Impact of Initial Antifungal Therapy on the Outcome of Patients With Candidemia and Septic Shock Admitted to Medical Wards: A Propensity Score-Adjusted Analysis.

BACKGROUND: Echinocandins are recommended as firstline therapy in patients with candidemia. However, there is debate on their efficacy in survival outcomes. The aim of this study is to evaluate whether the choice of initial antifungal therapy improves mortality in patients with candidemia in relation to the presence of septic shock. METHODS: Patients with candidemia hospitalized in internal medicine wards of 5 tertiary care centers were included in the study (December 2012-December 2014). Patient characteristics, therapeutic interventions, and outcome were reviewed. Propensity score (PS) was used as a covariate of the multivariate analysis to perform a stratified analysis according to PS quartiles and to match patients receiving "echinocandins" or "azoles." RESULTS: Overall, 439 patients with candidemia were included in the study. A total of 172 (39.2%) patients had septic shock. Thirty-day mortality was significantly higher in patients with septic shock (45.3%) compared with those without septic shock (31.5%; P = .003). Among patients with septic shock, the use of echinocandins in the first 48 hours, compared with azoles, did not affect 30-day mortality in the PS-adjusted Cox regression analysis (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.37-1.59; P = .48), the PS-stratified analysis, or the logistic regression model in matched cohorts (adjusted HR, 0.92; 95% CI, 0.51-1.63; P = .77). CONCLUSIONS: Echinocandin therapy seems not to improve the outcome of non-intensive care unit patients with septic shock due to candidemia. These findings support the urgent need of further studies in this patient population.

Herpes simplex virus (HSV) pneumonia in the non-ventilated immunocompromised host: Burden and predictors.

OBJECTIVES: To evaluate burden and predictors of HSV pneumonia among immunocompromised patients not undergoing invasive mechanical ventilation according to a tailored diagnostic algorithm. METHODS: This prospective, observational study included immunocompromised adults with pneumonia non-responding to empirical antibiotic therapy. Bronchoalveolar lavage (BAL) specimens were cultured for bacteria, mycobacteria and fungi. Real-time PCR for Herpesviruses and other microorganisms were performed on BAL and other specimens. Cytological examination of BAL samples was carried out for identification of intranuclear inclusion bodies and immunohistochemical staining for HSV. RESULTS: We enrolled 45 patients (mean age 64.6 years) from January 2015 to June 2016. Nineteen (42.2%) cases tested positive for HSV-1 PCR on BAL. According to our definitions, 11 (24.4%) patients had HSV-1 pneumonia with viral loads ranging between 103 copies/mL and 107 copies/mL. HSV-1 positive throat swab (OR 85.2, 95% CI 5.83-1245.1, P < 0.001) and solid organ transplant (SOT) (OR 53.3, 95% CI 1.37-2072.8, P < 0.03) as underlying condition were found to be independently associated with HSV pneumonia by multivariable analysis. CONCLUSIONS: HSV pneumonia turned out to be relatively common and should be investigated especially in individuals with HSV positive throat swab and SOT. Interventional studies are needed to assess the real clinical impact of HSV pneumonia in immunocompromised patients.

Nosocomial candidemia in patients admitted to medicine wards compared to other wards: a multicentre study.

PURPOSE: Risk factors for nosocomial candidemia, severity of sepsis, treatment, and outcome were compared between patients admitted to medicine wards and those to surgical and intensive care units (ICUs). METHODS: Data were retrospectively collected from patients belonging to six referral hospitals in Italy between January 2011 and December 2013. Risk factors for 30-day mortality were evaluated in the whole patient population. RESULTS: A total of 686 patients (mean age 70 ± 15 years) with candidemia were included. 367 (53.5 %) patients were in medicine wards, and 319 in surgery and ICUs. Host-related risk factors for candidemia were more common in medicine patients whereas healthcare-related factors in surgery/ICU patients. These patients showed severe sepsis and septic shock more commonly (71.7 %) than medicine patients (59.9 %) (p 0.003). The latter underwent central venous catheter (CVC) removal and adequate antifungal therapy less frequently than surgery/ICU patients. 149 (40.6 %) patients died with candidemia in medicine wards and 69 (21.6 %) in other wards (p < 0.001). Overall, the 30-day mortality was 36.3 %. At multivariate analysis, independent risk factors for death were aging, higher Charlson score, severe sepsis and septic shock, and no antifungal therapy, while major surgery and CVC removal were associated with higher probability of survival. CONCLUSIONS: The burden of risk factors for candidemia was different between medicine patients and those in other wards. Despite the lower severity of candidemia in medicine patients, their mortality turned out to be higher than in surgery or ICU patients. Awareness of the best management of candidemia should be pursued, especially in medicine wards.

A multicenter multinational study of abdominal candidiasis: epidemiology, outcomes and predictors of mortality.

PURPOSE: Clinical data on patients with intra-abdominal candidiasis (IAC) is still scarce. METHODS: We collected data from 13 hospitals in Italy, Spain, Brazil, and Greece over a 3-year period (2011-2013) including patients from ICU, medical, and surgical wards. RESULTS: A total of 481 patients were included in the study. Of these, 27% were hospitalized in ICU. Mean age was 63 years and 57% of patients were male. IAC mainly consisted of secondary peritonitis (41%) and abdominal abscesses (30%); 68 (14%) cases were also candidemic and 331 (69%) had concomitant bacterial infections. The most commonly isolated Candida species were C. albicans (n = 308 isolates, 64%) and C. glabrata (n = 76, 16%). Antifungal treatment included echinocandins (64%), azoles (32%), and amphotericin B (4%). Septic shock was documented in 40.5% of patients. Overall 30-day hospital mortality was 27% with 38.9% mortality in ICU. Multivariate logistic regression showed that age (OR 1.05, 95% CI 1.03-1.07, P < 0.001), increments in 1-point APACHE II scores (OR 1.05, 95% CI 1.01-1.08, P = 0.028), secondary peritonitis (OR 1.72, 95% CI 1.02-2.89, P = 0.019), septic shock (OR 3.29, 95% CI 1.88-5.86, P < 0.001), and absence of adequate abdominal source control (OR 3.35, 95% CI 2.01-5.63, P < 0.001) were associated with mortality. In patients with septic shock, absence of source control correlated with mortality rates above 60% irrespective of administration of an adequate antifungal therapy. CONCLUSIONS: Low percentages of concomitant candidemia and high mortality rates are documented in IAC. In patients presenting with septic shock, source control is fundamental.

Brain Abscesses Caused by Nocardia paucivorans in a Multiple Myeloma Patient Treated with Lenalidomide and Dexamethasone: a Case Report and Review of Literature.

We report the first case of multiple brain abscesses caused by Nocardia paucivorans in a patient suffering from multiple myeloma on treatment with lenalidomide and dexamethasone. N. paucivorans is a recently described species of the genus Nocardia, which is supposed to have a heightened neurotropism in cases of disseminated infection. Although nocardiosis itself is an uncommon infectious complication in multiple myeloma so far, nocardial brain abscess should be added to the spectrum of adverse effects due to this novel chemotherapy regimen.

Epidemiology and outcome of nosocomial candidemia in elderly patients admitted prevalently in medical wards.

BACKGROUND AND AIMS: Candidemia represents an important cause of morbidity and mortality. To-date, the highest rates of candidemia occur in elderly patients, but there are few data on such patient population. The aims of this study were to evaluate the epidemiology, treatment and outcome of candidemia in an elderly patient population. METHODS: Nosocomial candidemia episodes occurring in a university general hospital were included in this study. Demographic, clinical, and Candida susceptibility testing data were retrospectively collected. Potential risk factors for 30-day crude mortality rate including host factors, Candida species, concomitant bacteremia, severity of sepsis, and management of fungemia were assessed by hazard risk (HR) analyses. RESULTS: 145 consecutive episodes of candidemia occurring in 140 patients with a median age of 81 years (interquartile range, 78-86 years) were analyzed. At the onset of candidemia, 98 (67.6 %) cases were hospitalized in medical wards. Candida albicans accounted for 55 % of all candidemia episodes. Overall, resistance to fluconazole was detected in 8.0 % of Candida isolates. Crude hospital mortality at 30 days was 46 %. Failure to receive adequate antifungal therapy was the significant risk factor for death on multivariable analysis (adjusted HR 1.87, 95 % CI 0.94-2.79). DISCUSSION AND CONCLUSIONS: Over two-thirds of elderly patients with candidemia are admitted to medical wards in our series. 30-day crude mortality is high and seems to be related to inadequate antifungal therapy. Increased awareness of the burden of this disease also in medical wards is strongly required to recognize and treat properly this severe infection.

A multicenter study of septic shock due to candidemia: outcomes and predictors of mortality.

PURPOSE: Candida is the most common cause of severe yeast infections worldwide, especially in critically ill patients. In this setting, septic shock attributable to Candida is characterized by high mortality rates. The aim of this multicenter study was to investigate the determinants of outcome in critically ill patients with septic shock due to candidemia. METHODS: This was a retrospective study in which patients with septic shock attributable to Candida who were treated during the 3-year study period at one or more of the five participating teaching hospitals in Italy and Spain were eligible for enrolment. Patient characteristics, infection-related variables, and therapy-related features were reviewed. Multiple logistic regression analysis was performed to identify the risk factors significantly associated with 30-day mortality. RESULTS: A total of 216 patients (mean age 63.4 ± 18.5 years; 58.3 % males) were included in the study. Of these, 163 (75 %) were admitted to the intensive care unit. Overall 30-day mortality was 54 %. Significantly higher Acute Physiology and Chronic Health Evaluation (APACHE) II scores, dysfunctional organs, and inadequate antifungal therapy were compared in nonsurvivors and survivors. No differences in survivors versus nonsurvivors were found in terms of the time from positive blood culture to initiation of adequate antifungal therapy. Multivariate logistic regression identified inadequate source control, inadequate antifungal therapy, and 1-point increments in the APACHE II score as independent variables associated with a higher 30-day mortality rate.