Micafungin versus anidulafungin in critically ill patients with invasive candidiasis: a retrospective study.

BACKGROUND: In critically ill patients the incidence of invasive fungal infections caused by Candida spp. has increased remarkably. Echinocandins are recommended as initial treatment for invasive fungal infections. The safety and efficacy of micafungin compared to caspofungin is similar, but no comparison is made between anidulafungin and micafungin concerning safety and efficacy. We therefore performed a retrospective study to assess these aspects in critically ill patients with invasive candidiasis. METHODS: All patients in the intensive care unit (ICU) with invasive candidiasis, who were only treated with anidulafungin or micafungin, between January 2012 and December 2014 were retrospectively included. Baseline demographic characteristics, infection characteristics and patient courses were assessed. RESULTS: A total of 63 patients received either anidulafungin (n = 30) or micafungin (n = 33) at the discretion of the attending intensivist. Baseline characteristics were comparable between the two groups, suggesting similar risk for developing invasive candidiasis. Patients with invasive candidiasis and liver failure were more often treated with anidulafungin than micafungin. Response rates were similar for both groups. No difference was observed in 28-day mortality, but 90-day mortality was higher in patients on anidulafungin. Multivariable cox regression analysis showed that age and serum bilirubin were the best parameters for the prediction of 90-day mortality, whereas APACHE II, Candida score and antifungal therapy did not contribute (P > 0.05). None of the patients developed impaired liver function related to antifungal use and no differences were seen in prothrombin time, serum transaminases and bilirubin levels between the groups, after exclusion of patients with liver injury or failure. CONCLUSION: Micafungin can be safely and effectively used in critically ill patients with invasive candidiasis. The observed increased 90-day mortality with anidulafungin can be explained by intensivists unnecessarily avoiding micafungin in patients with liver injury and failure.

The intensive care infection score - a novel marker for the prediction of infection and its severity.

BACKGROUND: The prediction of infection and its severity remains difficult in the critically ill. A novel, simple biomarker derived from five blood-cell derived parameters that characterize the innate immune response in routine blood samples, the intensive care infection score (ICIS), could be helpful in this respect. We therefore compared the predictive value of the ICIS with that of the white blood cell count (WBC), C-reactive protein (CRP) and procalcitonin (PCT) for infection and its severity in critically ill patients. METHODS: We performed a multicenter, cluster-randomized, crossover study in critically ill patients between January 2013 and September 2014. Patients with a suspected infection for which blood cultures were taken by the attending intensivist were included. Blood was taken at the same time for WBC, ICIS, CRP and PCT measurements in the control study periods. Results of imaging and cultures were collected. Patients were divided into groups of increasing likelihood of infection and invasiveness: group 1 without infection or with possible infection irrespective of cultures, group 2 with probable or microbiologically proven local infection without blood stream infection (BSI) and group 3 with BSI irrespective of local infection. Septic shock was assessed. RESULTS: In total, 301 patients were enrolled. CRP, PCT and ICIS were higher in groups 2 and 3 than group 1. The area under the receiver operating characteristic curve (AUROC) for the prediction of infection was 0.70 for CRP, 0.71 for PCT and 0.73 for ICIS (P < 0.001). For the prediction of septic shock the AUROC was 0.73 for CRP, 0.85 for PCT and 0.76 for ICIS. These AUROC did not differ from each other. CONCLUSION: The data suggest that the ICIS is potentially useful for the prediction of infection and its severity in critically ill patients, non-inferiorly to CRP and PCT. In contrast to CRP and PCT, the ICIS can be determined routinely without extra blood sampling and lower costs, yielding results within 15 minutes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: ID NCT01847079 . Registered on 24 April 2013.

Echinocandin to fluconazole step-down therapy in critically ill patients with invasive, susceptible Candida albicans infections.

Invasive Candida spp. infections are increasingly diagnosed in critically ill patients. For initial treatment, an echinocandin is recommended with a possible step-down to fluconazole when the patients' condition is improving and the isolate appears susceptible, but there are no data to support such policy. We studied the safety and efficacy of step-down therapy in critically ill patients with culture proven deep seated or bloodstream infections by C. albicans susceptible to fluconazole. All patients admitted into the intensive care unit from January 2010 to December 2014, who had a culture proven invasive C. albicans infection and received initial treatment with an echinocandin for at least 4 days were included. Data on patient characteristics, treatment and vital outcomes were assessed. Of the 56 patients, 32 received step-down fluconazole therapy, at median day 5, whereas the echinocandin was continued in the other 24. No differences where seen in baseline characteristics or risk factors for invasive C. albicans infection between the two groups. Response rates were similar and no difference where seen in 28-day or 90-day mortality between the groups. Step-down therapy to fluconazole may be safe and effective in critically ill patients with invasive infections by C. albicans, susceptible to fluconazole, who have clinically improved as early as 4 days after start of treatment with an echinocandin.

Safety and efficacy of amphotericin-B deoxycholate inhalation in critically ill patients with respiratory Candida spp. colonization: a retrospective analysis.

BACKGROUND: Candida spp. are frequently cultured from the respiratory tract in critically ill patients. Most intensivists start amphotericin-B deoxycholate (ABDC) inhalation therapy to eradicate Candida spp. from the respiratory tract. However, the safety and efficacy of this treatment are not well established. The purpose of this study was to assess the safety and efficacy of ABDC inhalation for the treatment of respiratory Candida spp. colonization in critically ill patients. METHODS: All non-neutropenic patients admitted into the intensive care unit (ICU) of a university hospital from December 2010-2011, who had positive Candida spp. cultures of the respiratory tract for more than 1 day and required mechanical ventilation >48 h were retrospectively included. The decision to start ABDC inhalation had been made by attending intensivists on clinical grounds in the context of selective decontamination of the digestive tract. Infection characteristics and patient courses were assessed. RESULTS: Hundred and thirteen consecutive patients were studied. Fifty-one of them received ABDC inhalation and their characteristics at baseline and day 1 of respiratory colonization did not differ from those of colonized patients not receiving treatment (n = 62). The ABDC-treated group had a similar Candida spp. load but did not decolonize more rapidly as compared to untreated patients. The clinical pulmonary infection and lung injury scores did not decrease as in the untreated group. In a Cox proportional hazard model, the duration of mechanical ventilation was increased (P < 0.003) by ABDC treatment independently of other potential determinants and Candida spp. colonization. No differences in ventilator-associated pneumonia or in overall mortality (up to day 90) were observed. CONCLUSION: Treatment of respiratory Candida spp. colonization in non-neutropenic critically ill patients by inhaled ABDC may not affect respiratory colonization but may increase duration of mechanical ventilation, because of direct toxicity of the drug on the lung.

Determinants of door-in-door-out time in patients with ischaemic stroke transferred for endovascular thrombectomy.

BACKGROUND: Long door-in-door-out (DIDO) times are an important cause of treatment delay in patients transferred for endovascular thrombectomy (EVT) from primary stroke centres (PSC) to an intervention centre. Insight in causes of prolonged DIDO times may facilitate process improvement interventions. We aimed to quantify different components of DIDO time and to identify determinants of DIDO time. METHODS: We performed a retrospective cohort study in a Dutch ambulance region consisting of six PSCs and one intervention centre. We included consecutive adult patients with anterior circulation large vessel occlusion, transferred from a PSC for EVT between October 1, 2019 and November 31, 2020. We subdivided DIDO into several time components and quantified contribution of these components to DIDO time. We used univariable and multivariable linear regression models to explore associations between potential determinants and DIDO time. RESULTS: We included 133 patients. Median (IQR) DIDO time was 66 (52-83) min. The longest component was CTA-to-ambulance notification time with a median (IQR) of 24 (16-37) min. DIDO time increased with age (6 min per 10 years, 95% CI: 2-9), onset-to-door time outside 6 h (20 min, 95% CI: 5-35), M2-segment occlusion (15 min, 95% CI: 4-26) and right-sided ischaemia (12 min, 95% CI: 2-21). CONCLUSIONS: The CTA-to-ambulance notification time is the largest contributor to DIDO time. Higher age, onset-to-door time longer than 6 h, M2-segment occlusion and right-sided occlusions are independently associated with a longer DIDO time. Future interventions that aim to decrease DIDO time should take these findings into account.

Epidural analgesia is associated with improved health outcomes of surgical patients with chronic obstructive pulmonary disease.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) have increased postoperative morbidity and mortality. Epidural analgesia (EDA) improves postoperative outcome but may worsen postoperative lung function. It is unknown whether patients with COPD benefit from EDA. The objective of this study was to determine whether patients with COPD undergoing major abdominal surgery benefit from EDA in addition to general anesthesia. METHODS: This cohort study included 541 consecutive patients with COPD who underwent major abdominal surgery between 1995 and 2007 at a university medical center. Propensity scores estimating the probability of receiving EDA were used in multivariate correction. The primary outcome was postoperative pneumonia and 30-day mortality. RESULTS: There were 324 patients (60%) who received EDA in addition to general anesthesia. The incidence of postoperative pneumonia (16% vs. 11%; P = 0.08) and 30-day mortality (9% vs. 5%; P = 0.03) was lower in patients who received EDA. After correction EDA was associated with improved outcome for postoperative pneumonia (OR 0.5; 95% CI: 0.3-0.9; P = 0.03). The strongest preventive effect was seen in patients with the most severe type of COPD. CONCLUSION: This study provides evidence that in patients with COPD who are scheduled for major abdominal surgery, epidural analgesia decreases postoperative pulmonary complications.

Immature granulocytes predict microbial infection and its adverse sequelae in the intensive care unit.

BACKGROUND: We evaluated the predictive value of immature granulocyte (IG) percentage in comparison with white blood cell counts (WBC) and C-reactive protein (CRP), for infection, its invasiveness, and severity in critically ill patients. METHODS: In 46 consecutive patients, blood samples were collected at the day (0) of a clinical suspicion of microbial infection and at days 1 and 3 thereafter. We defined infections, bloodstream infection, and septic shock within 7 days after enrollment. RESULTS: Of the 46 patients, 31 patients had infection, 15 patients developed bloodstream infection, and 13 patients septic shock. C-reactive protein and IG percentage increased with increasing invasiveness and severity of infection, from day 0 onwards. Receiver operating characteristic analysis to predict infection showed an area under the curve of 0.66 (P=.10) for WBC vs 0.74 (P=.01) for CRP and 0.73 (P=.02) for IG percentage on day 0. Comparing WBC and CRP to WBC and IG percentage results in comparable prediction of microbial infection. Comparing WBC and CRP with WBC, CRP, and IG percentage suggests an additional early value of IG percentage, when not elevated, in ruling out infection. CONCLUSION: Immature granulocyte percentage is a useful marker, as CRP, to predict infection, its invasiveness, and severity, in critically ill patients. However, the IG percentage adds to WBC and CRP in the early exclusion of infection and can be obtained routinely without extra blood sampling or costs.

Risk modification for postoperative pulmonary embolism: timing of postoperative prophylaxis.

INTRODUCTION: Risk factors for postoperative pulmonary embolism can often not be modified and are patient related. The purpose of this case control study was to identify possible modifiable risk factors for postoperative pulmonary embolism. MATERIALS AND METHODS: We undertook a case control study among 210,269 patients who underwent noncardiac surgery from 2000 to 2009 at the Erasmus Medical Center. Case subjects were all 199 (0.09%) patients who experienced a pulmonary embolism within 30 days after surgery. From the remaining patients, 1 control was selected for each case and was stratified according to calendar year. For cases and controls, information was obtained regarding risk factors and the type and dose of thromboprophylaxis as well as the time of postoperative initiation. RESULTS: Overweight, surgery for malignancy, a history of cerebrovascular disease and a history of thromboemblic diseases, intraoperative blood transfusions and delayed use of thromboprophylaxis were more common in cases than in controls. After correction delayed use of thromboprophylaxis was associated with a 4 fold increased risk (OR 4.1; 95% CI: 2.1 - 7.7) for postoperative pulmonary embolism. CONCLUSION: Delayed timing of postoperative thromboprophylaxis is an important modifiable risk factor for postoperative pulmonary embolism after noncardiac surgery. This study emphasises the importance of on time administration of thromboprophylaxis.

Effect of chronic beta-blocker use on stroke after noncardiac surgery.

The incidence of postoperative stroke ranges from 0.08% to 0.7% in noncardiac surgery. Recently, the PeriOperative ISchemic Evaluation (POISE) study reported an incidence of postoperative stroke of 1% in patients scheduled for noncardiac surgery when beta blockers were initiated immediately before surgery. To assess the association between chronic beta-blocker use and postoperative stroke in noncardiac surgery, we undertook a case-control study among 186,779 patients who underwent noncardiac surgery from 2000 to 2008 at the Erasmus Medical Centre. Patients who were undergoing intracerebral surgery or carotid surgery or who had head and/or carotid trauma were excluded. The case subjects were 34 patients (0.02%) who had experienced a stroke within 30 days after surgery. Of the remaining patients, 2 controls were selected for each case and were stratified according to calendar year, type of surgery, and age. For cases and controls, information was obtained regarding beta-blocker use before surgery, the presence of cardiac risk factors, and the use of other cardiovascular medication. The use of beta blockers was as common in the cases as in the controls (29% vs 29%; p = 1.0). The adjusted odds ratio for postoperative stroke among beta-blocker users compared with nonusers was 0.4 (95% confidence interval 0.1 to 1.5). Similar results were obtained in the subgroups of patients stratified according to the use of cardiovascular therapy and the presence of cardiac risk factors. In conclusion, the present case-control study has shown no increased risk of postoperative stroke in patients taking chronic beta-blocker therapy.