Predominance of Clostridium difficile 027 during a five-year period in Bolzano, Northern Italy.

Toxigenic Clostridium difficile is responsible for antibiotic-associated diarrhoea and other diseases. The increasing frequency and severity is attributed to highly-virulent ribotypes such as 027. The aim of the study was to collect epidemiological and molecular data for C. difficile isolates during 2009-2013 in the Central Hospital of Bolzano, Northern Italy. Stool samples from inpatients of the Bolzano Central Hospital were screened for toxins A and B, and C. difficile was cultured and tested for antibiotic susceptibility. PCRs were performed for genes of toxin A, toxin B, binary toxin and ribotyping. During the period 2009-13 from 320 patients (9% of patients tested) at least one stool sample proved positive for C. difficile toxins, and incidences for all hospital inpatients per 10,000 patient days (per 1,000 admissions) varied between 2.2 (1.5) and 4.3 (3.0). Out of 138 isolates (43% of total isolates were studied), 24 different ribotypes were identified. Isolates with ribotype 027 were predominant (38%), followed by 018 (13%) and 607 (10%). Whereas for ribotype 018 a significant decrease was seen during the five-year period, ribotype 027 increased significantly from 0% in 2009 to 64% in 2012, decreasing then to 10% in 2013. Isolates were sensitive to metronidazole and vancomycin, whereas isolates of the three major ribotypes were resistant to moxifloxacin. Our data indicates a significant change in C. difficile incidence rates and ribotype frequencies during the five-year period in the Central Hospital in Bolzano.

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

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.

Increased IL-17, a Pathogenic Link between Hepatosplenic Schistosomiasis and Amyotrophic Lateral Sclerosis: A Hypothesis.

The immune system protects the organism from foreign invaders and foreign substances and is involved in physiological functions that range from tissue repair to neurocognition. However, an excessive or dysregulated immune response can cause immunopathology and disease. A 39-year-old man was affected by severe hepatosplenic schistosomiasis mansoni and by amyotrophic lateral sclerosis. One question that arose was, whether there was a relation between the parasitic and the neurodegenerative disease. IL-17, a proinflammatory cytokine, is produced mainly by T helper-17 CD4 cells, a recently discovered new lineage of effector CD4 T cells. Experimental mouse models of schistosomiasis have shown that IL-17 is a key player in the immunopathology of schistosomiasis. There are also reports that suggest that IL-17 might have an important role in the pathogenesis of amyotrophic lateral sclerosis. It is hypothesized that the factors that might have led to increased IL-17 in the hepatosplenic schistosomiasis mansoni might also have contributed to the development of amyotrophic lateral sclerosis in the described patient. A multitude of environmental factors, including infections, xenobiotic substances, intestinal microbiota, and vitamin D deficiency, that are able to induce a proinflammatory immune response polarization, might favor the development of amyotrophic lateral sclerosis in predisposed individuals.

Treatment of DIHS/DRESS syndrome with combined N-acetylcysteine, prednisone and valganciclovir--a hypothesis.

BACKGROUND: Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS) is a rare and severe adverse drug reaction with an associated mortality of 10-20%. Clinical worsening despite discontinuation of the culprit drug is considered a characteristic feature of DIHS/DRESS. Besides the early recognition of the syndrome and discontinuation of its causative drug, the mainstay of treatment is systemic corticosteroids. Nevertheless, treatment of severe DIHS/DRESS is not well defined, as corticosteroids may sometimes not be effective, and decreasing the dose may be associated with flaring of the disease. CASE REPORT: A 38-year-old woman with high fever, malaise, abdominal pain, rash, and elevated liver enzymes received immediate high-dose N-acetylcysteine, because acetaminophen hepatotoxicity was suspected. N-acetylcysteine administration was associated with a significant clinical improvement. However, within the next week DIHS/DRESS syndrome was diagnosed, which explained all the symptoms, and which was subsequently treated with prednisone and valganciclovir. CONCLUSIONS: New options necessary to improve treatment of severe DIHD/DRESS have to consider its sequential pathogenetic mechanisms. N-acetylcysteine might neutralize the drug-derived reactive metabolites, which are responsible for protein adduct formation and specific T cell stimulation, and replete the glutathione stores that counterbalance oxidative stress. Prednisone might inhibit lymphoproliferation and valganciclovir might prevent complications related to HHV-6 reactivation. We therefore propose the unprecedented combination of N-acetylcysteine, prednisone and valganciclovir as a treatment option for DIHS/DRESS.

Molecular epidemiology of methicillin-resistant Staphylococcus aureus from bacteraemia in northern Italy.

BACKGROUND: Vancomycin is frequently used in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia; reduced susceptibility to vancomycin is therefore disturbing. METHODS: molecular epidemiological analysis of 81 MRSA bacteraemia isolates collected during 2002-10 in the province of Bolzano, northern Italy was performed. MICs of a range of antimicrobials were determined by agar microdilution, screening for hGISA was by Macro-Etest and Etest GRD and confirmed by PAP-AUC with vancomycin and teicoplanin. All isolates were characterised by toxin gene profiling, agr, spa, and SCCmec-typing; MLST and PFGE were carried out on representative strains. RESULTS: The dominant clones identified were ST8-MRSA-IVc (55%) and ST228- and ST111-MRSA-I (25%); most of the latter two lineages (19/20; 95%) were GISA or PAP-AUC confirmed hGISA. One ST8-MRSA-IVc isolate harboured ccrA2B2 together with ccrA4B4. The remainder were diverse genotypically and belonged to MLST clonal complexes 1, 22, 45 and 398. CONCLUSIONS: Diverse lineages of MRSA were identified as causing bacteraemia in a province in northern Italy. The association of a specific genotype with the hGISA and GISA phenotypes among representatives of the second most common lineage identified is of clinical concern.

Fatal lactic acidosis precipitated by nifedipine in a patient treated with disulfiram and antiretrovirals.

A 43 year old man with HIV and HCV infection and liver cirrhosis developed fatal lactic acidosis within five days from starting nifedipine for arterial hypertension. Multiple drug interactions, current and accumulated drug toxicities and the reduced liver function, might in combination have led to the acute lactic acidosis.

Severe hepatotoxicity after therapeutic doses of acetaminophen.

BACKGROUND: Acetaminophen overdose is a frequent cause of acute liver failure. Controversy exists over the rare association of severe hepatotoxicity or acute liver failure with therapeutic doses of acetaminophen. CASE SUMMARY: A 45-year-old white man weighing 85 kg with asymptomatic HIV, hepatitis B virus, and hepatitis C virus (HCV) infection presented with signs of severe hepatotoxicity: aspartate aminotransferase (AST), 8,581 IU/L; alanine aminotransferase (ALT), 5,433 IU/L; L-lactate dehydrogenase, 13,641 IU/L; and prothrombin international normalized ratio, 2.15. He reported taking acetaminophen 1,000 mg QID for the previous 4 days and 1,000 mg that morning because of a febrile illness. Immediate administration of continuous IV N-acetylcysteine 150 mg/kg for the first 90 minutes and then 50 mg/kg q4h for the next 3 days was followed by clinical improvement and a rapid decrease in AST and ALT. AST levels decreased from 8,581 to 42 IU/L within 11 days. Several potential risk factors for acetaminophen hepatotoxicity (ie, chronic alcohol, tobacco, and opiate consumption, malnutrition, illness-induced starvation, HIV infection, and HCV infection) were present in this patient. CONCLUSIONS: This patient with multiple risk factors and severe hepatotoxicity after therapeutic dosage of acetaminophen was successfully treated with N-acetylcysteine.

Induction of oral tolerance as treatment or prevention of chronic diseases associated with Chlamydia pneumoniae infection--hypothesis.

BACKGROUND: Chlamydia pneumoniae infection is associated with chronic diseases such as asthma, reactive arthritis, and atherosclerosis. Several investigations and experimental results indicate an excessive immune response to heat shock protein (hsp) 60 as a possible common pathogenetic link between Chlamydia pneumoniae infection and the associated chronic diseases. CASE REPORT: A 46-year old woman with persistent C. pneumoniae infection and Reiter's syndrome had been treated for three years with antibiotics and nonsteroidal anti-inflammatory drugs without success. However, she was repeatedly free of complaints for several months following two-week cycles taking oral dilutions of Chlamydia trachomatis daily. CONCLUSIONS: The placebo effect does not seem sufficient to explain the clinical benefits obtained repeatedly by drinking dilutions of C. trachomatis. Induction of oral tolerance (immune modulation) to hsp60 may have occurred, leading to the clinical benefits. The known risk factors for atherosclerosis do not account for all cases of atherosclerosis. If autoimmunity to hsp60 is involved in the pathogenesis of atherosclerosis, so natural acquisition of oral tolerance to hsp60 may contribute to the geographical differences in atherosclerosis prevalence.

Soft tissue infection and bacteremia caused by Shewanella putrefaciens.

Shewanella putrefaciens is as yet rarely responsible for clinical syndromes in humans. However, a case involving multiple organs in an elderly male under treatment with appropriate steroids confirms that attention should be devoted to unusual pathogens.