In vitro activity of novobiocin and rifampin alone and in combination against oxacillin-resistant Staphylococcus aureus

Johnston, BL; Kwok, R. Y. Y.; Mulligan, Maury E.

doi:10.1016/0732-8893(87)90164-7

Cited by 7 publications

(6 citation statements)

References 18 publications

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“…Both regimens had minimal side effects. The fact that the combination of novobiocin plus rifampin delayed the emergence of resistance to rifampin in the present trial correlated with preclinical in vitro and in vivo studies (14,20,46,48). Host factors had an important relationship to the efficacy of therapy for the eradication of MRSA colonization.…”

Section: Discussionsupporting

confidence: 48%

“…It is also important that the prevention of rifampin resistance with the novobiocin plus rifampin regimen in the trial described here, preclinical evaluations (14,20,46,48), and earlier open trials (1) was not complete. Therefore, careful use of this regimen with monitoring for the development of resistance is essential.…”

Section: Discussionmentioning

confidence: 99%

“…The combination of novobiocin plus rifampin in vitro was found to prevent the emergence of resistant populations of initially susceptible strains of MRSA and to reduce the further development of in vitro resistance for strains with decreased susceptibility to one or both agents, especially to rifampin (20,48). This combination also was found to reduce but not eliminate the emergence of resistance in the rabbit model of MRSA endocarditis (46) and in a mouse thigh abscess model (14).…”

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confidence: 99%

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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

Standiford

Reboli

et al. 1993

Antimicrob Agents Chemother

134

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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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Section: Discussionsupporting

confidence: 48%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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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

Standiford

Reboli

et al. 1993

Antimicrob Agents Chemother

134

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“…The rifampin-fusidic acid combination appears to demonstrate synergy rather than indifference by several in vitro studies (82,86,254). The rifampin-novobiocin combination demonstrates synergy or indifference by in vitro studies, especially when there are heavy inocula of bacteria (48,135,258). Most of the in vitro data were reported many years ago, before standards were established for all laboratories, but the results are not discouraging.…”

Section: Staphylococcimentioning

confidence: 92%

Rifampin Combination Therapy for Nonmycobacterial Infections

2010

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SUMMARY The increasing emergence of antimicrobial-resistant organisms, especially methicillin-resistant Staphylococcus aureus (MRSA), has resulted in the increased use of rifampin combination therapy. The data supporting rifampin combination therapy in nonmycobacterial infections are limited by a lack of significantly controlled clinical studies. Therefore, its current use is based upon in vitro or in vivo data or retrospective case series, all with major limitations. A prominent observation from this review is that rifampin combination therapy appears to have improved treatment outcomes in cases in which there is a low organism burden, such as biofilm infections, but is less effective when effective surgery to obtain source control is not performed. The clinical data support rifampin combination therapy for the treatment of prosthetic joint infections due to methicillin-sensitive S. aureus (MSSA) after extensive debridement and for the treatment of prosthetic heart valve infections due to coagulase-negative staphylococci. Importantly, rifampin-vancomycin combination therapy has not shown any benefit over vancomycin monotherapy against MRSA infections either clinically or experimentally. Rifampin combination therapy with daptomycin, fusidic acid, and linezolid needs further exploration for these severe MRSA infections. Lastly, an assessment of the risk-benefits is needed before the addition of rifampin to other antimicrobials is considered to avoid drug interactions or other drug toxicities.

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“…The two drugs were chosen because of the ease of oral administration; similar half-lives in serum, which allowed convenience of dosing; good penetration and absorption (19); and their activity in vitro against MRSA (4,7,17). They were used together because of the tendency of bacteria to develop resistance to each of these antibiotics when they are used alone (8,13,18) were obtained prior to therapy.…”

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confidence: 99%

Efficacy of short courses of oral novobiocin-rifampin in eradicating carrier state of methicillin-resistant Staphylococcus aureus and in vitro killing studies of clinical isolates

Arathoon

Hamilton

Hench

et al. 1990

Antimicrob Agents Chemother

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Methicillin-resistant Staphylococcus aureus (MRSA) is an important nosocomial infection problem. Colonization appears to be more common than invasive disease is. Eradication of colonization or the carrier state could limit the spread of MRSA, thus reducing the potential for mortality and morbidity in other patients. The detection of patients with MRSA infection in a rehabilitation ward led to a study of the combination of novobiocin-rifampin in vivo and in vitro. We found that 300 mg of rifampin plus 500 mg of novobiocin orally twice daily for 5 days, in 18 courses of treatment given to 12 patients, resulted in the clearing of MRSA in 79% of the evaluable courses and 81% of the evaluable sites. A second course cleared MRSA from one of the patients with a treatment failure. Side effects were not noted. All 18 pretherapy isolates were susceptible to either drug in vitro, but 1 of 2 posttherapy isolates was rifampin resistant. Timed-kifl studies demonstrated that the rate of killing was the same with either drug alone or both drugs together. Pretherapy isolates from treatment successes or failure were killed at the same rate by the drug combination. However, with the rifampin-resistant isolate killing ceased after 48 h. Results of this study suggest that previously untreated patients are likely to have isolates that are susceptible to the combination of drugs and that the combination is commonly effective in eradicating MRSA carriage. Since the regimen is orally administered, and thus convenient, in conjunction with other measures it has the promise of reducing the spread of MRSA in hospitals.

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In vitro activity of novobiocin and rifampin alone and in combination against oxacillin-resistant Staphylococcus aureus

Cited by 7 publications

References 18 publications

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

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

Rifampin Combination Therapy for Nonmycobacterial Infections

Efficacy of short courses of oral novobiocin-rifampin in eradicating carrier state of methicillin-resistant Staphylococcus aureus and in vitro killing studies of clinical isolates

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