Search

A pandemia da doença coronavírus 2019 (COVID-19; SARS-Co-2) surgiu como um dos maiores desafios enfrentados pela humanidade. O diabetes mellitus, associado a hiperglicemia crônica, favorece comorbidades que podem ampliar o risco de severidade ou morte quando associado a viremia de COVID-19. A Idade avançada, múltiplas morbidades, hiperglicemia, doença cardíaca e resposta inflamatória severa são preditores de desfechos desfavoráveis na presença da viremia. Os diferentes aspectos da COVID-19 e suas associações com o diabetes mellitus, são abordados. A relação da enzima conversora de angiotensionogênio (ACE2), o controle glicêmico e diferentes aspectos da severidade e prognóstico são descritos em relação ao diabetes-COVID-19. Também são comentadas as medidas para prevenir a propagação da viremia com ênfase em orientações e no gerenciamento de procedimentos hospitalares e ambulatórias para o paciente com diabetes, em particular no sistema público de saúde. Esta revisão resume o conhecimento atual e os desafios percebidos para prevenção e gestão de COVID-19 em pessoas com diabetes.

International audience; Background - Infective endocarditis (IE) is a common and serious complication in patients receiving chronic hemodialysis (HD). Objectives - This study sought to investigate whether there are significant differences in complications, cardiac surgery, relapses, and mortality between IE cases in HD and non-HD patients. Methods - Prospective cohort study (International Collaboration on Endocarditis databases, encompassing 7,715 IE episodes from 2000 to 2006 and from 2008 to 2012). Descriptive analysis of baseline characteristics, epidemiological and etiological features, complications and outcomes, and their comparison between HD and non-HD patients was performed. Risk factors for major embolic events, cardiac surgery, relapses, and in-hospital and 6-month mortality were investigated in HD-patients using multivariable logistic regression. Results - A total of 6,691 patients were included and 553 (8.3%) received HD. North America had a higher HD-IE proportion than the other regions. The predominant microorganism was Staphylococcus aureus (47.8%), followed by enterococci (15.4%). Both in-hospital and 6-month mortality were significantly higher in HD versus non-HD-IE patients (30.4% vs. 17% and 39.8% vs. 20.7%, respectively; p

SARS-CoV-2 can attack the central nervous system in the early stages of infection. Headache, anosmia, and dysgeusia are common symptoms. Disturbance of consciousness and seizures can occur as complications in case of severe COVID-19. We described the case of a COVID-19 patient admitted for interstitial pneumonia and seizures. MRI showed newly diagnosed demyelinating lesions. High-dose steroid treatment allowed neurological and respiratory recovery. We speculated a delayed immune response induced by SARS-CoV-2. The virus may lead to a SIRS-like immune disorder or play a role of infective trigger. Prompt invasive treatment should be adopted to avoid hypoxic neurotoxicity and prevent CNS injuries.

Objectives To explore the real-life performance of meropenem/vaborbactam for treating serious KPC-producing Klebsiella pneumoniae infections, including those resistant to ceftazidime/avibactam. Methods A retrospective observational cohort study was conducted in 12 Italian hospitals. Enrolled patients had K. pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-Kp) infections (59.5% of which were ceftazidime/avibactam resistant). Patients who received ≥72 h of meropenem/vaborbactam therapy (with or without other antimicrobials) in a compassionate-use setting were included. Results The 37 infections (all hospital-acquired) were mainly bacteraemic (BSIs, n = 23) or lower respiratory tract infections (LRTIs, n = 10). Clinical cure was achieved in 28 (75.6%) cases and microbiologically confirmed in all 25 with follow-up cultures. Three (10.7%) of the 28 clinical cures (all BSIs, 2/3 microbiologically confirmed) were followed by in-hospital recurrences after meropenem/vaborbactam was discontinued (median interval: 18 days). All three recurrences were susceptible to meropenem/vaborbactam and successfully managed with meropenem/vaborbactam combined with colistin or fosfomycin. Nine patients (24.3%) (all with BSIs or LRTIs) died in hospital with persistent signs of infection. Most were aged over 60 years, with high comorbidity burdens and INCREMENT scores ≥8. Only one had received meropenem/vaborbactam monotherapy. Six began meropenem/vaborbactam therapy >48 h after infection onset. Outcomes were unrelated to the isolate’s ceftazidime/avibactam susceptibility status. The single adverse event observed consisted of severe leukopenia with thrombocytopenia. Conclusions With the well-known limitations of real-life retrospective studies, our results support previous findings indicating that meropenem/vaborbactam therapy will be a safe, effective tool for managing serious KPC-Kp infections, including the increasing proportion displaying resistance to ceftazidime/avibactam.

To explore the real-life performance of meropenem/vaborbactam for treating serious KPC-producingA retrospective observational cohort study was conducted in 12 Italian hospitals. Enrolled patients hadThe 37 infections (all hospital-acquired) were mainly bacteraemic (BSIs,With the well-known limitations of real-life retrospective studies, our results support previous findings indicating that meropenem/vaborbactam therapy will be a safe, effective tool for managing serious KPC

Supplemental Digital Content is available in the text., OBJECTIVES: To describe the epidemiology of superinfections (occurring > 48 hr after hospital admission) and their impact on the ICU and 28-day mortality in patients with coronavirus disease 2019 with acute respiratory distress syndrome, requiring mechanical ventilation. DESIGN: Retrospective analysis of prospectively collected observational data. SETTING: University-affiliated adult ICU. PATIENTS: Ninety-two coronavirus disease 2019 patients admitted to the ICU from February 21, 2020, to May 6, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The prevalence of superinfection at ICU admission was 21.7%, and 53 patients (57.6%) had at least one superinfection during ICU stay, with a total of 75 (82%) ventilator-associated pneumonia and 57 (62%) systemic infections. The most common pathogens responsible for ventilator-associated pneumonia were Pseudomonas aeruginosa (n = 26, 34.7%) and Stenotrophomonas maltophilia (n = 14, 18.7%). Bloodstream infection occurred in 16 cases, including methicillin-resistant Staphylococcus epidermidis (n = 8, 14.0%), Enterococcus species (n = 6, 10.5%), and Streptococcus species (n = 2, 3.5%). Fungal infections occurred in 41 cases, including 36 probable (30 by Candida albicans, six by C. nonalbicans) and five proven invasive candidiasis (three C. albicans, two C. nonalbicans). Presence of bacterial infections (odds ratio, 10.53; 95% CI, 2.31–63.42; p = 0.005), age (odds ratio, 1.17; 95% CI, 1.07–1.31; p = 0.001), and the highest Sequential Organ Failure Assessment score (odds ratio, 1.27; 95% CI, 1.06–1.63; p = 0.032) were independently associated with ICU or 28-day mortality. CONCLUSIONS: Prevalence of superinfections in coronavirus disease 2019 patients requiring mechanical ventilation was high in this series, and bacterial superinfections were independently associated with ICU or 28-day mortality (whichever comes first).

The SARS-nCoV-2019 epidemic has spread since December 2019, quickly gaining worldwide attention. Symptoms consist of fever, cough and breathing difficulties. An increasing number of studies are focusing on neurological manifestations. In addition to the typical ageusia and anosmia, up to 30% of cases can present headache, nausea and vomiting. More serious neurological manifestations, such as encephalitis, thrombosis and cerebral haemorrhage have been reported.We described the case of a 47-year-old man who tested positive for COVID-19 virus in early March 2020. After two negative nasopharyngeal swabs, 41 days after the diagnosis of COVID-19 infection, he developed intense headache with fever, and he was hospitalized. He had subsequent generalized epileptic seizures and intubation was necessary. Contrast Head MRI was negative for brain abscesses or tumours but detected severe vasogenic oedema of the white matter with 10 mm shift of the midline and compression of the right lateral ventricle. Massive cortisone support therapy was ineffective. We diagnosed brain death on day 43 from the infection diagnosis.COVID-19 virus can reach the brain, penetrating into the neuronal cells through the interaction between the spike protein S1 and the host ACE-2 receptor, expressed in the capillary endothelium. We believe that in this infection, the pro-inflammatory state induced by the cytokine storm can cause a cerebral cell-mediated response, with subsequent vasodilatation and brain oedema.To our knowledge, this is the first description of a delayed onset cell-mediated encephalitis caused by COVID-19 virus after more than 40 days from the diagnosis.

CMV infection is a major challenge in allogeneic stem cell transplantation (allo-SCT). The changing landscape in CMV management includes the introduction of letermovir in prophylaxis of high-risk patients and the source of CMV DNA monitoring (plasma—PL vs. whole blood—WB), for pre-emptive therapy (PET) initiation. We report here how our real-life experience in CMV management evolved, following letermovir registration. We focus on: (i) the effects of systematic use of letermovir for CMV prophylaxis in high-risk patients, (ii) the results of a longitudinal comparison of CMV DNAemia monitoring in PL and WB. From December 2018 to April 2020, 60 allo-SCTs have been performed in our center (LET ERA), of whom 45 received letermovir in prophylaxis from day 0 to day + 100, because of recipient positivity of anti CMV IgG. These patients were compared with a cohort of 41 allo-SCTs performed between November 2017 and November 2018 (NO LET ERA). Firstly, the incidence of CMV clinically significant infections, CMV disease, bacterial infections, proven/probable fungal infections, hospital re-admissions after allo-SCT by day + 100 in the two ERA were 8 vs. 44% (p = 0.0006), 2 vs. 12% (p = 0.02), 37 vs. 56% (p = 0.05), 8 vs. 19% (p = 0.09), and 23 vs. 39% (p = 0.09), respectively. By day + 180 these differences were 17 vs. 68% (p < 0.00001), 2 vs. 12% (p = 0.02), 45 vs. 78% (p = 0.09), 8 vs. 22% (p = 0.05), and 40 vs. 66% (p = 0.01), respectively. Secondly, from February to May 2019, we comparatively measured CMV DNA from WB and PL and we confirmed that there is a linear correlation between CMV DNA level in WB and PL (Spearman’s test r = 0.86). Moreover, CMV DNAemia at the time of PET in the 12 patients with a clinically significant CMV infection was higher in WB vs. PL (5.202 vs. 4.981 copies/ml, p = 0.1). Our real-life experience confirms that: (i) letermovir is highly effective, leading to a significant drop in CMV clinically significant infections and CMV-related complications by day + 100 and + 180 after allo-SCT; (ii) WB may be an effective alternative to PL as a source for CMV DNA monitoring, as a linear correlation of DNAemia was confirmed between WB and PL, even if the CMV DNAemia at PET initiation was comparable in the two sources.

Importance There are limited data on mortality and complications rates in patients with coronavirus disease 2019 (COVID-19) who undergo surgery. Objective To evaluate early surgical outcomes of patients with COVID-19 in different subspecialties. Design, Setting, and Participants This matched cohort study conducted in the general, vascular and thoracic surgery, orthopedic, and neurosurgery units of Spedali Civili Hospital (Brescia, Italy) included patients who underwent surgical treatment from February 23 to April 1, 2020, and had positive test results for COVID-19 either before or within 1 week after surgery. Gynecological and minor surgical procedures were excluded. Patients with COVID-19 were matched with patients without COVID-19 with a 1:2 ratio for sex, age group, American Society of Anesthesiologists score, and comorbidities recorded in the surgical risk calculator of the American College of Surgeons National Surgical Quality Improvement Program. Patients older than 65 years were also matched for the Clinical Frailty Scale score. Exposures Patients with positive results for COVID-19 and undergoing surgery vs matched surgical patients without infection. Screening for COVID-19 was performed with reverse transcriptase–polymerase chain reaction assay in nasopharyngeal swabs, chest radiography, and/or computed tomography. Diagnosis of COVID-19 was based on positivity of at least 1 of these investigations. Main Outcomes and Measures The primary end point was early surgical mortality and complications in patients with COVID-19; secondary end points were the modeling of complications to determine the importance of COVID-19 compared with other surgical risk factors. Results Of 41 patients (of 333 who underwent operation during the same period) who underwent mainly urgent surgery, 33 (80.5%) had positive results for COVID-19 preoperatively and 8 (19.5%) had positive results within 5 days from surgery. Of the 123 patients of the combined cohorts (78 women [63.4%]; mean [SD] age, 76.6 [14.4] years), 30-day mortality was significantly higher for those with COVID-19 compared with control patients without COVID-19 (odds ratio [OR], 9.5; 95% CI, 1.77-96.53). Complications were also significantly higher (OR, 4.98; 95% CI, 1.81-16.07); pulmonary complications were the most common (OR, 35.62; 95% CI, 9.34-205.55), but thrombotic complications were also significantly associated with COVID-19 (OR, 13.2; 95% CI, 1.48-∞). Different models (cumulative link model and classification tree) identified COVID-19 as the main variable associated with complications. Conclusions and Relevance In this matched cohort study, surgical mortality and complications were higher in patients with COVID-19 compared with patients without COVID-19. These data suggest that, whenever possible, surgery should be postponed in patients with COVID-19.

A hyperinflammatory syndrome (HIS) may cause a life-threatening acute respiratory distress syndrome (ARDS) in patients with COVID-19 pneumonia. A prospective series of 100 consecutive patients admitted to the Spedali Civili University Hospital in Brescia (Italy) between March 9th and March 20th with confirmed COVID-19 pneumonia and ARDS requiring ventilatory support was analyzed to determine whether intravenous administration of tocilizumab (TCZ), a monoclonal antibody that targets the interleukin 6 (IL-6) receptor, was associated with improved outcome. Tocilizumab was administered at a dosage of 8 mg/kg by two consecutive intravenous infusions 12 h apart. A third infusion was optional based on clinical response. The outcome measure was an improvement in acute respiratory failure assessed by means of the Brescia COVID Respiratory Severity Score (BCRSS 0 to 8, with higher scores indicating higher severity) at 24-72 h and 10 days after tocilizumab administration. Out of 100 treated patients (88 M, 12 F; median age: 62 years), 43 received TCZ in the intensive care unit (ICU), while 57 in the general ward as no ICU beds were available. Of these 57 patients, 37 (65%) improved and suspended noninvasive ventilation (NIV) (median BCRSS: 1 [IQR 0-2]), 7 (12%) patients remained stable in NIV, and 13 (23%) patients worsened (10 died, 3 were admitted to ICU). Of the 43 patients treated in the ICU, 32 (74%) improved (17 of them were taken off the ventilator and were discharged to the ward), 1 (2%) remained stable (BCRSS: 5) and 10 (24%) died (all of them had BCRSS≥7 before TCZ). Overall at 10 days, the respiratory condition was improved or stabilized in 77 (77%) patients, of whom 61 showed a significant clearing of diffuse bilateral opacities on chest x-ray and 15 were discharged from the hospital. Respiratory condition worsened in 23 (23%) patients, of whom 20 (20%) died. All the patients presented with lymphopenia and high levels of C-reactive protein (CRP), fibrinogen, ferritin and IL-6 indicating a HIS. During the 10-day follow-up, three cases of severe adverse events were recorded: two patients developed septic shock and died, one had gastrointestinal perforation requiring urgent surgery and was alive at day 10. In conclusion, our series showed that COVID-19 pneumonia with ARDS was characterized by HIS. The response to TCZ was rapid, sustained, and associated with significant clinical improvement.

Skull base osteomyelitis (SBO) is a potentially life-threatening inflammation of cranial base bony structures of variable origin. Criteria for diagnosis and treatment are still controversial. Demographics, predisposing factors, symptoms, imaging, and clinical, laboratory, histological, and microbiological data of patients managed for SBO at the University Hospital of Brescia (ASST Spedali Civili) between 2002 and 2017 were retrospectively reviewed. Patients were included in different etiological groups. The topographic distribution of magnetic resonance (MR) abnormalities was recorded on a bi-dimensional model of skull base, on which three different patterns of inflammatory changes (edematous, solid, or necrotic) were reported. In patients with a history of radiotherapy, the spatial distribution of SBO was compared with irradiation fields. The association between variables and etiological groups was verified with appropriate statistical tests. A classification tree analysis was performed with the aim of inferring a clinical-radiological diagnostic algorithm for SBO. The study included 47 patients, divided into 5 etiological groups: otogenic (n = 5), radio-induced (n = 16), fungal (n = 14), immune-mediated (n = 6), and idiopathic (n = 6). At MR, five types of topographical distribution were identified (central symmetric, central asymmetric, orbital apex, sinonasal, maxillary). In patients with a history of radiotherapy, the probability to develop SBO was significantly increased in areas receiving the highest radiation dosage. The analysis of patients allowed for design of a classification tree for the diagnosis of SBO. The integration of clinical and radiologic information is an efficient strategy to categorize SBO and potentially guide its complex management.

Introdução: Os Recursos Educacionais Abertos (REA) são definidos como materiais de ensino, pesquisa e extensão, publicados sob licença aberta ou em domínio público. Por isso, são caracterizados como um bem comum, com pouca ou nenhuma limitação de direito autoral. Visam promover a equidade na educação, tornando-a inclusiva e de qualidade, mediante colaboração e compartilhamento de conhecimento de forma gratuita1. Objetivo: relatar a experiência da criação de dois materiais educativos publicados como Recursos Educacionais Abertos no Repositório Digital da Universidade Federal do Paraná. Metodologia: trata-se de um relato de experiência de natureza descritiva. Resultados: Os REAs foram desenvolvidos nos meses de abril e junho de 2020 e orientados pelos princípios de colaboração e interatividade dos meios digitais. O primeiro REA, elaborado em formato de cartilha e intitulado “Manual de Tubos de Coleta de Sangue”, foi criado como proposta de intervenção em um dos equipamentos de saúde do município de Curitiba em que se desenvolvem atividades de preceptoria do grupo PET Saúde/Interprofissionalidade – Rede de Atenção. Esse REA contempla os principais tubos de coleta de sangue utilizados na rotina ambulatorial, abordando a finalidade e importância de cada um, para garantir a viabilidade das amostras e a qualidade dos resultados laboratoriais. Esse material atingiu, até agosto de 2020, 161 visualizações, sendo 70% (112) delas de alcance internacional2. O segundo REA, em formato de cartilha, “Diagnóstico Laboratorial do Coronavírus (Sars-Cov-2) (agente etiológico da COVID-19)”, mostra os princípios, vantagens e as principais diferenças entre os dois principais métodos laboratoriais utilizados para o diagnóstico da COVID-19: o teste molecular (RT-PCR em tempo real) e o teste sorológico (teste rápido). Com impacto semelhante, tal publicação obteve 179 visualizações, sendo a maioria delas 84% (150) realizadas em outros países3. Esse material objetiva oferecer suporte a acadêmicos, profissionais de saúde e à comunidade externa sobre temática relevante da atualidade. Considerações Finais: A utilização da modalidade de Educação Aberta apresenta vantagens como, o custo reduzido, promoção da ampliação do acesso à educação e o alcance global das publicações, conforme foi observado nos REA produzidos e disponibilizados pela equipe do PET Redes de Atenção da UFPR. Dessa forma, além de priorizar a difusão do conhecimento produzido em suas atividades, a equipe buscou novas maneiras de contribuir para o debate e intercâmbio entre diferentes teias da produção científica. Palavras-chave: Educação Continuada. Educação Interprofissional. Materiais de Ensino.

There are currently few data concerning the cerebrospinal fluid (CSF) penetration of daptomycin in patients with healthcare-associated meningitis. This study aims (1) to better characterize the pharmacokinetics of daptomycin in humans during a 7-day intravenous (IV) therapy course, and (2) to study the penetration of daptomycin in the CSF after IV infusion at the dose of 10 mg/kg. In this prospective observational study, we enrolled nine patients with an implanted external ventricular drainage and a diagnosis of a healthcare-associated meningitis. Daptomycin was administered at 10 mg/kg for a maximum of 7 days. The pharmacokinetic of daptomycin was studied using a two-compartment population/pharmacokinetic (POP/PK) model and by means of a nonlinear mixed effects modeling approach. A large inter-individual variability in plasma area under the curve (Range: 574.7–1366.3 h mg/L), paralleled by high-peak plasma concentration (Cmax) (all values > 60 mg/L), was noted. The inter-individual variability of CSF-AUC although significant (range: 1.17–6.81 h mg/L) was narrower than previously reported and with a late occurrence of CSF-Cmax (range: 6.04–9.54 h). The terminal half-life between plasma and CSF was similar. tmax values in CSF did not show a high inter-individual variability, and the fluctuations of predicted CSF concentrations were minimal. The mean value for daptomycin penetration obtained from our model was 0.45%. Our POP/PK model was able to describe the pharmacokinetics of daptomycin in both plasma and CSF, showing that daptomycin (up to 7 days at 10 mg/kg) has minimal penetration into central nervous system. Furthermore, the observed variability of AUC, tmax and predicted concentration in CSF was lower than what previously reported in the literature. Based on the present findings, it is unlikely that daptomycin could reach CSF concentrations high enough to have clinical efficacy; this should be tested in future studies.

Background Antimicrobial resistance (AMR) situation in Italian hospitals and regions represents a major public health threat [ECDC, 2017]. Antimicrobial stewardship programs (ASPs), particularly when based on local epidemiology, have been beneficial in optimizing antibiotic therapy as well as reducing hospital rates of Clostridium difficile infection (CDI) and AMR [Akpan MR, Antibiotics 2016].. Methods Our ASP program has been conducted at Spedali Civili General Hospital of Brescia, Northern Italy (1300-bed tertiary hospital), between the beginning of 2016 and the end of 2017. A preliminary analysis of local epidemiological data was performed (Table 1). Seven groups (“districts”) were identified according to microbiological and clinical similarities. This was a persuasive-based ASP. First, we trained physicians on general principles of AS, then guidelines for the management of “difficult-to-handle” infections were drafted based on international guidelines and local microbiological data (Table 2).. Results Here we show the results of pre-ASP (2015) vs. post-ASP (2018) analysis on antibiotic consumption (AC) and CDI rates. AC is expressed in DDD/100 bed-days. The overall hospital AC decreased from 84.31 to 76.84 (−9%), consistently with national recommendations [Italian National Plan against AMR, 2017]. In accordance with the local guidelines developed within our ASP, carbapenem consumption decreased from 5.77 to 4.87 (−16%) and fluoroquinolones (FLQ) from 14.45 to 9.94 (−31%). At the same time piperacillin/tazobactam use increased from 5.53 to 8.46 (53%). 3°–4°G cephalosporins and glycopeptides consumption slightly reduced from 11.78 to 11.42 (−3%) and from 4.07 to 3.83 (−6%), respectively. AC of the different districts involved is reported in Table 3. CDI rates decreased from 0.0434/100 bed-days in 2015 to 0.0315/100 bed-days in 2018 (−27%) (Figure 1). Conclusion Our ASP was a persuasive-based program in a setting of high AMR rates. In the short term, it has shown a positive impact in improving AC (in particular of broad-spectrum antibiotics with a high risk of resistance selection and CDI) and CDI rates. Audits for local guidelines adherence and the evaluation of AC, AMR and CDI rates are ongoing as long-term quality measures for assessing the impact of our ASP. Disclosures All authors: No reported disclosures.

Background : Blood stream infections (BSIs) represent a major complication of allo-SCT and are a major cause of morbidity and mortality during and after bone marrow aplasia. Objectives: The objective of this study was to describe the incidence and outcome of BSIs in a cohort of patients submitted to allo-SCT, in order to track changes of the epidemiology and bacteria resistance. Methods : We retrospectively analyzed the microbiological data of 162 patients allotransplanted in Brescia University Hospital, over a period of 6 years. Results : Eighty patients experienced a BSIs for a total of 119 isolates. In 77 cases (65%) a Gram positive bacteria was isolated, being coagulase negative Staphilococci the most frequent species (77% of the cases). In 42 cases (35%) a Gram negative bacteria was isolated (E. coli 57% and P. aeruginosa 24%). Fluoroquinolones resistance was frequent (90% for S. epidermidis , 92% for E. coli , 90% for P. aeruginosa ). Methycillin resistance of S. epidermidis was 100%, 76% of E. coli were ESBL positive and among P. aeruginosa resistance to carbapenems was 40%. The 2 years overall survival of patients with BSIs vs patients without BSIs was 46% vs 60% (HR1,48, p=0,07). P. areuginosa and E. coli were the species with the highest mortality (50% and 33%, respectively). Conclusions : These data confirms that BSIs, mainly sustained by Gram positive bacteria, are frequent in allotransplanted patients (50% of the cases) and may influence the outcome of allotransplanted patients, being antibiotics resistance highly frequent among these bacteria.

Background Host factors and complications have been associated with higher mortality in infective endocarditis ( IE ). We sought to develop and validate a model of clinical characteristics to predict 6‐month mortality in IE . Methods and Results Using a large multinational prospective registry of definite IE (International Collaboration on Endocarditis [ ICE ]–Prospective Cohort Study [ PCS ], 2000–2006, n=4049), a model to predict 6‐month survival was developed by Cox proportional hazards modeling with inverse probability weighting for surgery treatment and was internally validated by the bootstrapping method. This model was externally validated in an independent prospective registry ( ICE ‐ PLUS , 2008–2012, n=1197). The 6‐month mortality was 971 of 4049 (24.0%) in the ICE ‐ PCS cohort and 342 of 1197 (28.6%) in the ICE ‐ PLUS cohort. Surgery during the index hospitalization was performed in 48.1% and 54.0% of the cohorts, respectively. In the derivation model, variables related to host factors (age, dialysis), IE characteristics (prosthetic or nosocomial IE , causative organism, left‐sided valve vegetation), and IE complications (severe heart failure, stroke, paravalvular complication, and persistent bacteremia) were independently associated with 6‐month mortality, and surgery was associated with a lower risk of mortality (Harrell's C statistic 0.715). In the validation model, these variables had similar hazard ratios (Harrell's C statistic 0.682), with a similar, independent benefit of surgery (hazard ratio 0.74, 95% CI 0.62–0.89). A simplified risk model was developed by weight adjustment of these variables. Conclusions Six‐month mortality after IE is ≈25% and is predicted by host factors, IE characteristics, and IE complications. Surgery during the index hospitalization is associated with lower mortality but is performed less frequently in the highest risk patients. A simplified risk model may be used to identify specific risk subgroups in IE .

Background Blood stream infections (BSIs) represent a major complication of allo-SCT and are a major cause of morbidity and mortality during and after bone marrow aplasia. Objectives The objective of this study was to describe the incidence and outcome of BSIs in a cohort of patients submitted to allo-SCT, in order to track changes of the epidemiology and bacteria resistance. Methods We retrospectively analyzed the microbiological data of 162 patients allotransplanted in Brescia University Hospital, over a period of 6 years. Results Eighty patients experienced a BSIs for a total of 119 isolates. In 77 cases (65%) a Gram positive bacteria was isolated, being coagulase negative Staphilococci the most frequent species (77% of the cases). In 42 cases (35%) a Gram negative bacteria was isolated (E. coli 57% and P. aeruginosa 24%). Fluoroquinolones resistance was frequent (90% for S. epidermidis, 92% for E. coli, 90% for P. aeruginosa). Methycillin resistance of S. epidermidis was 100%, 76% of E. coli were ESBL positive and among P. aeruginosa resistance to carbapenems was 40%. The 2 years overall survival of patients with BSIs vs patients without BSIs was 46% vs 60% (HR1,48, p=0,07). P. aeruginosa and E. coli were the species with the highest mortality (50% and 33%, respectively). Conclusions These data confirm that BSIs, mainly sustained by Gram positive bacteria, are frequent in allotransplanted patients (50% of the cases) and may influence the outcome of allotransplanted patients, being antibiotics resistance highly frequent among these bacteria.

Background Regular monitoring of bacterial epidemiology allows evaluation of antibacterial strategies adopted. The aim of this study was to disclose evolving trends in the epidemiology of infections and emerging antibiotic resistance in unselected inpatients with haematological cancers. Methods Febrile/infectious episodes occurring in 823 patients consecutively admitted to a single institution during a 16 month period were analysed. Levofloxacin prophylaxis was used in patients with >7 days expected neutropenia. Results Fever developed in 364 patients (44.2%) and an infection was documented in 187 (22.7%), either clinically (6.1%) or microbiologically (16.6%). Levofloxacin prophylaxis, used in 39.4% of cases, caused a reduction in febrile episodes only among neutropenic patients and no difference in the frequency of documented infections. Among 164 pathogens isolated, gram-negative (49.4%) outweighed gram-positive bacteria (40.9%), Escherichia coli being most frequent (23.2%). Fluoroquinolone resistance and methicillin resistance were the most frequent types of antibiotic resistance, occurring in 56.1% of bacterial isolates and in 66.7% of staphylococci, respectively. Fluoroquinolone-resistant E. coli accounted for 20.1% of all isolates and for 86.8% of E. coli. Multivariate analysis of risk factors for fluoroquinolone resistance identified prophylaxis (P 7 days (P = 0.02) as independent. Methicillin resistance was independently associated with prophylaxis (P = 0.041) and central venous catheters (P = 0.036). Infections by fluoroquinolone-resistant strains did not show a worse outcome. Conclusions A shift towards gram-negative bacteria has been occurring in recent years in the bacterial epidemiology of haematological patients. Fluoroquinolone resistance is emerging as a major type of antibacterial resistance, particularly among E. coli strains. Further investigation is needed to explore the consequences of such epidemiological changes.

Objective: Use of external ventricular drains and lumbar catheters is associated with a risk of ventriculitis and meningitis ranging from 2% to 24% because of lack of standardized diagnostic criteria. We evaluated the prevalence of ventriculitis or meningitis in 13 Italian ICUs. Design: Multicenter, prospective study. Setting: Thirteen Italian ICUs. Patients: Two hundred seventy-one patients (mean age, 57 yr) receiving a total number of 311 catheters. Two hundred fifty patients (92.2%) had an external ventricular drain, 17 patients (6.3%) had a lumbar catheter, and four patients (1.5%) had both external ventricular drain and lumbar catheter. Interventions: ICUs enrolled at least 10 consecutive adult patients with an external ventricular drain or lumbar catheter in place for more than 24 hours. Confirmed cerebrospinal fluid infection was defined by presence of a positive cerebrospinal fluid culture, a cerebrospinal fluid/blood glucose ratio less than 0.5, a neutrophilic cerebrospinal fluid pleocytosis (> 5 cells/?L), and fever. Abnormal cerebrospinal fluid findings with negative cultures were defined as suspected infection. Measurements and Main Results: Median duration of device use was 13 days (interquartile range, 8-19). Fifteen patients (5.5%) had a confirmed ventriculitis or meningitis, and 15 patients (5.5%) had a suspected ventriculitis or meningitis. Cerebrospinal fluid glucose and cerebrospinal fluid/blood glucose ratio were lower in patients with confirmed ventriculitis or meningitis and suspected ventriculitis or meningitis; proteins and lactates were significantly higher in confirmed ventriculitis or meningitis. Gram-negative and Gram-positive bacteria were equally cultured. Risk factors for infection were a concomitant extracranial infection (odds ratio, 2.34; 95% CI, 1.01-5.40; p = 0.05) and placement of catheters outside the operation room (odds ratio, 4.01; 95% CI, 0.98-16.50; p = 0.05). Conclusions: Ventriculitis or meningitis remains a problem in Italian ICUs, and a strategy for reducing the prevalence is worth planning.

International audience; Background - The impact of early valve surgery (EVS) on the outcome of Staphylococcus aureus (SA) prosthetic valve infective endocarditis (PVIE) is unresolved. The objective of this study was to evaluate the association between EVS, performed within the first 60 days of hospitalization, and outcome of SA PVIE within the International Collaboration on Endocarditis-Prospective Cohort Study. Methods - Participants were enrolled between June 2000 and December 2006. Cox proportional hazards modeling that included surgery as a time-dependent covariate and propensity adjustment for likelihood to receive cardiac surgery was used to evaluate the impact of EVS and 1-year all-cause mortality on patients with definite left-sided S. aureus PVIE and no history of injection drug use. Results - EVS was performed in 74 of the 168 (44.3%) patients. One-year mortality was significantly higher among patients with S. aureus PVIE than in patients with non-S. aureus PVIE (48.2% vs 32.9%; P = .003). Staphylococcus aureus PVIE patients who underwent EVS had a significantly lower 1-year mortality rate (33.8% vs 59.1%; P = .001). In multivariate, propensity-adjusted models, EVS was not associated with 1-year mortality (risk ratio, 0.67 [95% confidence interval, .39-1.15]; P = .15). Conclusions - In this prospective, multinational cohort of patients with S. aureus PVIE, EVS was not associated with reduced 1-year mortality. The decision to pursue EVS should be individualized for each patient, based upon infection-specific characteristics rather than solely upon the microbiology of the infection causing PVIE.

Objective:To evaluate the secular trends in MRSA BSIs after the introduction of a nosocomial MRSA control intervention.Design:Before-after study.Setting:An 850-bed community hospital with an ICU and vascular surgery, neurosurgery, bone marrow transplantation, and AIDS units. MRSA is endemic at this hospital; the prevalence of methicillin resistance among patients withS. aureusinfection is greater than 50%.Patients:Among all inpatients, MRSA BSI was identified, its origin defined, and incidence rates calculated by ward and origin.Intervention:A MRSA control program was implemented based on active surveillance cultures to identify MRSA-colonized patients, followed by isolation using contact precautions. Incidence rates of MRSA BSI during the intervention (ie, July 1, 1997, to December 31, 2001) and preintervention (ie, January 1, 1996, to June 30, 1997) periods were compared.Results:Sixty-nine MRSA BSIs were identified. When compared with the preintervention period, the incidence rate of MRSA BSI was reduced from 0.64 to 0.30 per 1,000 admissions (RR, 0.46; CI95, 0.25–0.87;P= .02) during the intervention period. The impact was greater in the ICU, with an 89% reduction (RR, 0.11; CI95, 0.01–0.98;P= .03), and for CVC-associated MRSA BSIs, with an 82% decrease (RR, 0.17; CI95, 0.05–0.55;P= .002). Methicillin resistance amongS. aureusblood isolates decreased from 46% to 17% (RR, 0.36; CI95, 0.22–0.62;P= .0002).Conclusion:A reduction in MRSA bacteremia is achievable through use of the MRSA “search and isolate” intervention even in a hospital with high rates of endemic MRSA.

Clinical stability (CS), defined as normalization of vital signs, is often used to manage inpatients with community-acquired pneumonia (CAP). The main objective of our study was to identify a reliable definition of CS for human immunodeficiency virus (HIV)‐positive patients with CAP. During an 18-month period, 437 HIV-positive Italian inpatients with CAP were enrolled in the study. We used 3 definitions of CS (from a less conservative [definition 1] to a more conservative [definition 3] definition) based on combinations of different thresholds for vital signs. Assessments were performed at admission and daily during the hospital stay. For the 3 definitions, 14.9%, 8.0%, and 4.8% of patients were stable at baseline, with deterioration after reaching CS in 7.16%, 4.76%, and 2.05%, respectively. The 8 patients whose conditions deteriorated after reaching CS definition 3 (systolic blood pressure, 190 mm Hg; pulse, !90 beats/min; respiratory rate, !20 breaths/min; oxygen saturation, 190%; temperature, !37� C; ability to eat; and normal mental status) survived and were discharged from the hospital. The more conservative definition of CS appears to be reliable for the management of HIV-infected patients with CAP.

The management of central venous catheter-related bloodstream infections (CRBSI), though still debated, requires the removal of the line in most cases: we investigated the efficacy of an alternative approach, based on higher concentrations of antibiotics locked within the catheter lumen, in an open, pilot study aimed at preserving the line in place and at eradicating the infection. Thirty consecutive patients carrying a central line over 10 days and who fulfilled criteria for ascertained diagnosis of bacterial CRBSI, had the catheter "locked" with antimicrobials therein; all patients also received systemic antibiotic therapy within the first 48 hours. Subsequently, 15 patients underwent locks alone, and 15 locks plus systemic therapy. Twenty-eight out of 30 (93.3%) patients retained the catheter in place, appearing to be cleared of infection and no treatment-related untoward events were observed. Locks should be considered as effective as line removal in the management of bacterial CRBSI in unselected patients, and could thus provide advantages in terms of resource sparing and lowered antibiotic pressure in the hospital setting.

To the Editor: It has recently become apparent that livestock can constitute a new methicillin-resistant Staphylococcus aureus (MRSA) reservoir and be a source of a novel and rapidly emerging type of MRSA. These livestock-associated MRSA clones are nontypeable by use of pulsed-field gel electrophoresis with SmaI and belong to sequence type (ST) 398 (1). MRSA ST398 clones account for 20% of all MRSA in the Netherlands (2), but the emergence of such clones has been described worldwide (3). Although ST398 transmission has been reported primarily between animals, persons with occupational exposure to livestock are at higher risk for MRSA carriage than the general population. Even though MRSA ST398 usually causes colonization, several cases of infections of variable clinical relevance, varying from skin and soft tissue infections (4) to endocarditis (5) and pneumonia (6), have been described over the past few years. Most instances of ST398 human carriers have been identified among persons who work at pig farms (7). Data regarding MRSA colonization of dairy farmers are less exhaustive and, to our knowledge, only 1 instance of direct transmission between cattle and humans has been proven. MRSA isolates from cows with subclinical mastitis in 2007 in Hungary were indistinguishable from MRSA isolates from the tonsil swab of a farmer who worked with these animals (8). We report a case of MRSA ST398 invasive disease in a cattle farmer, as well as a case of MRSA ST398 necrotizing fasciitis. In early April 2008, a 52-year-old man was admitted to an intensive care unit in Manerbio, Italy, because of severe sepsis and a large ulcerative and suppurative lesion on the right side of his neck. His medical history was unremarkable. He was a worker at a dairy farm, was obese, and did not report any previous contact with the healthcare system. At the time of hospital admission, he was oriented and cooperative. His temperature was 38.4°C, heart rate was 125 beats per minute, and blood pressure was 165/75 mm Hg. Arterial blood gas analysis showed hypoxemia and mild hypocapnia (PaO2 53 mm Hg and PaCO2 33.8 mm Hg on room air). Leukocyte count was 21,280 cells/μL (81.9% polymorphonuclear cells), and platelet count was 310,000 cells/μL. After blood samples were collected and aggressive surgical debridement of affected tissue was performed, empirical treatment with intravenous teicoplanin and imipenem was started. On the basis of histologic appearance of the intraoperative material and computed tomography scan images, necrotizing fasciitis was diagnosed. Culture of blood and necrotic tissue yielded MRSA. On day 3 after admission, antimicrobial drug therapy was changed to teicoplanin and clindamycin and, on day 7, to linezolid. Fever resolved in 3 days and the patient’s condition progressively improved. The patient was discharged after 31 days of antimicrobial drug therapy. The MRSA isolate was susceptible to all the non–β-lactam antimicrobial drugs tested (excluding tetracycline), carried the staphylococcal cassette chromosome mec type V, and was negative for Panton-Valentine leukocidin (PVL) genes. Multilocus sequence typing and sequence typing of the tandem repeat region of protein A gene (spa typing) showed that the isolate belonged to ST398 and spa type 899, respectively. Some issues are of concern. Although the MRSA isolate was PVL negative, its virulence resembled that of PVL-positive strains. Furthermore, it was resistant to tetracycline, as we expected because oxytetracyclines are the antimicrobial drugs most frequently used in pig and cattle farming (3). The major limitation of our study was that data regarding MRSA colonization of the farm are missing, so cattle-to-human transmission cannot be proven. However, because our patient did not have any other potential risk factor, dairy cows were probably the source of the human infection. In countries where community-acquired MRSA is common, all patients with serious S. aureus infections should be treated for MRSA until antimicrobial susceptibilities are known. Our report suggests that even in countries where community-acquired MRSA is still rare, being a cattle farmer may be considered an indication for early treatment against MRSA. The expanding knowledge of this zoonotic potential may undermine existing nosocomial MRSA control programs. In countries where a search and destroy policy (9) is adopted, such as the Netherlands, pig and cattle farmers may warrant screening and isolation at the time of hospital admission. Nevertheless, the first MRSA ST398 nosocomial outbreak has already been described (10). It is difficult to prevent persons with constant exposure to MRSA in their work or home setting from becoming MRSA carriers. Revisiting policies for the use of antimicrobial drugs on livestock farms, as well as improving hygiene measures, may therefore be necessary in infection control programs. However, before final recommendations can be made, further investigation is needed to determine the prevalence of MRSA among livestock and their handlers.

We present a case of melioidosis in an Italian male returning from Singapore after a short travel. He probably acquired the disease by inhalation, which is not the typical mode of transmission, in the absence of evident risk factors. The diagnosis was confirmed by real-time polymerase chain reaction of the culture while serology was useful to assess professional exposure among laboratory workers. Treatment consisted of an initial intensive phase with meropenem and trimethoprim–sulfamethaxazole (TMP–SMX), followed by 6 months of eradication therapy with TMP–SMX.

In an Italian long-term-care facility (LTCF), we observed a 17.5% adherence to hand hygiene (HH), as well as 47.5% rate of glove use. Performing a procedure at high risk for cross-transmission of germs was the factor most strongly associated with noncompliance (odds ratio = 13.3; 95% confidence interval = 6.2 to 28.8; P < .0001). No significant differences in compliance related to health care worker category were found. Adherence to HH in the LTCF was similar to that found in a rehabilitation medicine unit of an acute care hospital (15.8%) but significantly lower than that reported in an infectious disease unit (53.7%; P < .0001). Our findings indicate that compliance with HH is a similar problem in LTCFs as in acute care facilities.

Background In order to better define the pathogenic role of cerebrospinal fluid (CSF) drainage catheters in postoperative patients, we comparatively analyze the clinical course of device and non-device-related meningitis. Methods This is an observational, partially prospective, study on consecutive adult patients who developed meningitis after undergoing neurosurgical procedures at the Neurosurgery and Neurointensive care Departments, Spedali Civili, Brescia, Italy, between January 1999 and August 2007. Results All 77 consecutive post-neurosurgical meningitis events in 65 patients were included in the analysis. Most were classified as external ventricular drainage (EVD)-related meningitis (23 cases, group A), external spinal drainage (ESD)-related meningitis (12 cases, group B), and non-device-related post-neurosurgical meningitis (30 cases, group C). Proven meningitis was identified in 78.3%, 91.7% and 56.7% of the events, respectively. ESD-related meningitis had a shorter onset time vs EVD and non-device-associated meningitis (3 days versus 6 and 7 days, respectively). Median antibiotic treatment duration was 20, 17, and 22.5 days in groups A, B, and C, respectively. Overall, 8 patients (34.8%) in group A, 3 (25.0%) in group B, and 3 (10.0%) in group C died. Median time to become afebrile was shorter in group C than in group A (10 days versus 12 days, P = 0.04). Removal of the device later than 48 hours after meningitis onset, as well as implantation of a second device were associated with a slower time of meningitis resolution. Conclusions Early device removal and avoiding implantation of a second device were associated with short illness duration. Larger studies are warranted to confirm the conclusions of this study.

The last decade has been characterized by the emergence of CA-MRSA strains associated with the production of Panton-Valentine leukocidin. We report a case of necrotizing pneumonia and septic shock caused by CA-MRSA, in which early recognition of the syndrome and appropriate treatment with two toxin-suppressing antibiotics improved the patient's outcome.

Healthcare workers (HCW) are exposed to many different pathogens, and cases of occupational infection have been reported involving the vast majority of known and emerging agents. The risk is present during all the phases of patient care and manipulation of biologic materials, and the implementation of Standard Precautions--and biosafety level 2 measures in the laboratory--and Transmission-Based Precautions in all health settings represents the necessary preventive intervention required by law. Percutaneous exposures represent an extremely frequent event in healthcare facilities; among the many pathogens acquired through this type of exposure, those of highest concern due to the frequency of exposure are HIV, HBV and HCV. Over the last 10 years, though the risk of exposure is still not negligible, occupational infection with HBV has become a rare event; conversely, the incidence of acute C hepatitis became significantly higher among HCW (1,6 per 100.000 inhabitants) with respect to the general population (0,6), with a seroconversion rate following an occupational exposure between 0,5% and 1,8%; finally, reports of occupational HIV infection have decreased, probably also as a secondary beneficial effect of antiretroviral treatment in patients and post-exposure prophylaxis in HCW. The Studio Italiano Rischio Occupazionale da HIV (SIROH) documented from 1986 to 2009 one occupational HBV case, 6 HIV cases (the last one in 2007) and 32 HCV cases. In Europe, the Directive 2010/32/EU approved on May 10 2010 requires Member State to implement within three years a global strategy to prevent occupational exposures in the healthcare setting, particularly with respect to needlestick and sharp injuries, including the adoption, based on risk assessment, of devices incorporating safety features. In Italy the introduction of these devices, according to data collected by the SIROH, showed the possibility to decrease percutaneous exposures by 75%, an effect sustained over time if supported by information, education and training.