rifampin and Critical-Illness

Extensively drug-resistant (XDR) Acinetobacter baumannii may cause serious infections in critically ill patients. Colistin often remains the only therapeutic option. Addition of rifampicin to colistin may be synergistic in vitro. In this study, we assessed whether the combination of colistin and rifampicin reduced the mortality of XDR A. baumannii infections compared to colistin alone.. This multicenter, parallel, randomized, open-label clinical trial enrolled 210 patients with life-threatening infections due to XDR A. baumannii from intensive care units of 5 tertiary care hospitals. Patients were randomly allocated (1:1) to either colistin alone, 2 MU every 8 hours intravenously, or colistin (as above), plus rifampicin 600 mg every 12 hours intravenously. The primary end point was overall 30-day mortality. Secondary end points were infection-related death, microbiologic eradication, and hospitalization length.. Death within 30 days from randomization occurred in 90 (43%) subjects, without difference between treatment arms (P = .95). This was confirmed by multivariable analysis (odds ratio, 0.88 [95% confidence interval, .46-1.69], P = .71). A significant increase of microbiologic eradication rate was observed in the colistin plus rifampicin arm (P = .034). No difference was observed for infection-related death and length of hospitalization.. In serious XDR A. baumannii infections, 30-day mortality is not reduced by addition of rifampicin to colistin. These results indicate that, at present, rifampicin should not be routinely combined with colistin in clinical practice. The increased rate of A. baumannii eradication with combination treatment could still imply a clinical benefit.. NCT01577862.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Critical Illness; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Intensive Care Units; Length of Stay; Male; Middle Aged; Rifampin; Survival Analysis; Tertiary Care Centers; Treatment Outcome

To determine the efficacy of minocycline and rifampin-impregnated catheters compared to non-impregnated catheters in critically ill patients.. Prospective, randomized, double-blind, controlled, multicenter trial.. Intensive care units of seven acute-care teaching hospitals in Spain. PATIENTS. Intensive care unit patients requiring triple-lumen central venous catheter for more than 3 days.. At catheter insertion, 228 patients were randomized to minocycline and rifampin-impregnated catheters and 237 to non-impregnated catheters. Skin, catheter tip, subcutaneous segment, hub cultures, peripheral blood and infusate cultures were performed at catheter withdrawal. The rate of colonization, catheter-related bloodstream infection (CRBSI) and catheter-related clinical infectious complications (purulence at the insertion site or CRBSI) were assessed.. In the intention-to-treat analysis (primary analysis), the episodes per 1000 catheter days of clinical infectious complications decreased from 8.6 to 5.7 (RR =0.67, 95% CI 0.31-1.44), CRBSI from 5.9 to 3.1 (RR =0.53, 95% CI 0.2-1.44) and tip colonization from 24 to 10.4 (RR =0.43, 95% CI 0.26-0.73). Antimicrobial-impregnated catheters were associated with a significant decrease of coagulase-negative staphylococci colonization (RR =0.24, 95% CI 0.13-0.45) and a significant increase of Candida spp. colonization (RR =5.84, 95% CI 1.31-26.1).. The use of antimicrobial-impregnated catheters was associated with a significantly lower rate of coagulase-negative staphylococci colonization and a significant increase in Candida spp. colonization, although a decrease in CRBSI, increase in 30-day survival or reduced length of stay was not observed.

Topics: Anti-Bacterial Agents; Bacterial Infections; Blood-Borne Pathogens; Catheterization, Central Venous; Catheters, Indwelling; Critical Illness; Cross Infection; Double-Blind Method; Drug Delivery Systems; Humans; Intensive Care Units; Minocycline; Prospective Studies; Rifampin; Treatment Outcome

Although rifampicin (RIF) is used as a synergistic agent for multidrug-resistant Acinetobacter baumannii (MDR-AB) infection, the optimal pharmacokinetic (PK) indices of this medication have not been studied in the intensive care unit (ICU) settings. This study aimed to evaluate the PK of high dose oral RIF following fasting versus fed conditions in terms of achieving the therapeutic goals in critically ill patients with MDR-AB infections.. 29 critically ill patients were included in this study. Under fasting and non-fasting conditions, RIF was given at 1200 mg once daily through a nasogastric tube. Blood samples were obtained at seven time points: exactly before administration of the drug, and at 1, 2, 4, 8, 12, and 24 h after RIF ingestion. To quantify RIF in serum samples, high-performance liquid chromatography (HPLC) was used. The MONOLIX Software and the Monte Carlo simulations were employed to estimate the PK parameters and describe the population PK model.. In critically ill patients with MDR-AB infections, neither fasting nor non-fasting administrations of high-dose oral RIF achieve the therapeutic aims. More research is needed in larger populations and with measuring the amount of protein-unbound RIF levels.

Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Critical Illness; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Rifampin

Linezolid is a valuable treatment option for treating infections caused by multi-resistant gram-positive pathogens. Lack of effective linezolid levels due to the co-administration of rifampicin has been described in healthy subjects. However, the clinical significance of this potential drug interaction (DI) for critically ill patients is still unclear. This was a retrospective analysis of 3 critically ill patients with the combination therapy of linezolid and rifampicin or rifampicin pre-treatment. Despite increasing the dose of linezolid, the majority of observed linezolid trough concentrations in all 3 patients were below 2 mg/l. Furthermore, linezolid trough concentrations remained below 2 mg/l after discontinuation of rifampicin. This potential DI between linezolid and rifampicin could lead to treatment failure. Therefore, we strongly recommend that linezolid serum concentrations be monitored in patients with rifampicin co-administration or rifampicin pretreatment.

Topics: Aged; Anti-Bacterial Agents; Critical Illness; Drug Interactions; Drug Therapy, Combination; Humans; Linezolid; Methicillin-Resistant Staphylococcus aureus; Rifampin; Staphylococcal Infections

Functional adrenal insufficiency (FAI) is associated with increased mortality and is defined as subnormal cortisol production during acute severe illness.. After screening 200 adult patients admitted in the medical emergency unit of Mulago Hospital, Kampala, Uganda, 113 critically ill HIV-infected adults not receiving corticosteroids were enrolled after obtaining informed consent to determine the prevalence and factors associated with FAI.. Functional adrenal insufficiency, defined in this study as morning total serum cortisol level of 3%) occurred in 52% (11 of 21) patients with FAI compared to 24% (22 of 92) patients with normal adrenal function (p= 0.01). Factors predicting FAI on multivariate analysis were use of rifampicin and eosinophilia. The mortality rate among patients with FAI (19%) was not significantly different when compared to that among patients with a normal cortisol response (33%) (p=0.221). Hyponatremia, hypoglycemia, hyperkalemia, postural hypotension and the use of ketoconazole were not associated with FAI in this study.. The diagnosis of FAI should be considered in severely ill patients with stage IV HIV disease using rifampicin or those found to have unexplained eosinophilia. Further studies to determine benefits of corticosteroids in critically ill HIV patients are needed in this setting.

Topics: Adrenal Cortex Hormones; Adrenal Insufficiency; Critical Illness; Enzyme Inhibitors; Eosinophilia; Female; HIV Infections; Humans; Longitudinal Studies; Male; Prospective Studies; Rifampin; Risk Factors; Uganda

The number of Methicillin-resistant Staphylococcus aureus (MRSA) pneumonia cases is increasing in many European countries. In this observational study in one medical and three surgical ICUs multiple interventions for the treatment and eradication of nosocomial MRSA-pneumonia were used.. Twenty-one critically ill patients (age: 59 +/- 14 years, 15 males/6 females, 18 ventilator-associated, 3 nosocomial, clinical pulmonary infection score > 6 in all patients, APACHE II 18 +/- 5) were enrolled. The patients were treated with a 7-day course of iv linezolid (600 mg bid) plus rifampicin (600 mg bid), endotracheal vancomycin 100 mg qid, thrice daily mouth and throat washing with chlorhexidine 1% fluid and nasal mupirocin ointment, twice daily skin and hair washings with chlorhexidine gluconate 4% and tracheostomy (n = 8) wound care with povidone-iodine spray. Control samples (endotracheal secretions, nose, wound, and pharyngeal swabs) were taken 2, 3, 4, 7 days and 2 months thereafter. Multilobular pneumonia was seen in 16, pleural effusion in 12, and MRSA bacteremia in 4 patients.. One patient died during the follow-up period due to cerebral bleeding. In the remaining 20 patients, pneumonia was clinically cured in all patients and all patients were free of MRSA after eradication. Six patients died due to myocardial infarction (n = 3), gram-negative septic shock (n = 2), herpes encephalitis (n = 1) > 7 days after eradication. No MRSA reinfection occurred during the control period.. We conclude that in patients with MRSA pneumonia an approach using a 7-day course of intravenous linezolid plus rifampicin, intratracheal vancomycin, nasal mupirocin, cutaneous and oropharyngeal chlorhexidin plus povidone-iodine cures pneumonia and is effective for MRSA eradication.

Topics: Acetamides; Aged; Anti-Bacterial Agents; Critical Illness; Cross Infection; Drug Utilization; Female; Humans; Infection Control; Intensive Care Units; Linezolid; Male; Methicillin Resistance; Middle Aged; Oxazolidinones; Pneumonia, Staphylococcal; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome; Vancomycin

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Carbapenems; Colistin; Critical Illness; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Rifampin; Treatment Outcome

A patient with fulminant pulmonary tuberculosis died after 41 days of intensive care despite pansensitive organisms and no known underlying immunosuppression. Two factors leading to death in this patient were a delay in seeking medical attention and a subtherapeutic serum level of rifampin, though no obvious evidence of malabsorption existed. Malabsorption of antitubercular drugs is under-recognized and of extreme importance in the treatment of critically ill patients with active pulmonary tuberculosis. Factors associated with mortality from tuberculosis and selected aspects of critical care management are discussed.

Topics: Absorption; Antibiotics, Antitubercular; Antitubercular Agents; Critical Care; Critical Illness; Fatal Outcome; Female; Humans; Isoniazid; Middle Aged; Mycobacterium tuberculosis; Rifampin; Time Factors; Tuberculosis, Pulmonary

To report the influence of rifampin coadministration on the pharmacokinetics of fluconazole in 2 critically ill patients.. The pharmacokinetics of fluconazole are reported in 5 patients in the intensive care unit (ICU), 2 of whom received rifampin and 3 who received only fluconazole. Patient 1 was a 52 year-old man with bilateral pneumonia who received rifampin for 9 days in addition to other antibiotics when fluconazole was added for suspected fungal superinfection. Patient 2, a 39-year-old man with steroid-dependent asthma was admitted to the ICU with a right middle lobe pneumonia and ventilatory insufficiency. Because of rapid clinical deterioration, intravenous rifampin 600 mg q12h and fluconazole 100 mg q24h were added to conventional antibacterial therapy. Patients 3-5 received intravenous fluconazole therapy, but were never administered rifampin prior to their antifungal therapy.. Fluconazole has gained wide use as an antifungal agent because of its efficacy, limited toxicity, and the paucity of reported drug interactions. In some clinical situations, however, the drug must be coadministered with rifampin. Limited data in healthy volunteers suggest that the coadministration of rifampin and fluconazole results in a 23% reduction in the fluconazole area under the concentration-time curve (AUC). In this report, we found a statistically significant lowering of the AUC (52%) and a 93% higher total body clearance of fluconazole in patients treated with rifampin.. Although limited data are available describing the magnitude of the interaction between fluconazole and rifampin in patients, our data suggest a more significant interaction than previously reported. If the concurrent administration of the 2 drugs in unavoidable, the patient's clinical response to treatment should be monitored closely, as the unexpectedly large reduction in fluconazole serum concentrations may lead to poor treatment outcomes.

Topics: Adult; Anti-Bacterial Agents; Antifungal Agents; Biological Availability; Critical Illness; Drug Interactions; Fluconazole; Humans; Intensive Care Units; Male; Middle Aged; Rifampin