Clinical characteristics, management and outcome of patients with invasive candidiasis hospitalized in Internal Medicine Units: findings from a registry by the Italian Scientific Society FADOI.

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.

Successful Antifungal Combination Therapy and Surgical Approach for Aspergillus fumigatus Suppurative Thyroiditis Associated with Thyrotoxicosis and Review of Published Reports.

In immunocompromised patients, Aspergillus infections are important causes of morbidity and mortality. We describe a patient with cryoglobulinemic vasculitis who developed disseminated invasive aspergillosis with thyrotoxicosis caused by Aspergillus fumigatus. The diagnosis was based upon radiological, microbiological and pathological findings. The patient was treated successfully with voriconazole and caspofungin treatment followed by total thyroidectomy. We provide an overview of published reports on Aspergillus thyroiditis with an emphasis on therapeutic approaches.

Current and future trends in antibiotic therapy of acute bacterial skin and skin-structure infections.

In 2013 the US Food and Drug Administration (FDA) issued recommendations and guidance on developing drugs for treatment of skin infection using a new definition of acute bacterial skin and skin-structure infection (ABSSSI). The new classification includes cellulitis, erysipelas, major skin abscesses and wound infection with a considerable extension of skin involvement, clearly referring to a severe subset of skin infections. The main goal of the FDA was to better identify specific infections where the advantages of a new antibiotic could be precisely estimated through quantifiable parameters, such as improvement of the lesion size and of systemic signs of infection. Before the spread and diffusion of methicillin-resistant Staphylococcus aureus (MRSA) in skin infections, antibiotic therapy was relatively straightforward. Using an empiric approach, a ß-lactam was the preferred therapy and cultures from patients were rarely obtained. With the emergence of MRSA in the community setting, initial ABSSSI management has been changed and readdressed. Dalbavancin, oritavancin and tedizolid are new drugs, approved or in development for ABSSSI treatment, that also proved to be efficient against MRSA. Dalbavancin and oritavancin have a long half-life and can be dosed less frequently. This in turn makes it possible to treat patients with ABSSSI in an outpatient setting, avoiding hospitalization or potentially allowing earlier discharge, without compromising efficacy. In conclusion, characteristics of long-acting antibiotics could represent an opportunity for the management of ABSSSI and could profoundly modify the management of these infections by reducing or in some cases eliminating both costs and risks of hospitalization.

Neurological complications of HIV infection in pre-HAART and HAART era: a retrospective study.

The introduction of highly active anti-retroviral therapy (HAART) led to a radical change in the natural history of HIV infection and of the associated neurological opportunistic infections. However, the mortality of central nervous system (CNS) complications and opportunistic infections is still high in untreated HIV-infected individuals or in patients unaware of their HIV infection. We describe the outcome of HIV-infected patients followed at a single center for AIDS-related neurological syndromes in the 16 years following the introduction of HAART, and compare the findings with those in patients admitted up to 1996. We have conducted a retrospective study of patients with HIV infection or AIDS (based on WHO criteria and classified according to the 1993 CDC criteria) admitted during 20 years (January 1992 to March 2012) to the Infectious Diseases Unit of the University of Verona for the presence of focal or widespread CNS lesion on neuroimaging. Clinical history, CD4 cell count, HIV-RNA level, neurological examination, imaging, cerebrospinal fluid examination and eventual cerebral biopsy results were reviewed as well as the final neurological diagnosis and the treatment. The survival time from the clinical onset of the neurologic syndrome to death was calculated for each patient who died. A statistical analysis was performed comparing data collected up to and after 1996, i.e., before and after HAART introduction. Among 1043 patients with HIV infection or AIDS admitted to the Infectious Diseases Unit of the University of Verona between January 1992 and March 2012, 114 had a CNS lesion. The following diseases were observed: neurotoxoplasmosis (NT), progressive multifocal leukoencephalopathy), primary central nervous system lymphoma (PCNSL), the severe form of HIV-associated neurocognitive disorder, cryptococcal encephalitis (CE) and lesions of undetermined origin. The follow-up period was 4 weeks to 72 months both in the pre-HAART and HAART era. Cerebral lesions were detected in 53/243 patients (21.8%) in the pre-HAART era and in 61/801 patients (7.6%) in the HAART era (p < 0.001). Most patients who developed a neurological complication in the HAART period (40/59, 67.8%) were untreated or did not know to be HIV-infected; in particular, 27.9% of patients with a CNS lesion in the HAART era were unaware of their HIV infection vs 13.2% in the pre-HAART era (p < 0.05). Some patients were not virologically suppressed (14/59, 23.7%) or were immunological non-responders (undetectable viral load, with CD4 count <200 cells/µL; 4/59, 6.8%). Other statistically significant data were the mean age at the onset of neurological complications (32.6 ± 5.4 years in the pre-HAART, 40.3 ± 9.5 in the HAART group, p < 0.001) and the mean CD4 cell count at the onset of illness (median of 38 cells/µL (2-215) in the pre-HAART, 77 cells/µL (2-752) in the HAART group; p < 0.001). In the HAART era a reduction of PCNSL and NT was observed. Our results, while confirming a decrease in the incidence of opportunistic infections of the CNS in the HAART era, show that late presentation of patients with HIV infection remains an important issue in our catchment area.

Interference of confounding factors on the use of (1,3)-beta-D-glucan in the diagnosis of invasive candidiasis in the intensive care unit.

Invasive fungal infections (IFIs) are an increasing problem in intensive care units (ICUs), and conventional diagnostic methods are not always reliable or timely enough to deliver appropriate antimicrobial therapy. The dosage of fungal antigens in serum is a promising diagnostic technique, but several confounding factors, such as treatment with immunoglobulins (Ig), albumin, or antifungals, could interfere with the correct interpretation of the (1,3)-beta-D-glucan (BG) assay. This study assessed the reliability of the BG assay and the influence of timing and dosage of major confounding factors on circulating levels of IFI biomarkers. 267 ICU patients who underwent a BG assay were retrospectively studied. The timing and dosage of albumin, use of azole treatment, and infusions of intravenous IgG, red blood cells, concentrated platelets, and frozen plasma were analyzed to find possible correlations with the BG results. The sensitivity and specificity of the BG assay were calculated. The BG test in serum showed high sensitivity (82.9 %) but low specificity (56.7 %). The optimal cut-off for the test was 95.9 pg/mL. The mean BG level in proven invasive candidiasis was around 400 pg/mL. The only factor that was found to significantly confound (p < 0.05) the diagnostic performance of the BG assay was the administration of more than 30 g of albumin within 2 days prior to BG testing. The BG assay remains a useful diagnostic test in ICU patients and the levels of BG are useful in evaluating the positive predictive value of this biomarker. The only confounding factor in our study was the use of albumin.

Treatment of chronic pulmonary aspergillosis with voriconazole: review of a case series.

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)-ß-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. [(18)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.

SIMIFF study: Italian fungal registry of mold infections in hematological and non-hematological patients.

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.

Lymphocyte subpopulations in active tuberculosis: association with disease severity and the QFT-GIT assay.

Cell-mediated immune response plays an essential role in the pathogenesis of tuberculosis (TB). We retrospectively evaluated lymphocyte subpopulations in 177 active TB patients compared to 93 healthy controls, finding a relevant decrease in total lymphocytes and CD8+ cells. Conversely, activated human leukocyte antigen (HLA-DR+) and CD4+CD57+ cells were higher in the TB group. B-1a (CD5+CD19+) lymphocytes were reduced in TB subjects, particularly those with extended and cavitary pulmonary forms, suggesting increased compartmentalisation at the infection site. QuantiFERON-TB Gold In-Tube positive results were associated with higher HLA-DR+CD4+ and CD4+CD57+ cells, while interferon-gamma response and total lymphocyte levels were lower in advanced pulmonary TB cases.

Prolonged hospitalisation for immigrants and high risk patients with positive smear pulmonary tuberculosis.

BACKGROUND AND OBJECTIVE: Tuberculosis (TB) occurring in immigrants and resistance to drugs are major problems for TB control in Western countries. Directly observed therapy (DOT) reduces disease transmission, but this approach may have poor results among illegal immigrants. Our aim was to evaluate a prolonged hospitalisation programme to improve early outcome of TB treatment in high risk patients. METHODS: All the consecutive adult patients with sputum smear-positive pulmonary TB admitted to 2 Italian referral TB Centres were evaluated. Hospital-based DOT was provided to high risk patients up-to smear conversion. Demographic, microbiological and clinical conditions, as potential factors associated with confirmed smear conversion at 60 and 90 days of anti-tuberculous therapy were evaluated. RESULTS: 122 patients were studied, 45.9% of them were immigrants (20% illegal) from high-prevalence TB countries. HIV testing was negative in all cases. Twelve patients had M. tuberculosis resistant to > or = 1 first-line anti-tuberculous agents. The rate of defaulting from TB treatment was 73%. Sputum smear became negative in 84.4% cases after 60 days and 933% cases after 90 days. At such time, smear conversion rates were similar among different high risk subgroups such as illegal immigrants (95.9%), legal foreign-born (92.5%) and Italian persons (94.8%). Persistent sputum smear positivity was independently correlated with the extent of pulmonary lesions at 60 (p < 0.0001) and 90 days (p = 0.038) of hospital-based DOT. CONCLUSIONS: These findings suggest that prolonged hospitalisation for illegal immigrants and high risk TB patients, may positively influence the early outcome of TB treatment despite of drug resistance and legal status.

[Survey on the ability to prescribe antibiotic therapy among Italian residents in geriatrics and internal medicine]. / Indagine sulla capacità deglispecializzandi in geriatriae in medicina interna diprescrivere terapia antibioticain Italia.

Antibiotic therapy is a crucial and often life-saving strategy. This study assessed the ability to prescribe antibiotic therapy among a series of Italian postgraduate students in geriatrics and internal medicine. Participants were administered an anonymous questionnaire consisting of self-assessment of their ability to prescribe antibiotics and then manage a case of community-acquired pneumonia. The Wilcoxon test for comparisons between two independent samples was used for statistical analysis. Almost half the 70 students considered their knowledge of antibiotic therapy insufficient and were not satisfied with the notions received during their studies. Indeed, the change in antibiotic therapy required to control acute exacerbation of pneumonia was correctly identified by only 36% of students. Moreover, 38% of them gave the correct answer on factors influencing the duration of antibiotic therapy in the presence of definite improvement of pneumonia. No significant difference was found between the responses of residents in geriatrics and internal medicine. Overall, our study shows that nearly half of our students think they have inadequate antibiotic prescribing skills. This is confirmed by a low ability to establish the best management of the clinical case. To repair this severe shortcoming, different training methods need to be compared and more effective forms of instruction adopted.

[Herpes zoster in general medicine: experience of the Italian group Netaudit]. / Herpes zoster e medicinagenerale: l'esperienza deimedici del gruppo Netaudit.

Herpes zoster is caused by the reactivation of the varicella-zoster virus (VZV) and usually appears many years after primary infection (varicella), induced by immunosuppression due to underlying diseases. Few epidemiological data in Italy are available concerning Herpes zoster, mainly because disease notification is not mandatory. An observational perspective trial was conducted for 12 months by 41 Italian general practitioners belonging to the Netaudit network to determine herpes zoster incidence and its correlation to patients' characteristics (age, gender, educational qualification, co-morbidities), the delay from correct diagnosis to the start of treatment and different drug prescription. In all, the study involved 193 patients with herpes zoster: this population included mostly female (60.6%) and elderly subjects (59.6%) with a mean age of 60.4 years. 46.1% of patients presented underlying diseases (diabetes 13%, solid tumours 5.7%). Correct diagnosis was achieved after a mean delay of 49 hours while therapy was started within 48 hours in most cases (75.1%). Aciclovir (51%) and valaciclovir (24%) were the most commonly used drugs. A significant correlation between educational level and prompt treatment suggests the major role of education in primary health prevention campaigns.

Prevalence of Strongyloides stercoralis infection among HIV-positive immigrants attending two Italian hospitals, from 2000 to 2009.

In patients with Strongyloides stercoralis infection, a dysregulation of host immunity can lead to hyperinfection syndrome (HS) and disseminated strongyloidiasis (DS), characterized by high fatality rate. HS has been reported in HIV-positive patients following use of corticosteroids or during immune reconstitution inflammatory syndrome (IRIS). A retrospective study was conducted to estimate the prevalence of S. stercoralis infection among HIV-positive immigrants, attending two Italian hospitals. From January 2000 to August 2009, 138 HIV-positive immigrants were systematically screened for strongyloidiasis, as a part of their routine care, with an indirect immunofluorescent antibody test (IFAT) developed at the Centre for Tropical Diseases, Sacro Cuore Hospital of Negrar, Verona. The majority were also submitted to stool examination. Fifteen (11%) resulted infected by S. stercoralis, of whom four (27%) had a negative serology (diagnosis made with stool examination). A higher eosinophil count (0·94 versus 0·24×10(9)/l, P<0·01) and more frequent gastrointestinal and cutaneous symptoms (odds ratio: 4·8 and 5·8, respectively) were found in patients with strongyloidiasis compared with controls. The IFAT is more sensitive than direct parasitological methods. The proportion of false negative results was higher than expected based on the theoretical test sensitivity. Considering the high prevalence detected and the apparent, lower sensitivity of serology, we propose a systematic screening for Strongyloides infection, with both serology and stool culture, for all HIV-positive immigrants coming from endemic areas.