Tumor necrosis factor-α inhibitor-related autoimmune disorders

Biotechnological monoclonal antibodies and receptor antagonists capable of targeting specific inflammatory actors, such as cytokines, cytokines receptors, co-stimulatory molecules or leukocyte populations, have emerged as an alternative to conventional therapies for treating systemic inflammatory diseases with immune pathogenesis. However, there is no doubt that, with a frequency that is not exceptionally high but also not negligible, immunotherapies can favour the development of systemic and organ-specific immune-mediated disorders. It has become increasingly evident that interference with a specific immune pathway may favour the activation of opposing compensatory signalling, which may exacerbate underlying subclinical disorders or cause immune-mediated diseases completely different from the underlying disease. The 'compensatory immunological switch' has emerged primarily in patients treated with tumor necrosis factor (TNF) -α inhibitors, the first biological drugs approved for treating systemic inflammatory diseases with immune pathogenesis. In this Review, we describe the clinical features and predisposing factors of the main TNF-α inhibitor-related autoimmune disorders, organising them into subclinical serological autoimmunity, autoimmune disorders other than those for which TNF-α inhibitors are indicated, and paradoxical reactions. We also discuss the underlying pathogenetic mechanisms and precautions for use in the therapeutic management of these patients. Better understanding of the complex phenomenon of the 'compensatory immunological switch', which TNF-α inhibitors and other biological drugs might trigger, can help not only appropriately managing immune-mediated disorders, but also better interpreting the heterogeneity of the pathogenetic mechanisms underlying certain chronic inflammatory conditions that, although different from each other, are arbitrarily placed in the context of overly generic nosological entities

Anaerobic bloodstream infections in Italy (ITANAEROBY): A 5-year retrospective nationwide survey

36noIntroduction: A lack of updated data on the burden and profile of anaerobic bloodstream infections (ABIs) exists. We assessed the incidence of ABIs and trends in antimicrobial resistance in anaerobes isolated from blood in Italy. Material and methods: We conducted a retrospective study on 17 Italian hospitals (2016-2020). Anaerobes isolated from blood culture and their in vitro susceptibility profiles (EUCAST-interpreted) were registered and analyzed. Results: A total of 1960 ABIs were identified. The mean age of ABIs patients was 68.6 ± 18.5 years, 57.6% were males. The overall incidence rate of ABIs was 1.01 per 10.000 patient-days. Forty-seven% of ABIs occurred in medical wards, 17% in ICUs, 14% in surgical wards, 7% in hemato-oncology, 14% in outpatients. The three most common anti-anaerobic tested drugs were metronidazole (92%), clindamycin (89%) and amoxicillin/clavulanate (83%). The three most common isolated anaerobes were Bacteroides fragilis (n = 529), Cutibacterium acnes (n = 262) and Clostridium perfringens (n = 134). The lowest resistance rate (1.5%) was to carbapenems, whereas the highest rate (51%) was to penicillin. Clindamycin resistance was >20% for Bacteroides spp., Prevotella spp. and Clostridium spp. Metronidazole resistance was 9.2% after excluding C. acnes and Actinomyces spp. Bacteroides spp. showed an increased prevalence of clindamycin resistance through the study period: 19% in 2016, 33% in 2020 (p ≤ 0.001). Conclusions: Our data provide a comprehensive overview of the epidemiology of ABIs in Italy, filling a gap that has existed since 1995. Caution is needed when clindamycin is used as empirical anti-anaerobic drug.nonemixedDi Bella, Stefano; Antonello, Roberta Maria; Sanson, Gianfranco; Maraolo, Alberto Enrico; Giacobbe, Daniele Roberto; Sepulcri, Chiara; Ambretti, Simone; Aschbacher, Richard; Bartolini, Laura; Bernardo, Mariano; Bielli, Alessandra; Busetti, Marina; Carcione, Davide; Camarlinghi, Giulio; Carretto, Edoardo; Cassetti, Tiziana; Chilleri, Chiara; De Rosa, Francesco Giuseppe; Dodaro, Saveria; Gargiulo, Raffaele; Greco, Francesca; Knezevich, Anna; Intra, Jari; Lupia, Tommaso; Concialdi, Erika; Bianco, Gabriele; Luzzaro, Francesco; Mauri, Carola; Morroni, Gianluca; Mosca, Adriana; Pagani, Elisabetta; Parisio, Eva Maria; Ucciferri, Claudio; Vismara, Chiara; Luzzati, Roberto; Principe, LuigiDi Bella, Stefano; Antonello, Roberta Maria; Sanson, Gianfranco; Maraolo, Alberto Enrico; Giacobbe, Daniele Roberto; Sepulcri, Chiara; Ambretti, Simone; Aschbacher, Richard; Bartolini, Laura; Bernardo, Mariano; Bielli, Alessandra; Busetti, Marina; Carcione, Davide; Camarlinghi, Giulio; Carretto, Edoardo; Cassetti, Tiziana; Chilleri, Chiara; De Rosa, Francesco Giuseppe; Dodaro, Saveria; Gargiulo, Raffaele; Greco, Francesca; Knezevich, Anna; Intra, Jari; Lupia, Tommaso; Concialdi, Erika; Bianco, Gabriele; Luzzaro, Francesco; Mauri, Carola; Morroni, Gianluca; Mosca, Adriana; Pagani, Elisabetta; Parisio, Eva Maria; Ucciferri, Claudio; Vismara, Chiara; Luzzati, Roberto; Principe, Luig

Human Campylobacter spp. infections in Italy

Purpose: Campylobacter is a frequent cause of enteric infections with common antimicrobial resistance issues. The most recent reports of campylobacteriosis in Italy include data from 2013 to 2016. We aimed to provide national epidemiological and microbiological data on human Campylobacter infections in Italy during the period 2017-2021. Methods: Data was collected from 19 Hospitals in 13 Italian Regions. Bacterial identification was performed by mass spectrometry. Antibiograms were determined with Etest or Kirby-Bauer (EUCAST criteria). Results: In total, 5419 isolations of Campylobacter spp. were performed. The most common species were C. jejuni (n = 4535, 83.7%), followed by C. coli (n = 732, 13.5%) and C. fetus (n = 34, 0.6%). The mean age of patients was 34.61 years and 57.1% were males. Outpatients accounted for 54% of the cases detected. Campylobacter were isolated from faeces in 97.3% of cases and in 2.7% from blood. C. fetus was mostly isolated from blood (88.2% of cases). We tested for antimicrobial susceptibility 4627 isolates (85.4%). Resistance to ciprofloxacin and tetracyclines was 75.5% and 54.8%, respectively; resistance to erythromycin was 4.8%; clarithromycin 2% and azithromycin 2%. 50% of C. jejuni and C. coli were resistant to ≥ 2 antibiotics. Over the study period, resistance to ciprofloxacin and tetracyclines significantly decreased (p < 0.005), while resistance to macrolides remained stable. Conclusion: Campylobacter resistance to fluoroquinolones and tetracyclines in Italy is decreasing but is still high, while macrolides retain good activity