Randomized double-blinded trial of rifampin with either novobiocin or trimethoprim-sulfamethoxazole against methicillin-resistant Staphylococcus aureus colonization

Prevention of antimicrobial resistance and effect of host factors on outcome

T. J. Walsh, H. C. Standiford, A. C. Reboli, J. F. John, M. E. Mulligan, B. S. Ribner, J. Z. Montgomerie, M. B. Goetz, C. G. Mayhall, D. Rimland, D. A. Stevens, S. L. Hansen, G. C. Gerard, R. J. Ragual

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen in hospitals. Current antimicrobial regimens for eradicating colonizing strains are not well defined and are often complicated by the emergence of resistance. The combination of novobiocin plus rifampin in vitro and in vivo was found to prevent the emergence of resistant populations of initially susceptible strains of MRSA, particularly resistance to rifampin. We therefore studied, in a randomized, double-blind, multicenter comparative trial, the combination of novobiocin plus rifampin versus trimethoprim- sulfamethoxazole (T/S) plus rifampin in order to determine the efficacy of each regimen in eradicating MRSA colonization and to further characterize the host factors involved in the response to this antimicrobial therapy. Among the 126 individuals enrolled in the study, 94 (80 patients; 14 hospital personnel) were evaluable. Among the 94 evaluable subjects, no significant demographic or medical differences existed between the two treatment groups. Successful clearance of the colonizing MRSA strains was achieved in 30 of 45 (67%) subjects receiving novobiocin plus rifampin, whereas successful clearance was achieved in 26 of 49 (53%) subjects treated with T/S plus rifampin (P = 0.18). The emergence of resistance to rifampin developed more frequently in 14% (7 of 49) of subjects treated with T/S plus rifampin than in 2% (1 of 45) of subjects treated with novobiocin plus rifampin (P = 0.04). Restriction endonuclease studies of large plasmid DNA demonstrated that the same strain was present at pretherapy and posttherapy in most refractory cases (24 of 29 [83%] subjects). Among the 56 successfully treated subjects, clearance of MRSA was age dependent: 29 of 36 (80%) subjects in the 18- to 49-year-old age group, 19 of 35 (54%) subjects in the 50- to 69-year-old age group, and 8 of 23 (35%) in the 70- to 94-year-old age group (P < 0.01). Clearance was also site dependent; culture-positive samples from wounds were related to a successful outcome in only 22 (48%) of 46 subjects, whereas culture-positive samples from sites other than wounds (e.g., nares, rectum, and sputum) were associated with a success rate of 34 of 48 (71%) subjects (P = 0.02). Foreign bodies in wounds did not prevent the eradication of MRSA by either regimen. T/S plus rifampin was less effective in clearing pressure wounds compared with other wounds, whereas novobiocin plus rifampin was equally effective in clearing both pressure and other wounds. There were no significant differences in toxicity between the two regimens. Thus, the combination of novobiocin plus rifampin, in comparison with T/S plus rifampin, was more effective in preventing the emergence of resistance to rifampin and demonstrated a trend toward greater activity in clearing the MRSA carrier state. The response to either combination depended on host factors, particularly age and the site of MRSA colonization.

Original languageEnglish (US)
Pages (from-to)1334-1342
Number of pages9
JournalAntimicrobial Agents and Chemotherapy
Volume37
Issue number6
StatePublished - 1993
Externally publishedYes

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Novobiocin
Sulfamethoxazole Drug Combination Trimethoprim
Rifampin
Methicillin-Resistant Staphylococcus aureus
Wounds and Injuries
Age Groups
Hospital Personnel
Pressure
Carrier State
Age Factors
DNA Restriction Enzymes
Foreign Bodies
Sputum
Rectum

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Randomized double-blinded trial of rifampin with either novobiocin or trimethoprim-sulfamethoxazole against methicillin-resistant Staphylococcus aureus colonization : Prevention of antimicrobial resistance and effect of host factors on outcome. / Walsh, T. J.; Standiford, H. C.; Reboli, A. C.; John, J. F.; Mulligan, M. E.; Ribner, B. S.; Montgomerie, J. Z.; Goetz, M. B.; Mayhall, C. G.; Rimland, D.; Stevens, D. A.; Hansen, S. L.; Gerard, G. C.; Ragual, R. J.

In: Antimicrobial Agents and Chemotherapy, Vol. 37, No. 6, 1993, p. 1334-1342.

Research output: Contribution to journalArticle

Walsh, TJ, Standiford, HC, Reboli, AC, John, JF, Mulligan, ME, Ribner, BS, Montgomerie, JZ, Goetz, MB, Mayhall, CG, Rimland, D, Stevens, DA, Hansen, SL, Gerard, GC & Ragual, RJ 1993, 'Randomized double-blinded trial of rifampin with either novobiocin or trimethoprim-sulfamethoxazole against methicillin-resistant Staphylococcus aureus colonization: Prevention of antimicrobial resistance and effect of host factors on outcome', Antimicrobial Agents and Chemotherapy, vol. 37, no. 6, pp. 1334-1342.
Walsh, T. J. ; Standiford, H. C. ; Reboli, A. C. ; John, J. F. ; Mulligan, M. E. ; Ribner, B. S. ; Montgomerie, J. Z. ; Goetz, M. B. ; Mayhall, C. G. ; Rimland, D. ; Stevens, D. A. ; Hansen, S. L. ; Gerard, G. C. ; Ragual, R. J. / Randomized double-blinded trial of rifampin with either novobiocin or trimethoprim-sulfamethoxazole against methicillin-resistant Staphylococcus aureus colonization : Prevention of antimicrobial resistance and effect of host factors on outcome. In: Antimicrobial Agents and Chemotherapy. 1993 ; Vol. 37, No. 6. pp. 1334-1342.
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abstract = "Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen in hospitals. Current antimicrobial regimens for eradicating colonizing strains are not well defined and are often complicated by the emergence of resistance. The combination of novobiocin plus rifampin in vitro and in vivo was found to prevent the emergence of resistant populations of initially susceptible strains of MRSA, particularly resistance to rifampin. We therefore studied, in a randomized, double-blind, multicenter comparative trial, the combination of novobiocin plus rifampin versus trimethoprim- sulfamethoxazole (T/S) plus rifampin in order to determine the efficacy of each regimen in eradicating MRSA colonization and to further characterize the host factors involved in the response to this antimicrobial therapy. Among the 126 individuals enrolled in the study, 94 (80 patients; 14 hospital personnel) were evaluable. Among the 94 evaluable subjects, no significant demographic or medical differences existed between the two treatment groups. Successful clearance of the colonizing MRSA strains was achieved in 30 of 45 (67{\%}) subjects receiving novobiocin plus rifampin, whereas successful clearance was achieved in 26 of 49 (53{\%}) subjects treated with T/S plus rifampin (P = 0.18). The emergence of resistance to rifampin developed more frequently in 14{\%} (7 of 49) of subjects treated with T/S plus rifampin than in 2{\%} (1 of 45) of subjects treated with novobiocin plus rifampin (P = 0.04). Restriction endonuclease studies of large plasmid DNA demonstrated that the same strain was present at pretherapy and posttherapy in most refractory cases (24 of 29 [83{\%}] subjects). Among the 56 successfully treated subjects, clearance of MRSA was age dependent: 29 of 36 (80{\%}) subjects in the 18- to 49-year-old age group, 19 of 35 (54{\%}) subjects in the 50- to 69-year-old age group, and 8 of 23 (35{\%}) in the 70- to 94-year-old age group (P < 0.01). Clearance was also site dependent; culture-positive samples from wounds were related to a successful outcome in only 22 (48{\%}) of 46 subjects, whereas culture-positive samples from sites other than wounds (e.g., nares, rectum, and sputum) were associated with a success rate of 34 of 48 (71{\%}) subjects (P = 0.02). Foreign bodies in wounds did not prevent the eradication of MRSA by either regimen. T/S plus rifampin was less effective in clearing pressure wounds compared with other wounds, whereas novobiocin plus rifampin was equally effective in clearing both pressure and other wounds. There were no significant differences in toxicity between the two regimens. Thus, the combination of novobiocin plus rifampin, in comparison with T/S plus rifampin, was more effective in preventing the emergence of resistance to rifampin and demonstrated a trend toward greater activity in clearing the MRSA carrier state. The response to either combination depended on host factors, particularly age and the site of MRSA colonization.",
author = "Walsh, {T. J.} and Standiford, {H. C.} and Reboli, {A. C.} and John, {J. F.} and Mulligan, {M. E.} and Ribner, {B. S.} and Montgomerie, {J. Z.} and Goetz, {M. B.} and Mayhall, {C. G.} and D. Rimland and Stevens, {D. A.} and Hansen, {S. L.} and Gerard, {G. C.} and Ragual, {R. J.}",
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TY - JOUR

T1 - Randomized double-blinded trial of rifampin with either novobiocin or trimethoprim-sulfamethoxazole against methicillin-resistant Staphylococcus aureus colonization

T2 - Prevention of antimicrobial resistance and effect of host factors on outcome

AU - Walsh, T. J.

AU - Standiford, H. C.

AU - Reboli, A. C.

AU - John, J. F.

AU - Mulligan, M. E.

AU - Ribner, B. S.

AU - Montgomerie, J. Z.

AU - Goetz, M. B.

AU - Mayhall, C. G.

AU - Rimland, D.

AU - Stevens, D. A.

AU - Hansen, S. L.

AU - Gerard, G. C.

AU - Ragual, R. J.

PY - 1993

Y1 - 1993

N2 - Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen in hospitals. Current antimicrobial regimens for eradicating colonizing strains are not well defined and are often complicated by the emergence of resistance. The combination of novobiocin plus rifampin in vitro and in vivo was found to prevent the emergence of resistant populations of initially susceptible strains of MRSA, particularly resistance to rifampin. We therefore studied, in a randomized, double-blind, multicenter comparative trial, the combination of novobiocin plus rifampin versus trimethoprim- sulfamethoxazole (T/S) plus rifampin in order to determine the efficacy of each regimen in eradicating MRSA colonization and to further characterize the host factors involved in the response to this antimicrobial therapy. Among the 126 individuals enrolled in the study, 94 (80 patients; 14 hospital personnel) were evaluable. Among the 94 evaluable subjects, no significant demographic or medical differences existed between the two treatment groups. Successful clearance of the colonizing MRSA strains was achieved in 30 of 45 (67%) subjects receiving novobiocin plus rifampin, whereas successful clearance was achieved in 26 of 49 (53%) subjects treated with T/S plus rifampin (P = 0.18). The emergence of resistance to rifampin developed more frequently in 14% (7 of 49) of subjects treated with T/S plus rifampin than in 2% (1 of 45) of subjects treated with novobiocin plus rifampin (P = 0.04). Restriction endonuclease studies of large plasmid DNA demonstrated that the same strain was present at pretherapy and posttherapy in most refractory cases (24 of 29 [83%] subjects). Among the 56 successfully treated subjects, clearance of MRSA was age dependent: 29 of 36 (80%) subjects in the 18- to 49-year-old age group, 19 of 35 (54%) subjects in the 50- to 69-year-old age group, and 8 of 23 (35%) in the 70- to 94-year-old age group (P < 0.01). Clearance was also site dependent; culture-positive samples from wounds were related to a successful outcome in only 22 (48%) of 46 subjects, whereas culture-positive samples from sites other than wounds (e.g., nares, rectum, and sputum) were associated with a success rate of 34 of 48 (71%) subjects (P = 0.02). Foreign bodies in wounds did not prevent the eradication of MRSA by either regimen. T/S plus rifampin was less effective in clearing pressure wounds compared with other wounds, whereas novobiocin plus rifampin was equally effective in clearing both pressure and other wounds. There were no significant differences in toxicity between the two regimens. Thus, the combination of novobiocin plus rifampin, in comparison with T/S plus rifampin, was more effective in preventing the emergence of resistance to rifampin and demonstrated a trend toward greater activity in clearing the MRSA carrier state. The response to either combination depended on host factors, particularly age and the site of MRSA colonization.

AB - Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen in hospitals. Current antimicrobial regimens for eradicating colonizing strains are not well defined and are often complicated by the emergence of resistance. The combination of novobiocin plus rifampin in vitro and in vivo was found to prevent the emergence of resistant populations of initially susceptible strains of MRSA, particularly resistance to rifampin. We therefore studied, in a randomized, double-blind, multicenter comparative trial, the combination of novobiocin plus rifampin versus trimethoprim- sulfamethoxazole (T/S) plus rifampin in order to determine the efficacy of each regimen in eradicating MRSA colonization and to further characterize the host factors involved in the response to this antimicrobial therapy. Among the 126 individuals enrolled in the study, 94 (80 patients; 14 hospital personnel) were evaluable. Among the 94 evaluable subjects, no significant demographic or medical differences existed between the two treatment groups. Successful clearance of the colonizing MRSA strains was achieved in 30 of 45 (67%) subjects receiving novobiocin plus rifampin, whereas successful clearance was achieved in 26 of 49 (53%) subjects treated with T/S plus rifampin (P = 0.18). The emergence of resistance to rifampin developed more frequently in 14% (7 of 49) of subjects treated with T/S plus rifampin than in 2% (1 of 45) of subjects treated with novobiocin plus rifampin (P = 0.04). Restriction endonuclease studies of large plasmid DNA demonstrated that the same strain was present at pretherapy and posttherapy in most refractory cases (24 of 29 [83%] subjects). Among the 56 successfully treated subjects, clearance of MRSA was age dependent: 29 of 36 (80%) subjects in the 18- to 49-year-old age group, 19 of 35 (54%) subjects in the 50- to 69-year-old age group, and 8 of 23 (35%) in the 70- to 94-year-old age group (P < 0.01). Clearance was also site dependent; culture-positive samples from wounds were related to a successful outcome in only 22 (48%) of 46 subjects, whereas culture-positive samples from sites other than wounds (e.g., nares, rectum, and sputum) were associated with a success rate of 34 of 48 (71%) subjects (P = 0.02). Foreign bodies in wounds did not prevent the eradication of MRSA by either regimen. T/S plus rifampin was less effective in clearing pressure wounds compared with other wounds, whereas novobiocin plus rifampin was equally effective in clearing both pressure and other wounds. There were no significant differences in toxicity between the two regimens. Thus, the combination of novobiocin plus rifampin, in comparison with T/S plus rifampin, was more effective in preventing the emergence of resistance to rifampin and demonstrated a trend toward greater activity in clearing the MRSA carrier state. The response to either combination depended on host factors, particularly age and the site of MRSA colonization.

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