreaks of MRSA skin and soft-tissue infections observed in correctional facilities and among athletes have been associated with the USA 300 pulsed-field type, while outbreaks associated with severe and fatal disease in children, as well as skin and soft-tissue infections in Native American populations, have been associated with the USA 400 pulsed-field type (6).
Kleper N.F. de Almeida
JFK Medical Center, Atlantis, FL
March 19, 2006
Linezolid or vancomycin in the treatment of CA-MRSA skin and soft-tissue infections?
To the Editor:
We were delighted to read the article by King and associates (1) on the emergence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) USA 300 clone as the predominant cause of community-onset S. aureus skin and soft tissue infections, in the Atlanta, Georgia area. However, we disagree with the author's statement, in discussing therapeutic options, that "the efficacy of non-glycopeptide antimicrobial agents in treating MRSA skin and soft-tissue infections remains incompletely defined, and clinical trials are needed to better define their role". Despite wide clinical experience and acceptance of glycopeptides (i.e.vancomycin) as the treatment of choice, limited controlled data exist to support this notion. Previously, the lack of antimicrobial agents with reliable activity against MRSA precluded comparative trials, but several alternatives to glycopeptide agents have recently become available. Linezolid, for example, has been extensively studied for the treatment of complicated skin and soft-tissue infections (2). One trial (2) found linezolid to be at least as efficacious as, if not superior to, vancomycin in the therapy of skin and soft-tissue infections where the majority of identified causative bacterial isolates were MRSA. Linezolid also inhibits toxin production, which may prove to be of significant benefit since the gene encoding for the production of Panton-Valentine leukocidin toxin (which promotes inflammation and tissue necrosis), is almost always found in CA-MRSA strains (3). Coincidently, this trial also serves to provide some of the best available data on the efficacy of vancomycin for these types of infections. Although recommendations are made for the empiric use of trimethoprim/ sulfamethoxazole, minocycline, doxycycline and clindamycin, little published clinical data are available to substantiate their use and most data precede the recent emergence of MRSA as a common pathogen in community acquired skin and soft-tissue infections (4,5). Daptomycin and tigecycline are additional treatment options, though somewhat less studied, with less cases of MRSA in the trials, and hampered by their parenteral only route of administration. Perhaps linezolid should be given consideration as one of the antimicrobial agents of choice for empirical treatment of skin and soft- tissue infections in areas with a high prevalence of CA-MRSA, especially with its 100% oral bioavailability, thereby potentially eliminating the need for hospital admission in many such cases.
REFERENCES 1. King MD, Humphrey BJ, Wang YF, Kourbatova EV, Ray SM, Blumberg HM. Emergence of community-acquired methicillin-resistant Staphylococcus aureus USA 300 clone as the predominant cause of skin and soft-tissue infections. Ann Intern Med. 2006;144:309-17. 2.Weigelt J, Itani K, Stevens D, Lau W, Dryden M, Knirsch C, Linezolid CSSTI Study Group. Linezolid versus Vancomycin in treatment of complicated skin and soft-tissue infections. Antimicrob Agents Chemother. 2005;49(6):2260-2266. 3.Kollef MH, Micek ST. Methicillin-resistant Staphylococcus aureus: a new community-acquired pathogen? Curr Opinion Infec Dis. 2006;19(2):161-168. 4. Markowitz N, Quinn EL, Saravolatz LD. Trimethoprim/sulfamethoxazole compared with vancomycin for the treatment of Staphylococcal aureus infection. Ann Intern Med. 1992;117(5):390-398. 5. Martinez-Aguilar G, Hammerman WA, Mason EO Jr, Kaplan SL. Clindamycin treatment of invasive infections caused by community-acquired, methicillin -resistant and methicillin-susceptible Staphylococcus aureus in children. J Pediatr Infec Dis. 2003;22(7):593-598.
Kleper N. F. de Almeida, MD Larry M. Bush, MD, FACP JFK Medical Center Atlantis, Florida 33462
Kleper N.F. de Almeida, Pfizer speaker bureau
James R. Johnson
VA Medical Center and University of Minnesota
April 10, 2006
minocycline for MRSA
To the editor:
King et al. cite clindamycin, trimethoprim-sulfamethoxazole, and linezolid as alternatives to vancomycin for outpatient treatment of localized skin and soft tissue infections due to methicillin-resistant Staphylococcus aureus (MRSA) . However, they point out the uncertain efficacy of these agents in MRSA infections and the problem of inducible clindamycin resistance. Missing from this list of alternatives, and from the susceptibility data included in the report and editors' comment, are the tetracyclines, of which minocycline is the most potent against staphylococci and with which there is the most clinical experience in treating MRSA infections .
Tetracyclines are highly orally bioavailable, inexpensive, and well tolerated, and remain active against nearly 100% of S. aureus isolates (whether methicillin-resistant or -susceptible) in many U.S. locales. These agents represent an economical option that avoids certain problems associated with clindamycin and trimethoprim-sulfamethoxazole. They deserve more attention in commentaries, and should be studied in clinical trials to establish their comparative efficacy for treatment of MRSA infections.
James R. Johnson, MD
1. King MD, Humphrey BJ, Wang YF, Kourbatova EV, Ray SM, Blumberg, HM. Emergence of community-acquired methicillin-resistant Staphyloccoccus aureus USA 300 clone as the predominant cause of skin and soft-tissue infections. Ann Intern Med. 2006;144:309-17.
2. Cunha BA. Methicillin-resistant Staphylococcus aureus: clinical manifestations and antimicrobial therapy. Clin Microbiol Infect. 2005;11 Suppl 4:33-42.
Research grants from Bayer, Merck, Ortho-Mcneil, Wyeth-Ayerst, Procter & Gamble
Henry M. Blumberg
May 8, 2006
We thank Drs. de Almeida and Bush and Dr. Johnson for their interest in our study which focused on the clinical and molecular epidemiology of community-onset Staphylococcus aureus skin and soft tissue infections (SSTIs) among the population served by the Grady Health System in urban Atlanta. Our study demonstrated that the USA300 methicillin-resistant S. aureus (MRSA) has emerged as the predominant cause of community-onset SSTIs (accounting for nearly two-thirds of all such infections). Our findings have important consequences on empiric antibiotic selection for SSTIs. Vancomycin is now the preferred choice for empiric therapy for patients with severe SSTIs who require admission to Grady Memorial Hospital, pending results of culture and susceptibility tests. Newer agents for the treatment of complicated gram-positive SSTIs including linezolid, daptomcyin, and tigecylcine have become available in recent years as noted by de Almeida and Bush. However, data from controlled trials comparing linezolid and vancomycin  and more limited data comparing the other newer agents to vancomycin suggest that these newer agents may be equivalent but not superior to vancomycin for the treatment of complicated SSTIs, including those due to MRSA. These newer agents are significantly more expensive than vancomycin (daily cost at our institution for vancomycin is $10 compared to $134 for linezolid, $159 for daptomycin and $133 for tigecycline). As noted by Moellering  in an editorial about our study and stated in a recent publication by an expert panel convened by CDC, "data from controlled clinical trials are needed to establish optimal therapy for MRSA SSTIs" . This is particularly the case for those patients with mild to moderate infection who can be treated as outpatients and may require oral therapy. Incision and drainage is recommended primary therapy for furuncles and abscesses; in some cases additional oral therapy may be of benefit. To treat the large numbers of patients who have community-acquired MRSA SSTI with oral linezolid as suggested by de Almeida and Bush would prove to be extremely expensive and there are major concerns about the potential for emergence of linezolid-resistant MRSA such that the CDC expert panel recommended "clinicians should consider reserving linezolid for use in more severe infections in consultation with an infectious disease specialist" . We agree with Dr. Johnson's comments that tetracyclines (e.g, minocycline or doxycyline) should be studied in controlled trials. This should occur in conjunction with the investigation of the efficacy of other older agents (e.g., trimethoprim-sulfamethoxazole, clindamycin) which generally have excellent activity in vitro against community-acquired MRSA (in particular USA300) because of the current lack of data from controlled trials with these agents [4,5]. Fortunately, it now appears that this is likely to happen given the recent request for proposals from NIH for a clinical trial for treatment of community-acquired MRSA infections.
Henry M. Blumberg, M.D. Susan M Ray, M.D. Emory University School of Medicine Atlanta, GA 30303
Mark D. King, M.D., MSc Beacon Clinic Boulder, CO 80304
1. Stevens DL, Herr D, Lampiris H, Hunt JL, Batts DH, Hafkin B. Linezolid versus vancomycin for the treatment of methicillin-resistant Staphylococcus aureus infections. Clin Infect Dis 2002; 34:1481-90.
2. Moellering RC Jr. The growing menace of community-acquired methicillin-resistant Staphylococcus aureus. Ann Intern Med 2006; 144:368- 70.
3. Gorwitz RJ, Jernigan DB, Powers JH, Jernigan JA, and Participants in the CDC Convened Experts' Meeting on Management of MRSA in the Community. Strategies for clinical management of MRSA in the community: Summary of an experts' meeting convened by the Centers for Disease Control and Prevention. 2006. Available at http://www.cdc.gov/ncidod/dhqp/ar_mrsa_ca.html.
4. Ruhe JJ, Monson T, Bradsher RW, Menon A. Use of long-acting tetracyclines for methicillin-resistant Staphylococcus aureus infections: case series and review of the literature. Clin Infect Dis. 2005; 40:1429- 34.
5. Johnson JR. Linezolid versus vancomycin for methicillin-resistant Staphylococcus aureus infections. Clin Infect Dis 2003; 36:236-7.
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