A multi-society position paper on the prevention and management of nosocomial and severe infections: the Italian Society for Infectious Diseases, the Italian Multidisciplinary Society of Hospital Infections, the Italian Society of Chemotherapy, the Italian Society of Respiratory Medicine, the Italian Society of Clinical Microbiology, the Italian Society of Microbiology, and GISIG (Italian Study Group on Severe Infections)

Amulti-society position paper on the prevention and management of nosocomial and severe infections: the Italian Society for Infectious Diseases, the Italian Multidisciplinary Society of Hospital Infections, the Italian Society of Chemotherapy, the Italian Society of Respiratory Medicine, the Italian Society of Clinical Microbiology, the Italian Society of Microbiology, and GISIG (Italian Study Group on Severe Infections

Consensus document on controversial issues in the diagnosis and treatment of bloodstream infections and endocarditis.

Summary Background The treatment of severe bloodstream infections (sepsis, endocarditis, and infections of vascular prostheses) caused by Gram-positive microorganisms is made even more difficult by the emergence of resistant strains. The introduction of new antibiotics with activity against these strains has created new opportunities, but many controversial issues remain. Controversial issues The aim of this GISIG (Gruppo Italiano di Studio sulle Infezioni Gravi) working group – a panel of multidisciplinary experts – was to define recommendations for some controversial issues using an evidence-based and analytical approach. The controversial issues concerned the duration of therapy and role of aminoglycosides and teicoplanin in the treatment of Gram-positive bacterial endocarditis, the optimal use of the new antibiotics in the treatment of bloodstream infections caused by resistant Gram-positive strains, and the use of microbiological techniques (i.e., bactericidal serum testing and synergy testing) and of pharmacokinetic data (e.g., monitoring of plasma levels of antibiotics) in the treatment of difficult-to-treat Gram-positive bloodstream infections. Methods A systematic literature search of randomized controlled trials and/or non-randomized studies was performed mainly using the MEDLINE database. A matrix was created to extract evidence from original studies using the CONSORT method to evaluate randomized clinical trials and the Newcastle–Ottawa Quality Assessment Scale for non-randomized studies. The GRADE method for grading the quality of evidence and strength of recommendation was applied

Consensus document on controversial issues for the treatment of infections of the central nervous system: bacterial brain abscesses

Summary Background Bacterial brain abscesses remain a serious central nervous system problem despite advances in neurosurgical, neuroimaging, and microbiological techniques and the availability of new antibiotics. The successful treatment of brain abscesses requires surgery, appropriate antibiotic therapy, and eradication of the primary source; nevertheless many controversial issues on the management of this serious infection remain unresolved. Controversial issues The aim of this GISIG (Gruppo Italiano di Studio sulle Infezioni Gravi) working group – a panel of multidisciplinary experts – was to define recommendations for some controversial issues using an evidence-based and analytical approach. The controversial issues were: (1) Which patients with bacterial brain abscesses can be managed safely using medical treatment alone? (1a) What is the efficacy in terms of outcome, tolerability, cost/efficacy, and quality of life of the different antibiotic regimens used to treat bacterial cerebral abscesses? (1b) Which antibiotics have the best pharmacokinetics and/or tissue penetration of brain and/or brain abscess? 2) What is the best surgical approach in terms of outcome in managing bacterial brain abscesses? Results are presented and discussed in detail. Methods A systematic literature search using the MEDLINE database for the period 1988 to 2008 of randomized controlled trials and/or non-randomized studies was performed. A matrix was created to extract evidence from original studies using the CONSORT method to evaluate randomized clinical trials and the Newcastle–Ottawa Quality Assessment Scale for case–control studies, longitudinal cohorts, and retrospective studies. The GRADE method for grading quality of evidence and strength of recommendation was applied

A case of pulmonary tuberculosis presenting as diffuse alveolar haemorrhage: is there a role for anticardiolipin antibodies?

<p>Abstract</p> <p>Background</p> <p>Diffuse alveolar haemorrhage (DAH) has been rarely reported in association with pulmonary infections.</p> <p>Case Presentation</p> <p>We report the case of a 43 year old immunocompetent man presenting with dyspnoea, fever and haemoptysis. Chest imaging showed bilateral ground glass opacities. Microbiological and molecular tests were positive for <it>Mycobacterium tuberculosis </it>and treatment with isoniazid, rifampicin, ethambutol and pyrazinamide was successful. In this case the diagnosis of DAH relies on clinical, radiological and endoscopic findings. Routine blood tests documented the presence of anticardiolipin antibodies. In the reported case the diagnostic criteria of antiphospholipid syndrome were not fulfilled.</p> <p>Conclusions</p> <p>The transient presence of anticardiolipin antibodies in association with an unusual clinical presentation of pulmonary tuberculosis is intriguing although a causal relationship cannot be established.</p

Patient to patient transmission of hepatitis B virus: a systematic review of reports on outbreaks between 1992 and 2007

<p>Abstract</p> <p>Background</p> <p>Hepatitis B outbreaks in healthcare settings are still a serious public health concern in high-income countries. To elucidate the most frequent infection pathways and clinical settings involved, we performed a systematic review of hepatitis B virus outbreaks published between 1992 and 2007 within the EU and USA.</p> <p>Methods</p> <p>The research was performed using two different databases: the PubMed Database and the Outbreak Database, the worldwide database for nosocomial outbreaks. Selection of papers was carried out using the Quorom algorithm, and to avoid selection biases, the inclusion criteria were established before the articles were identified.</p> <p>Results</p> <p>Overall, 30 papers were analyzed, reporting on 33 hepatitis B virus outbreaks that involved 471 patients, with 16 fatal cases. Dialysis units accounted for 30.3% of outbreaks followed by medical wards (21.2%), nursing homes (21.2%), surgery wards (15.2), and outpatient clinics (12.1%). The transmission pathways were: multi-vial drugs (30.3%), non-disposable multi-patient capillary blood sampling devices (27.2%), transvenous endomyocardial biopsy procedures (9.1%), and multiple deficiencies in applying standard precautions (9.1%).</p> <p>Conclusion</p> <p>The analysis of transmission pathways showed that some breaches in infection control measures, such as administration of drugs using multi-vial compounds and capillary blood sampling, are the most frequent routes for patient-to-patient transmission of hepatitis B virus. Moreover some outbreak reports underlined that heart-transplant recipients are at risk of contracting hepatitis B virus infection during the transvenous endomyocardial biopsy procedure through indirect contact with infected blood as a result of environmental contamination. To prevent transmission, healthcare workers must adhere to standard precautions and follow fundamental infection control principles, such as the use of sterile, single-use, disposable needles and avoiding the use of multi-vial compounds in all healthcare settings including outpatient settings.</p

New tools for detecting latent tuberculosis infection: evaluation of RD1-specific long-term response

<p>Abstract</p> <p>Background</p> <p>Interferon-gamma (IFN-γ) release assays (IGRAs) were designed to detect latent tuberculosis infection (LTBI). However, discrepancies were found between the tuberculin skin test (TST) and IGRAs results that cannot be attributed to prior Bacille Calmètte Guerin vaccinations. The aim of this study was to evaluate tools for improving LTBI diagnosis by analyzing the IFN-γ response to RD1 proteins in prolonged (long-term response) whole blood tests in those subjects resulting negative to assays such as QuantiFERON-TB Gold In tube (QFT-IT).</p> <p>Methods</p> <p>The study population included 106 healthy TST⁺individuals with suspected LTBI (recent contact of smear-positive TB and homeless) consecutively enrolled. As controls, 13 healthy subjects unexposed to <it>M. tuberculosis </it>(TST^-, QFT-IT^-) and 29 subjects with cured pulmonary TB were enrolled. IFN-γ whole blood response to RD1 proteins and QFT-IT were evaluated at day 1 post-culture. A prolonged test evaluating long-term IFN-γ response (7-day) to RD1 proteins in diluted whole blood was performed.</p> <p>Results</p> <p>Among the enrolled TST⁺subjects with suspected LTBI, 70/106 (66.0%) responded to QFT-IT and 64/106 (60.3%) to RD1 proteins at day 1. To evaluate whether a prolonged test could improve the detection of LTBI, we set up the test using cured TB patients (with a microbiologically diagnosed past pulmonary disease) who resulted QFT-IT-negative and healthy controls as comparator groups. Using this assay, a statistically significant difference was found between IFN-γ levels in cured TB patients compared to healthy controls (p < 0.006). Based on these data, we constructed a receiver operating characteristic (ROC) curve and we calculated a cut-off. Based on the cut-off value, we found that among the 36 enrolled TST+ subjects with suspected LTBI not responding to QFT-IT, a long term response to RD1 proteins was detected in 11 subjects (30.6%).</p> <p>Conclusion</p> <p>These results indicate that IFN-γ long-term response to <it>M. tuberculosis </it>RD1 antigens may be used to detect past infection with <it>M. tuberculosis </it>and may help to identify additional individuals with LTBI who resulted negative in the short-term tests. These data may provide useful information for improving immunodiagnostic tests for tuberculosis infection, especially in individuals at high risk for active TB.</p

IP-10 detection in urine is associated with lung diseases

<p>Abstract</p> <p>Background</p> <p>blood cytokines and chemokines have been proposed as biomarkers for tuberculosis (TB). Recently, some immune mediators found in the urine of patients with renal dysfunctions have also been suggested as potential biomarkers. Finding biomarkers for TB in urine would present several advantages over blood in terms of collection and safety. The objective of this study was to investigate the presence of cytokines and chemokines in the urine of patients with pulmonary TB at the time of diagnosis. In a subgroup, the evaluation was also performed during TB treatment and at therapy completion. Patients with lung diseases other than TB, and healthy subjects were also enrolled.</p> <p>Methods</p> <p>urine samples from 138 individuals, after exclusion of renal dysfunctions, were collected during an 18 month-period. Among them, 58 received a diagnosis of pulmonary TB, 28 resulted having lung diseases other than TB, and 34 were healthy subjects. Moreover, 18 TB patients, 9 of whom were tested 2 months after AFB smear sputum reversion and 9 of whom were cured of TB were also included. Cytokines and chemokines in urine were evaluated using a Cytometric-Bead-Array-Flex-Set. IP-10 detection in 49 subjects was also carried out in parallel by using an Enzyme Linked ImmunoSorbent Assay (ELISA).</p> <p>Results</p> <p>IFN-γ, TNF-α, IL-2, IL-8, MIP-1α, MIP-1β and RANTES were poorly detected in all urine samples. Conversely, IP-10 was consistently detected in urine and its level was significantly increased in patients with lung disease compared to healthy subjects (p < 0.001). Increased IP-10 levels were found in both pulmonary TB and lung diseases other than TB. Moreover lower IP-10 levels were found in cured-TB patients compared to the levels at the time of diagnosis, and this difference was close to significance (p = 0.06). Interestingly, we demonstrated a significant correlation between the data obtained by flow cytometry and ELISA (r²0.82, p < 0.0001).</p> <p>Conclusions</p> <p>IP-10, in contrast to IFN-γ, TNF-α, IL-2, IL-8, MIP-1α, MIP-1β and RANTES, is detectable in the urine of patients with pulmonary diseases in the absence of renal dysfunctions. Moreover, the IP-10 level in cured-TB patients is comparable to that found in healthy subjects. More studies are needed to further investigate the clinical utility of these findings.</p

The rapid spread of SARS-COV-2 Omicron variant in Italy reflected early through wastewater surveillance

The SARS-CoV-2 Omicron variant emerged in South Africa in November 2021, and has later been identified worldwide, raising serious concerns. A real-time RT-PCR assay was designed for the rapid screening of the Omicron variant, targeting characteristic mutations of the spike gene. The assay was used to test 737 sewage samples collected throughout Italy (19/21 Regions) between 11 November and 25 December 2021, with the aim of assessing the spread of the Omicron variant in the country. Positive samples were also tested with a real-time RT-PCR developed by the European Commission, Joint Research Centre (JRC), and through nested RT-PCR followed by Sanger sequencing. Overall, 115 samples tested positive for Omicron SARS-CoV-2 variant. The first occurrence was detected on 7 December, in Veneto, North Italy. Later on, the variant spread extremely fast in three weeks, with prevalence of positive wastewater samples rising from 1.0% (1/104 samples) in the week 5–11 December, to 17.5% (25/143 samples) in the week 12–18, to 65.9% (89/135 samples) in the week 19–25, in line with the increase in cases of infection with the Omicron variant observed during December in Italy. Similarly, the number of Regions/Autonomous Provinces in which the variant was detected increased fromone in the first week, to 11 in the second, and to 17 in the last one. The presence of the Omicron variant was confirmed by the JRC real-time RT-PCR in 79.1% (91/115) of the positive samples, and by Sanger sequencing in 66% (64/97) of PCR amplicons

Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis

Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.Objective: To identify the genetic variants associated with juvenile ALS.Design, Setting, and Participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism.Main Outcomes and Measures: De novo variants present only in the index case and not in unaffected family members.Results: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway.Conclusions and Relevance: These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.</p