rifampin and Diabetes-Mellitus

Diabetes mellitus has a negative impact on the treatment outcome of tuberculosis, increasing the incidence of treatment failure and relapse. There is a scarcity of knowledge concerning the impact of diabetes mellitus on the pharmacokinetics of rifampicin. This study was conducted to evaluate the impact of diabetes mellitus on the pharmacokinetics of rifampicin among patients with tuberculosis.. We explored the Web of Science, Cochrane Library, PubMed, and Scopus databases for articles that reported the pharmacokinetic parameters of rifampicin in diabetic and nondiabetic patients with tuberculosis published until September 2020. Based on the presence or absence of heterogeneity, pooled estimates were calculated using a random or fixed effect model.. Seven studies were relevant and included in this study. The Tmax of rifampicin increased in diabetic patients with tuberculosis compared with nondiabetic patients with tuberculosis (MD 0.84, 95% CI (0.32, 1.35), p = 0.002). No significant differences were detected in rifampicin Cmax (MD 0.18, 95% CI (-0.52, 0.88), p = 0.61), AUC0-24 (SMD -0.02, 95% CI (-0.34, 0.30), p = 0.90), Vd (MD -3.89, 95% CI (-11.17, 3.38), p = 0.29), CL (MD -0.13, 95%CI (-0.88, 0.61), p = 0.72), and MRT (MD 1.89, 95% CI (-0.03, 3.81), p = 0.05) between diabetic and nondiabetic patients with tuberculosis.. Diabetes mellitus increased the Tmax of rifampicin without further impact on other rifampicin pharmacokinetic parameters such as Cmax, AUC0-24, Vd, CL and MRT. Early therapeutic drug monitoring of rifampicin is necessary for diabetic tuberculosis patients.

Topics: Antibiotics, Antitubercular; Diabetes Mellitus; Humans; Rifampin; Tuberculosis

Rifapentine is a rifamycin derivate approved by the US Food and Drug Administration in 1998 for the treatment of active, drug-susceptible tuberculosis (TB). In 2014, rifapentine was approved for the treatment of latent TB infection in patients at high risk of progression to active disease and is currently under evaluation by the European Medicines Agency. Expanding indications of rifapentine largely affect diabetes patients, since about one-third of them harbor latent TB. Clinical consequences of rifapentine use in this population and potentially harmful interactions with hypoglycemic agents are widely underexplored and generally considered similar to the ones of rifampicin. Indeed, rifapentine too may decrease blood levels of many oral antidiabetics and compete with them for protein-binding sites and/or transporters. However, the two drugs differ in protein-binding degree, the magnitude of cytochrome P450 induction and auto-induction, the degree of renal elimination, and so on. Rifapentine seems to be more suitable for use in diabetes patients with renal impairment, owing to the fact that it does not cause renal toxicity, and it is eliminated via kidneys in smaller proportions than rifampicin. On the other hand, there are no data related to rifapentine use in patients >65 years, and hypoalbuminemia associated with diabetic kidney disease may affect a free fraction of rifapentine to a greater extent than that of rifampicin. Until more pharmacokinetic information and information on the safety of rifapentine use in diabetic patients and drug-drug interactions are available, diabetes in TB patients treated with rifapentine should be managed with insulin analogs, and glucose and rifapentine plasma levels should be closely monitored.

Topics: Antibiotics, Antitubercular; Diabetes Mellitus; Drug Interactions; Humans; Hypoglycemic Agents; Latent Tuberculosis; Rifampin; Tuberculosis

The pregnane X receptor (PXR) is a nuclear receptor that is traditionally thought to be specialized for sensing xenobiotic exposure. In concurrence with this feature PXR was originally identified to regulate drug-metabolizing enzymes and transporters. During the last ten years it has become clear that PXR harbors broader functions. Evidence obtained both in experimental animals and humans indicate that ligand-activated PXR regulates hepatic glucose and lipid metabolism and affects whole body metabolic homeostasis. Currently, the consequences of PXR activation on overall metabolic health are not yet fully understood and varying results on the effect of PXR activation or knockout on metabolic disorders and weight gain have been published in mouse models. Rifampicin and St. John's wort, the prototypical human PXR agonists, impair glucose tolerance in healthy volunteers. Chronic exposure to PXR agonists could potentially represent a risk factor for diabetes and metabolic syndrome. This article is part of a Special Issue entitled: Xenobiotic nuclear receptors: New Tricks for An Old Dog, edited by Dr. Wen Xie.

Topics: Animals; Diabetes Mellitus; Gene Expression Regulation; Gluconeogenesis; Glucose; Glycolysis; Humans; Hypericum; Inactivation, Metabolic; Lipogenesis; Liver; Metabolic Syndrome; Pregnane X Receptor; Receptors, Steroid; Rifampin; Signal Transduction

The aim of the study was to compare plasma concentrations of rifampicin (RMP), isoniazid (INH) and pyrazinamide (PZA) between tuberculosis (TB) patients with and without diabetes mellitus (DM).. Two-hour post-dosing concentrations of RMP, INH and PZA were determined in adult TB patients that were studied with (n = 452) and without DM (n = 1460), treated with a thrice-weekly regimen in India. Drug concentrations were estimated by HPLC.. The median (IQR) INH [6.6 (3.9-10.0) and 7.8 (4.6-11.3)] and PZA [31.0 (22.3-38.0) and 34.1 (24.6-42.7)] microgram per milliliter concentrations were significantly lower in diabetic than non-diabetic TB patients (p < 0.001 for both drugs). Blood glucose was negatively correlated with plasma INH (r = -0.09, p < 0.001) and PZA (r = -0.092, p < 0.001). Multiple linear regression analysis showed RMP, INH and PZA concentrations were influenced by age and drug doses, INH and PZA by DM, RMP by alcohol use and PZA by gender and category of ATT. DM reduced INH and PZA concentrations by 0.8 and 3.0 μg/ml, respectively.. TB patients with DM had lower INH and PZA concentrations. Negative correlation between blood glucose and drug concentrations suggests delayed absorption/faster elimination of INH and PZA in the presence of elevated glucose.

Topics: Adult; Antitubercular Agents; Diabetes Mellitus; Female; Humans; Isoniazid; Male; Middle Aged; Pyrazinamide; Rifampin; Tuberculosis

The advent of antibiotic-coated devices has reduced the rate of inflatable penile prosthesis (IPP) infections; however, this may have altered microbial profiles when infections do occur.. To describe the timing and causative organisms behind infection of infection retardant-coated IPPs in the context of our institution's perioperative antimicrobial protocols.. We retrospectively reviewed all patients undergoing IPP placement at our institution from January 2014 to January 2022. In all patients, perioperative antibiotic administration was congruent with American Urological Association guidelines. Boston Scientific devices are impregnated with InhibiZone (rifampin and minocycline), and all Coloplast devices were soaked in rifampin and gentamicin. Intraoperative irrigation was performed with betadine 5% irrigation prior to November 2016 and with vancomycin-gentamicin solution afterward. Cases involving prosthesis infection were identified, and variables were extracted from the medical record. Descriptive and comparative statistics were tabulated to identify clinical characteristics, including patient comorbidities, prophylaxis regimen, symptom onset, and intraoperative culture result. We previously reported an increased infection risk with Betadine irrigation and stratified results accordingly.. The primary outcome was time to infectious symptoms, while the secondary outcome was description of device cultures at the time of explantation.. A total of 1071 patients underwent IPP placement over 8 years with an overall infection rate of 2.6% (28/1071). After discontinuation of Betadine, the overall infection rate was significantly lower at 0.9% (8/919) with a relative risk of 16.9 with Betadine (P < .0001). Primary procedures represented 46.4% (13/28). Of 28 patients with infection, only 1 had no identified risk factors; the remainder included Betadine at 71% (20/28), revision/salvage procedure at 53.6% (15/28), and diabetes at 50% (14/28). Median time to symptoms was 36 days (IQR, 26-52); almost 30% of patients had systemic symptoms. Organisms with high virulence, or ability to cause disease, were found in 90.5% (19/21) of positive cultures.. Our study revealed a median time to symptoms of just over 1 month. Risk factors for infection were Betadine 5% irrigation, diabetes, and revision/salvage cases. Over 90% causative organisms were virulent, demonstrating a microbial profile trend since antibiotic coating development.. The large prospectively maintained database is a strength along with the ability to follow specific changes in perioperative protocols. The retrospective nature of the study is a limitation as well as the low infection rate, which limits certain subanalyses from being performed.. IPP infections present in a delayed manner despite the rising virulence of infecting organisms. These findings highlight areas for improvement in perioperative protocols in the contemporary prosthetics era.

Topics: Anti-Bacterial Agents; Diabetes Mellitus; Gentamicins; Humans; Male; Penile Diseases; Penile Implantation; Penile Prosthesis; Povidone-Iodine; Retrospective Studies; Rifampin

Topics: Clindamycin; Diabetes Mellitus; Diabetic Foot; Drug Monitoring; Humans; Osteomyelitis; Rifampin

Esaxerenone is a novel, non-steroidal mineralocorticoid receptor (MR) blocker with improved selectivity and affinity for MR. The objectives of this study were to model the population pharmacokinetics of esaxerenone in a diverse population and to evaluate the effect of covariates on pharmacokinetics parameters.. A total of 8263 plasma esaxerenone concentrations from 166 healthy volunteers, 1097 hypertensive patients and 360 patients with diabetic nephropathy were pooled. A three-compartment model with sequential zero- and first-order absorption was used to describe the time-courses of plasma esaxerenone following single and multiple doses once daily for up to 12 weeks. Covariate effects were estimated using the full covariate modeling approach. Clinical relevance of covariates was ascertained using tornado plots.. Esaxerenone was estimated to have high bioavailability (85.3%), low clearance (3.28 L/h) and relatively large distribution volume at steady state (94.8 L). Body weight (-26 to +36%) and coadministration of itraconazole (+64%) or rifampicin (-68%) were associated with a greater influence on esaxerenone exposure.. The most influential covariates on esaxerenone exposure were coadministrations of itraconazole and rifampicin, followed by body weight. The clinical relevance of effects of renal impairment, mild to moderate hepatic impairment, and age is limited.

Topics: Body Weight; Diabetes Mellitus; Diabetic Nephropathies; Essential Hypertension; Healthy Volunteers; Humans; Itraconazole; Receptors, Mineralocorticoid; Rifampin

Topics: Agar; Anti-Bacterial Agents; Bacteria; Calcium Sulfate; Diabetes Mellitus; Diabetic Foot; Floxacillin; Gentamicins; Humans; Microbial Sensitivity Tests; Rifampin; Vancomycin

To investigate the epidemiology of S. aureus and MRSA nasal carriage among people with diabetes at the Korle Bu Teaching Hospital in Accra, including the prevalence, predictors of carriage, and antibiotic resistance.. This study was cross-sectional, involving 300 diabetes patients and 106 non-diabetic individuals. Swab specimens of the nares were obtained from the participants and bacteriologically-cultured. Identification and characterization of S. aureus and MRSA were based on standard bacteriological methods; antimicrobial susceptibility testing was by the Kirby-Bauer method.. The prevalence of staphylococcal carriage, the diabetes group relative to the non-diabetes group, were 31.0% and 10.4% (S. aureus), and 3.3% and 0.0% (MRSA). Presence of diabetes predisposed to S. aureus carriage, but not MRSA nor coagulase-negative staphylococci (CoNS) carriage (OR = 3.88; p < 0.0001). Colonization with CoNS was protective of S. aureus (OR = 0.039, p < 0.001) and MRSA (OR = 0.115, p = 0.043) colonization among the diabetics. The antimicrobial resistance patterns recorded among the S. aureus isolated from the diabetic individuals relative to the non-diabetics were as follows: penicillin (95% vs. 91%), tetracycline (37% vs. 27%), cotrimoxazole (30% vs. 36%), erythromycin (17% vs. 0%), norfloxacin (13% vs. 0%), clindamycin (12% vs. 0%), gentamicin (9% vs. 0%), fusidic acid (10% vs. 9%), linezolid (4% vs. 0%), and rifampicin (5% vs. 0%). The proportion of multidrug resistant S. aureus was 41% (n = 38) in the diabetes group and 0% in the non-diabetes group; this difference was statistically significant (p = 0.01).. The presence of diabetes predisposed the participants to S. aureus carriage by almost four folds, but not MRSA carriage. Colonization with CoNS was protective of S. aureus and MRSA carriage in the diabetes group. Finally, linezolid remains a good therapeutic agent for anti-MRSA therapy.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Carrier State; Clindamycin; Cross-Sectional Studies; Diabetes Complications; Diabetes Mellitus; Drug Resistance, Multiple, Bacterial; Erythromycin; Female; Fusidic Acid; Gentamicins; Humans; Linezolid; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Middle Aged; Nasal Cavity; Norfloxacin; Penicillins; Rifampin; Staphylococcal Infections; Tetracycline; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Antitubercular Agents; Diabetes Mellitus; Humans; Isoniazid; Patients; Plasma; Rifampin; Tuberculosis

Diabetes mellitus (DM) is associated with poor TB treatment outcome. Previous studies examining the effect of DM on TB drug concentrations yielded conflicting results. No studies have been conducted to date in an African population.. To compare exposure to TB drugs in Tanzanian TB patients with and without DM.. A prospective pharmacokinetic study was performed among 20 diabetic and 20 non-diabetic Tanzanian TB patients during the intensive phase of TB treatment. Plasma pharmacokinetic parameters of isoniazid, rifampicin, pyrazinamide and ethambutol were compared using an independent-sample t-test on log-transformed data. Multiple linear regression analysis was performed to assess the effects of DM, gender, age, weight, HIV status and acetylator status on exposure to TB drugs.. A trend was shown for 25% lower total exposure (AUC0-24) to rifampicin among diabetics versus non-diabetics (29.9 versus 39.9 mg·h/L, P=0.052). The AUC0-24 and peak concentration (Cmax) of isoniazid were also lower in diabetic TB patients (5.4 versus 10.6 mg·h/L, P=0.015 and 1.6 versus 2.8 mg/L, P=0.013). Pyrazinamide AUC0-24 and Cmax values were non-significantly lower among diabetics (P=0.08 and 0.09). In multivariate analyses, DM remained an independent predictor of exposure to isoniazid and rifampicin, next to acetylator status for isoniazid.. There is a need for individualized dosing of isoniazid and rifampicin based on plasma concentration measurements (therapeutic drug monitoring) and for clinical trials on higher doses of these TB drugs in patients with TB and DM.

Topics: Adult; Aged; Aged, 80 and over; Antitubercular Agents; Diabetes Complications; Diabetes Mellitus; Female; Humans; Isoniazid; Male; Middle Aged; Plasma; Prospective Studies; Pyrazinamide; Rifampin; Tanzania; Treatment Outcome; Tuberculosis, Pulmonary; Young Adult

Diabetes mellitus (DM) and tuberculosis (TB) are two common diseases with increasing geographic overlap and clinical interactions. The effect of DM and hemoglobin A1c (HbA1c) values on the pharmacokinetics (PK) and pharmacodynamics (PD) of anti-TB drugs remains poorly characterized. Newly diagnosed TB patients with and without DM starting fixed-dose, thrice-weekly treatment underwent sampling for PK assessments (predose and 0.5, 2, and 6 h postdose) during the intensive and continuation phases of treatment. The effect of DM and HbA1c values on the maximum concentration (

Topics: Adult; Antitubercular Agents; Diabetes Mellitus; Female; Glycated Hemoglobin; Humans; Isoniazid; Male; Middle Aged; Pyrazinamide; Rifampin; Sputum; Tuberculosis, Pulmonary; Young Adult

The objectives of this study were to determine the impact of diabetes mellitus (DM) on antituberculosis drug resistance in new cases of tuberculosis (TB). A case-control study was conducted on all newly diagnosed pulmonary TB adult patients with DM as cases and without DM as controls who were hospitalised from May 2013 to October 2013 in Iran. A molecular resistance test for rapid detection of resistance to isoniazid and rifampicin was done. Multivariate analysis was performed to determine the impact of DM on any anti-TB drug resistance. In total, 62 TB cases with DM and 64 TB cases without DM were included. TB cases with DM were more likely to be older (59 years vs. 43 years; P=0.001). Two TB-DM patients had multidrug-resistant TB (MDR-TB) (3.2%) compared with no cases of MDR-TB in the control group, and more TB-DM cases had isolates that were resistant to at least one drug (12.9% vs. 10.9%). DM [odds ratio (OR)=4.82, 95% confidence interval (CI) 1-23.57], age <40 years (OR=5.48, 95% CI 1.19-25.29) and history of TB contact (OR=5.86, 95% CI 1.69-20.36) remained significantly associated with any drug resistance in the multivariate analysis. In conclusion, new TB patients with DM are at increased risk of anti-TB drug resistance. More studies are needed to confirm these results.

Topics: Adult; Aged; Case-Control Studies; Diabetes Mellitus; Drug Resistance, Bacterial; Female; Humans; Iran; Isoniazid; Male; Middle Aged; Rifampin; Tuberculosis

Multidrug resistant tuberculosis (MDR-TB) poses problems in treatment, costs and treatment outcomes. It is not known if classically described risk factors for MDR-TB in other countries are the same in Mexico and the frequency of the association between diabetes mellitus (DM) and MDR-TB in our country is not clear. We undertook this study to analyze risk factors associated with the development of MDR-TB, with emphasis on DM.. A case-control study in the state of San Luis Potosi (SLP), Mexico was carried out. All pulmonary MDR-TB patients diagnosed in the state of SLP between 1998 and 2013 (36 cases) evaluated at a state pharmacoresistant tuberculosis (TB) clinic and committee; 139 controls were randomly selected from all pulmonary non-multidrug-resistant tuberculosis (non-MDR-TB) cases identified between 2003 and 2008. Cases and controls were diagnosed and treated under programmatic conditions.. Age, gender, malnutrition, being a health-care worker, HIV/AIDS status, and drug abuse were not significantly different between MDR-TB and non-MDR-TB patients. Significant differences between MDR-TB and non-MDR-TB patients were DM (47.2 vs. 28.1%; p = 0.028); previous anti-TB treatments (3 vs. 0, respectively; p <0.001), and duration of first anti-TB treatment (8 vs. 6 months, respectively; p <0.001).. MDR-TB and DM are associated in 47.2% of MDR TB cases (17/36) in this study. Other recognized factors were not found to be significantly different in MDR-TB compared to non-MDR-TB in this study. Cost-feasible strategies must be implemented in the treatment of DM-TB in order to prevent the selection of MDR-TB.

Topics: Adult; Ambulatory Care Facilities; Antibiotics, Antitubercular; Bacterial Typing Techniques; Case-Control Studies; Diabetes Complications; Diabetes Mellitus; Drug Resistance, Multiple, Bacterial; Female; Health Care Costs; Health Personnel; Humans; Isoniazid; Male; Mexico; Microbial Sensitivity Tests; Middle Aged; Mycobacterium tuberculosis; Rifampin; Risk Factors; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary

Despite increasing reports of the linkage between diabetes and tuberculosis (TB), there is limited information regarding diabetes and TB drug resistance.. In this cross-sectional study, sputum and blood samples were collected from 304 adult patients in rural Andhra Pradesh. Rifampin resistance was assessed by Xpert MTB/RIF (Xpert), and diabetes status was based on self-report. Additionally, samples were assayed by acid-fast bacilli sputum smear microscopy (AFB) and QuantiFERON-TB Gold In-Tube (QFT-G), in order to compare relative diagnostic performances.. Among patients with confirmed TB (n = 194), diabetes was associated with 3.0-fold higher risk of rifampin resistance (95 % CI 1.3-6.7). Considering Xpert MTB/RIF the gold standard, AFB had lower sensitivity (72.2 vs. 82.5 %) and higher specificity (96.4 vs. 37.0 %) compared to QFT-G for diagnosing TB.. The increased risk of rifampin resistance in patients with diabetes highlights the need for integrated diabetes surveillance in TB programs, particularly in settings undergoing the epidemiological transition.

Topics: Adult; Cross-Sectional Studies; Diabetes Mellitus; Female; Humans; India; Male; Mycobacterium tuberculosis; Rifampin; Rural Population; Sensitivity and Specificity; Sputum; Tuberculosis; Tuberculosis, Multidrug-Resistant

Poor response to tuberculosis (TB) therapy might be attributable to subtherapeutic levels in drug-compliant patients. Pharmacokinetic (PK) parameters can be affected by several factors, such as comorbidities or the interaction of TB drugs with food. This study aimed to determine the PK of isoniazid (INH) in a Peruvian TB population under observed daily and twice-weekly (i.e., biweekly) therapy. Isoniazid levels were analyzed at 2 and 6 h after drug intake using liquid chromatography mass spectrometric methods. A total of 107 recruited patients had available PK data; of these 107 patients, 42.1% received biweekly isoniazid. The mean biweekly dose (12.8 mg/kg of body weight/day) was significantly lower than the nominal dose of 15 mg/kg/day (P < 0.001), and this effect was particularly marked in patients with concurrent diabetes and in males. The median maximum plasma concentration (Cmax) and area under the concentration-time curve from 0 to 6 h (AUC0-6) were 2.77 mg/liter and 9.71 mg · h/liter, respectively, for daily administration and 8.74 mg/liter and 37.8 mg · h/liter, respectively, for biweekly administration. There were no differences in the Cmax with respect to gender, diabetes mellitus (DM) status, or HIV status. Food was weakly associated with lower levels of isoniazid during the continuation phase. Overall, 34% of patients during the intensive phase and 33.3% during the continuation phase did not reach the Cmax reference value. However, low levels of INH were not associated with poorer clinical outcomes. In our population, INH exposure was affected by weight-adjusted dose and by food, but comorbidities did not indicate any effect on PK. We were unable to demonstrate a clear relationship between the Cmax and treatment outcome in this data set. Twice-weekly weight-adjusted dosing of INH appears to be quite robust with respect to important potentially influential patient factors under program conditions.

Topics: Adolescent; Adult; Anti-HIV Agents; Antitubercular Agents; Area Under Curve; Comorbidity; Diabetes Mellitus; Dietary Fats; Drug Administration Schedule; Female; Food-Drug Interactions; HIV Infections; Humans; Hypoglycemic Agents; Isoniazid; Male; Middle Aged; Peru; Rifampin; Sex Factors; Treatment Outcome; Tuberculosis, Pulmonary

Drug resistance substantially increases tuberculosis (TB) mortality. This study aimed to describe the prevalence of mycobacterial drug resistance pattern and association of common resistance patterns with TB mortality in Thailand.. A retrospective cohort study was conducted using TB surveillance data. A total of 9,518 culture-confirmed, pulmonary TB patients registered from 1 October 2004 to 31 December 2008 from the Thailand TB Active Surveillance Network were included in this study. Patients were followed up until TB treatment completion or death. Mycobacterial drug resistance patterns were categorized as pan-susceptible, rifampicin resistance, isoniazid monoresistance, and ethambutol/streptomycin resistance. Drug susceptibility testing (DST) was determined by Mycobacterial Growth Indicator Tube (MGIT) liquid culture systems. Survival analysis was applied.. Isoniazid monoresistance was the most common pattern, while rifampicin resistance had the largest impact on mortality. Cox regression analysis showed a significantly higher risk of death among patients with rifampicin resistance (adjusted hazard ratio (aHR) 1.9, 95% confident interval (CI), 1.5-2.5) and isoniazid monoresistance (aHR 1.4, 95% CI 1.1-1.7) than those with pan-susceptible group after adjustment for age, nationality, human immunodeficiency virus (HIV) and antiretroviral therapy (ART) status, diabetes mellitus, cavitary disease on chest x-ray, treatment observation, and province. HIV co-infection was associated with higher mortality in patients both on ART (aHR 1.9, 95% CI 1.5-2.5) and not on ART (aHR 8.1, 95% CI 6.8-9.8).. Rifampicin resistance and isoniazid monoresistance were associated with increased TB mortality. HIV-coinfection was associated with a higher risk of death including among those taking antiretroviral therapy.

Topics: Adolescent; Adult; Aged; Anti-Retroviral Agents; Antitubercular Agents; Child; Child, Preschool; Diabetes Mellitus; Female; HIV Infections; Humans; Infant; Isoniazid; Male; Middle Aged; Retrospective Studies; Rifampin; Thailand; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary; Young Adult

As the global prevalence of diabetes mellitus (DM) increases, especially in low-to-middle income countries where tuberculosis (TB) remains endemic, we will encounter a growing number of TB patients with DM. This is a major concern for TB control programs, clinicians and patients alike because DM patients are at an increased risk of TB and are more likely to face poor TB treatment outcomes, including treatment failure, relapse and even death. Priority should be placed on early detection of both diseases through active screening, monitoring of adherence to medications for both diseases, and integration of TB and DM management strategies that would facilitate the provision of more comprehensive services that TB patients with DM require.

Topics: Antitubercular Agents; Diabetes Complications; Diabetes Mellitus; Disease Management; Humans; Mycobacterium tuberculosis; Patient Compliance; Recurrence; Rifampin; Risk Factors; Treatment Failure; Tuberculosis

The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor pravastatin has been reported to have a beneficial effect on reducing the new onset of diabetes as well as lowering plasma lipids. Because pravastatin is a water-soluble organic anion, it cannot easily penetrate the lipid bilayer of the cell membrane. As the precise mechanisms of the effect of pravastatin on glucose metabolism and diabetes have not been clarified, we examined the roles of the organic anion transporter family on pravastatin-treated islet and adipocyte functions. Rat oatp1/slco1a1, oatp2/slco1a4 and oatp3/slco1a5 were expressed in the pancreas, and rat oatp3/slco1a5 was also detected in rat insulinoma cell line INS-1e. Pravastatin was transported not only by oatp1/slco1a1 and oatp2/slco1a4, but also by rat oatp3/slco1a5. Pravastatin uptake into INS-1e cells was detected and this transport was inhibited by sulfobromophthalein and rifampicin, both of which are known to inhibit oatp family-mediated uptake. In addition, pravastatin enhanced the glucose-stimulated insulin secretion from INS-1e cells. When fat-loaded db/db mice were treated with pravastatin, glucose intolerance and insulin resistance were prevented. In addition, insulin secretion from isolated islets was enhanced by pravastatin. These data suggest that pravastatin has pleiotropic effects on islets through membrane transport under high fat/glucose conditions.

Topics: Adiponectin; Animals; Biological Transport; Cell Line, Tumor; Diabetes Mellitus; Hydroxymethylglutaryl CoA Reductases; Immunohistochemistry; Insulin; Insulin Secretion; Islets of Langerhans; Male; Mice; Mice, Inbred Strains; Models, Animal; Organic Anion Transporters, Sodium-Independent; Pancreas; Pravastatin; Rats; Rifampin; Sulfobromophthalein

Incidence of tuberculosis worldwide will increase progressively unless the effective program is implemented immediately. In Japan, the decreasing of tuberculosis incidence has been very slow since 1977 and this trend has not been improved till now. Six-month regimens for the treatment of tuberculosis were recommended by IUATLD, ATS, CDC, and WHO and have been adopted in most developed countries since late 1980s, but not adopted in Japan till April, 1996. We studied effectiveness of 6-month regimen including pyrazinamide (2HRZS or E/4HRE) on newly diagnosed pulmonary tuberculosis who started the treatment in the Fukujuji Hospital, Japan Anti-Tuberculosis Association (JATA). From January 1991 to December 1997, 726 newly diagnosed pulmonary tuberculosis patients started treatment with 6-month regimen. Bacillary negative conversion rate among 424 patients whose bacilli were susceptible to both isoniazid and rifampicin, was 92.9% after 2 months of treatment and who completed treatment without change of treatment regimen. Among 726 cases, 593 (81.7%) succeeded, 48 (6.6%) defaulted, 53 (7.3%) were referred to other doctors, and 32 (4.4%) died. The relapse rate after completion of the treatment was 3.2 percent among 345 patients whose bacilli were susceptible to both isoniazid and rifampicin and who completed the treatment without change of regimen. The relapse rate among the patients complicated with diabetes mellitus (DM) was higher than that among non-DM patients (6.31/100 person-years vs 0.90/100 person-years) (P < 0.001). When drug-induced hepatitis was defined as the elevation of serum liver enzyme levels with the clinical symptoms of hepatitis or their elevation over 5 times of normal upper limit, the incidence of drug-induced hepatitis among the patients treated with pyrazinamide-containing 6-month regimen was not higher than that among the patients treated with 9-month regimen without pyrazinamide (6HRS or E/3HR) (7.9% vs 7.3%). The risk factors for drug-induced hepatitis included elderly, history of gastrectomy, hypoalbuminemia, the higher dose of isoniazid over than 7.5 mg/kg, higher than 30 mg/kg of pyrazinamide and positive HCV antibody. The effectiveness of 6-month regimen on the patients whose organisms were resistant to isoniazid and susceptible to rifampicin was studied. The average duration of the treatment for the patients started 6-month regimen was 3.2 months shorter than for the patients started 9-month regimen (10.2 months vs 13.4 months).

Topics: Adult; Aged; Aged, 80 and over; Antitubercular Agents; Chemical and Drug Induced Liver Injury; Diabetes Mellitus; Drug Therapy, Combination; Female; Humans; Isoniazid; Male; Middle Aged; Pyrazinamide; Recurrence; Rifampin; Risk Factors; Time Factors; Tuberculosis, Pulmonary

A 62-year-old man who had been taking 250 mg of chlorpropamide daily for several years received rifampin concomitantly and had a subsequent increased dosing requirement of chlorpropamide. When rifampin was discontinued several months later, the serum chlorpropamide concentration rose dramatically.

Topics: Blood Glucose; Chlorpropamide; Diabetes Mellitus; Drug Interactions; Humans; Male; Middle Aged; Rifampin

Topics: Diabetes Mellitus; Humans; Male; Middle Aged; Rifampin

Topics: Aged; Alcoholism; Bronchial Neoplasms; Chronic Disease; Diabetes Mellitus; Eczema; Evaluation Studies as Topic; Humans; Male; Middle Aged; Radiography; Rifampin; Tuberculosis, Pulmonary