Therapy for Methicillin-Resistant Staphylococcus aureus
http://www.100md.com
《新英格兰医药杂志》
To the Editor: In the study by Fowler et al. (Aug. 17 issue),1 the standard therapy for Staphylococcus aureus infection is not a homogeneous entity. One cannot compare a new drug (daptomycin) with a mixture of two regimens (vancomycin or an antistaphylococcal penicillin) when the first regimen is reported to be considerably inferior to the other.2,3 Although Table 2 of the article lists success rates according to the susceptibility of S. aureus to methicillin, a breakdown in success rates according to the receipt of vancomycin or an antistaphylococcal penicillin is lacking. Patients with methicillin-susceptible S. aureus (MSSA) infections could have received vancomycin for a variety of reasons, thus blurring the possible difference in outcomes between the two regimens. The authors should analyze the outcomes separately for patients who received vancomycin and for patients who received an antistaphylococcal penicillin. Daptomycin may prove to be inferior to the highly effective antistaphylococcal penicillins, and such information should be disclosed appropriately.
Yardena Siegman-Igra, M.D.
Tel Aviv Sourasky Medical Center
64239 Tel Aviv, Israel
zihum@tasmc.health.gov.il
References
Fowler VG Jr, Boucher HW, Corey GR, et al. Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus. N Engl J Med 2006;355:653-665.
Chang FY, Peacock JE Jr, Musher DM, et al. Staphylococcus aureus bacteremia: recurrence and the impact of antibiotic treatment in a prospective multicenter study. Medicine (Baltimore) 2003;82:333-339.
Siegman-Igra Y, Reich P, Orni-Wasserlauf R, Schwartz D, Giladi M. The role of vancomycin in the persistence or recurrence of Staphylococcus aureus bacteraemia. Scand J Infect Dis 2005;37:572-578.
To the Editor: Fowler et al. conclude that daptomycin therapy is not inferior to standard therapy for patients with S. aureus bacteremia and right-sided endocarditis. The two study groups were very heterogeneous: each included several types of infections involving a small number of patients (making it difficult to interpret the results) and strains with different degrees of susceptibility to methicillin. Vancomycin is associated with a slow clinical response,1 and as compared with antistaphylococcal penicillins,2 it has a lower rate of clinical efficacy for severe S. aureus infections. Thus, the comparison with daptomycin is distorted by the fact that the control group included infections caused by MSSA and infections caused by methicillin-resistant strains of S. aureus (MRSA), which were treated with therapies of different efficacy. However, the reported success rate associated with cloxacillin plus an aminoglycoside for uncomplicated right-sided endocarditis is excellent (94.4%).3 The success rates for the treatment of uncomplicated right-sided endocarditis in the study by Fowler et al. (50% among patients who received daptomycin vs. 25% among those who received standard therapy) are not acceptable, and could be explained by the small number of patients (six vs. four). Thus, the lack of statistical significance between these two subgroups should not be interpreted as indicating noninferiority between them.4
Manuel Torres-Tortosa, M.D.
Francisco J. Caballero-Granado, M.D.
Jesús Canueto, M.D.
Hospital Punta de Europa
11207 Algeciras, Spain
mtt@comcadiz.com
References
Levine DP, Fromm BS, Reddy BR. Slow response to vancomycin or vancomycin plus rifampin in methicillin-resistant Staphylococcus aureus endocarditis. Ann Intern Med 1991;115:674-680.
Gonzalez C, Rubio M, Romero-Vivas J, Gonzalez M, Picazo JJ. Bacteremic pneumonia due to Staphylococcus aureus: a comparison of disease caused by methicillin-resistant and methicillin-susceptible organisms. Clin Infect Dis 1999;29:1171-1177.
Torres-Tortosa M, de Cueto M, Vergara A, et al. Prospective evaluation of a two-week course of intravenous antibiotics in intravenous drug addicts with infective endocarditis. Eur J Clin Microbiol Infect Dis 1994;13:559-564.
Altman DG, Bland JM. Absence of evidence is not evidence of absence. BMJ 1995;311:485-485.
To the Editor: With regard to the article by Moran et al. (Aug. 17 issue),1 it appears that MRSA abscesses will have to be treated as they were in the days before penicillin — that is, by means of incision and drainage. As any surgeon or emergency department doctor knows, the appropriate treatment for an abscess is incision and drainage. Add an antibiotic if you think the attendant cellulitis warrants it (although practically everyone will add an antibiotic, regardless).
Lynn Jetton, M.D.
1910 Cherokee Ave. SW
Cullman, AL 35055
References
Moran GJ, Krishnadasan A, Gorwitz RJ, et al. Methicillin-resistant S. aureus infections among patients in the emergency department. N Engl J Med 2006;355:666-674.
Dr. Cosgrove and colleagues reply: Siegman-Igra and Torres-Tortosa and colleagues inquired about the choice of standard therapies for this trial. We chose to use an antistaphylococcal penicillin or vancomycin to ensure that patients received the best and most appropriate therapy on the basis of the susceptibility of the infecting organism and the presence or absence of an allergy to penicillin. Ten patients in the study with MSSA bacteremia received vancomycin. Seven of these patients had documented penicillin allergies, and three patients did not. Of these 10 patients, 6 (60%), including 2 of the 3 who did not have a penicillin allergy, had a successful outcome 42 days after the end of therapy; the outcomes of 3 patients could not be evaluated because they withdrew consent, and therapy failed in 1 patient. One patient with MRSA infection inappropriately received an antistaphylococcal penicillin for 8 days. We have analyzed the data according to the pathogen-specific therapy — that is, according to whether patients received an antistaphylococcal penicillin for MSSA infection or vancomycin for MRSA infection (Table 1). The performance of daptomycin was similar to that of the standard therapies for both MSSA and MRSA infections in this analysis; however, the power to detect a difference in outcome is quite limited.
Table 1. Distribution of Successful Outcomes 42 Days after the End of Therapy.
Sara E. Cosgrove, M.D.
Johns Hopkins University School of Medicine
Baltimore, MD 21205
Vance G. Fowler, Jr., M.D., M.H.S.
Duke University Medical Center
Durham, NC 27710
vance.fowler@duke.edu
Helen W. Boucher, M.D.
Tufts–New England Medical Center
Boston, MA 02111
Drs. Moran and Talan reply: Jetton is correct that the primary treatment for a skin abscess is incision and drainage, as noted in our article. The additional benefit of antimicrobial therapy remains unclear. Previous investigations suggested similar cure rates with or without antibiotics, but these studies were performed before the emergence of community-associated MRSA and were limited by their use of nonrandomized designs, small numbers of subjects, vague definitions of outcomes, nonstandardized drainage, or antibiotics lacking appropriate activity.1,2,3 In one retrospective study of children, treatment failure with drainage alone was associated with an abscess size of 5 cm2 or larger.4 Inadequate drainage due to poor technique or misdiagnosis of the abscess as simple cellulitis can lead to treatment failure. Until we have better studies to clarify this issue, antimicrobial therapy known to be active against MRSA should be given to patients with systemic illness or clinically significant associated cellulitis, immunovascular or vascular compromise, an abscess in a high-risk location (e.g., a hand or the face), or a lack of a response to incision and drainage alone, and such antimicrobial therapy should be considered for recurrent infection.5
Gregory J. Moran, M.D.
David A. Talan, M.D.
Olive View–UCLA Medical Center
Sylmar, CA 91342
idnet@ucla.edu
References
Meislin HW, Lerner SA, Graves MH, et al. Cutaneous abscesses: anaerobic and aerobic bacteriology and outpatient management. Ann Intern Med 1977;87:145-149.
Llera JL, Levy RC. Treatment of cutaneous abscess: a double-blind clinical study. Ann Emerg Med 1985;14:15-19.
Macfie J, Harvey J. The treatment of acute superficial abscesses: a prospective clinical trial. Br J Surg 1977;64:264-266.
Lee MC, Rios AM, Aten MF, et al. Management and outcome of children with skin and soft tissue abscesses caused by community-acquired methicillin-resistant Staphylococcus aureus. Pediatr Infect Dis J 2004;23:123-127.
Gorwitz RJ, Jernigan DB, Powers JH, Jernigan JA, 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. March 2006. (Accessed October 26, 2006, at http://www.cdc.gov/ncidod/dhqp/ar_mrsa_ca.html.)
Yardena Siegman-Igra, M.D.
Tel Aviv Sourasky Medical Center
64239 Tel Aviv, Israel
zihum@tasmc.health.gov.il
References
Fowler VG Jr, Boucher HW, Corey GR, et al. Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus. N Engl J Med 2006;355:653-665.
Chang FY, Peacock JE Jr, Musher DM, et al. Staphylococcus aureus bacteremia: recurrence and the impact of antibiotic treatment in a prospective multicenter study. Medicine (Baltimore) 2003;82:333-339.
Siegman-Igra Y, Reich P, Orni-Wasserlauf R, Schwartz D, Giladi M. The role of vancomycin in the persistence or recurrence of Staphylococcus aureus bacteraemia. Scand J Infect Dis 2005;37:572-578.
To the Editor: Fowler et al. conclude that daptomycin therapy is not inferior to standard therapy for patients with S. aureus bacteremia and right-sided endocarditis. The two study groups were very heterogeneous: each included several types of infections involving a small number of patients (making it difficult to interpret the results) and strains with different degrees of susceptibility to methicillin. Vancomycin is associated with a slow clinical response,1 and as compared with antistaphylococcal penicillins,2 it has a lower rate of clinical efficacy for severe S. aureus infections. Thus, the comparison with daptomycin is distorted by the fact that the control group included infections caused by MSSA and infections caused by methicillin-resistant strains of S. aureus (MRSA), which were treated with therapies of different efficacy. However, the reported success rate associated with cloxacillin plus an aminoglycoside for uncomplicated right-sided endocarditis is excellent (94.4%).3 The success rates for the treatment of uncomplicated right-sided endocarditis in the study by Fowler et al. (50% among patients who received daptomycin vs. 25% among those who received standard therapy) are not acceptable, and could be explained by the small number of patients (six vs. four). Thus, the lack of statistical significance between these two subgroups should not be interpreted as indicating noninferiority between them.4
Manuel Torres-Tortosa, M.D.
Francisco J. Caballero-Granado, M.D.
Jesús Canueto, M.D.
Hospital Punta de Europa
11207 Algeciras, Spain
mtt@comcadiz.com
References
Levine DP, Fromm BS, Reddy BR. Slow response to vancomycin or vancomycin plus rifampin in methicillin-resistant Staphylococcus aureus endocarditis. Ann Intern Med 1991;115:674-680.
Gonzalez C, Rubio M, Romero-Vivas J, Gonzalez M, Picazo JJ. Bacteremic pneumonia due to Staphylococcus aureus: a comparison of disease caused by methicillin-resistant and methicillin-susceptible organisms. Clin Infect Dis 1999;29:1171-1177.
Torres-Tortosa M, de Cueto M, Vergara A, et al. Prospective evaluation of a two-week course of intravenous antibiotics in intravenous drug addicts with infective endocarditis. Eur J Clin Microbiol Infect Dis 1994;13:559-564.
Altman DG, Bland JM. Absence of evidence is not evidence of absence. BMJ 1995;311:485-485.
To the Editor: With regard to the article by Moran et al. (Aug. 17 issue),1 it appears that MRSA abscesses will have to be treated as they were in the days before penicillin — that is, by means of incision and drainage. As any surgeon or emergency department doctor knows, the appropriate treatment for an abscess is incision and drainage. Add an antibiotic if you think the attendant cellulitis warrants it (although practically everyone will add an antibiotic, regardless).
Lynn Jetton, M.D.
1910 Cherokee Ave. SW
Cullman, AL 35055
References
Moran GJ, Krishnadasan A, Gorwitz RJ, et al. Methicillin-resistant S. aureus infections among patients in the emergency department. N Engl J Med 2006;355:666-674.
Dr. Cosgrove and colleagues reply: Siegman-Igra and Torres-Tortosa and colleagues inquired about the choice of standard therapies for this trial. We chose to use an antistaphylococcal penicillin or vancomycin to ensure that patients received the best and most appropriate therapy on the basis of the susceptibility of the infecting organism and the presence or absence of an allergy to penicillin. Ten patients in the study with MSSA bacteremia received vancomycin. Seven of these patients had documented penicillin allergies, and three patients did not. Of these 10 patients, 6 (60%), including 2 of the 3 who did not have a penicillin allergy, had a successful outcome 42 days after the end of therapy; the outcomes of 3 patients could not be evaluated because they withdrew consent, and therapy failed in 1 patient. One patient with MRSA infection inappropriately received an antistaphylococcal penicillin for 8 days. We have analyzed the data according to the pathogen-specific therapy — that is, according to whether patients received an antistaphylococcal penicillin for MSSA infection or vancomycin for MRSA infection (Table 1). The performance of daptomycin was similar to that of the standard therapies for both MSSA and MRSA infections in this analysis; however, the power to detect a difference in outcome is quite limited.
Table 1. Distribution of Successful Outcomes 42 Days after the End of Therapy.
Sara E. Cosgrove, M.D.
Johns Hopkins University School of Medicine
Baltimore, MD 21205
Vance G. Fowler, Jr., M.D., M.H.S.
Duke University Medical Center
Durham, NC 27710
vance.fowler@duke.edu
Helen W. Boucher, M.D.
Tufts–New England Medical Center
Boston, MA 02111
Drs. Moran and Talan reply: Jetton is correct that the primary treatment for a skin abscess is incision and drainage, as noted in our article. The additional benefit of antimicrobial therapy remains unclear. Previous investigations suggested similar cure rates with or without antibiotics, but these studies were performed before the emergence of community-associated MRSA and were limited by their use of nonrandomized designs, small numbers of subjects, vague definitions of outcomes, nonstandardized drainage, or antibiotics lacking appropriate activity.1,2,3 In one retrospective study of children, treatment failure with drainage alone was associated with an abscess size of 5 cm2 or larger.4 Inadequate drainage due to poor technique or misdiagnosis of the abscess as simple cellulitis can lead to treatment failure. Until we have better studies to clarify this issue, antimicrobial therapy known to be active against MRSA should be given to patients with systemic illness or clinically significant associated cellulitis, immunovascular or vascular compromise, an abscess in a high-risk location (e.g., a hand or the face), or a lack of a response to incision and drainage alone, and such antimicrobial therapy should be considered for recurrent infection.5
Gregory J. Moran, M.D.
David A. Talan, M.D.
Olive View–UCLA Medical Center
Sylmar, CA 91342
idnet@ucla.edu
References
Meislin HW, Lerner SA, Graves MH, et al. Cutaneous abscesses: anaerobic and aerobic bacteriology and outpatient management. Ann Intern Med 1977;87:145-149.
Llera JL, Levy RC. Treatment of cutaneous abscess: a double-blind clinical study. Ann Emerg Med 1985;14:15-19.
Macfie J, Harvey J. The treatment of acute superficial abscesses: a prospective clinical trial. Br J Surg 1977;64:264-266.
Lee MC, Rios AM, Aten MF, et al. Management and outcome of children with skin and soft tissue abscesses caused by community-acquired methicillin-resistant Staphylococcus aureus. Pediatr Infect Dis J 2004;23:123-127.
Gorwitz RJ, Jernigan DB, Powers JH, Jernigan JA, 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. March 2006. (Accessed October 26, 2006, at http://www.cdc.gov/ncidod/dhqp/ar_mrsa_ca.html.)