rifampin and Renal-Insufficiency

Rifampin has been studied as prophylaxis against Staphylococcus aureus-related infections in patients on dialysis.. We performed a meta-analysis of randomized controlled trials (RCTs) that compared the effectiveness and safety of oral rifampin with another regimen or no therapy in reducing S. aureus-related infections in dialysis patients.. Four RCTs evaluated oral rifampin (administered for 5 days every 3 months, or for 5 days once) as prophylaxis in dialysis patients. Oral rifampin with or without bacitracin was associated with less access-site infections with S. aureus compared with no treatment (odds ratio = 0.16, 95% confidence intervals: 0.06-0.44, 3 RCTs). There was no difference between prophylaxis with oral rifampin and topical mupirocin applied at the catheter site, for all studied outcomes, in the RCT comparing these regimens. Withdrawal from the study due to drug-related toxicity occurred in 7/107 (6.6%) of the studied patients with renal failure. Development of resistance of S. aureus to rifampin ranged from 0 to 18.2% (reported in three out of four included RCTs).. Prophylactic use of oral rifampin reduces access-site infections with S. aureus in patients with renal failure undergoing dialysis. However, development of toxicity and antimicrobial resistance during the treatment with rifampin occur in considerable proportions of patients, limiting its use and supporting the guidelines that recommend the use of local antibiotics at the exit site, such as mupirocin, for these indications. The available data are rather limited and more studies should be performed to examine this important clinical question.

Topics: Administration, Oral; Antibiotics, Antitubercular; Humans; Randomized Controlled Trials as Topic; Renal Dialysis; Renal Insufficiency; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome

Repaglinide is a novel, fast-acting prandial oral hypoglycaemic agent developed for the treatment of patients with type 2 diabetes whose disease cannot be controlled by diet and exercise alone. Although repaglinide binds to the sulphonylurea binding sites on pancreatic beta-cells and has a similar mechanism of action, repaglinide exhibits distinct pharmacological properties compared with these agents. Following administration, repaglinide is absorbed rapidly and has a fast onset of dose-dependent blood-glucose lowering effect. The drug is eliminated rapidly via the biliary route, without accumulation in the plasma after multiple doses. Repaglinide is well tolerated in patients with type 2 diabetes, including elderly patients and patients with hepatic or renal impairment. The pharmacokinetic profile of repaglinide and the improvements in post-prandial hyperglycaemia and overall glycaemic control make repaglinide suitable for administration preprandially, with the opportunity for flexible meal arrangements, including skipped meals, without the risk of hypoglycaemia.

Topics: Adult; Aged; Blood Glucose; Carbamates; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Interactions; Female; Humans; Hypoglycemic Agents; Liver Diseases; Male; Piperidines; Renal Insufficiency; Rifampin

This analysis reports a quantitative modeling and simulation approach for oral dapagliflozin, a primarily uridine diphosphate-glucuronosyltransferase (UGT)-metabolized human sodium-glucose cotransporter 2 selective inhibitor. A mechanistic dapagliflozin physiologically based pharmacokinetic (PBPK) model was developed using in vitro metabolism and clinical pharmacokinetic (PK) data and verified for context of use (e.g., exposure predictions in pediatric subjects aged 1 month to 18 years). Dapagliflozin exposure is challenging to predict in pediatric populations owing to differences in UGT1A9 ontogeny maturation and paucity of clinical PK data in younger age groups. Based on the exposure-response relationship of dapagliflozin, twofold acceptance criteria were applied between model-predicted and observed drug exposures and PK parameters (area under the curve and maximum drug concentration) in various scenarios, including monotherapy in healthy adults (single/multiple dose), monotherapy in hepatically or renally impaired patients, and drug-drug interactions with UGT1A9 modulators, such as mefenamic acid and rifampin. The PBPK model captured the observed exposure within twofold of the observed monotherapy data in adults and adolescents and in special population. As a guide to determining dosing regimens in pediatric studies, the verified PBPK model, along with UGT enzyme ontogeny maturation understanding, was used for predictions of dapagliflozin monotherapy exposures in pediatric subjects aged 1 month to 18 years that best matched exposure in adult patients with a 10-mg single dose of dapagliflozin.

Topics: Administration, Oral; Adolescent; Antibiotics, Antitubercular; Area Under Curve; Benzhydryl Compounds; Child; Child, Preschool; Computer Simulation; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Drug Interactions; Female; Glucosides; Glucuronosyltransferase; Healthy Volunteers; Hepatic Insufficiency; Humans; Infant; Infant, Newborn; Male; Mefenamic Acid; Models, Biological; Predictive Value of Tests; Renal Insufficiency; Rifampin; Sodium-Glucose Transporter 2 Inhibitors; UDP-Glucuronosyltransferase 1A9

A combination of olanzapine and samidorphan was recently approved by the US Food and Drug Administration for the treatment of patients with schizophrenia or bipolar I disorder. Population pharmacokinetic models for olanzapine and samidorphan were developed using data from 11 clinical studies in healthy subjects or patients with schizophrenia. A 2-compartment disposition model with first-order absorption and elimination and a lag time for absorption adequately described concentration-time profiles of both olanzapine and samidorphan. Age, sex, race, smoking status, and body weight were identified as covariates that impacted the pharmacokinetics of olanzapine. A moderate effect of body weight on samidorphan pharmacokinetics was identified by the model but was not considered clinically meaningful. The effects of food, hepatic or renal impairment, and coadministration with rifampin on the pharmacokinetics of olanzapine and samidorphan, as estimated by the population pharmacokinetic analysis, were consistent with findings from dedicated clinical studies designed to evaluate these specific covariates of interest. Food intake did not have a clinically relevant effect on the pharmacokinetics of olanzapine or samidorphan. Consistent with the known metabolic pathways for olanzapine (primarily via uridine 5'-diphospho-glucuronosyltransferase-mediated direct glucuronidation and cytochrome P450 [CYP]-mediated oxidation) and for samidorphan (predominantly mediated by CYP3A4), coadministration of olanzapine and samidorphan with rifampin, a strong inducer of CYP3A4 and an inducer of uridine 5'-diphospho-glucuronosyltransferase enzymes, significantly decreased the systemic exposure of both olanzapine and samidorphan. Severe renal impairment or moderate hepatic impairment resulted in a modest increase in olanzapine and samidorphan exposure.

Topics: Adolescent; Adult; Age Factors; Aged; Antipsychotic Agents; Body Weight; Cigarette Smoking; Cytochrome P-450 CYP3A; Drug Combinations; Female; Food-Drug Interactions; Humans; Liver Failure; Male; Middle Aged; Naltrexone; Narcotic Antagonists; Olanzapine; Racial Groups; Renal Insufficiency; Rifampin; Schizophrenia; Sex Factors; Young Adult

To analyze the influence of adding gentamicin to a regimen consisting of β-lactam or vancomycin plus rifampicin on survival in patients suffering from Staphylococcal prosthetic valve endocarditis (SPVE).. From January 2008 to September 2016, 334 patients with definite SPVE were attended in the participating hospitals. Ninety-four patients (28.1%) received treatment based on β-lactam or vancomycin plus rifampicin and were included in the study. Variables were analyzed which related to patient survival during admission, including having received treatment with gentamicin.. Seventy-seven (81.9%) were treated with cloxacillin (or vancomycin) plus rifampicin plus gentamicin, and 17 patients (18.1%) received the same regimen without gentamicin. The causative microorganism was Staphylococcus aureus in 40 cases (42.6%) and coagulase-negative staphylococci in 54 cases (57.4%). Overall, 40 patients (42.6%) died during hospital admission, 33 patients (42.9%) in the group receiving gentamicin and 7 patients in the group that did not (41.2%, P = 0.899). Worsening renal function was observed in 42 patients (54.5%) who received gentamicin and in 9 patients (52.9%) who did not (p = 0.904). Heart failure as a complication of endocarditis (OR: 4.58; CI 95%: 1.84-11.42) and not performing surgery when indicated (OR: 2.68; CI 95%: 1.03-6.94) increased mortality. Gentamicin administration remained unrelated to mortality (OR: 1.001; CI 95%: 0.29-3.38) in the multivariable analysis.. The addition of gentamicin to a regimen containing vancomycin or cloxacillin plus rifampicin in SPVE was not associated to better outcome.

Topics: Aged; Anti-Bacterial Agents; Cloxacillin; Endocarditis, Bacterial; Female; Gentamicins; Heart Failure; Heart Valve Prosthesis; Humans; Male; Middle Aged; Multivariate Analysis; Prospective Studies; Prosthesis-Related Infections; Renal Insufficiency; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Vancomycin

Infections with carbapenem-resistant Gram-negative bacteria (CRGNB) are increasing and are associated with a high mortality. Synergistic effects of combination therapy with a polymyxin, carbapenem, and rifampin have been observed in in vitro studies. Clinical data are limited to retrospective studies.. We performed an observational cohort study of patients over 18 y of age who were treated with polymyxin B combination therapy.. One hundred and four patients were studied. The mean age was 77 y; 73% had recently received antibiotics, 67% had recently been hospitalized, and 47% lived in a nursing facility. The most common infections were pneumonia and urinary tract infection due to Acinetobacter baumannii (33%), Klebsiella pneumoniae (24%), and Pseudomonas aeruginosa (11%). Treatment regimens included polymyxin B with a carbapenem in 48%, with additional rifampin in 23%. Clinical success was achieved in 50% and reinfection occurred in 25%. Treatment-related acute renal failure occurred in 14.4%. No treatment-related hemodialysis was needed. All-cause hospital mortality was 47% and mortality after 6 months was 77%. No significant difference was found between treatment regimens. Age (odds ratio (OR) 10.4 per 10 y, p = 0.04), severity of acute illness (OR 2.2 per point, p < 0.001), and Charlson score (OR 1.12 per point, p = 0.04) were associated with hospital mortality. K. pneumoniae was associated with increased hospital survival compared to other CRGNB (p = 0.03).. CRGNB infections are associated with previous antibiotic and health care exposure. Mortality is related to age and the severity of chronic and acute illness.

Topics: Age Factors; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactam Resistance; Carbapenems; Cohort Studies; Drug Therapy, Combination; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Male; Middle Aged; Polymyxin B; Prospective Studies; Renal Insufficiency; Rifampin; Survival Analysis; Treatment Outcome

Vancomycin is the drug of choice in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infection. However, the presence of certain clinical complications like renal failure alters vancomycin pharmacokinetics, leading to drug accumulation and toxicity. This highlights the need to identify an effective substitute for treating MRSA infections when vancomycin cannot be used. We report the case of a 57-y-old Indian male diagnosed with tricuspid valve endocarditis with septicaemia and a right upper lobe cavity caused by MRSA. The patient also presented with renal failure, which precluded the use of vancomycin for treatment. A 6-week regimen of teicoplanin and rifampicin was used instead, and the infection was successfully treated. This case report provides evidence of the effectiveness of teicoplanin and rifampicin in the treatment of MRSA bacteraemia in situations where the use of vancomycin is contraindicated.

Topics: Anti-Bacterial Agents; Drug Therapy, Combination; Endocarditis, Bacterial; Humans; India; Male; Methicillin-Resistant Staphylococcus aureus; Middle Aged; Renal Insufficiency; Rifampin; Sepsis; Staphylococcal Infections; Teicoplanin; Treatment Outcome

A 79-year-old man was admitted to a previous hospital complaining of left precordial swelling. Chest CT scan showed destruction of left sternoclavicular joint and a mass of 5 cm in diameter. Needle biopsy was performed and the diagnosis of sternoclavicular joint tuberculosis was made on the basis of presence of M. tuberculosis in the specimen. The patient was treated with isoniazid, ethambutol, rifampicin, and pyrazinamid but he developed renal failure. Then, he was transferred to our hospital. All medications were suspended because of the possibility of the side effect of drugs. We performed renal biopsy and histopathological examination revealed interstitial nephritis and minimal-change glomerulonephritis. From the result of examination, we considered interstitial nephritis was due to rifamicin. The treatment with 50 mg/day of prednisolone and isoniazid, ethambutol, and levofloxacin was administrated and renal failure and precordial mass were improved. Tuberculous arthritis usually affect hip and knee joint and sternoclavicular joint involvement is very rare.

Topics: Aged; Humans; Male; Renal Insufficiency; Rifampin; Sternoclavicular Joint; Tuberculosis, Osteoarticular

Cryoglobulinemia has been described in infectious diseases, but in only three patients with brucellosis. We report a 59-year-old male with Brucella peritonitis with cutaneous vasculitis and renal failure that could be related to mixed cryoglobulinemia. As in cryoglobulinemia associated with other infections, resolution of the disease was obtained with specific antimicrobial therapy.

Topics: Anti-Bacterial Agents; Ascitic Fluid; Brucella melitensis; Brucellosis; Cryoglobulinemia; Doxycycline; Humans; Male; Middle Aged; Ofloxacin; Peritonitis; Renal Insufficiency; Rifampin; Vasculitis, Leukocytoclastic, Cutaneous