Caratterizzazione molecolare di isolati nosocomiali di Staphylococcus aureus tramite spa typing e sequenziamento del gene rpoB: prevalenza di un clone multiresistente "spa type t001"

La resistenza multipla in Staphylococcus aureus meticillino-resistente (MRSA) è un problema di crescente importanza. Il successo di Staphylococcus aureus (S. aureus) come patogeno umano risiede nella sua versatilità e, come parte del suo adattamento nell’era antibiotica, è stato capace di evolvere acquisendo resistenza a quasi tutti gli antibiotici potenzialmente attivi. La rifampicina è uno dei farmaci che conserva più frequentemente una buona attività anti-stafilococcica e viene quindi spesso impiegata in terapia di associazione. Lo scopo del lavoro è stato quello di caratterizzare una popolazione di isolati clinici nosocomiali di S.aureus tramite: (i) tipizzazione molecolare della popolazione batterica attraverso spa (S. aureus protein A) typing; (ii) caratterizzazione dell’elemento SCCmec; (iii) caratterizzazione delle mutazioni nel gene rpoB; (iv) analisi della correlazione tra pattern di resistenza e diffusione di specifici spa tipi; v) studio della presenza del gene mecA

Evolution of macrolide resistance in streptococcus pyogenes over 14 years in an area of central Italy

We evaluated temporal fluctuations in macrolide resistance rates, analysing genetic determinants of resistance and clonal evolution in a population of 2744 S. pyogenes isolates collected in the period 2000–2013. The total resistance rate to erythromycin of the isolates was 17.9%. A maximum of erythromycin resistance emerged in 2000 (38.6%), followed by a significant decrease to 5.2% in 2012 (P<0.0001). Molecular analysis revealed the presence and co-presence of known genetic resistance determinants mefA, mefE, ermTR and ermB, in line with phenotypes. PFGE analysis identified genetically related groups in 2000 and 2007–2008, mainly the MLS and M phenotypes, respectively. The most prevalent emm types among a representative subset of resistant isolates were emm2, emm75 and emm77. All emm2 and 88.2% of the strains harbouring the emm75 gene were only recorded in M-phenotype strains, whilst all emm77-positive strains had the inducible MLS phenotype. The analysed susceptible isolates showed several emm types partially shared with resistant ones. Our results suggest that changes in bacterial population clonality, rather than horizontal transfer of resistance determinants, plays a major epidemiological role in S. pyogenes. Continuous monitoring of microbiological epidemiology seems to be crucial for correct and effective management of streptococcal infections

Rapid Decrease in Fluoroquinolones Consumption following Implementation of a Simple Antimicrobial Stewardship Bundled Intervention in a University Hospital during the COVID-19 Pandemic

Fluoroquinolones (FQs) represent an class of antibiotics of medical importance, but their use has been restricted due to their ecologic impact and associated side effects. The reduction of FQs use is an important goal of antimicrobial stewardship programs (ASP). This work describes an ASP focused on overall antibiotics and FQs consumption reduction. From January 2021, an ASP was implemented in a 700-bed teaching hospital. The ASP was based on: (i) antibiotics consumption monitoring system (DDD/100 bed days); (ii) mandatory antibiotic prescription-motivation (using a dedicated informatic format) with the goal of >75% of motivated prescriptions; and (iii) data feedback and training on FQs use indications. We evaluated the impact of the intervention on overall systemic antibiotics and FQs consumption according to the objectives posed by Italian PNCAR (National Action Plan on Antimicrobial Resistance). A decrease of 6.6% in antibiotic use was observed (2019 vs. 2021). Notably, the FQs consumption fell by 48.3% from 7.1 DDD/100 bd in 2019 to 3.7 DDD/100 bd in 2021 (p < 0.001). After six months of mandatory antibiotic prescription-indication, all units achieved the target set. The study suggests that a simple, bundled ASP intervention can be rapidly effective obtaining the objectives of PNCAR on the reduction of overall antibiotics and FQs consumption

Using IFN-gamma release assay to confirm tuberculin skin test improves the screening of latent tuberculosis infection in Italian healthcare workers

Background Healthcare workers (HCWs) represent a tuberculosis (TB) risk group for a wide range of tasks in healthcare, even in countries with low TB incidence, like Italy. Latent Tuberculosis Infection (LTBI) screening programs are an important tool for TB prevention in these setting. Methods A retrospective study under a LTBI screening program among HCWs at the Siena University Hospital (Italy), was conducted between September 2011 and July 2015. Tuberculin Skin Test (TST) was used as a first level examination; all TST-positive cases were tested with QuantiFERON-TB Gold In-Tube (QFT-GIT) test, together with a group of TST-negative subjects. Results Among the 2136 HCWs screened, 144 (6.7 %) were TST-positive and therefore tested with QFT-GIT, confirming a positive result in 36 cases (25 %). Agreement between two tests was poor (k = 0.092; 95 %, Confidence Interval [CI]- 0.048–0.136, p = 0.002). Among TST-positive cases, discordant results occurred more frequently in BCG vaccinated than unvaccinated HCWs (86.3 %, p < 0.001). The probability of a QFT-GIT-positive result increased according to the TST diameter (p = 0.001). No putative risk factor was associated with LTBI occurrence. Conclusions The use of QFT-GIT test as a second step in TST-positive cases offers an appropriate tool for LTBI detection, especially among BCG-vaccinated HCWs

Musculoskeletal manifestations of childhood cancer and differential diagnosis with juvenile idiopathic arthritis (ONCOREUM): a multicentre, cross-sectional study

Summary Background Presenting symptoms of childhood cancers might mimic those of rheumatic diseases. However, the evidence available to guide differential diagnosis remains scarce. Preventing wrong or delayed diagnosis is therefore important to avoid incorrect administration of glucocorticoid or immunosuppressive therapy and worsening of prognosis. As such, we aimed to assess the prevalence and characteristics of presenting musculoskeletal manifestations in patients at cancer onset and to identify the factors that differentiate childhood malignancies with arthropathy from juvenile idiopathic arthritis. Methods We did a multicentre, cross-sectional study at 25 paediatric haemato-oncology centres and 22 paediatric rheumatology centres in Italy. We prospectively recruited patients who were younger than 16 years that were newly diagnosed with cancer or juvenile idiopathic arthritis. We excluded patients with glucocorticoid pre-treatment (&gt;1 mg/kg per day of oral prednisone or equivalent for ≥2 consecutive weeks). We collected data for patients with a new diagnosis of cancer or juvenile idiopathic arthritis using an electronic case report form on a web-based platform powered by the Cineca Interuniversity Consortium. The primary outcome was to describe the frequency and characteristics of musculoskeletal manifestations at cancer onset; and the secondary outcome was to identify factors that could discriminate malignancies presenting with arthropathy, with or without other musculoskeletal symptoms, from juvenile idiopathic arthritis using multivariable logistic regression analysis. Findings Between May 1, 2015, and May 31, 2018, 1957 patients were eligible, of which 1277 (65%) had cancer and 680 (35%) had juvenile idiopathic arthritis. Musculoskeletal symptoms occurred in 324 (25% [95% CI 23·0–27·8]) of 1277 patients with cancer, of whom 207 had arthropathy. Patients with malignant bone tumours had the highest frequency of musculoskeletal symptoms (53 [80%] of 66), followed by patients with Langerhans histiocytosis (16 [47%] of 34), leukaemia (189 [32%] of 582), soft-tissue sarcomas (16 [24%] of 68), and neuroblastoma (21 [19%] of 109). In the 324 patients with cancer and musculoskeletal symptoms, the most common complaints were joint pain (199 [61%]), followed by limb bone pain (112 [35%]). Joint involvement had a prevalent monoarticular pattern (100 [48%] of 207) and oligoarticular pattern (86 [42%] had 2–4 joints involved and 20 [10%] had &gt;4 joints involved), with the most frequently involved joints being the hip (88 [43%] of 207) and knee (81 [39%]). On multivariable analysis, limb bone pain was the independent variable most strongly associated with cancer (odds ratio [OR] 87·80 [95% CI 18·89–408·12]), followed by weight loss (59·88 [6·34–565·53]), thrombocytopenia (12·67 [2·40–66·92]), monoarticular involvement (11·30 [4·09–31·19]), hip involvement (3·30 [1·13–9·61]), and male sex (2·40 [1·03–5·58]). Factors independently associated with juvenile idiopathic arthritis were morning stiffness (OR 0·04 [95% CI 0·01–0·20]), joint swelling (0·03 [0·01–0·09]), and involvement of the small hand joints (0·02 [0–1·05]). Interpretation Our study provides detailed information about presenting musculoskeletal manifestations of childhood cancers and highlights the clinical and laboratory features that are most helpful in the differential diagnosis with juvenile idiopathic arthritis

Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants.

We conducted a genome-wide association study testing single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) for association with early-onset myocardial infarction in 2,967 cases and 3,075 controls. We carried out replication in an independent sample with an effective sample size of up to 19,492. SNPs at nine loci reached genome-wide significance: three are newly identified (21q22 near MRPS6-SLC5A3-KCNE2, 6p24 in PHACTR1 and 2q33 in WDR12) and six replicated prior observations (9p21, 1p13 near CELSR2-PSRC1-SORT1, 10q11 near CXCL12, 1q41 in MIA3, 19p13 near LDLR and 1p32 near PCSK9). We tested 554 common copy number polymorphisms (>1% allele frequency) and none met the pre-specified threshold for replication (P < 10(-3)). We identified 8,065 rare CNVs but did not detect a greater CNV burden in cases compared to controls, in genes compared to the genome as a whole, or at any individual locus. SNPs at nine loci were reproducibly associated with myocardial infarction, but tests of common and rare CNVs failed to identify additional associations with myocardial infarction risk

Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants

We conducted a genome-wide association study testing single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) for association with early-onset myocardial infarction in 2,967 cases ad 3,075 controls. We carried out replication in an independent sample with an effective sample size of up to 19,492. SNPs at nine loci reached genome-wide significance: three are newly identified (21q22 near MRPS6-SLC5A3-KCNE2, 6p24 in PHACTR1 and 2q33 in WDR12) and six replicated prior observations(1-4) (9p21, 1p13 near CERSL2-PSRC1-SORT1, 10q11 near CXCL12, 1q41 in MIA3, 19p13 near LDLR and 1p32 near PCSK9). We tested 554 common copy number polymorphisms (> 1% allele frequency) and none met the pre-specified threshold for replication (P < 10(-3)). We identified 8,065 rare CNVs but did not detect a greater CNV burden in cases compared to controls, in genes compared to the genome as a whole, or at any individual locus. SNPs at nine loci were reproducibly associated with myocardial infarction, but tests of common and rare CNVs failed to identify additional associations with myocardial infarction risk