Publications by authors named "Maria Merelli"

33 Publications

MR-proADM as prognostic factor of outcome in COVID-19 patients.

Sci Rep 2021 03 4;11(1):5121. Epub 2021 Mar 4.

Istituto Di Patologia Clinica, Azienda Sanitaria Universitaria Integrata Di Udine (ASUID), Udine, Italy.

Mid Regional pro-ADM (MR-proADM) is a promising novel biomarker in the evaluation of deteriorating patients and an emergent prognosis factor in patients with sepsis, septic shock and organ failure. It can be induced by bacteria, fungi or viruses. We hypothesized that the assessment of MR-proADM, with or without other inflammatory cytokines, as part of a clinical assessment of COVID-19 patients at hospital admission, may assist in identifying those likely to develop severe disease. A pragmatic retrospective analysis was performed on a complete data set from 111 patients admitted to Udine University Hospital, in northern Italy, from 25th March to 15th May 2020, affected by SARS-CoV-2 pneumonia. Clinical scoring systems (SOFA score, WHO disease severity class, SIMEU clinical phenotype), cytokines (IL-6, IL-1b, IL-8, TNF-α), and MR-proADM were measured. Demographic, clinical and outcome data were collected for analysis. At multivariate analysis, high MR-proADM levels were significantly associated with negative outcome (death or orotracheal intubation, IOT), with an odds ratio of 4.284 [1.893-11.413], together with increased neutrophil count (OR = 1.029 [1.011-1.049]) and WHO disease severity class (OR = 7.632 [5.871-19.496]). AUROC analysis showed a good discriminative performance of MR-proADM (AUROC: 0.849 [95% Cl 0.771-0.730]; p < 0.0001). The optimal value of MR-proADM to discriminate combined event of death or IOT is 0.895 nmol/l, with a sensitivity of 0.857 [95% Cl 0.728-0.987] and a specificity of 0.687 [95% Cl 0.587-0.787]. This study shows an association between MR-proADM levels and the severity of COVID-19. The assessment of MR-proADM combined with clinical scoring systems could be of great value in triaging, evaluating possible escalation of therapies, and admission avoidance or inclusion into trials. Larger prospective and controlled studies are needed to confirm these findings.
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http://dx.doi.org/10.1038/s41598-021-84478-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933259PMC
March 2021

Blood ozonization in patients with mild to moderate COVID-19 pneumonia: a single centre experience.

Intern Emerg Med 2021 04 1;16(3):669-675. Epub 2020 Nov 1.

SOC Anestesia e Rianimazione Uno, Università di Udine e Azienda Sanitaria Universitaria Integrata di Udine, Via Pozzuolo, 330, 33100, Udine, Italy.

The emerging outbreak of the coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread worldwide. We prescribed some promising medication to our patients with mild to moderate pneumonia due to SARS-CoV-2, however such drugs as chloroquine, hydrossichloroquine, azithromycin, antivirals (lopinavir/ritonavir, darunavir/cobicistat) and immunomodulating agents (steroids, tocilizumab) were not confirmed as effective against SARS-CoV2. We, therefore, started to use auto-hemotherapy treated with an oxygen/ozone (O/O) gaseous mixture as adjuvant therapy. In Udine University Hospital (Italy) we performed a case-control study involving hospitalized adult patients with confirmed COVID-19 with mild to moderate pneumonia. Clinical presentations are based upon clinical phenotypes identified by the Italian Society of Emergency and Urgency Medicine (SIMEU-Società Italiana di Medicina di Emergenza-Urgenza) and patients that met criteria of phenotypes 2 to 4 were treated with best available therapy (BAT), with or without O-autohemotherapy. 60 patients were enrolled in the study: 30 patients treated with BAT and O/O mixture, as adjuvant therapy and 30 controls treated with BAT only. In the group treated with O-autohemotherapy plus BAT, patients were younger but with more severe clinical phenotypes. A decrease of SIMEU clinical phenotypes was observed (2.70 ± 0.67 vs. 2.35 ± 0.88, p = 0.002) in all patients during hospitalization but this clinical improvement was statistically significant only in O-treated patients (2.87 ± 0.78 vs. 2.27 ± 0.83, p < 0.001), differently to the control group (2.53 ± 0.51 vs. 2.43 ± 0.93, p = 0.522). No adverse events were observed associated with the application of O/O gaseous mixture. O/O therapy as adjuvant therapy could be useful in mild to moderate pneumonia due to SARS-CoV-2. Randomized prospective study is ongoing [Clinical Trials.gov ID: Z7C2CA5837].
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http://dx.doi.org/10.1007/s11739-020-02542-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603641PMC
April 2021

Clinical Features and Mortality of Nosocomial Candidemia in Very Old Patients: A Multicentre Italian Study.

Gerontology 2020 16;66(6):532-541. Epub 2020 Oct 16.

Infectious Diseases Unit, University Hospital of Trieste, Trieste, Italy.

Introduction: Being elderly is a well-known risk factor for candidemia, but few data are available on the prognostic impact of candidemia in the very old (VO) subjects, as defined as people aged ≥75 years.

Objective: The aim of this study was to assess risk factors for nosocomial candidemia in two groups of candidemia patients, consisting of VO patients (≥75 years) and adult and old (AO) patients (18-74 years). In addition, risk factors for death (30-day mortality) were analysed separately in the two groups.

Methods: We included all consecutive candidemia episodes from January 2011 to December 2013 occurring in six referral hospitals in north-eastern Italy.

Results: A total of 683 nosocomial candidemia episodes occurred. Of those, 293 (42.9%) episodes were in VO and 390 (57.1%) in AO patients. Hospitalization in medical wards, chronic renal failure, urinary catheter, and peripheral parenteral nutrition (PPN) were more common in VO than in AO patients. In the former patient group, adequate antifungal therapy (73.2%) and central venous catheter (CVC) removal (67.6%) occurred less frequently than in AO patients (82.5 and 80%, p < 0.002 and p < 0.004, respectively). Thirty-day mortality was higher in VO compared to AO patients (47.8 vs. 23.6%, p < 0.0001). In AO patients, independent risk factors for death were age (OR 1.04, 95% CI 1.00-1.09, p = 0.038), recent history of chemotherapy (OR 22.01, 95% CI 3.12-155.20, p = 0.002), and severity of sepsis (OR 40.68, 95% CI 7.42-223.10, p < 0.001); CVC removal was associated with higher probability of survival (OR 0.10, 95% CI 0.03-0.33, p < 0.001). In VO patients, independent risk factors for death were PPN (OR 3.5, 95% CI 1.17-10.47, p = 0.025) and hospitalization in medical wards (OR 2.58, 95% CI 1.02-6.53, p = 0.046), while CVC removal was associated with improved survival (OR 0.40, 95% CI 0.16-1.00, p = 0.050).

Conclusion: Thirty-day mortality was high among VO patients and was associated with inadequate management of candidemia, especially in medical wards.
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http://dx.doi.org/10.1159/000510638DOI Listing
September 2021

Comparison of the Safety and Tolerance Profile of Micafungin with that of Other Echinocandins and Azoles in Patients with Pre-existing Child-Pugh B or C Liver Disease: A Case-Control Retrospective Study.

Infect Dis Ther 2020 Mar 21;9(1):151-163. Epub 2020 Feb 21.

Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain.

Introduction: To assess the association between exposure to micafungin, other echinocandins, or azoles and the development of short-term liver injury (STLI) or long-term liver injury (LTLI) in patients with Child-Pugh B or C liver disease.

Methods: Multicenter case-control study of patients with Child-Pugh B or C liver disease who received antifungals (AF) for ≥ 72 h (May 2009-May 2015) in six Spanish and Italian hospitals. All micafungin patients were randomly matched with one patient who received another echinocandin and with one patient who received azole treatment. Primary outcome was development of STLI or LTLI (development of any type of liver tumor during the follow-up period).

Results: Of 2335 patients with chronic liver disease admitted to the six centers, 20 (0.85%) were found to have Child-Pugh B or C liver disease and received micafungin for ≥ 72 h. During AF treatment, the frequency of STLI was 10% in each group. Most cases of STLI were asymptomatic, and AFs had to be switched to another class of AF in only two patients (one micafungin and one azole). No patients developed acute liver insufficiency, were admitted to the ICU, or had to undergo transplantation. Follow-up data (median of 1.3 years) were available for 30 patients. LTLI was observed in only one patient, who had previously received treatment with azoles.

Conclusions: Our study suggests that the administration of micafungin to patients with end-stage liver disease does not imply a higher risk of developing STLI or LTLI.
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http://dx.doi.org/10.1007/s40121-020-00282-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054556PMC
March 2020

Incremental value of FDG-PET/CT to monitor treatment response in infectious spondylodiscitis.

Skeletal Radiol 2020 Jun 4;49(6):903-912. Epub 2020 Jan 4.

Infectious Diseases Division, Santa Maria della Misericordia University Hospital, 50, Colugna Street, 33100, Udine, Italy.

Objective: To assess the added value of serial 2-deoxy-2-[18F]fluoro-D-glucose (FDG) uptake analysis in predicting clinical response to treatment in infectious spondylodiscitis (IS). We sought to analyze changes in quantitative FDG-PET/CT parameters among patients with clinical response or treatment failure and to compare the sensitivity and specificity of serial FDG-PET/CT and MRI in predicting treatment response in IS.

Materials And Methods: This retrospective study consisted of 68 FDG-PET/CT examinations in 34 patients performed before and after at least 2 weeks of antibiotic treatment. Serial MRI scans were available in 32 (94%) patients before and after treatment. FDG-avid lesions were quantified as maximum standardized uptake value (SUV), partial-volume corrected lesion metabolic volume (LMV), and partial-volume corrected lesion metabolic activity (LMA).

Results: All FDG-PET/CT parameters significantly decreased in patients with clinical improvement (31/34, 91%, P < 0.001), while patients with disease progression did not show FDG-PET/CT improvement. FDG uptake decrease was similar between patients undergoing early assessment (< 6 weeks) compared with those performing FDG-PET/CT after 6 weeks of treatment. SUV, LMV, and LMA decrease over time was 39.0%, 97.4%, and 97.1%, respectively. In predicting clinical responses, SUV reduction > 15% and > 25% showed 94% and 89% sensitivity and 67% and 100% specificity compared with 37% and 50% of MRI, respectively. Low degree of agreement with clinical response was shown for MRI compared with FDG-PET/CT parameters using the Cohen kappa coefficient.

Conclusions: FDG-PET/CT monitoring is a valuable tool to predict clinical response to treatment in IS and has greater sensitivity and specificity compared with MRI.
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http://dx.doi.org/10.1007/s00256-019-03328-4DOI Listing
June 2020

Proactive therapeutic drug monitoring (TDM) may be helpful in managing long-term treatment with linezolid safely: findings from a monocentric, prospective, open-label, interventional study.

J Antimicrob Chemother 2019 12;74(12):3588-3595

Department of Medicine, University of Udine, Udine, Italy.

Background: Thrombocytopenia may be a dose-dependent adverse effect of linezolid therapy.

Objectives: To assess whether proactive therapeutic drug monitoring (TDM) could be helpful in preventing and/or in recovering from the occurrence of linezolid-induced thrombocytopenia during long-term treatment.

Methods: This was a monocentric, prospective, open-label, interventional study conducted between June 2015 and December 2017 among adult patients receiving >10 days of linezolid therapy and undergoing proactive TDM (desired trough level 2-8 mg/L) and platelet count assessment at day 3-5 and then once weekly up to the end of treatment.

Results: Sixty-one patients were included. Twenty-eight (45.9%) always had desired trough level (group A) and 33 (54.1%) experienced linezolid overexposure (group B) [29/33 transiently (subgroup B1) and 4/33 persistently (subgroup B2)]. No patient experienced linezolid underexposure. Median duration of treatment for the different groups ranged between 19 and 54 days. Thrombocytopenia occurred overall in 14.8% of cases (9/61). The incidence rate of thrombocytopenia was significantly lower (P=0.012) in both group A (10.7%; 3/28) and subgroup B1 (10.3%; 3/29) than in subgroup B2 (75.0%; 3/4). Thrombocytopenic patients belonging to both group A and group B1 recovered from thrombocytopenia without the need for discontinuing therapy. Multivariate linear regression analysis revealed that thrombocytopenia was independently associated with baseline platelet count and with median linezolid trough concentrations.

Conclusions: Proactive TDM of linezolid may be beneficial either in preventing or in recovering from dose-dependent thrombocytopenia, even when treatment lasts for more than 28 days. Larger prospective studies are warranted to confirm our findings.
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http://dx.doi.org/10.1093/jac/dkz374DOI Listing
December 2019

Role of procalcitonin in predicting etiology in bacteremic patients: Report from a large single-center experience.

J Infect Public Health 2020 Jan 24;13(1):40-45. Epub 2019 Jun 24.

Department of Medicine, University of Udine and Azienda Sanitaria Universitaria Integrata, Udine, Italy.

Background: Procalcitonin (PCT) is routinely used for an early recognition of severe infections and for promoting appropriate use of antibiotics. However, limited data correlating values of PCT with etiology of infection has been reported.

Methods: During 2016, all positive blood cultures (BC) were retrospectively extracted in a 1100-beds Italian tertiary-care hospital. PCT and C-reactive protein (CRP) values were recorded within 24h from BC collection. Primary endpoint of the study was to investigate the correlation between PCT and CRP values and the occurrence of bloodstream infections (BSI) caused by bacteria or fungi.

Results: During the study period, 1296 positive BC were included: 712 (54.9%) due to Gram-positive (GP), 525 (40.5%) due to Gram-negative (GN) strains, and 59 (4.6%) caused by fungi. Among GN isolates, enterobacteriaceae were reported in 453 (86.3%) cases. PCT values were higher in patients with GN etiology (26.1±14.2ng/mL) compared to GP (6.9±4.5) and fungi (3.3±2.4). Mean values for CRP in GN, GP, and fungi were not different. Receiver Operating Characteristic (ROC) curves showed an area under curve (AUC) of 0.71 for PCT and 0.51 for CRP among GN isolates; an AUC of 0.7 for PCT and 0.52 for CRP among enterobacteriaceae. Lower AUC for PCT were reported for GP and fungi.

Conclusions: PCT showed moderate performance in early detection (within 24h) of Gram-negative infections, especially those caused by enterobacteriaceae. Further prospective studies are mandatory to confirm these observations.
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http://dx.doi.org/10.1016/j.jiph.2019.06.003DOI Listing
January 2020

Incidence and outcome of invasive candidiasis in intensive care units (ICUs) in Europe: results of the EUCANDICU project.

Crit Care 2019 Jun 14;23(1):219. Epub 2019 Jun 14.

Department of Health Sciences, University of Genoa, Genoa, Italy.

Background: The objective of this study was to assess the cumulative incidence of invasive candidiasis (IC) in intensive care units (ICUs) in Europe.

Methods: A multinational, multicenter, retrospective study was conducted in 23 ICUs in 9 European countries, representing the first phase of the candidemia/intra-abdominal candidiasis in European ICU project (EUCANDICU).

Results: During the study period, 570 episodes of ICU-acquired IC were observed, with a cumulative incidence of 7.07 episodes per 1000 ICU admissions, with important between-center variability. Separated, non-mutually exclusive cumulative incidences of candidemia and IAC were 5.52 and 1.84 episodes per 1000 ICU admissions, respectively. Crude 30-day mortality was 42%. Age (odds ratio [OR] 1.04 per year, 95% CI 1.02-1.06, p < 0.001), severe hepatic failure (OR 3.25, 95% 1.31-8.08, p 0.011), SOFA score at the onset of IC (OR 1.11 per point, 95% CI 1.04-1.17, p 0.001), and septic shock (OR 2.12, 95% CI 1.24-3.63, p 0.006) were associated with increased 30-day mortality in a secondary, exploratory analysis.

Conclusions: The cumulative incidence of IC in 23 European ICUs was 7.07 episodes per 1000 ICU admissions. Future in-depth analyses will allow explaining part of the observed between-center variability, with the ultimate aim of helping to improve local infection control and antifungal stewardship projects and interventions.
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http://dx.doi.org/10.1186/s13054-019-2497-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6567430PMC
June 2019

Role of procalcitonin in bacteremic patients and its potential use in predicting infection etiology.

Expert Rev Anti Infect Ther 2019 02 30;17(2):99-105. Epub 2018 Dec 30.

a Department of Medicine , University of Udine and Azienda Sanitaria Universitaria Integrata , Udine , Italy.

Introduction: Bloodstream infections (BSI) and their evolution to sepsis or septic shock are one of the most important causes of morbidity and mortality; for this reason, arapid recognition and diagnosis of these infections are crucial to improve patients' outcome. Area covered: Procalcitonin (PCT) is considered an important biomarker for diagnosis of infection, routinely used to identify patients developing severe bacterial infections. In this scenario, management of BSI is complicated by the increasing rate of multidrug-resistantstrains, and an early recognition of severe infections is mandatory. Moreover, an appropriate use and prescription of antibiotics is important to reduce the risk of development of further antibiotic resistances. Expert opinion: we reviewed recent literature about the use of PCT in bacteremic patients to determine its role to predict infections, severity of clinical condition and antibiotic therapy duration; its role was defined in many studies to reduce duration of antibiotic treatment, especially in critically ill patients and for lower respiratory tract infections. Moreover, we reported recent studies in which PCT showed ahigh performance to detect precociously infections due to Gram-negativestrains. Data from the literature confirm that PCT should not be used as astand-alonetest in the absence of clinical judgment.
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http://dx.doi.org/10.1080/14787210.2019.1562335DOI Listing
February 2019

Epidemiological and clinical features of imported malaria at the three main hospitals of the Friuli-Venezia Giulia Region, Italy.

Infect Dis Health 2018 03 13;23(1):17-22. Epub 2017 Oct 13.

Clinical Microbiology and Virology Laboratory, Department of Laboratory Medicine, Azienda per l'Assistenza Sanitaria N.5 "Friuli Occidentale", Hospital of Pordenone, Via Montereale, 24, 33170 Pordenone, Italy. Electronic address:

Background: Imported malaria cases continue to occur in non-endemic regions among travellers returning from tropical and subtropical countries. At particular risk of acquiring malaria is the group of travellers identified as immigrants who return to their home country with the specific intent of visiting friends or relatives (VFRs) and who commonly believe they are immune to malaria and fail to seek pre-travel advice. Our aim was to review the current trends of imported malaria in the three main hospitals of the Friuli-Venezia Giulia region (FVG), North Eastern Italy, focusing in particular on patient characteristics and laboratory findings.

Methods: In this retrospective study, we examined all malaria cases among patients admitted from January 2010 through December 2014 to the emergency department of the three main hospitals located in FVG.

Results: During the 5-year study period from 2010 to 2014, there were a total of 140 patients with a diagnosis of suspected malaria and who received microscopic confirmation of malaria. The most common species identified was P. falciparum, in 96 of 140 cases (69%), followed by P. vivax (13%), P. ovale (4%), P. malariae (4%), and mixed infection (4%). The most common reason for travel was VFRs (54%), followed by work (17%), and recent immigration (15%). Moreover, 78% of all patients took no chemoprophylaxis, 80 (79%) of whom were foreigners. Notably, the percentage of Italian travellers who took chemoprophylaxis was only 20% (8 of 39 Italian cases), and the regimen was appropriate in only four cases. Parasitaemia greater than 5% was observed in 11 cases (10%), all due to P. falciparum infection.

Conclusions: We highlight that VFRs have the highest proportion of malaria morbidity and the importance of improving patient management in this category. These data are useful for establishing appropriate malaria prevention measures and recommendations for international travellers.
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http://dx.doi.org/10.1016/j.idh.2017.08.007DOI Listing
March 2018

Successful and safe long-term treatment of cerebral aspergillosis with high-dose voriconazole guided by therapeutic drug monitoring.

Br J Clin Pharmacol 2019 01 9;85(1):266-269. Epub 2018 Nov 9.

Department of Medicine, University of Udine, Udine, Italy.

We report the case of a patient who had cerebral aspergillosis after otorhinolaryngologic surgery and who was successfully and safely treated with high-dose voriconazole (200 mg q6h) for more than 1 year thanks to a TDM-guided approach coupled with pharmacological review and with genotyping of CYP2C19 polymorphisms. The findings support the idea that personalized medicine based on TDM coupled with the need of avoiding drug-drug interactions may be helpful for maximizing the net benefit (probability of efficacy vs. probability of adverse events) of voriconazole in the management of long-term treatment of cerebral aspergillosis.
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http://dx.doi.org/10.1111/bcp.13789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6303198PMC
January 2019

Disposition of ceftobiprole during continuous venous-venous hemodiafiltration (CVVHDF) in a single critically ill patient.

Eur J Clin Pharmacol 2018 Dec 10;74(12):1671-1672. Epub 2018 Aug 10.

Institute of Clinical Pharmacology, Santa Maria della Misericordia University Hospital of Udine, Azienda Sanitaria Universitaria Integrata di Udine, P. le S. Maria della Misericordia 3, 33100, Udine, Italy.

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http://dx.doi.org/10.1007/s00228-018-2535-0DOI Listing
December 2018

Independent risk factors for mortality in critically ill patients with candidemia on Italian Internal Medicine Wards.

Intern Emerg Med 2018 03 10;13(2):199-204. Epub 2018 Jan 10.

First Division of Infectious Diseases, Cotugno Hospital, Azienda Ospedaliera dei Colli, Naples, Italy.

Candida is an increasing cause of bloodstream infection and is associated with significant morbidity and mortality. The aim of our study is to analyze risk factors for short-term mortality in patients with bloodstream Candida spp. infections admitted to Internal Medicine Wards (IMWs). This was a retrospective case-control study between January 2012 and December 2014 from four University Hospitals in Italy, where patients with candidemia dying within 30 days from diagnosis were matched to control cases with candidemia who survived in the same period of time. Two-hundred and fifty cases of candidemia were registered during the 36 months of enrollment. Among these, 112 patients died (45%) within 30 days from the first blood culture's positivity for Candida spp. At multivariate analysis, septic shock [odds ratio (95% CI) = 2.919 (1.62-5.35), p < 0.001] and concomitant chronic kidney failure [odds ratio (95% CI) = 2.296 (1.07-5.12), p = 0.036] were independent predictors of mortality. Low-dose chronic steroid therapy was protective [odds ratio (95% CI) = 0.461 (0.25-0.83), p = 0.011).
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http://dx.doi.org/10.1007/s11739-017-1783-9DOI Listing
March 2018

The role of biofilm forming on mortality in patients with candidemia: a study derived from real world data.

Infect Dis (Lond) 2018 03 9;50(3):214-219. Epub 2017 Oct 9.

i Infectious Diseases Clinic , Nuovo Santa Chiara University Hospital, Azienda Ospedaliera Universitaria Pisana , Pisa , Italy.

Background: Evaluation of the role on patient mortality exerted by biofilm forming (BF) Candida strains, by using predictive clinical data.

Methods: Eighty-nine strains isolated from Candida bloodstream infection, occurring in two Italian University Hospitals, were employed in this study. A random forest (RF) model was built with a procedure of iterative selection of the risk factors potentially able to predict the probability of death. The similarity between patient conditions and Bayesian clustering was calculated in order to evaluate the role of predictors in the stratification of the death risk.

Results: Three different groups of patients with different probability of death were obtained with a RF approach: Group 1 (mortality in 33.3% of cases), Group 2 (death in 50% of cases), and Group 3 (mortality in 76.9% of cases). The comparison between these three groups showed that BF correlated well with increased mortality in patients, admitted for medical diagnosis, with high APACHE II score and treated with azoles. Early treatment within 24 h between candidemia diagnosis and the beginning of antifungal therapy was associated with the lowest of BF rate and mortality.

Conclusions: BF by Candida spp. seems to be clinically associated with increased mortality especially in medical patients with higher Apache II score or treated with azoles.
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http://dx.doi.org/10.1080/23744235.2017.1384956DOI Listing
March 2018

Invasive Candida Infections in Liver Transplant Recipients: Clinical Features and Risk Factors for Mortality.

Transplant Direct 2017 May 18;3(5):e156. Epub 2017 Apr 18.

Infectious Disease Department, Cisanello Hospital, Pisa, Italy.

Background: Invasive fungal infections remain a leading cause of morbidity and mortality among liver transplant recipients (LTRs). In this patient population, invasive Candida infections (ICIs) account for the large majority of cases. To date, only small studies and case-series analysing clinical presentation and risk factors for mortality in LTRs with ICIs are available.

Methods: We performed a retrospective multicenter multinational study in 10 centers in Europe and Brazil. All consecutive LTRs developing ICIs during the period January 2011 to December 2013 were included in the study.

Results: A total of 42 LTRs were included. Median age was 52.5 years, and 78.6% of patients were men. Viral hepatitis was the most common cause for liver transplantation (42.9%). Candidemia represented the majority of cases (24, 57.1%), followed by intra-abdominal candidiasis (18, 42.9%). Overall 30-day mortality was 23.8%, with higher mortality in patients with candidemia compared with intra-abdominal candidiasis (37.5% vs 5.6%, = 0.02). Multivariate analysis showed candidemia to be a risk factor associated with mortality among LTRs presenting ICIs (odds ratio, 11.86; 95% confidence interval, 1.5-280; = 0.01). represented the most common isolate (59.5%). High rates of antifungal resistances were found, with 16.7% and 4.8% of isolates displaying resistance to azoles and caspofungin, respectively.

Conclusions: Our study confirms the occurrence of high mortality rates in LTRs developing ICIs. Mortality rates varied according to the type of infection, with candidemia representing a risk factor for mortality. The high rates of antifungal resistance should be considered in the choice of the empiric antifungal regimen.
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http://dx.doi.org/10.1097/TXD.0000000000000673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5441987PMC
May 2017

Elderly versus non-elderly patients with intra-abdominal candidiasis in the ICU.

Minerva Anestesiol 2017 11 11;83(11):1126-1136. Epub 2017 May 11.

Infectious Diseases Clinic, Santa Maria Misericordia University Hospital, Udine, Italy.

Background: Intra-abdominal candidiasis (IAC) has a considerable cost in terms of mortality and morbidity. We sought to study the epidemiology, characteristics and outcome of elderly (>75 years old) versus non-elderly patients with IAC and risk factors for mortality in elderly patients.

Methods: Post-hoc analysis of a retrospective multinational cohort study over a 3-year period (2011-2013).

Results: Of 482 patients, 124 (25.7%) were elderly and 358 (74.3%) were non-elderly. The mean age was 80.4±3.9 and 56.3±13.8 years, respectively. Fifty-four of 124 (43.5%) and 75/358 (20.9%) died until the end of observation. The majority of isolates were Candida albicans. Echinocandins were the most prescribed initial agent. Elderly patients were more likely to have a higher APACHE II Score, and to suffer from chronic obstructive pulmonary disease and heart disease. Non-elderly patients were more likely to be treated with immunosuppressants and steroids, and to have received solid organ transplantation. Mortality was significantly higher in the elderly group. Regarding risk factors for mortality in elderly patients, non-survivors were more likely to be males, reoperated, develop septic shock, receive vasopressors, suffer from end-stage renal disease (ESRD), and have inadequate abdominal source control within 48 hours. They had a higher APACHE II Score and a higher number of acquired organ dysfunction. ESRD and inadequate abdominal source control were significantly associated with mortality.

Conclusions: Factors independently predicting mortality in elderly patients with IAC were ESRD and inadequate abdominal source control. Elderlies were found to have more pulmonary and cardiac morbidities and had higher mortality than non-elderlies.
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http://dx.doi.org/10.23736/S0375-9393.17.11528-2DOI Listing
November 2017

Higher fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) uptake in tuberculous compared to bacterial spondylodiscitis.

Skeletal Radiol 2017 Jun 15;46(6):777-783. Epub 2017 Mar 15.

Infectious Diseases Division, Santa Maria della Misericordia University Hospital, 50, Colugna Street, Udine, 33100, Italy.

Background: Tuberculous spondylodiscitis can be difficult to diagnose because of its nonspecific symptoms and the similarities with non-tubercular forms of spinal infection. Fluorine-18-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG PET-CT) is increasingly used for the diagnosis and monitoring of tubercular diseases.

Methods: Retrospective, case-control study comparing tuberculous spondylodiscitis with biopsy-confirmed pyogenic spondylodiscitis in the period 2010-2012.

Results: Ten cases of tuberculous spondylodiscitis and 20 controls were included. Compared to pyogenic, tuberculous spondylodiscitis was more frequent in younger patients (P = 0.01) and was more often associated with thoraco-lumbar tract lesions (P = 0.01) and multiple vertebral involvement (P = 0.01). Significantly higher maximum standardized uptake values (SUV) at FDG-PET were displayed by tuberculous spondylodiscitis compared to controls (12.4 vs. 7.3, P = 0.003). SUV levels above 8 showed the highest value of specificity (0.80). Mean SUV reduction of 48% was detected for tuberculous spondylodiscitis at 1-month follow-up.

Conclusions: Higher SUV levels at FDG-PET were detected in tuberculous compared with pyogenic spondylodiscitis. PET-CT use appeared useful in the disease follow-up after treatment initiation.
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http://dx.doi.org/10.1007/s00256-017-2615-8DOI Listing
June 2017

Clinical characteristics and predictors of mortality in cirrhotic patients with candidemia and intra-abdominal candidiasis: a multicenter study.

Intensive Care Med 2017 Apr 7;43(4):509-518. Epub 2017 Mar 7.

Clinica Malattie Infettive, Università degli Studi di Udine, Azienda Sanitaria Universitaria Integrata, Presidio Ospedaliero "Santa Maria della Misericordia", Piazzale S. Maria della Misericordia n. 15, 33100, Udine, Italy.

Purpose: The aim of the study was to describe the characteristics of cirrhotic patients with candidemia and intra-abdominal candidiasis (IAC) and to evaluate the risk factors associated with 30-day mortality.

Methods: A multicenter multinational retrospective study including all consecutive episodes of candidemia and IAC in adult patients with liver cirrhosis in 14 European hospitals during the period 2011-2013 was performed.

Results: A total of 241 episodes (169 candidemia, 72 IAC) were included. Most Candida infections were acquired in hospital (208, 86.3%), mainly in the intensive care unit (ICU) (121, 50.2%). At clinical presentation, fever was seen in 60.6% of episodes (146/241) and septic shock in 34.9% (84/241). C. albicans was the most common species (found in 131 episodes, 54.4%), followed by C. glabrata (35, 14.5%) and C. parapsilosis (34, 14.1%). Overall, the 30-day mortality was 35.3%. Multivariable analysis identified candidemia (OR 2.2, 95% CI 1.2-4.5) and septic shock (OR 3.2, 95% CI 1.7-6) as independent factors associated with 30-day mortality. Adequate antifungal treatment (OR 0.4, 95% CI 0.3-0.9) was associated with survival benefit.

Conclusions: A shift towards increasing prevalence of C. glabrata and C. parapsilosis species in patients with liver disease was documented. Candidemia and IAC were associated with significant mortality in cirrhotic patients. Thirty-day mortality was associated with candidemia and severe clinical presentation, whereas adequate antifungal treatment improved the prognosis.
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http://dx.doi.org/10.1007/s00134-017-4717-0DOI Listing
April 2017

Pulmonary nodules in African migrants caused by chronic schistosomiasis.

Lancet Infect Dis 2017 05 15;17(5):e159-e165. Epub 2017 Feb 15.

Centre for Tropical Diseases, Sacro Cuore-Don Calabria Hospital, Negrar, Verona, Italy; Global Health Center, Florence, Italy.

Schistosomiasis is a neglected tropical disease that can cause mainly hepatic and genitourinary damage, depending on the species. Involvement of the lungs has been commonly described in acute infection (Katayama syndrome) and chronic infection (pulmonary hypertension). Although rarely reported in the scientific literature, cases of lung nodules due to chronic schistosome infection are also possible and are probably more frequent than commonly thought. Here we report seven cases of African migrants who were diagnosed with chronic schistosomiasis and pulmonary nodules due to deposition of schistosome eggs, and we compare our findings to the case reports found in the scientific literature. We discuss the management of these patients in a non-endemic setting, beginning with a first fundamental step that is to include parasitic infections, namely schistosomiasis, in the differential diagnosis of pulmonary nodules in African immigrants. All patients responded to antiparasitic treatment with praziquantel after a relatively short time. We therefore conclude that lung biopsies and other invasive procedures (performed in the first cases to rule out other potential causes, such as tuberculosis or malignant nodules) can be avoided or postponed.
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http://dx.doi.org/10.1016/S1473-3099(16)30530-8DOI Listing
May 2017

Candidemia in Patients with Body Temperature Below 37°C and Admitted to Internal Medicine Wards: Assessment of Risk Factors.

Am J Med 2016 Dec 22;129(12):1330.e1-1330.e6. Epub 2016 Jul 22.

Infectious Diseases Clinic, Nuovo Santa Chiara University Hospital, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy. Electronic address:

Background: An increasing number of candidemia episodes has been reported in patients cared for in internal medicine wards. These usually older and frail patients may not be suspected as having candidemia because they lack fever at the onset of the episode. To identify the risk factors associated with the lack of fever at the onset of candidemia (ie, the collection of the first positive blood culture for Candida spp.) in patients cared for in internal medicine wards, we compared 2 group of patients with or without fever.

Methods: We retrospectively review data charts from 3 tertiary care, university hospitals in Italy, comparing patients with or without fever at onset of candidemia. Consecutive candidemic episodes in afebrile patients and matched febrile controls were identified during the 3-year study period. Patient baseline characteristics and several infection-related variables were examined. Random forest analysis was used, given the number of predictors to be considered and the potential complexity of their relations with the onset of fever.

Results: We identified 147 candidemic episodes without fever at onset and 147 febrile candidemia episodes. Factors associated with the lack of fever at onset of candidemia were diabetes, Clostridium difficile infection, and a shorter delta time from internal medicine wards admission to the onset of candidemia. The only variable associated with fever was the use of intravascular devices. Quite unexpectedly, antifungal therapy was administered more frequently to patients without fever, and no differences on 30-day mortality rate were documented in the 2 study groups.

Conclusions: Clinicians should be aware that an increasing number of patients with invasive candidiasis cared for in internal medicine wards may lack fever at onset, especially those with diabetes and C. difficile infection. Candidemia should be suspected in patients with afebrile systemic inflammatory response syndrome or in worsening clinical condition: blood cultures should be taken, and a timely and appropriate antifungal therapy should be considered.
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http://dx.doi.org/10.1016/j.amjmed.2016.06.043DOI Listing
December 2016

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

Infection 2016 Dec 11;44(6):747-755. Epub 2016 Jul 11.

Infectious Diseases Division, Santa Maria Misericordia University Hospital, Piazzale Santa Maria della Misericordia 15, 33010, Udine, Italy.

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.
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http://dx.doi.org/10.1007/s15010-016-0924-9DOI Listing
December 2016

Exploring ecological modelling to investigate factors governing the colonization success in nosocomial environment of Candida albicans and other pathogenic yeasts.

Sci Rep 2016 06 1;6:26860. Epub 2016 Jun 1.

Infectious Diseases Clinic, Santa Maria Misericordia University Hospital, Piazzale Santa Maria della Misericordia, 15, 33100 Udine, Italy.

Two hundred seventy seven strains from eleven opportunistic species of the genus Candida, isolated from two Italian hospitals, were identified and analyzed for their ability to form biofilm in laboratory conditions. The majority of Candida albicans strains formed biofilm while among the NCAC species there were different level of biofilm forming ability, in accordance with the current literature. The relation between the variables considered, i.e. the departments and the hospitals or the species and their ability to form biofilm, was tested with the assessment of the probability associated to each combination. Species and biofilm forming ability appeared to be distributed almost randomly, although some combinations suggest a potential preference of some species or of biofilm forming strains for specific wards. On the contrary, the relation between biofilm formation and species isolation frequency was highly significant (R(2) around 0.98). Interestingly, the regression analyses carried out on the data of the two hospitals separately were rather different and the analysis on the data merged together gave a much lower correlation. These findings suggest that, harsh environments shape the composition of microbial species significantly and that each environment should be considered per se to avoid less significant statistical treatments.
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http://dx.doi.org/10.1038/srep26860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4887984PMC
June 2016

Determination of PCT on admission is a useful tool for the assessment of disease severity in travelers with imported Plasmodium falciparum malaria.

Acta Parasitol 2016 Mar;61(2):412-8

Procalcitonin (PCT) and C-reactive protein (CRP) may be useful to predict complicated forms of malaria. A total of 30 consecutive travelers diagnosed with Plasmodium falciparum malaria over a two-year period were included in the study. Patients with complicated Plasmodium falciparum malaria showed higher levels of parasitemia (P = 0.0001), PCT (P = 0.0018), CRP (P = 0.0005), bilirubinemia (P = 0.004), and a lower platelet count (P<0.0001) compared with patients with uncomplicated forms. PCT levels above 5 ng/mL showed the highest value of specificity (0.86) and positive predictive factor (0.67) among other parameters, and equal sensitivity (0.67) was displayed by CRP levels above 150 mg/dl. None of the patients with complicated malaria showed PCT levels within normal limits (<0.5 ng/ml). Both PCT and CRP correlated with parasitemia (P<0.001) and showed areas under ROC curve of 0.83. At multivariate analysis, only PCT was associated with an increased risk of complicated malaria (OR 8.2, IC 95% 1.2-57.2, P = 0.03). The determination of PCT on admission showed better results compared to CRP, platelet count, and bilirubinemia and can be useful in non-endemic areas for the initial clinical assessment of disease severity in travelers with Plasmodium falciparum malaria.
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http://dx.doi.org/10.1515/ap-2016-0055DOI Listing
March 2016

Tick-borne encephalitis in north-east Italy: a 14-year retrospective study, January 2000 to December 2013.

Euro Surveill 2015 ;20(40)

Department of Infectious, Parasitic and Immunomediated Diseases, National Institute of Health, Rome, Italy.

Italy is considered at low incidence of tick-borne encephalitis (TBE), and the occurrence of human cases of TBE appears to be geographically restricted to the north east of the country. However, most information to date derives from case series, with no systematic data collection. To estimate incidence rates (IR) and spatial distribution of TBE cases, we conducted a retrospective study in north-eastern Italy. Data were collected through the infectious disease units and public health districts of three regions (Friuli Venezia Giulia, Trentino Alto Adige and Veneto) between 2000 and 2013. Overall, 367 cases were identified (IR: 0.38/100,000). The cases' median age was 56 years and 257 (70%) were male. Central nervous system involvement was reported in 307 cases (84%). Annual fluctuations in case numbers occurred, with peaks in 2006 and in 2013, when 44 and 42 cases were respectively observed. A strong seasonality effect was noted, with the highest number of cases in July. In terms of geographical location, three main endemic foci with high TBE IR (>10/100,000) were identified in three provinces, namely Belluno (Veneto region), Udine (Friuli Venezia Giulia) and Trento (Trentino Alto-Adige). When investigating the whole study area in terms of altitude, the IR between 400 and 600 m was greater (2.41/100,000) than at other altitudes (p<0.01). In conclusion, the incidence of TBE in Italy is relatively low, even considering only the three known affected regions. However, three endemic foci at high risk were identified. In these areas, where the risk of TBEV infection is likely high, more active offer of TBE vaccination could be considered.
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http://dx.doi.org/10.2807/1560-7917.ES.2015.20.40.30034DOI Listing
April 2016

Persistent viremia and urine shedding of tick-borne encephalitis virus in an infected immunosuppressed patient from a new epidemic cluster in North-Eastern Italy.

J Clin Virol 2015 Aug 29;69:48-51. Epub 2015 May 29.

Department of Medical, Surgical and Health Sciences, University of Trieste, Italy; Institute for Maternal and Child Health - IRCCS Burlo Garofolo, Trieste, Italy. Electronic address:

A persistent tick-borne encephalitis virus infection in an immune-suppressed patient is presented. Such an unusual clinical case offers the unique chance of detecting persistent viremia associated to the erythrocyte fraction and shedding of the virus in the urine for more than six weeks. The infection occurred in a new area of the Friuli Venezia-Giulia region (North Eastern Italy) where two additional cases are also being reported.
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http://dx.doi.org/10.1016/j.jcv.2015.05.019DOI Listing
August 2015

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

Intensive Care Med 2015 Sep 19;41(9):1601-10. Epub 2015 May 19.

Infectious Diseases Division, Santa Maria Misericordia University Hospital, Piazzale Santa Maria della Misericordia 15, 33100, Udine, Italy,

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.
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http://dx.doi.org/10.1007/s00134-015-3866-2DOI Listing
September 2015

Clinical and therapeutic aspects of candidemia: a five year single centre study.

PLoS One 2015 26;10(5):e0127534. Epub 2015 May 26.

Infectious Diseases Division, Santa Maria Misericordia University Hospital, Udine, Italy.

Background: Candida is an important cause of bloodstream infections (BSI) in nosocomial settings causing significant mortality and morbidity. This study was performed to evaluate contemporary epidemiology, species distribution, antifungal susceptibility and outcome of candida BSI in an Italian hospital.

Methods: All consecutive patients who developed candidemia at Santa Maria della Misericordia University Hospital (Italy) between January 2009 and June 2014 were enrolled in the study.

Results: A total of 204 episodes of candidemia were identified during the study period with an incidence of 0.79 episodes/1000 admissions. C. albicans was isolated in 60.3% of cases, followed by C. parapsilosis (16.7%), C. glabrata (11.8%) and C. tropicalis (6.4%). Of all Candida BSI, 124 (60.8 %) occurred in patients admitted to IMW, 31/204 (15.2 %) in ICUs, 33/204 (16.2%) in surgical units and 16/204 (7.8%) in Hematology/Oncology wards. Overall, 47% of patients died within 30 days from the onset of candidemia. C. parapsilosis and C. glabrata candidemia were associated with the lowest mortality rate (36%), while patients with C. tropicalis BSI had the highest mortality rate (58.3%). Lower mortality rates were detected in patients receiving therapy within 48 hours from the time of execution of the blood cultures (57,1% vs 38,9%, P < 0.05). At multivariate analysis, steroids treatment (OR = 0.27, p = 0.005) and CVC removal (OR = 3.77, p = 0.014) were independently associated with lower and higher survival probability, respectively. Candidemia in patients with peripherally inserted central catheters (PICC) showed to be associated with higher mortality in comparison with central venous catheters (CVC, Short catheters and Portacath) and no CVC use. For each point increase of APACHE III score, survival probability decreased of 2%. Caspofungin (OR = 3.45, p = 0.015) and Amphothericin B lipid formulation (OR = 15.26, p = 0.033) were independently associated with higher survival probability compared with no treatment.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0127534PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4444310PMC
April 2016

Comparison of clinical characteristics of tuberculosis between two age groups at an Italian Tertiary Hospital.

Infection 2015 Jun 26;43(3):361-6. Epub 2015 Mar 26.

Infectious Diseases Division, Santa Maria della Misericordia University Hospital, 50, Colugna Street, 33100, Udine, UD, Italy,

Differences in clinical characteristics and outcome between elderly (>60 years) and younger (18-59 years) tuberculosis (TB) patients were retrospectively evaluated. Alcohol abuse, radiological evidence of cavitation, and cough at presentation were more frequent among younger patients. Older patients were more likely to have comorbidities, disseminated TB, longer duration of symptoms and higher TB-related mortality (19 vs 0%). Very old patients (≥80 years) showed increased liver toxicity and hospital acquired infections compared to patients aged 60-79 years.
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http://dx.doi.org/10.1007/s15010-015-0765-yDOI Listing
June 2015
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