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Highlights • Tuberculin skin test (TST) is over a century old but it continues to be used widely. • When IGRAs were introduced it was anticipated that they would rapidly replace TST. • Neither TST nor IGRAs have a high accuracy for predicting active TB. • Latest WHO recommendations are that either TST or IGRA can be used to test for LTBI. • TST will be clinically useful until more accurate tests become available. Abstract Objective To make an informed viewpoint on the usefulness of Tuberculin Skin test (TST) compared to Interferon Gamma Release Assays (IGRAs) for diagnosis of Latent TB Infection (LTBI) in different geographical settings. Methods We reviewed the current literature on TST compared to IGRA, including national implementation of WHO LTBI recommendations and retrospective data over the past 7 years at the National Institute for Infectious Diseases "L. Spallanzani" as indirect indicator of usage of both tests under actual programmatic conditions. Results Current national guidelines vary considerably, reflecting the uncertainty and rapidly evolving evidence about the potential use of these tests. Data from Institute "L. Spallanzani" showed IGRA concordance in TST positive subjects only in 54.74% of subjects, while there was strong concordance between two tests in TST negative subjects (93.78%). Conclusion Neither IGRAs nor TST can distinguish active TB from LTBI. TST will continue to be clinically useful in low and high TB endemic areas until more accurate and predictive tests will become available. Clinical judgment remains fundamental in choosing between IGRA/TST tests and interpreting their results. [ABSTRACT FROM AUTHOR]

Summary: Background: Five thematic working groups composed of Italian infectious disease experts and a group coordinator, supported by a scientific secretary, identified controversial issues in the field of severe healthcare-associated infections caused by multidrug-resistant organisms. The five group coordinators received training courses on data sources and electronic databases, literature search strategies, the scientific revision methods of quality assessment, and the construction of an evidence matrix. Working plan and methods: The working plan identified the following step: definition of the controversial issues and identification of documents for a systematic literature review. A specific methodology to classify the selected evidence was used that required the evaluation of the quality of review documents and statement documents and evaluation of the quality of original research. An original method to assess review documents and statement documents was proposed. A matrix model to extract and evaluate the evidence from original studies was designed using the CONSORT method to evaluate randomized clinical trials and the Newcastle–Ottawa Quality Assessment Scale for case–control studies, cohorts, and retrospective studies. Quality of evidence: A modified GRADE working group method was applied for grading quality of evidence and strength of recommendations. The working groups reviewed the available studies and formulated recommendations to be voted on at the national consensus conference held in Rome in June 2009. [Copyright &y& Elsevier]

Median age at diagnosis for chronic lymphocytic leukaemia (CLL) patients is now 72 years, thus a consistent number of patients may not tolerate standard doses i.v. of fludarabine, cyclophosphamide and rituximab (FCR), the best available therapy, due to unacceptable myelotoxicity and risk of severe infections. We studied safety and efficacy of the addition of rituximab to the oral low-dose FC regimen (old-FCR) in a selected population of 30 elderly (median age 75, 15 untreated, 15 treated with 1 prior therapy) CLL patients. Complete remission (CR) rate was 80% in the untreated patients (overall response rate, ORR 93%), and 30% in pretreated patients (ORR 74%). Progression free survivals (PFS) were 45 months and 30 months in the untreated and treated patients, respectively. In patients achieving CR, old-FCR led to PFS of 67 months. Moreover, haematological toxicity was mild (grade 3-4: 15%) and patients were treated mostly in outpatient clinic. Old-FCR could be a good therapy option for elderly CLL patients outside clinical trials, larger studies are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Summary: Over the last decade, methicillin-resistant Staphylococcus aureus (MRSA) strains have emerged as serious pathogens in the nosocomial and community setting. Hospitalization costs associated with MRSA infections are substantially greater than those associated with methicillin-sensitive S. aureus (MSSA) infections, and MRSA has wider economic effects that involve indirect costs to the patient and to society. In addition, there is some evidence suggesting that MRSA infections increase morbidity and the risk of mortality. Glycopeptides are the backbone antibiotics for the treatment of MRSA infections. However, several recent reports have highlighted the limitations of vancomycin, and its role in the management of serious infections is now being reconsidered. Several new antimicrobials demonstrate in vitro activity against MRSA and other Gram-positive bacteria. Data from large surveys indicate that linezolid, daptomycin, and tigecycline are almost universally active against MRSA. This review will briefly discuss the epidemiology, costs, outcome, and therapeutic options for the management of MRSA infections. [Copyright &y& Elsevier]

Abstract: By using GRADE system we updated the guidelines for management of CLL issued in 2006 from SIE, SIES and GITMO group. We recommended fludarabine, cyclophosphamide, rituximab (FCR) in younger and selected older patients with a good fitness status, no unfavourable genetics (deletion 17p and/or p53 mutations), and a less toxic treatment in nonfit and elderly patients. In patients without unfavourable genetics, relapsed after 24 months the same initial treatment including rituximab can be considered. In patients with unfavourable genetics, refractory or relapsed within 24 months from a prior fludarabine-based treatment, allogeneic SCT or experimental treatments should be given. [Copyright &y& Elsevier]

A new t(20;21)(q11;q11), associated with a deletion on the long arm of chromosome 20, was found in one patient with an acute myelocytic leukemia (AML) and in one with myelodysplastic syndrome (MDS). In both cases deletion was interstitial, extending from band q11 to band q13, as shown by comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH). FISH analysis with whole arm paints, subtelomeric probes, and locus-specific probes for the long arms of chromosomes 20 and 21 revealed in patient 1 a reciprocal translocation between the deleted 20q and the long arm of chromosome 21, that is, del(20)(q11q13)t(20;21)(q11;q11), and in patient 2, material from 21q was inserted into the deleted 20q, that is, del(20)(q11q13)ins(20;21)(q11;q11q22). This is the first identification of a complex 20;21 rearrangement in MDS/AML. Deletion at 20q and juxtaposition between 20q11 and 21q11 appear to be the critical genomic events. [Copyright &y& Elsevier]

Emergence of additional cytogenetic clones in chronic myelocytic leukemia (CML) patients who become Philadelphia chromosome–negative (Ph−) after α-interferon therapy (or more recently with imatinib mesylate) have been described. We report here a case of a novel t(6;7)(p21;q23) that developed in a CML patient in complete cytogenetic remission during imatinib therapy. In this case, fluorescence in situ hybridization and reverse transcriptase polymerase chain reaction showed a normal pattern for BCR and ABL genes, suggesting that a different and unrelated clone developed after the disappearance of the Ph chromosome. [Copyright &y& Elsevier]

Summary: Background: Complicated skin and skin-structure infections (cSSSI), including surgical site infections (SSI), cellulitis, and abscesses, have been extensively studied, but controversial issues still exist. 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 the following controversial issues: (1) What is the efficacy of topical negative pressure wound treatment as compared to standard of care in the treatment of severe surgical site infections, i.e., deep infections, caused by Gram-positive microorganisms? (2) Which are the most effective antibiotic therapies in the treatment of cSSSI, including SSI, due to methicillin-resistant staphylococci? Results are presented and discussed. Methods: A systematic literature search using the MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and www.clinicaltrials.gov databases 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 was used for grading quality of evidence. An analysis of the studies published between 1990 and 2008 is presented and discussed in detail. [Copyright &y& Elsevier]

Summary: Background: Joint replacement surgery has been on the increase in recent decades and prosthesis infection remains the most critical complication. Many aspects of the primary prevention and clinical management of such prosthesis infections still need to be clarified. 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 the following controversial issues: (1) Is a conservative surgical approach for the management of prosthetic joint infections effective? (2) Is the one-stage or the two-stage revision for the management of prosthetic joint infections more effective? (3) What is the most effective treatment for the management of prosthetic joint infections due to methicillin-resistant staphylococci? 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. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]

Summary: Background: Hospital-associated pneumonia (HAP) remains an important cause of morbidity and mortality despite advances in antimicrobial therapy. Many aspects of the treatment of HAP caused by multi-resistant Gram-positive microorganisms have been extensively studied, but 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 were: (1) Is combination antibiotic therapy or monotherapy more effective in the treatment of HAP? (2) What role do pharmacokinetic/pharmacodynamic antibiotic features have as a guide in the selection of treatment for HAP? (3) Is a de-escalation approach for the management of HAP effective? An analysis of the studies published up until April 2009 is presented and discussed in detail. Methods: A systematic literature search using PubMed, MEDLINE, and EMBASE databases and the Cochrane Library 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 was applied. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]