Clinical challenges in a patient with dabigatran-induced fatal hemorrhage.

OBJECTIVE: To report clinical challenges in managing dabigatran-induced bleeding. METHODS: A 78-year-old woman came to the hospital with severe coagulopathy, respiratory failure, hypotension, and bleeding secondary to dabigatran therapy. At admission, creatinine clearance was 15 mL/min; prothrombin time, 147.5 seconds; activated partial thromboplastin time, >200 seconds; and international normalized ratio, 12.42. Medications taken at home included dabigatran, 150 mg BID. During the hospitalization, multiple blood product transfusions were given, vitamin K and prothrombin complex concentrate were administered, and dialysis was initiated in an attempt to achieve hemostasis. Despite multiple interventions, coagulopathy persisted (prothrombin time, 70.8 seconds; activated partial thromboplastin time, >200 seconds; and international normalized ratio, 6.05), with continued bleeding. On hospital day 5, the patient died. CONCLUSIONS: According to the Naranjo probability scale, bleeding associated with dabigatran revealed a probable relationship. This fatal case illustrates our concern about the usefulness of currently recommended anticoagulation laboratory tests and of the efficacy of blood transfusion, dialysis, and prothrombin complex concentrate in managing life-threatening bleeding secondary to dabigatran. In addition, clinicians should be cognizant of the renal recommendations for the newer oral anticoagulant agents to prevent potentially catastrophic results.

Incidence and predictors of nephrotoxicity associated with intravenous colistin in overweight and obese patients.

Intravenous colistin is used to treat resistant Gram-negative infections and is associated with nephrotoxicity. In overweight and obese adults, a paucity of data exists regarding the incidence and predictors of such toxicity. A retrospective nested case-control study was performed over 35 months for patients receiving intravenous colistin for ≥ 72 h with a body mass index (BMI) of ≥ 25 kg/m(2). The objective was to investigate the incidence and predictors of nephrotoxicity. Severity of acute kidney injury was defined by RIFLE (risk, injury, failure, loss, and end-stage kidney disease) criteria. Dosing and mortality were secondarily investigated. Forty-two patients met the inclusion criteria, and 20 (48%) developed nephrotoxicity. Patients with toxicity were in the risk (15%), injury (5%), and failure (80%) categories based on RIFLE criteria. A logistic regression model identified four predictors of colistin-associated nephrotoxicity: a BMI of ≥ 31.5 kg/m(2) (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.15 to 8.35), diabetes (OR, 2.11; 95% CI, 0.84 to 5.29), the length of hospitalization in days prior to receipt of colistin (OR, 1.04; 95% CI, 0.99 to 1.08), and age (OR, 1.08; 95% CI, 1.00 to 1.17). Among all of the patients, dosing based on the actual body weight and excessive dosing due to the use of the actual body weight were frequent at 64% and 92%, respectively. The 30-day all-cause in-hospital mortality rate was 40% in the toxicity group and 14% in the nontoxicity group (P = 0.14). Patients receiving intravenous colistin should be monitored for nephrotoxicity, especially when the BMI exceeds 31.5 kg/m(2). Prospective, randomized, controlled trials are warranted to further examine nephrotoxicity incidence and predictors and appropriate dosing strategies in this population.

Incidence of nephrotoxicity and association with vancomycin use in intensive care unit patients with pneumonia: retrospective analysis of the IMPACT-HAP Database.

BACKGROUND: The 2005 guidelines from the American Thoracic Society and the Infectious Diseases Society of America recommend vancomycin trough levels of 15 to 20 mg/L for the therapy of hospital-acquired (HAP), ventilator-associated (VAP), and health care-associated (HCAP) pneumonia. OBJECTIVE: The goal of this article was to report the incidence of nephrotoxicity and associated risk factors in intensive care unit patients who received vancomycin for the treatment of HAP, VAP, and HCAP. METHODS: This was a retrospective analysis of data from a multicenter, observational study of pneumonia patients. Antibiotic-associated nephrotoxicity was defined as either an increase in serum creatinine ≥0.5 mg/dL or 50% above baseline, from initiation of vancomycin to 72 hours after completion of therapy. Univariate and multivariate logistic regression analyses were performed to identify risk factors for development of renal dysfunction. RESULTS: Of the 449 patients in the database, 240 received at least one dose of vancomycin and 188 had sufficient data for analysis. In these 188 patients, 63% were male. Mean (SD) age was 58.5 (17.2) years, and the mean Acute Physiology and Chronic Health Evaluation II score was 19.4 (6.4). Nephrotoxicity occurred in 29 of 188 (15.4%) vancomycin-treated patients. In multivariate analysis, initial vancomycin trough levels ≥15 mg/L (odds ratio [OR], 5.2 [95% CI, 1.9-13.9]; P = 0.001), concomitant aminoglycoside use (OR, 2.67 [95% CI, 1.09-6.54]; P = 0.03), and duration of vancomycin therapy (OR for each additional treatment day, 1.12 [95% CI, 1.02-1.23]; P = 0.02) were independently associated with nephrotoxicity. The incidence of nephrotoxicity increased as a function of the initial vancomycin trough level, rising from 7% at a trough <10 mg/L to 34% at >20 mg/L (P = 0.001). The mean time to nephrotoxicity decreased from 8.8 days at vancomycin trough levels <15 mg/L to 7.4 days at >20 mg/L (Kaplan-Meier analysis, P = 0.0003). CONCLUSIONS: Nephrotoxicity may be common among intensive care unit patients with pneumonia treated with broad-spectrum antibiotic therapy that includes vancomycin. The finding that an initial vancomycin trough level ≥15 mg/L may be an independent risk factor for nephrotoxicity highlights the need for additional studies to assess current recommendations for vancomycin dosing for ICU patients with pneumonia.

Implementation of guidelines for management of possible multidrug-resistant pneumonia in intensive care: an observational, multicentre cohort study.

BACKGROUND: The American Thoracic Society and Infectious Diseases Society of America provide guidelines for management of hospital-acquired, ventilator-associated, and health-care-associated pneumonias, consisting of empirical antibiotic regimens for patients at risk for multidrug-resistant pathogens. We aimed to improve compliance with these guidelines and assess outcomes. METHODS: We implemented a performance-improvement initiative in four academic medical centres in the USA with protocol-based education and prospective observation of outcomes. Patients were assessed for severity of illness and followed up until death, hospital discharge, or day 28. We included patients in intensive-care units who were at risk for multidrug-resistant pneumonia and were treated empirically. FINDINGS: 303 patients at risk for multidrug-resistant pneumonia were treated empirically, and prescribed treatment was guideline compliant in 129 patients and non-compliant in 174 patients. 44 (34%) patients died before 28 days in the compliance group and 35 (20%) died in the non-compliance group. Five patients in the compliance group and seven in the non-compliance group were lost to follow-up after day 14. Kaplan-Meier estimated survival to 28 days was 65% in the compliance group and 79% in the non-compliance group (p=0·0042). This difference persisted after adjustment for severity of illness. Median length of stay and duration of mechanical ventilation did not differ between groups. Compliance failures included non-use of dual treatment for Gram-negative pathogens in 154 patients and absence of meticillin-resistant Staphylococcus aureus coverage in 24 patients. For patients in whom pathogens were subsequently identified, empirical treatment was active in 79 (81%) of 97 of patients receiving compliant therapy compared with 109 (85%) of 128 of patients receiving non-compliant therapy. INTERPRETATION: Because adherence with empirical treatment was associated with increased mortality, we recommend a randomised trial be done before further implementation of these guidelines. FUNDING: Pfizer, US Medical.

Relationship of vancomycin minimum inhibitory concentration to mortality in patients with methicillin-resistant Staphylococcus aureus hospital-acquired, ventilator-associated, or health-care-associated pneumonia.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and health-care-associated pneumonia (HCAP). These infections are associated with significant morbidity, mortality, and cost. The impact of vancomycin minimum inhibitory concentration (MIC) on mortality for patients with MRSA pneumonia has not been determined. METHODS: Adult patients in ICUs with a diagnosis of MRSA HAP, VAP, or HCAP were entered in the study. Clinical and laboratory information were prospectively collected. Vancomycin MIC and heteroresistance were determined for each MRSA isolate. Data were collected from February 2006 through August 2007. The primary outcome variable was all-cause mortality at day 28. A propensity score approach was used to adjust for confounding variables. RESULTS: The study sample consisted of 158 patients. All-cause mortality at day 28 was 32.3%. The majority of MRSA isolates had a vancomycin MIC ≥ 1.5 mg/mL (115/158, 72.8%). Propensity score analysis demonstrated an increase in 28-day mortality as vancomycin MIC increased from 0.75 to 3 mg/mL (P ≤ .001). Heteroresistance to vancomycin, demonstrated in 21.5% isolates, was not associated with mortality. CONCLUSIONS: Mortality in patients with MRSA HAP, VAP, and HCAP increases as a function of the vancomycin MIC, even for strains with MIC values within the susceptible range. Evaluation of vancomycin MICs should be contemplated at the institutional level and for individual cases of MRSA pneumonia. The use of vancomycin therapy in patients with MRSA pneumonia caused by isolates with MICs between 1 and 2 mg/mL should be undertaken with caution, and alternative therapies should be considered.