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Background Recombinant zoster vaccine [RZV] reduces the short-term risk of herpes zoster [HZ] in patients with inflammatory bowel disease [IBD]. However, there is lack of data regarding the long-term effectiveness in this population. Methods A retrospective cohort study was conducted in adults ≥50 years old using TriNetX database between patients with IBD who received two doses of RZV [IBD-RZV cohort] and patients who did not receive RZV [IBD control cohort]. The primary outcome was risk of incident HZ. One-to-one propensity score matching was performed for demographic parameters, comorbid conditions, and IBD medications. Risk was expressed as adjusted odds ratio [aOR] with 95% confidence intervals [CI]. Results The IBD-RZV cohort [ n  = 5489; mean age 63.2 ± 9.1 years; 57.2% females] was identified with a mean follow-up of 900.9 days. IBD-RZV cohort had a lower risk of HZ [aOR 0.44, 95% CI 0.32-0.62] compared with IBD control cohort. The risk of HZ was lower in patients aged 50–65 years [aOR 0.41, 95% CI 0.25-0.68] and patients >65 years [aOR 0.64, 95% CI 0.42-0.96]. There was a lower risk of HZ in patients with ulcerative colitis [aOR 0.41, 95% CI 0.27-0.63] and Crohn's disease [aOR 0.44, 95% CI 0.26-0.74] in the IBD-RZV cohort compared with IBD control cohort. Conclusion RZV is associated with a lower long-term risk of HZ in patients ≥50 years old with IBD. Given the widespread availability and safety of RZV, more effective vaccination strategies are needed to improve RZV use in this high-risk population. [ABSTRACT FROM AUTHOR]

This prospective study enrolled healthcare workers (HCWs) who were nonresponders following at least 5 doses of aluminum-adjuvanted hepatitis B vaccine who received the 2-dose Heplisav-B (HepB-CpG) (Dynavax Technologies Corporation, Emeryville, CA) series. After 2 doses of HepB-CpG, 43/47 (91%) participants, and with 1 dose, 41/49 (84%) responded. HepB-CpG could be the preferred vaccine in HCW nonresponders. Clinical Trials Registration. Clinicaltrials.gov NCT04456504. [ABSTRACT FROM AUTHOR]

Background. Cell wall peptidoglycan stimulates interleukin 10 (IL-10) production in Staphylococcus aureus bacteremia (SaB) animal models, but clinical data are not available. This study evaluates the impact of intravascular bacterial cell numbers (ie, the level of bacteremia), in patients at the time of clinical presentation on IL-10 production and its association with S. aureus bacteremia (SaB) mortality. Methods. Blood and isolates were collected in 133 consecutive SaB patients. Serum IL-10 was quantified by an electrochemoluminescence assay. Bacterial inoculum was measured in patient sera with elevated (n = 8) or low (n = 8) IL-10 using a magnetic bacterial capture assay. Staphylococcus aureus from these 2 groups were introduced into whole blood ex vivo to determine IL-10 production with variable inocula. Results. IL-10 serum concentration was higher in SaB patient mortality (n = 27) vs survival (n = 106) (median, 36.0 pg/mL vs 10.4 pg/mL, respectively, P < .001). Patients with elevated IL-10 more often had endovascular SaB sources. The inoculum level of SaB was higher in patients with elevated serum IL-10 vs patients with low IL-10 (35.5 vs 0.5 median CFU/mL; P = .044). Ex vivo studies showed that 108 CFU/mL yielded greater IL-10 than did 103 CFU/mL (4.4 ± 1.8 vs 1.0 ± 0.6 pg/mL; P < .01). Conclusions. Elevated IL-10 serum concentrations at clinical presentation of SaB were highly associated with mortality. High intravascular peptidoglycan concentration, driven by a higher level of bacteremia, is a key mediator of IL-10 anti-inflammatory response that portends poor clinical outcome. Using IL-10 as an initial biomarker, clinicians may consider more aggressive antimicrobials for rapid bacterial load reduction in high-risk SaB patients. [ABSTRACT FROM AUTHOR]

Background Toxins contribute to the pathogenicity of Staphylococcus aureus infections by inducing a dysregulated inflammatory response. This study evaluated the impact of anti-staphylococcal antibiotic exposures over an increasing concentration range on cytokine production from peripheral blood mononuclear cells (PBMCs) after S. aureus toxin exposures. Methods Human PBMCs were suspended in complete Roswell Park Memorial Institute (RPMI) 1640 medium with 10% fetal bovine serum at 106 cells/mL with 100 ng/mL S. aureus toxic shock syndrome toxin-1 (TSST-1), staphylococcal enterotoxin A (SEA), α-toxin or Panton–Valentine leucocidin (PVL). Vancomycin, trimethoprim/sulfamethoxazole, tigecycline, daptomycin, linezolid, clindamycin and azithromycin were added at a concentration range of 0.5–100 mg/L. Cytokine [interleukin-1β (IL-1β), IL-6, IL-8, interferon-γ (IFN-γ) and tumour necrosis factor-α (TNF-α)] concentrations were measured in duplicate by ELISA following exposure and were compared with response with toxin alone. Results At concentrations approximating serum Cmax, tigecycline decreased IL-6 by 52%–57% and IFN-γ production by 43%–53% compared with toxin alone (P ≤ 0.05) and linezolid inhibited TNF-α by 12%–35% and IL-8 by 25%–42% (P ≤ 0.02). However, trimethoprim/sulfamethoxazole increased TNF-α and IL-8 production (P = 0.002). Clindamycin, daptomycin, vancomycin and azithromycin had no consistent significant effect at approximate serum Cmax concentrations. All antibiotics had a concentration-dependent effect on cytokine production, with tigecycline, clindamycin and trimethoprim/sulfamethoxazole being the most potent inhibitors of cytokine production at concentrations exceeding 25 mg/L. Conclusions S. aureus toxins stimulate production of inflammatory cytokines in PBMCs. Antimicrobials with high tissue penetration, including tigecycline, clindamycin, trimethoprim/sulfamethoxazole and linezolid, reduced cytokine production, which, along with their antimicrobial effects, may have importance in the therapeutic outcome of severe infections. [ABSTRACT FROM PUBLISHER]

Discusses the impact of pharmacogenomics on the prevention, diagnosis and treatment of infectious diseases. Consideration of the genomes of both the pathogen and the host; Association between polymorphisms in genes of the host immune system and susceptibility to infections and response to treatment; Detection of genes conferring resistance to antibiotics.

Discusses the clinical course of smallpox infection with current and future roles of vaccination and strategies for controlling smallpox outbreaks. Factors that make smallpox a desirable biological weapon; Analysis of virology and epidemiology of smallpox; Factors that facilitate spread of the disease; Comparison of varicella-zoster and smallpox; Availability of modes of treatments available for the disease.