Ignite Creation Date:
2024-05-05 @ 4:43 PM
Last Modification Date:
2024-10-26 @ 9:23 AM
Study NCT ID:
NCT00304811
Status:
COMPLETED
Last Update Posted:
2009-09-28
First Post:
2006-03-16
Brief Title:
Vancomycin vs Vancomycin Plus Gentamycin in Treatment of MRSA Infection
Sponsor:
Michael E DeBakey VA Medical Center
Organization:
Michael E DeBakey VA Medical Center
Study Overview
Official Title:
Vancomycin Versus Vancomycin Plus Gentamycin For Treating Bacteremic Infection Due to Methicillin-Resistant Staphylococcus Aureus MRSA
Status:
COMPLETED
Status Verified Date:
2009-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this study is to compare the outcome of treatment for bacteremic MRSA infection with vancomycin alone vancomycin plus gentamicin vancomycin plus rifampin and vancomycin plus gentamicin and rifampin
Detailed Description:
Treatment of bacteremic infection infection associated with positive blood cultures due to Staphylococcus aureus has become increasingly problematic as a result of the increasing prevalence of strains that are resistant to beta-lactam antibiotics so-called methicillin-resistant Staphylococcus aureus MRSA About 70 of hospital-related strains of S aureus are MRSA and in the past 4 years the incidence of MRSA in community-acquired infection has risen to about 50 these data are quite representative of what is being seen elsewhere in the United States and other parts of the world
Bacteremic MRSA infections are highly problematic for at least two reasons 1they are serious with substantial morbidity and about a 25 rate of mortality in middle-aged adults the principal patients in our system and 2available antibiotic therapy is suboptimal
In the pre-MRSA era before 1982 in the United States treatment of bacteremic S aureus infection with a beta-lactam antibiotic such as nafcillin produced a uniform microbiological cure Musher DM McKenzie SO Infections due to Staphylococcus aureus Medicine 56383-409 1977 This means that in the absence of an untreated focus of infection that required surgical removal such as a myocardial abscess antibiotics rapidly sterilized the blood stream This does not mean that no one died deaths from complications of infection remained common But at autopsy there was generally no evidence for active infection Extensive literature examined the question of whether gentamicin should be added to nafcillin to treat this kind of disease reviewed critically in DM Verner EF Treatment of Infections due to Staphylococcus aureus IN The Staphylococci Ed by J Jeljascewicz Gustave Fischer Verlag Stuttgart New York pp407-419 1986 Gentamicin produced a synergistic bactericidal effect agains S aureus in vitro and in animal models In humans the addition of gentamicin was associated with more rapid sterilization of the blood stream but prolonged gentamicin therapy was also associated with nephrotoxicity
In contrast in the MRSA era treatment with vancomycin is associated with persistence of bacteremia positive blood cultures and death from active infection We have recently participated in a prospective observational study that documented the association between vancomycin treatment persistently positive blood cultures and persistence of active infection during treatment of S aureus bacteremia with vancomycin Chang F-Y McDonald BB Peacock Jr JE Musher DM et al Staphylococcus aureus bacteremia recurrence and the impact of antibiotic treatment in a prospective multicenter study Medicine 82333-339 2003
There appears to be a very close correlation between the outcome of treatment for serious S aureus infection and the bactericidal activity of the treating antibiotic in vitro using conventional techniques Musher DM Verner EF Treatment of infections due to Staphylococcus aureus IN The Staphylococci Ed by J Jeljascewicz Gustave Fischer Verlag Stuttgart New York pp407-419 1986 We recently showed that adding low concentrations of gentamicin to vancomycin led to substantial synergistic bactericidal activity against MRSA Shelburne SA Musher DM Hulten K Ceasar H Lu MY Bhaila I Hamill RJ In-vitro killing of community-associated methicillin-resistant Staphylococcus aureus with drug combinations Antimicrob Agents Chemother 484016-9 2004
Based in part on the analogy of nafcillin for treating methicillin-susceptible S aureus infection and in part of in vitro studies such as ours cited above some physicians regularly add gentamicin to vancomycin for treating MRSA infection Others without even the in vitro support add rifampin either instead of gentamicin or together with gentamicin There are no clinical studies to support or to refute any of these clinically motivated usages
Thus at present about one-third of patients with MRSA bacteremia at VAMC are treated with vacomycin plus gentamicin and two-thirds receive vancomycin alone some in each group receive rifampin The decisionto add gentamicin is made a haphazard fashion Our proposal is once MRSA has been identified in acceptable regimens by stratifying patients prospectively to vancomycin alone or vancomycin plus gentamicin and further stratifying each of those groups to be with or without rifampin
Bacteremic MRSA infections are highly problematic for at least two reasons 1they are serious with substantial morbidity and about a 25 rate of mortality in middle-aged adults the principal patients in our system and 2available antibiotic therapy is suboptimal
In the pre-MRSA era before 1982 in the United States treatment of bacteremic S aureus infection with a beta-lactam antibiotic such as nafcillin produced a uniform microbiological cure Musher DM McKenzie SO Infections due to Staphylococcus aureus Medicine 56383-409 1977 This means that in the absence of an untreated focus of infection that required surgical removal such as a myocardial abscess antibiotics rapidly sterilized the blood stream This does not mean that no one died deaths from complications of infection remained common But at autopsy there was generally no evidence for active infection Extensive literature examined the question of whether gentamicin should be added to nafcillin to treat this kind of disease reviewed critically in DM Verner EF Treatment of Infections due to Staphylococcus aureus IN The Staphylococci Ed by J Jeljascewicz Gustave Fischer Verlag Stuttgart New York pp407-419 1986 Gentamicin produced a synergistic bactericidal effect agains S aureus in vitro and in animal models In humans the addition of gentamicin was associated with more rapid sterilization of the blood stream but prolonged gentamicin therapy was also associated with nephrotoxicity
In contrast in the MRSA era treatment with vancomycin is associated with persistence of bacteremia positive blood cultures and death from active infection We have recently participated in a prospective observational study that documented the association between vancomycin treatment persistently positive blood cultures and persistence of active infection during treatment of S aureus bacteremia with vancomycin Chang F-Y McDonald BB Peacock Jr JE Musher DM et al Staphylococcus aureus bacteremia recurrence and the impact of antibiotic treatment in a prospective multicenter study Medicine 82333-339 2003
There appears to be a very close correlation between the outcome of treatment for serious S aureus infection and the bactericidal activity of the treating antibiotic in vitro using conventional techniques Musher DM Verner EF Treatment of infections due to Staphylococcus aureus IN The Staphylococci Ed by J Jeljascewicz Gustave Fischer Verlag Stuttgart New York pp407-419 1986 We recently showed that adding low concentrations of gentamicin to vancomycin led to substantial synergistic bactericidal activity against MRSA Shelburne SA Musher DM Hulten K Ceasar H Lu MY Bhaila I Hamill RJ In-vitro killing of community-associated methicillin-resistant Staphylococcus aureus with drug combinations Antimicrob Agents Chemother 484016-9 2004
Based in part on the analogy of nafcillin for treating methicillin-susceptible S aureus infection and in part of in vitro studies such as ours cited above some physicians regularly add gentamicin to vancomycin for treating MRSA infection Others without even the in vitro support add rifampin either instead of gentamicin or together with gentamicin There are no clinical studies to support or to refute any of these clinically motivated usages
Thus at present about one-third of patients with MRSA bacteremia at VAMC are treated with vacomycin plus gentamicin and two-thirds receive vancomycin alone some in each group receive rifampin The decisionto add gentamicin is made a haphazard fashion Our proposal is once MRSA has been identified in acceptable regimens by stratifying patients prospectively to vancomycin alone or vancomycin plus gentamicin and further stratifying each of those groups to be with or without rifampin
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None