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Background: SARS-CoV-2 mRNA vaccination, recognized for high immunogenicity, frequently induces adverse reactions, especially fever. We previously reported a correlation between post-vaccination fever and specific antibody responses to the primary series and first booster. We herein report changes in adverse reactions and the correlation between post-vaccination fever and antibody responses across successive vaccinations, from monovalent to bivalent mRNA vaccines. Methods: This cohort study was conducted at a Japanese hospital to investigate adverse reactions to the monovalent primary, first booster, and BA.4/5 bivalent BNT162b2 vaccinations. Local and systemic reactions were reported through a self-reporting diary after each dose. The spike-specific IgG titers were measured following each vaccination. Results: Across 727 vaccinations in the vaccine series, the bivalent booster induced fewer adverse reactions than earlier doses. Fever ≥ 38.0 °C was significantly less frequent in the bivalent booster (12.3 %) compared to the primary series and monovalent booster (22.0 %, 26.2 %, p

Objectives: Differences in virulence genes, including psm-mec, which is a phenol-soluble modulin-mec (PSM-mec) encoding gene, of predominant staphylococcal cassette chromosome mec (SCCmec) types II and IV Methicillin-resistant Staphylococcus aureus (MRSA) may contribute to the virulence and clinical features of MRSA in Japan. We aimed to clarify the clinical characteristics and risk factors of infection among SCCmec types II and IV MRSA isolates from a Japanese secondary acute care hospital. Methods: We analysed 58 SCCmec type II and 83 SCCmec type IV MRSA isolates collected from blood, central venous catheter tips, deep or superficial tissues, and sputum. Results: SCCmec type II MRSA risk factors for progression to infection were seb, enterotoxin gene cluster, psm-mec mutation, and vancomycin minimum inhibitory concentrations (MIC) of 1 or 2 mg/L as virulence factors (adjusted odds ratio [aOR] = 11.8; 95% confidence interval [CI]: 2.49–77.7; P = 0.004); solid tumour was a host factor (aOR = 25.9; 95% CI: 3.66–300; P = 0.003). SCCmec type IV MRSA risk factors were sea, cna, and vancomycin MIC of 1 or 2 mg/L as virulence factors (aOR = 3.14; 95% CI: 1.06–10.6; P = 0.049) and intravascular indwelling catheter as host factors (aOR = 3.78; 95% CI: 1.03–14.5; P = 0.045). Compared with SCCmec type II, SCCmec type IV MRSA resulted in more frequent bloodstream infections and higher Sequential Organ Failure Assessment scores. Conclusion: We found that factors related to virulence genes and bacteriological and host characteristics are associated with SCCmec types II and IV MRSA infection and severity. These risk factors may be useful criteria for designing infection control programs.

Summary: The efficacy of vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the elderly is partially hindered by immunosenescence, resulting from decreased mtDNA levels. This study evaluated the correlation between mtDNA levels in peripheral leukocytes and immune response to the SARS-CoV-2 vaccine. Two hundred ten participants (median age 79.5 years), including 83 frail residents/inpatients and 70 robust outpatients, were analyzed. Anti-spike IgG antibody (IgG(S)) titers were serially measured from before the first vaccination to after the third vaccination. The mtDNA levels and cell-mediated immunity were measured in 45 elderly and 22 elderly individuals two months after the third vaccination. The robust group had consistently higher IgG(S) titers than the frail group. The mtDNA levels positively correlated with IgG(S) titers, as well as with cell-mediated immunity. These findings suggest that mtDNA levels positively impact vaccine-induced immunity. Further studies into maintaining mtDNA levels may provide insights into immunosenescence in the elderly.

ABSTRACT: Objectives: The dissemination of difficult-to-treat carbapenem-resistant Enterobacterales (CRE) is of great concern. We clarified the risk factors underlying CRE infection mortality in Japan. Methods: We conducted a retrospective, multicentre, observational cohort study of patients with CRE infections at 28 university hospitals from September 2014 to December 2016, using the Japanese National Surveillance criteria. Clinical information, including patient background, type of infection, antibiotic treatment, and treatment outcome, was collected. The carbapenemase genotype was determined using PCR sequencing. Multivariate analysis was performed to identify the risk factors for 28-day mortality. Results: Among the 179 patients enrolled, 65 patients (36.3%) had bloodstream infections, with 37 (20.7%) infections occurring due to carbapenemase-producing Enterobacterales (CPE); all carbapenemases were of IMP-type (IMP-1: 32, IMP-6: 5). Two-thirds of CPE were identified as Enterobacter cloacae complex. Combination therapy was administered only in 46 patients (25.7%), and the 28-day mortality rate was 14.3%. Univariate analysis showed that solid metastatic cancer, Charlson Comorbidity Index ≥3, bloodstream infection, pneumonia, or empyema, central venous catheters, mechanical ventilation, and prior use of quinolones were significant risk factors for mortality. Multivariate analysis revealed that mechanical ventilation (OR: 6.71 [1.42–31.6], P = 0.016), solid metastatic cancers (OR: 5.63 [1.38–23.0], P = 0.016), and bloodstream infections (OR: 3.49 [1.02–12.0], P = 0.046) were independent risk factors for 28-day mortality. Conclusion: The significant risk factors for 28-day mortality in patients with CRE infections in Japan are mechanical ventilation, solid metastatic cancers, and bloodstream infections.

Objectives: Many countries are administering a third dose of some coronavirus disease 2019 (COVID-19) vaccines, but the evaluation of vaccine-induced immunity after boosting in East Asia is insufficient. This study aimed to evaluate anti-spike immunoglobulin G [IgG(S)] titers after the third BNT162b2 vaccination. Methods: The dynamics of IgG(S) titers were assessed two months following the third BNT162b2 vaccination in 52 participants. All participants received the primary series of vaccination with BNT162b2 and received the third dose eight months after the second vaccination. Associations among the IgG(S) titer, baseline characteristics, and adverse reactions were also evaluated. Results: The geometric mean titer of IgG(S) one month after the third vaccination was 17,400 AU/ml, which increased by approximately 30 times that immediately before the third vaccination. The rate of IgG(S) titer decline was significantly slower after the third vaccination (35.7%) than after the second vaccination (59.1%). The IgG(S) titer was significantly negatively associated with age (r = −0.31). Participants who had a headache at the time of vaccination showed significantly higher IgG(S) titers than those without a headache. Conclusions: The IgG(S) titer induced by primary immunization with BNT162b2 waned over time. The third dose of BNT162b2 substantially increased the IgG(S) titer, with a slower rate of decline.

The relation between pre-vaccination antipyretic use and antibody responses to SARS-CoV-2 vaccination has been unclear. We measured the pre- and post-BNT162b2 booster spike-specific IgG titers and recorded antipyretic use and adverse reactions for SARS-CoV-2-naive hospital healthcare workers. The data of 20 cases who used antipyretics within 24 h before vaccination were compared to that of 281 controls. The post-booster geometric mean IgG titers were 15,559 AU/mL (95 % CI, 11,474–21,203) for the cases and 16,850 AU/mL (95 % CI, 15,563–18,243) for the controls (p = 0.622). No significant reduction in the frequency or severity of any of the solicited adverse reactions was found for the cases. Similar results were obtained after adjustment with propensity-score matching for demographic characteristics, baseline IgG titer, and post-vaccination antipyretic use. Antipyretic use within 24 h before vaccination would not affect mRNA COVID-19 vaccine-induced specific antibody responses and that postponement of vaccination due to pre-vaccination antipyretic use would be unnecessary.

Objectives: Antimicrobial stewardship is a strategy to combat antimicrobial resistance in hospitals. Given the burden and impact of antimicrobial resistance in the Asia Pacific, it is important to document capacity and gaps in antimicrobial stewardship programmes (ASP). We aimed to understand existing capacities and practices, and define the resources needed to establish antimicrobial stewardship where it is lacking. Methods: An anonymous online survey, consisting of questions on antimicrobial control at country, hospital and programme levels, was circulated to healthcare providers in the field of infectious diseases and microbiology through Asian Network for Surveillance of Resistant Pathogens, ReAct Group and the Australasian Society for infectious Diseases. Results: 139 participants from 16 countries or regions completed the survey. The majority of participants were adult infectious diseases physicians (61/139, 43.9%) and microbiologists (31/139, 22.3%). Participants from 7 countries reported that antimicrobials can be obtained without prescriptions. Despite the high percentage (75.5%) of respondents working in large hospitals, only 22/139 participants (15.8%) from Australia, China, Singapore, Taiwan, Thailand and Vietnam reported having more than 10 infectious diseases physicians. Hospital empiric antimicrobial guidelines for common infections were available according to 110/139 (79.1%) participants. Pre-authorisation of antimicrobials was reported by 88/113 (77.9%) respondents while prospective audit and feedback was reported by 93/114 (81.6%). Automatic stop orders and culture-guided de-escalation were reported by only 52/113 (46.0%) and 27/112 (24.1%) respectively. Conclusion: The survey reveals a wide range of ASP development in Asia Pacific. Establishing national workgroups and guidelines will help advance antimicrobial stewardship in this diverse region.