Mg Of Rifampin Research Articles

Effect of Itraconazole, a CYP3A4 Inhibitor, and Rifampin, a CYP3A4 Inducer, on the Pharmacokinetics of Vatiquinone.

Vatiquinone is a small molecule inhibitor of 15-lipoxygenase in development for patients with Friedreich's ataxia. The objective of this analysis was to determine the effect of a cytochrome P450 isoform 3A4 (CYP3A4) inhibitor and inducer on vatiquinone pharmacokinetics (PKs). The coadministration of 400mg of vatiquinone with 200mg of itraconazole (a CYP3A4 inhibitor) resulted in increased maximum observed concentration (Cmax) of vatiquinone and systemic exposure (AUC0-inf) by approximately 3.5- and 2.9-fold, respectively. The coadministration of 400mg of vatiquinone with 600mg of rifampin (a CYP3A4 inducer) resulted in decreased vatiquinone Cmax and AUC0-inf by approximately 0.64- and 0.54-fold, respectively. The terminal half-life of vatiquinone was not affected by itraconazole or rifampin. These clinical study results confirm the in vitro reaction phenotyping data that shows that CYP3A4 plays an important role in vatiquinone metabolism. The result of this analysis together with phase 3 efficacy and safety data, population PK analysis, and the exposure-response relationship will determine if the extent of vatiquinone changes in the presence of CYP3A4 inhibitors and inducers are considered clinically relevant.

Effect of Strong CYP3A4 Inhibition, CYP3A4 Induction, and OATP1B1/3 Inhibition on the Pharmacokinetics of a Single Oral Dose of Sotorasib.

Sotorasib is a small molecule that irreversibly inhibits the Kirsten rat sarcoma viral oncogene homolog (KRAS) protein with a G12C amino acid substitution mutant protein. The impact of cytochrome P450 (CYP) 3A4 inhibition and induction on sotorasib pharmacokinetics (PKs) was evaluated in 2 separate studies in healthy volunteers (N = 14/study). The impact of CYP3A4 inhibition was interrogated utilizing repeat doses of 200mg of itraconazole, a strong CYP3A4 inhibitor, on 360mg of sotorasib PKs. The impact of CYP3A4 induction was interrogated utilizing multiple doses of 600mg of rifampin, a strong CYP3A4 inducer. Additionally, the impact of organic anion transporting polypeptide (OATP) 1B1/3 inhibition on 960mg of sotorasib PKs was interrogated after a single dose of 600mg of rifampin. CYP3A4 inhibition did not significantly impact sotorasib Cmax but did lead to a 26% increase in sotorasib AUCinf. CYP3A4 induction decreased sotorasib Cmax by 35% and AUCinf by 51%. OATP1B1/3 inhibition decreased sotorasib Cmax and AUCinf by 16% and 23%, respectively. These results support that sotorasib can be given together with strong CYP3A4 and OATP1B1/3 inhibitors but the co-administration of sotorasib and strong CYP3A4 inducers should be avoided.

Biofilm Related Total Knee Arthroplasty Infection: Prevention, Diagnosis and Treatment.

Biofilm related implant infection is undoubtedly a relevant challenge in total knee arthroplasty (TKA) with our comprehension steadily progressing and novel management approaches being developed. The aim of this article was to review the most important advances in approaches to combat infections due to biofilm-forming bacteria in TKA. The main conclusions were the following: 1) Fundamental management techniques for infected TKA include open DAIR (debridement, antibiotics, and implant retention), and one and two-stage revision TKA; 2) Continuous local antibiotic perfusion (CLAP) appears to diminish the risk of periprosthetic joint infection (PJI); 3) Restraint of quorum sensing seems to avert PJI after TKA; 4) A recent in vitro study showed promising results in the prevention and management of PJI after TKA using PMMA [poly(methyl methacrylate)] loaded with up to 100 mg of rifampin.

Mechanically stable rifampin antibiotic cement inhibits Pseudomonas aeruginosa biofilm surface growth.

Rifampin has been proven to be effective in the treatment of prosthetic infections due to its ability to intercalate into biofilms. The use of rifampin in antibiotic spacers is not well described, which would be especially important in the local periprosthetic environment where parenteral doses have poor penetration. The null hypothesis tests if rifampin use in polymethyl methacrylate (PMMA) cement will show no clinically significant impact on mechanical strength at antibiotic concentrations that remain bactericidal. Test antibiotic cement samples supplemented with 0, 30, 50, 100, 150, or 200 mg of rifampin into a standard 40 g bag were tested for compression to failure using published ASTM standards. The samples were then inoculated with Pseudomonas aeruginosa and either evaluated for lipopolysaccharide (LPS) presence as a marker of biofilm or tested by elution as the Kirby Bauer assay. Rifampin concentrations of 30 and 50 mg, showed no statistically different mechanical characteristics from control PMMA (p > 0.05). The 100-mg sample fell within the acceptable range of compressive strength and had significantly less LPS and bacterial presence compared to the control at 12 and 24 h. The ability of PMMA with 100 mg of rifampin to maintain its structural integrity and have significant bacterial inhibition at 12 and 24 h makes it a great candidate as an antibiotic bone cement additive. PMMA loaded with up to 100 mg of rifampin shows promise in the treatment and prevention of periprosthetic joint infection for total knee and total hip arthroplasty.

Intensified Antituberculosis Therapy in Adults with Tuberculous Meningitis

BackgroundTuberculous meningitis is often lethal. Early antituberculosis treatment and adjunctive treatment with glucocorticoids improve survival, but nearly one third of patients with the condition still die. We hypothesized that intensified antituberculosis treatment would enhance the killing of intracerebral Mycobacterium tuberculosis organisms and decrease the rate of death among patients.MethodsWe performed a randomized, double-blind, placebo-controlled trial involving human immunodeficiency virus (HIV)–infected adults and HIV-uninfected adults with a clinical diagnosis of tuberculous meningitis who were admitted to one of two Vietnamese hospitals. We compared a standard, 9-month antituberculosis regimen (which included 10 mg of rifampin per kilogram of body weight per day) with an intensified regimen that included higher-dose rifampin (15 mg per kilogram per day) and levofloxacin (20 mg per kilogram per day) for the first 8 weeks of treatment. The primary outcome was death by 9 months after randomization.ResultsA total of 817 patients (349 of whom were HIV-infected) were enrolled; 409 were randomly assigned to receive the standard regimen, and 408 were assigned to receive intensified treatment. During the 9 months of follow-up, 113 patients in the intensified-treatment group and 114 patients in the standard-treatment group died (hazard ratio, 0.94; 95% confidence interval, 0.73 to 1.22; P=0.66). There was no evidence of a significant differential effect of intensified treatment in the overall population or in any of the subgroups, with the possible exception of patients infected with isoniazid-resistant M. tuberculosis. There were also no significant differences in secondary outcomes between the treatment groups. The overall number of adverse events leading to treatment interruption did not differ significantly between the treatment groups (64 events in the standard-treatment group and 95 events in the intensified-treatment group, P=0.08).ConclusionsIntensified antituberculosis treatment was not associated with a higher rate of survival among patients with tuberculous meningitis than standard treatment. (Funded by the Wellcome Trust and the Li Ka Shing Foundation; Current Controlled Trials number, ISRCTN61649292.)

Effects of rifampin and ketoconazole on pharmacokinetics of morinidazole in healthy chinese subjects.

Morinidazole, a 5-nitroimidazole antimicrobial drug, has been approved for the treatment of amoebiasis, trichomoniasis, and anaerobic bacterial infections in China. It was reported that drug-drug interaction happened after the coadministration of ornidazole, an analog of morinidazole, and rifampin or ketoconazole. Therefore, we measured the plasma pharmacokinetics (PK) of morinidazole and its metabolites in the healthy Chinese volunteers prior to and following the administration of rifampin or ketoconazole using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The area under the concentration-time curve from time 0 to time t (AUC0-t) and maximum concentration in serum (Cmax) of morinidazole were decreased by 28% and 23%, respectively, after 6 days of exposure to 600 mg of rifampin once daily; the Cmaxs of N(+)-glucuronides were increased by 14%, while their AUC0-ts were hardly changed. After 7 days of exposure to 200 mg of ketoconazole once daily, the AUC0-t and Cmax of the parent drug were not affected significantly. Cmaxs of N(+)-glucuronides were decreased by 23%; AUC0-ts were decreased by 14%. The exposure of sulfate conjugate was hardly changed after the coadministration of rifampin or ketoconazole. Using recombinant enzyme of UGT1A9 and human hepatocytes, the mechanism of the altered PK behaviors of morinidazole and its metabolites was investigated. In human hepatocytes, ketoconazole dose dependently inhibited the formation of N(+)-glucuronides (50% inhibitory concentration [IC50], 1.5 μM), while rifampin induced the mRNA level of UGT1A9 by 28% and the activity of UGT1A9 by 53%. In conclusion, the effects of rifampin and ketoconazole on the plasma exposures of morinidazole and N(+)-glucuronide are less than 50%; therefore, rifampin and ketoconazole have little clinical significance in the pharmacokinetics of morinidazole.

Safety, Tolerability, and Pharmacokinetics of the HIV Integrase Inhibitor Dolutegravir Given Twice Daily With Rifampin or Once Daily With Rifabutin

Cotreatment of tuberculosis (TB) and HIV among coinfected patients is now the standard of care. Rifampin (RIF) is a standard part of TB treatment but is a potent inducer of drug metabolizing enzymes. This study evaluated the effect of RIF or rifabutin (RBT) on the pharmacokinetics of the investigational HIV integrase inhibitor, dolutegravir (DTG). Phase I pharmacokinetic drug interaction study. In arm 1, healthy subjects received 50 mg of DTG once daily for 7 days (period 1), then 50 mg of DTG twice daily for 7 days (period 2), then 50 mg of DTG twice daily together with 600 mg of RIF once daily for 14 days (period 3). In arm 2, subjects received 50 mg of DTG once daily for 7 days (period 1) then 50 mg of DTG once daily together with 300 mg of RBT once daily for 14 days (period 2). PK sampling was performed at the end of each period. In arm 1, comparing period 3 to period 1, the geometric mean ratio (GMR) for the 24-hour area under the time-concentration curve (AUC0-24) was 1.33 [90% confidence interval (CI): 1.14 to 1.53], and the GMR for the trough (Cτ) was 1.22 (90% CI: 1.01 to 1.48). Comparing period 2 to period 1 in arm 2, the GMR for the AUC0-24 was 0.95 (90% CI: 0.82 to 1.10), and the GMR for the Cτ was 0.70 (90% CI: 0.57 to 0.87). Regimens including twice-daily DTG and RIF or once-daily DTG and RBT may represent a new treatment option for patients who require concomitant treatment of HIV and TB.

Cutaneous leukocytoclastic vasculitis due to anti-tuberculosis medications, rifampin and pyrazinamide

Anti-tuberculosis drugs frequently result in cutaneous adverse reactions, including pruritus, maculopapular exanthems, and urticaria. However, anti-tuberculosis drug-associated cutaneous leukocytoclastic vasculitis (CLV) has been rarely reported. We describe a case of CLV induced by rifampin and pyrazinamide. A 38-year-old male had been diagnosed with pulmonary tuberculosis two months ago and then he started standard anti-tuberculosis therapy with isoniazid, rifampin, ethambutol, and pyrazinamide. Purpuric lesions developed in the extremities after 1.5 months of anti-tuberculosis medication; the lesions progressively spread over the entire body. Histopathology of the purpuric skin lesion was consistent with leukocytoclastic vasculitis. The skin lesion improved after cessation of anti-tuberculosis medications and treatment with oral corticosteroids and antihistamines. Anti-tuberculosis drugs were rechallenged one at a time over 3 days. Purpura recurred on the right forearm and forehead after taking 300 mg of rifampin. The skin lesion disappeared after taking oral prednisolone. Finally, 1,500 mg of pyrazinamide was readministrated, and then purpuric lesions recurred on both forearms. This report describes a case of leukocytoclastic vasculitis secondary to rifampin and pyrazinamide therapy.

Inadvertent intrathecal administration of rifampicin

Rifampicin is a broad-spectrum antibiotic against bacterial pathogens and is a key component of anti-TB therapy [1] Rifampicin is usually administered orally. Intrathecal administration of rifampicin is not recognized and is under trial [2] We report an incident of inadvertent intrathecal rifampicin administration with no adverse effects. A forty-one year old patient underwent revision of his spinal decompression. The procedure was complicated with postoperative infection confirmed with MRI. The patient underwent debridement and intrathecal pus was noted discharging through a dural tear. Intrathecal catheter was inserted for intrathecal vancomycin. The patient was prescribed intravenous rifampicin. The rifampicin was connected to the intrathecal catheter with a rate of 125 ml h−1 (600 mg). The infusion was given for a period of 4 h before mistake was identified and was discontinued. The patient did not show any reaction to the intrathecal rifampicin. No new neurological signs were noted and the patient was closely monitored. The patient's urine became orange coloured characteristic of rifampicin administration. The rifampicin belongs to the group of complex macrolide antibiotics produced by Streptomyces mediterranei[3]. Rifampin acts by inhibiting DNA-dependent RNA polymerase of mycobacteria and other micro-organisms by forming a stable drug–enzyme complex leading to suppression of initiation of chain formation in RNA synthesis. When given orally the drug is absorbed and is distributed throughout the body and is found in effective concentrations in many organs and body fluids including CSF [4]. Intrathecal rifampin is under trial and still not used in human beings. The side-effects of intrathecal use are not known. Intravenous preparation has trace doses of formaldehyde. Our patient received 600 mg of rifampin intrathecally over 4-h period. No adverse events occurred. No side-effects noted at 6-month follow-up. Inadvertent uses of medications are reported in the literature even though strict precautions are followed during the administration. No adverse events occurred during this patient's intrathecal administration of rifampicin.

The utility of rifampin in diagnosing Gilbert’s syndrome

OBJECTIVE: The aim of this study was to evaluate the effect of rifampin (the “rifampin test”) on serum bilirubin in patients with and without Gilbert’s syndrome. METHODS: We conducted a clinical trial in which the effect of rifampin on serum bilirubin level in 15 patients with Gilbert’s syndrome was compared with 10 patients without Gilbert’s syndrome (controls) in a General Internal Medicine/Primary Care clinic of a Veterans Affairs medical center. Each participant underwent a “rifampin test,” i.e., bilirubin measurement at baseline and 2, 4, and 6 h after the administration of 900 mg of rifampin. Measurements included complete blood count, blood chemistry including liver panel tests (ALP, AST, LDH, and albumin) along with total serum bilirubin levels. Ten patients with Gilbert’s and nine control patients had haptoglobin level measured at baseline and 6 h after the administration of rifampin. RESULTS: While fasting, the mean rise in total serum bilirubin at 2, 4, and 6 h after the administration of rifampin, respectively, was 0.5, 0.7, and 0.7 mg/dl (analysis of variance, p < 0.001) in control patients and 0.6, 1.0, and 1.1 mg/dl ( p < 0.001) in the study patients. In 15 fed subjects (six control and nine study), the mean rise in total serum bilirubin at 2, 4, and 6 h, respectively, was 0.3, 0.5, and 0.6 mg/dl ( p < 0.001) in controls and 0.5, 1.0, and 1.2 mg/dl ( p < 0.001) in study subjects. In the fasting state, rise in total serum bilirubin to >1.9 mg/dl distinguished patients with Gilbert’s syndrome from those without at 2, 4, and 6 h (sensitivity 100%, 93%, and 93%; specificity 100%, 100%, and 100% at 2, 4, and 6 h, respectively). In the nonfasting state, rise in total serum bilirubin to >1.5 mg/dl at 4 and 6 h after rifampin administration distinguished the two groups (sensitivity 90% and 100%; specificity 100% and 100%, respectively). CONCLUSIONS: Rifampin increases total serum bilirubin levels in patients with and without Gilbert’s syndrome. On fasting for 12 to 24 h, an absolute increase of bilirubin to >1.9 mg/dl 2 to 6 h after the administration of 900 mg of rifampin distinguishes patients with Gilbert’s syndrome from those without it. In the nonfasting state, an increase in total serum bilirubin to >1.5 mg/dl 4 to 6 h after the administration of rifampin distinguishes persons with Gilbert’s syndrome from those without it.

Rifampin concentrations in various compartments of the human brain: a novel method for determining drug levels in the cerebral extracellular space.

Antimicrobial therapy for brain infections is notoriously difficult because of the limited extent of knowledge about drug penetration into the brain. Therefore, we determined the penetration of rifampin into various compartments of the human brain, including the cerebral extracellular space (CES). Patients undergoing craniotomy for resection of primary brain tumors were given a standard dose of 600 mg of rifampin intravenously before the operation. A microdialysis probe (10 by 0.5 mm) was inserted into the cortex distantly from the resection and was perfused with two different rifampin solutions. Rifampin concentrations in the CES were calculated by the no-net-flux method. Intraoperatively, samples were taken from brain tumor tissue, perifocal tissue, and normal brain tissue in the case of pole resections. Rifampin concentrations in the various samples were determined by using a bioassay with Sarcinea lutea. In the various compartments, rifampin concentrations were highest within tumors (1.37 +/- 1.34 microg/ml; n = 8), followed by the perifocal region (0.62 +/- 0.67 microg/ml; n = 8), the CES (0.32 +/- 0.11 microg/ml; n = 6), and normal brain tissue (0.29 +/- 0.15 microg/ml; n = 7). Rifampin concentrations in brain tumors do not adequately reflect concentrations in normal brain tissue or in the CES. Rifampin concentrations in the CES, as determined by microdialysis, are the most reproducible, and the least scattered, of the values for all compartments evaluated. Rifampin concentrations in all compartments exceed the MIC for staphylococci and streptococci. However, CES concentrations may be below the MICs for some mycobacterial strains.

Acute Hypertension as an Adverse Effect of Pyrazinamide

To the Editor. —Pyrazinamide has been associated with nausea, vomiting, hepatotoxicity, 1 interstitial nephritis, 2 rhabdomyolysis, polymyalgia, photosensitivity, and urate retention. 3 To our knowledge the development of acute hypertension has not been reported as an adverse effect of pyrazinamide. We report a case suggestive of pyrazinamide-induced acute hypertension. Report of a Case. —A 65-year-old woman with no previous medical history and blood pressure (BP) of 130/80 mm Hg was diagnosed with pulmonary tuberculosis. She was started on a combination tablet containing 300 mg of rifampin 300 mg, 150 mg of isoniazid, and 500 mg of pyrazinamide. (Rifater, Marion Merrell Dow, Kansas City, Mo). After she received the first dose, she reported an episode of intense headache and tachycardia that lasted 3 hours until she was admitted to the hospital. Physical examination revealed a supine BP of 170/110 mm Hg and pulse of 120 beats per minute and regular. Examination

Treponema maltophilum sp. nov., a small oral spirochete isolated from human periodontal lesions.

A novel culture medium for cultivation of fastidious oral anaerobes is described. This medium, OMIZ-Pat, consists of a rich chemically defined basal medium supplemented with asialofetuin, as well as yeast extract and Neopeptone fractions. Addition of 1 mg of rifampin per liter and 100 mg of fosfomycin per liter allowed routine isolation of spirochetes by a limit dilution method in 96-well plates containing liquid OMIZ-Pat. In addition to members of the four previously recognized species of oral treponemes (Treponema denticola, Treponema pectinovorum, Treponema socranskii, and Treponema vincentii), 26 previously undescribed spirochete strains belonging to one group were isolated. We propose the name Treponema maltophilum sp. nov. for these small spirochetes, which have two endoflagella; one endoflagellum is attached at each cell pole, and the endoflagella overlap in the middle of the cell. Growth of these organisms was dependent on a carbohydrate like D-arabinose, L-fucose, D-maltose, L-rhamnose, D-ribose, D-sucrose, or D-trehalose and was inhibited by fetal bovine serum. T. Maltophilum is distinguished from other oral Treponema species by its 16S rRNA sequence, its protein and antigen patterns as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting, and its characteristic alpha-glucosidase activity. The strains included in the new species on the basis of their 16S rRNA sequences are heterogeneous with respect to their alpha-fucosidase, and beta-glucuronidase activities, their dependence on N-acetylglucosamine, and their antigens as detected with patient antibodies. Strain BR is designated the type strain, and strains HO2A and PNA1 are reference strains of the new species.

Preventive chemotherapy of tuberculosis in Cornell model mice with combinations of rifampin, isoniazid, and pyrazinamide.

The efficacies of rifampin-containing preventive regimens were measured in Cornell model mice in which an initially severe infection with Mycobacterium tuberculosis H37Rv was first treated for 7 weeks with 25 mg of isoniazid and 1,000 mg of pyrazinamide per kg of body weight in the diet and then with one of four test regimens given by daily oral gavage for 6 weeks. These regimens were 15 mg of rifampin per kg alone (R), rifampin plus 25 mg of isoniazid per kg (RH), rifampin plus 150 mg of pyrazinamide per kg (RZ), or rifampin plus isoniazid and pyrazinamide (RHZ). The interval between the rifampin gavage and the gavage with the other drugs ranged from 10 to 45 min, so that interference with rifampin absorption did not occur. Mice were sacrificed at 11 and 20 weeks after the termination of chemotherapy, with each killing being preceded by 3 weeks of high-dose dihydrocortisone treatment. Entire spleens and lungs were cultured. The proportions of mice with positive spleens at either killing time were 74% of 43 mice treated with R, 63% of 41 mice treated with RH, 65% of 43 mice treated with RZ, and 53% of 45 mice treated with RHZ, a just significant (P = 0.04) trend for fewer positive spleens with increasing numbers of drugs in the regimen. However, no trend was found in the corresponding proportions of mice with positive spleens or lungs, which were 81, 63, 65, and 71% for mice treated with R, RH, RZ, and RHZ, respectively. Thus, in the Cornell model, R alone, RH, RZ, and RHZ all had similar efficacies.

Colonization and Infection with Methicillin-Resistant Staphylococcus aureus: Associated Factors and Eradication

To identify characteristics associated with methicillin-resistant Staphylococcus aureus (MRSA) colonization and infection, and to evaluate the efficacy of systemic and topical antimicrobials in the eradication of MRSA carriage among hospitalized patients.A case-control study was done to identify associations. Odds ratios were estimated by unconditional multiple logistic regression. Cohort study was done to evaluate MRSA decolonization efficacy by an oral regimen. Patients infected or colonized with MRSA received a 5-day course of oral (160 mg/800 mg) trimethoprim-sulfametroxazole twice daily and 600 mg of rifampin once daily as decolonization treatment. The proportion of MRSA-free patients after decolonization treatment was determined. Persistence of clearing was estimated by the Kaplan-Meier method.Ramón y Cajal Hospital, a 1,249-bed, tertiary-care teaching hospital in Madrid, Spain.One hundred ninety-two patients with hospital-acquired MRSA infection/colonization and 195 MRSA-free random controls.Six factors were associated independently with MRSA infection/colonization: age (every 10 years of age, odds ratio [OR] = 1.3); ward (surgical, OR = 1; medical, OR = 3.1; intensive care unit, OR = 60); previous hospitalization (OR = 6.9); coma (OR = 25.3); invasive procedures (each, OR = 1.7); 3 or more weeks of hospitalization (OR = 3.8). We failed to show antibiotic therapy to be an independent risk factor for MRSA hospital infection/colonization. Overall, MRSA eradication was 64.2% by day 2 to 9 after completion of treatment. Kaplan-Meier product limit survival analysis showed that the probability of remaining MRSA-free was 65.3% (SE = 0.09) at 32 days after completion of treatment.The results offer a rationale for reduction of MRSA infection/colonization in the hospital by interventions aimed at early identification of patients at higher risk, at prompt discharge of patients, and at preventing dissemination while performing invasive procedures. They also provide estimates of antibiotic treatment efficacy to reduce the reservoir of MRSA in the hospital.

Colonization and infection with methicillin-resistant Staphylococcus aureus: associated factors and eradication.

To identify characteristics associated with methicillin-resistant Staphylococcus aureus (MRSA) colonization and infection, and to evaluate the efficacy of systemic and topical antimicrobials in the eradication of MRSA carriage among hospitalized patients. A case-control study was done to identify associations. Odds ratios were estimated by unconditional multiple logistic regression. Cohort study was done to evaluate MRSA decolonization efficacy by an oral regimen. Patients infected or colonized with MRSA received a 5-day course of oral (160 mg/800 mg) trimethoprim-sulfametroxazole twice daily and 600 mg of rifampin once daily as decolonization treatment. The proportion of MRSA-free patients after decolonization treatment was determined. Persistence of clearing was estimated by the Kaplan-Meier method. Ramón y Cajal Hospital, a 1,249-bed, tertiary-care teaching hospital in Madrid, Spain. One hundred ninety-two patients with hospital-acquired MRSA infection/colonization and 195 MRSA-free random controls. Six factors were associated independently with MRSA infection/colonization: age (every 10 years of age, odds ratio [OR] = 1.3); ward (surgical, OR = 1; medical, OR = 3.1; intensive care unit, OR = 60); previous hospitalization (OR = 6.9); coma (OR = 25.3); invasive procedures (each, OR = 1.7); 3 or more weeks of hospitalization (OR = 3.8). We failed to show antibiotic therapy to be an independent risk factor for MRSA hospital infection/colonization. Overall, MRSA eradication was 64.2% by day 2 to 9 after completion of treatment. Kaplan-Meier product limit survival analysis showed that the probability of remaining MRSA-free was 65.3% (SE = 0.09) at 32 days after completion of treatment. The results offer a rationale for reduction of MRSA infection/colonization in the hospital by interventions aimed at early identification of patients at higher risk, at prompt discharge of patients, and at preventing dissemination while performing invasive procedures. They also provide estimates of antibiotic treatment efficacy to reduce the reservoir of MRSA in the hospital.

Early detection of rifampin in human nerve tissue after an oral dose of 600 milligrams.

Rifampin in picogram quantities inhibited the ability of Mycobacterium bovis 44 BCG P3 to release 14CO2 from the oxidation of [14C]palmitic acid. By using these mycobacteria in a bioassay, samples of serum and posterior tibial nerve were assayed for inhibitory concentrations of rifampin. Within 8 to 12 h after ingestion of 600 mg of rifampin, the drug was detected in eight patients in concentrations ranging from 0.52 to 4.1 micrograms/ml in serum and in concentrations ranging from 0.6 to 6.3 ng/mg in posterior tibial nerve fiber tissue.

Eradication of colonization by methicillin-resistant Staphylococcus aureus by using oral minocycline-rifampin and topical mupirocin

In an attempt to control the spread of methicillin-resistant Staphylococcus aureus (MRSA) within a spinal cord injury unit, we investigated the mode of transmission and implemented a multidisciplinary approach for control that consisted of grouping of patients into cohorts, contact isolation, and antibiotics. Surveillance cultures of patients and nose and hand cultures of medical personnel were performed. Of 11 colonized patients, 6 had MRSA isolates that shared a similar plasmid profile and antibiogram, raising the possibility of interpatient spread of the organism. Medical personnel had no evident role in transmitting MRSA. All patients' pretherapy MRSA isolates were susceptible to minocycline and, except for one, to rifampin. Time-kill studies showed an indifferent interaction of these two antibiotics. Ten colonized patients received a 2-week oral course of 100 mg of minocycline twice daily and 600 mg of rifampin once daily, while the 11th patient was treated for only 1 week. Patients with colonization of the nares also had twice daily nasal application of 2% mupirocin for 5 days. Colonization with MRSA cleared in 10 of 11 patients (91%) and 20 of 21 sites (95%). When the individual circumstances of a medical facility justify eradication of MRSA colonization, a multidisciplinary approach that includes antibiotic therapy with oral minocycline and rifampin, along with topical mupirocin for those with nasal carriage, may be successful.

Treatment of pruritus of primary biliary cirrhosis with rifampin

Pruritus can be a debilitating symptom in patients with chronic cholestasis. Based on previous reports of its efficacy, we evaluated the impact of rifampin on the pruritus associated with primary biliary cirrhosis. Fourteen patients were included in a randomized, crossover study. After a 15-day washout period, subjects were followed for three weeks. During the first and third week, patients received 600 mg of rifampin or placebo; no treatment was administered during the second week. Pruritus was subjectively scored on a scale from 0 to 100. With rifampin, pruritus disappeared in 11 patients and partially improved in three; with placebo, only two had a partial response (P less than 0.001). Six patients with a prior poor or no response to cholestyramine improved with rifampin. No changes in biochemical tests or side effects were observed during this period. We conclude that short-term administration of rifampin relieves pruritus in primary biliary cirrhosis. When administered over a period of eight months in an open study, the relief of pruritus was maintained, while one individual developed an allergic reaction. Rifampin appears to be a safe drug in the management of the pruritus of primary biliary cirrhosis.

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

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-kill 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.