Effect of Rifampin on Nasal Carriage of
            <i>Staphylococcus aureus</i>

Sande, Merle A.; Mandell, Gerald L.

doi:10.1128/aac.7.3.294

Cited by 76 publications

(18 citation statements)

References 10 publications

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“…Such cases, exemplified by rifampicin treatment of Escherichia coli, may reflect our inability to achieve drug concentrations that are high enough to block mutant growth (single-step mutants are highly protective). A wide selection window explains why rifampicin, a very active agent with S. aureus, is often unsuitable for monotherapy with this pathogen [21,22].…”

Section: Measuring the Mutant Selection Windowmentioning

confidence: 99%

Mutant Selection Window Hypothesis Updated

Drlica¹,

Zhao²

2007

Clinical Infectious Diseases

352

338

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The mutant selection window hypothesis postulates that, for each antimicrobial-pathogen combination, an antimicrobial concentration range exists in which selective amplification of single-step, drug-resistant mutants occurs. This hypothesis suggests an antimutant dosing strategy that is keyed to the upper boundary of the selection window: the mutant prevention concentration. Correlations are described between the mutant prevention concentration-a static parameter that is measured with agar plates-and fluctuating drug concentrations that restrict mutant amplification in vitro and in animals. When drug resistance is acquired stepwise, the mutant selection window increases, making the suppression of each successive mutant increasingly more difficult. For agents that kill drug-resistant mutants in a drug concentration-dependent manner, the use of the area under the 24-h time-drug concentration curve value divided by the value of the mutant prevention concentration is suggested as an index for designing antimutant dosing regimens. The need for such regimens is emphasized by a clinical example in which acquisition of drug resistance occurs concurrently with eradication of susceptible bacterial cells. These data support using the mutant selection window to optimize antimicrobial dosing regimens.Antimicrobial resistance is a complex problem that is likely to require attention at many levels [1]. Issues concerning dosing are addressed by the mutant selection window hypothesis [2,3]. This hypothesis maintains that drug-resistant mutant subpopulations present prior to initiation of antimicrobial treatment are enriched and amplified during therapy when antimicrobial concentrations fall within a specific range (the mutant selection window). The upper boundary of the mutant selection window is the MIC of the least drugsusceptible mutant subpopulation, a value called the mutant prevention concentration (MPC) [4]. The lower boundary of the mutant selection window is the lowest concentration that exerts selective pressure, often approximated by the minimal concentration that inhibits colony formation by 99% (MIC 99 ). Two principles emerge from the hypothesis. First, traditional dos-

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Section: Measuring the Mutant Selection Windowmentioning

confidence: 99%

Mutant Selection Window Hypothesis Updated

Drlica¹,

Zhao²

2007

Clinical Infectious Diseases

352

338

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“…Rifampin has a high degree of activity against MRSA; however, the development of resistance is a well-recognized problem when rifampin is used alone (6,42,51,56). When T/S plus rifampin is used in combination, the level of resistance to rifampin is reduced.…”

mentioning

confidence: 99%

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

136

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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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“…Nevertheless, the only references on the subject are by Spink et al (32), who in 1951 reported the absence of resistance in eight patients with brucellosis and bacteremia persisting after 10 to 14 days of treatment with sulfamide and streptomycin; Hall and Spink (15) also mention a patient who developed streptomycin resistance during treatment with the drug. The question of the development of resistance is of particular interest for patients relapsing after rifampin treatment with regard to the emergence of rifampin-resistant Brucella variants observed in in vitro studies (8) and reported for the same drug in other types of infections (4,27,33).…”

mentioning

confidence: 99%

Relevance of in vitro antimicrobial susceptibility of Brucella melitensis to relapse rate in human brucellosis

Ariza¹,

Bosch²,

Gudiol³

et al. 1986

Antimicrob Agents Chemother

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The in vitro susceptibility of Brucella melitensis was examined vis-a-vis the clinical outcome in 75 patients with brucellosis. The initial MICs for Brucella isolates from patients who relapsed and from those who did not were similar. Furthermore, the MICs for isolates from patients whose infections relapsed were no different from those for original isolates. Our results clearly showed that neither initial nor subsequent antibiotic susceptibility plays a role in the likelihood of relapse of patients with brucellosis.

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Effect of Rifampin on Nasal Carriage of Staphylococcus aureus

Cited by 76 publications

References 10 publications

Mutant Selection Window Hypothesis Updated

Mutant Selection Window Hypothesis Updated

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

Relevance of in vitro antimicrobial susceptibility of Brucella melitensis to relapse rate in human brucellosis

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