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Purpose: Invasive candidiasis (IC) is a challenging clinical condition, burdened by relevant mortality and morbidity. There is limited knowledge on the occurrence and management of IC in Internal Medicine Units (IMUs). Aim of this study was to provide real-world data on this topic. Methods: Consecutive objectively diagnosed cases of IC were collected in this prospective registry, which involved 18 IMUs in Italy. Patients were followed-up to 90 days from the diagnosis of candidemia. Results: A total of 111 patients were observed (median age 78, IQR 67–83) for an overall incidence of infection of 1.89 cases/1000 hospital admissions. Candida albicans was the most frequent isolated species (62%), followed by Candida parapsilosis (17%) and Candida glabrata (13%). Echinocandins and fluconazole were used as initial therapy in 56.8 and 43.2% of patients, respectively. Antifungal therapy was started within 24 h in 18.9% of patients, in 40.6% in the period 1–3 days, and in 40.5% of patients more than 3 days after blood cultures. Death rate was 19.8% at 30 days and 40.5% at 90 days. At multivariable analysis concomitant bacteremia (i.e. polymicrobial sepsis), and fluconazole as the initial therapy were associated with an increased risk of death at 90 days. Conclusions: The incidence of IC is not negligible, and our registry confirmed that these patients have a relevant mortality rate at 90 days. Concomitant bacteremia, featuring polymicrobial sepsis, and starting antifungal treatment with fluconazole instead of echinocandins independently increase the risk of death. Efforts are needed to improve the awareness and management of IC in IMUs. [ABSTRACT FROM AUTHOR]

Byline: M. Lanzafame (1), M. Trevenzoli (1), F. Faggian (1), P. Marcati (1), F. Gatti (1), G. Carolo (1), E. Concia (1) Keywords: Key Words Hypothyroidism; HIV infection; Levothyroxine; Indinavir; Hyperthyroidism Abstract: Drug interactions are an important and emerging problem in the treatment of HIV-infected patients. Protease inhibitors, like nonnucleoside reverse transcriptase inhibitors, are metabolized by the cytochrome P-450 enzyme system and each of these antiretroviral agents may interact with other drugs metabolized by this system. Some protease inhibitors may also interact with glucuronosyl transferase activity affecting plasma concentrations of drugs metabolized through this pathway. We describe a case of an HIV-infected patient, taking levothyroxine for hypothyroidism and clinically stable, who, after the introduction of an antiretroviral regimen containing indinavir, developed a pharmacological hyperthyroidism. Author Affiliation: (1) Division of Clinical Infectious Disease, Ospedale Civile Maggiore (Borgo Trento), Via Piazzale Stefani 1, I-37100 Verona, Italy Phone: (+39/45) 8073150, Fax: -6104200, e-mail: masino69@hotmail.com, IT Article note: Received: June 2, 2001 * Revision accepted: November 4, 2001

Purpose: Chronic pulmonary aspergillosis (CPA) is a rare disease that primarily affects subjects with moderate immunodepression and/or structural alterations in the lung. Methods: Data for patients with probable CPA were collected over 24 months. Patients with probable CPA received oral voriconazole, and clinical, laboratory and radiological follow-up was performed at 3, 6 and 12 months. Results: 21 patients (mean age 52.4 years) were evaluated. Factors predisposing to CPA were tuberculosis ( n = 8), chronic obstructive pulmonary disease ( n = 7), corticosteroids ( n = 14), chemo- or radio-therapy ( n = 6), tracheostomy or endotracheal prosthesis ( n = 5), smoking ( n = 4), asthma ( n = 3), and chronic liver disease ( n = 3). Sputum or bronchial aspirate cultures were positive for Aspergillus spp. in 14 cases (66.6 %). (1,3)-β- d-glucan on serum was positive in 16 cases (76.2 %). Excavated pulmonary thickening was evident in 14 patients (66.6 %) and in 9 of these cases (64.2 %) aspergilloma was present. [F]2-fluoro-2-deoxy- d-glucose-PET-CT was positive in 13/15 patients, and simple aspergilloma was diagnosed after surgical excision in one of the negative cases. All patients were treated with oral voriconazole. Therapy was discontinued due to skin toxicity ( n = 3), liver toxicity ( n = 2) and severe mental disorder ( n = 1). At 12 months' follow-up, nine patients (42.9 %) were considered cured or improved. Seven patients (33.3 %) died during follow-up, mainly due to underlying disease. Conclusions: A reasonable proportion of patients achieved cure or improvement with voriconazole, but 28.5 % of treated patients had to discontinue therapy because of toxicity. The high mortality makes it difficult to fully assess the real efficacy of voriconazole and to establish the correct duration of therapy. [ABSTRACT FROM AUTHOR]

Purpose: We compared the risk factors, the diagnostic tools and the outcome of filamentous fungal infections (FFIs) in hematological patients (HAEs) and non-hematological patients (non-HAEs). Methods: Prospective surveillance (2009-2011) of proven and probable FFIs was implemented in 23 Italian hospitals. Results: Out of 232 FFIs, 113 occurred in HAEs and 119 in non-HAEs. The most frequent infection was invasive aspergillosis (76.1 % for HAEs, 56.3 % for non-HAEs), and the localization was principally pulmonary (83.2 % for HAEs, 74.8 % for non-HAEs). Neutropenia was a risk factor for 89.4 % HAEs; the main underlying condition was corticosteroid treatment (52.9 %) for non-HAEs. The distribution of proven and probable FFIs was different in the two groups: proven FFIs occurred more frequently in non-HAEs, whereas probable FFIs were correlated with the HAEs. The sensitivity of the galactomannan assay was higher for HAEs than for non-HAEs (95.3 vs. 48.1 %). The overall mortality rate was 44.2 % among the HAEs and 35.3 % among the non-HAEs. The etiology influenced the patient outcomes: mucormycosis was associated with a high mortality rate (57.1 % for HAEs, 77.8 % for non-HAEs). Conclusions: The epidemiological and clinical data for FFIs were not identical in the HAEs and non-HAEs. The differences should be considered to improve the management of FFIs according to the patients' setting. [ABSTRACT FROM AUTHOR]

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Purpose: Candidemia is a highly lethal infection; several scores have been developed to assist the diagnosis process and recently different models have been proposed. Aim of this work was to assess predictive performance of a Random Forest (RF) algorithm for early detection of candidemia in the internal medical wards (IMWs)., Methods: A set of 42 potential predictors was acquired in a sample of 295 patients (male: 142, age: 72 ± 15 years; candidemia: 157/295; bacteremia: 138/295). Using tenfold cross-validation, a RF algorithm was compared with a classic stepwise multivariable logistic regression model; discriminative performance was assessed by C-statistics, sensitivity and specificity, while calibration was evaluated by Hosmer-Lemeshow test., Results: The best tuned RF algorithm demonstrated excellent discrimination (C-statistics = 0.874 ± 0.003, sensitivity = 84.24% ± 0.67%, specificity = 91% ± 2.63%) and calibration (Hosmer-Lemeshow statistics = 12.779 ± 1.369, p = 0.120), markedly greater than the ones guaranteed by the classic stepwise logistic regression (C-statistics = 0.829 ± 0.011, sensitivity = 80.21% ± 1.67%, specificity = 84.81% ± 2.68%; Hosmer-Lemeshow statistics = 38.182 ± 15.983, p < 0.001). In addition, RF suggests a major role of in-hospital antibiotic treatment with microbioma highly impacting antimicrobials (MHIA) that are found as a fundamental risk of candidemia, further enhanced by TPN. When in-hospital MHIA therapy is not performed, PICC is the dominant risk factor for candidemia, again enhanced by TPN. When PICC is not used and MHIA therapy is not performed, the risk of candidemia is minimum, slightly increased by in-hospital antibiotic therapy., Conclusion: RF accurately estimates the risk of candidemia in patients admitted to IMWs. Machine learning technique might help to identify patients at high risk of candidemia, reduce the delay in empirical treatment and improve appropriateness in antifungal prescription.

Purpose: Increasing prevalence of candidemia in Internal Medicine wards (IMWs) has been reported in recent years, but risk factors for candida bloodstream infection in patients admitted to IMW may differ from those known in other settings. The aim of this study was to identify risk factors and define a prediction rule for the early recognition of the risk of candidemia in IMW inpatients., Methods: This was a multicentric, retrospective, observational case-control study on non-neutropenic patients with candidemia admitted to IMWs of four large Italian Hospitals. Each eligible patient with candidemia (case) was matched to a control with bacteremia. Stepwise logistic regression analyses were performed., Results: Overall, 300 patients (150 cases and 150 controls) were enrolled. The following factors were associated with an increased risk of candidemia and weighted to build a score: total parenteral nutrition (OR 2.45, p = 0.008; 1 point); central venous catheter (OR 2.19, p = 0.031; 1 point); peripherally inserted central catheter (OR 5.63, p < 0.0001; 3 points), antibiotic treatment prior (OR 2.06; p = 0.059; 1 point) and during hospitalization (OR2.38, p = 0.033; 1 point); neurological disability (OR 2.25, p = 0.01; 1 point); and previous hospitalization within 3 months (OR 1.56, p = 0.163; 1 point). At ROC curve analysis, a final score ≥ 4 showed 84% sensitivity, 76% specificity, and 80% accuracy in predicting the risk of candidemia., Conclusions: The proposed scoring system showed to be a simple and highly performing tool in distinguishing bloodstream infections due to Candida and bacteria in patients admitted to IMW. The proposed rule might help to reduce delay in empirical treatment and improve appropriateness in antifungal prescription in septic patients.

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.