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The purpose of this study was to determine whether fungicidal versus fungistatic pharmacotherapy of invasive candidiasis/candidemia yields superior outcomes. Data sources included MEDLINE (1966–June 2017), EMBASE (1980–June 2017), PubMed (1966–June 2017), Global Health-Ovid (inception to June 2017), LILACS Virtual Health Library (inception to June 2017) and the Cochrane Central Register of Controlled Trials (to 2nd quarter 2017). The ClinicalTrial.gov database, the SCOPUS database, SIGLE (System for Information on Grey Literature) and Google Scholar were also utilised to search for relevant studies. Randomised studies of any pharmacotherapy of invasive candidiasis including candidemia using a fungicidal (amphotericin B or echinocandin compound) versus a fungistatic (triazole) compound in adolescent or adult non-neutropenic patients. Eight studies met the inclusion criteria. Pooled odds ratios demonstrated an advantage of fungicidal therapy with respect to early therapeutic success (OR 1.61, 95% CI 1.27–2.03, p

Given conflicting data and current guidelines, low-dose corticosteroids are often used in the treatment of septic shock. To evaluate the therapeutic benefit of early low-dose corticosteroid in patients with septic shock.Retrospective, multicenter, propensity-matched cohort study.ICUs of 28 academic and community hospitals in three countries between 1996 and 2007.Six thousand six hundred sixty-three eligible patients with septic shock of whom 1,838 received IV low-dose corticosteroid treatment within 48 hours of the diagnosis of septic shock and were matched to a comparable group who did not receive low-dose corticosteroid.The primary outcome was 30-day mortality. Mortality analyses were stratified by severity of illness (Acute Physiology and Chronic Health Evaluation II quartile). Using a Cox proportional hazards model, corticosteroid therapy was associated with similar 30-day mortality when compared with the matched control cohort (652/1,838 [35.5%] vs 641/1,838 [34.9%]; hazard ratio, 0.98; 95% CI, 0.88-1.10; p = 0.77). In the subgroup of patients with the Acute Physiology and Chronic Health Evaluation II score quartile more than or equal to 30, low-dose corticosteroid was associated with lower mortality (232/461 [50.6%] vs 251/450 [55.8%]; hazard ratio, 0.81; 95% CI, 0.68-0.97; p = 0.02). In logistic regression models, corticosteroid therapy was not associated with reductions in ICU (556/1,838 [30.3%] vs 558/1,838 [30.4%]; odds ratio, 0.99; 95% CI, 0.86-1.15; p = 0.94) or hospital mortality (797/1,838 [43.4%] vs 773/1,838 [42.1%]; odds ratio, 1.05; 95% CI, 0.93-1.20; p = 0.42). Similarly, there were no significant differences in ventilator- (median and interquartile range, 13 [0-25] vs 15 [0-25]; p = 0.8) and pressor/inotrope-free days (median and interquartile range, 25 [3-27] vs 24 [2-28]; p = 0.63) up to 30 days between groups.Early administration of low-dose corticosteroid is not associated with decreased mortality when it is administered to unselected patients with septic shock. A beneficial effect of low-dose corticosteroid on mortality may exist in patients with the highest severity of illness. Future trials of low-dose corticosteroid in septic shock should consider restricting the study population to this cohort.

Whether the enteric absorption of the neuraminidase inhibitor oseltamivir is impaired in critically ill patients is unknown. We documented the pharmacokinetic profile of oseltamivir in patients admitted to intensive care units (ICUs) with suspected or confirmed pandemic (H1N1) influenza.We included 41 patients 18 years of age and older with suspected or confirmed pandemic (H1N1) influenza who were admitted for ventilatory support to nine ICUs in three cities in Canada and Spain. Using tandem mass spectrometry, we assessed plasma levels of oseltamivir free base and its active metabolite carboxylate at baseline (before gastric administration of the drug) and at 2, 4, 6, 9 and 12 hours after the fourth or later dose.Among the 36 patients who did not require dialysis, the median concentration of oseltamivir free base was 10.4 (interquartile range [IQR] 4.8-14.9) microg/L; the median concentration of the carboxylate metabolite was 404 (IQR 257-900) microg/L. The volume of distribution of the carboxylate metabolite did not increase with increasing body weight (R2=0.00, p=0.87). The rate of elimination of oseltamivir carboxylate was modestly correlated with estimations of creatinine clearance (R2=0.27, p0.001). Drug clearance in the five patients who required continuous renal replacement therapy was about one-sixth that in the 36 patients with relatively normal renal function.Oseltamivir was well absorbed enterically in critically ill patients admitted to the ICU with suspected or confirmed pandemic (H1N1) influenza. The dosage of 75 mg twice daily achieved plasma levels that were comparable to those in ambulatory patients and were far in excess of concentrations required to maximally inhibit neuraminidase activity of the virus. Adjustment of the dosage in patients with renal dysfunction requiring continuous renal replacement therapy is appropriate; adjustment for obesity does not appear to be necessary.

Introduction Despite recent advances in the management of septic shock, mortality remains unacceptably high. Earlier initiation of key therapies including appropriate antimicrobials and fluid resuscitation appears to reduce the mortality in this condition. This study examined whether early initiation of vasopressor therapy is associated with improved survival in fluid therapy-refractory septic shock. Methods Utilizing a well-established database, relevant information including duration of time to vasopressor administration following the initial documentation of recurrent/persistent hypotension associated with septic shock was assessed in 8,670 adult patients from 28 ICUs in Canada, the United States of America, and Saudi Arabia. The primary endpoint was survival to hospital discharge. Secondary endpoints were length of ICU and hospital stay as well as duration of ventilator support and vasopressor dependence. Analysis involved multivariate linear and logistic regression analysis. Results In total, 8,640 patients met the definition of septic shock with time of vasopressor/inotropic initiation documented. Of these, 6,514 were suitable for analysis. The overall unadjusted hospital mortality rate was 53%. Independent mortality correlates included liver failure (odds ratio (OR) 3.46, 95% confidence interval (CI), 2.67 to 4.48), metastatic cancer (OR 1.63, CI, 1.32 to 2.01), AIDS (OR 1.91, CI, 1.29 to 2.49), hematologic malignancy (OR 1.88, CI, 1.46 to 2.41), neutropenia (OR 1.78, CI, 1.27 to 2.49) and chronic hypertension (OR 0.62 CI, 0.52 to 0.73). Delay of initiation of appropriate antimicrobial therapy (OR 1.07/hr, CI, 1.06 to 1.08), age (OR 1.03/yr, CI, 1.02 to 1.03), and Acute Physiology and Chronic Health Evaluation (APACHE) II Score (OR 1.11/point, CI, 1.10 to 1.12) were also found to be significant independent correlates of mortality. After adjustment, only a weak correlation between vasopressor delay and hospital mortality was found (adjusted OR 1.02/hr, 95% CI 1.01 to 1.03, P 14.1 hours). There was no significant relationship of vasopressor initiation delay to duration of vasopressor therapy (P = 0.313) and only a trend to longer duration of ventilator support (P = 0.055) among survivors. Conclusion Marked delays in initiation of vasopressor/inotropic therapy are associated with a small increase in mortality risk in patients with septic shock.