Early administration of appropriate antimicrobials has been correlated with a better prognosis in patients with bacteremia, but the optimum timing of early antibiotic administration as one of the resuscitation strategies for severe bacterial infections remains unclear. In a retrospective cohort study, adults with community-onset bacteremia at the emergency department (ED) were analyzed. Effects of different cutoffs of time to appropriate antibiotic (TtAa) administration after arrival at the ED on 28-day mortality were examined, after adjustment for independent predictors of mortality identified by multivariate regression analysis. Among 2349 patients, the mean (interquartile range) TtAa was 2.0 (<1 to 12) hours. All selected cutoffs of TtAa, ranging from 1 to 96 hours, were significantly associated with 28-day mortality (adjusted odds ratio (AOR), 0.54–0.65, all P < 0.001), after adjustment of the following prognostic factors: fatal comorbidities (McCabe classification), critical illness (Pitt bacteremia score (PBS) ≥4) on arrival at the ED, polymicrobial bacteremia, extended-spectrum beta-lactamase-producer bacteremia, underlying malignancies or liver cirrhosis, and bacteremia caused by pneumonia or urinary tract infections. The adverse impact of TtAa on 28-day mortality was most evident at the cutoff of 48 hours, as the lowest AOR was identified (0.54, P < 0.001). In subgroup analyses, the most evident TtAa cutoff (i.e., the lowest AOR) remained at 48 hours in mildly ill (PBS = 0; AOR 0.47; P = 0.04) and moderately ill (PBS = 1–3; AOR 0.55; P = 0.02) patients, but shifted to 1 hour in critically ill patients (PBS ≥4; AOR 0.56; P < 0.001). The time from triage to administration of appropriate antimicrobials is one of the primary determinants of mortality. The optimum timing of appropriate antimicrobial administration is the first 48 hours after non-critically ill patients arrive at the ED. As bacteremia severity increases, effective antimicrobial therapy should be empirically prescribed within 1 hour after critically ill patients arrive at the ED.

Nirmatrelvir/ritonavir (Paxlovid™) is an effective and safe antiviral drug that inhibits the main protease (M^pro), 3CL protease, of SARS-CoV-2. A reduction in COVID-19-related hospitalization or death was observed in patients treated with nirmatrelvir/ritonavir within five days of symptom onset. Moreover, good oral availability enables the usage of nirmatrelvir/ritonavir, not only in hospitalized patients, but also among outpatients. Nirmatrelvir (PF-07321332) has been demonstrated to stop the spread of COVID-19 in animal models. Despite frequent mutations in the viral genomes of SARS-CoV-2, nirmatrelvir shows an effective antiviral effect against recent coronavirus mutants. Despite the promising antiviral effect of nirmatrelvir, there are several unresolved concerns. First, the final results of large-scale clinical trials for early therapy of mild cases of COVID-19 are not yet published. Second, the effectiveness of nirmatrelvir against upcoming variants in the coming years requires close monitoring. Considering the promising preliminary results of the EPIC-HR trial, nirmatrelvir/ritonavir in conjunction with vaccines and non-pharmacological interventions, may represent the dawn in the dark of the COVID-19 pandemic.

Since December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly resulted in a global pandemic with approximately 4 million deaths. Effective oral antiviral agents are urgently needed to treat coronavirus disease-2019 (COVID-19), block SARS-CoV-2 transmission, and prevent progression to severe illness. Molnupiravir (formerly EIDD-2801), a prodrug of beta-d-N4-hydroxycytidine (EIDD-1931) and an inhibitor of RNA-dependent RNA polymerase, possesses significant activity against SARS-CoV-2. Its prophylactic efficacy has been evidenced in a ferret model. Two phase-I trials (NCT04392219 and NCT04746183) have demonstrated that oral molnupiravir is safe and well-tolerated at therapeutic doses. After five-days of oral molnupiravir therapy, satisfactory efficacies, assessed by eliminating nasopharyngeal virus in patients with early and mild COVID-19, were disclosed in two phase-II trials (NCT04405739 and NCT 04405570). Two phase-II/III trials, NCT04575597 and NCT04575584, with estimated enrollments of 1850 and 304 cases, respectively, are ongoing. The NCT04575597 recently released that molnupiravir significantly reduced the risk of hospitalization or death in adults experiencing mild or moderate COVID-19. To benefit individual and public health, clinical applications of molnupiravir to promptly treat COVID-19 patients and prevent SARS-CoV-2 transmission may be expected.

It is known that the risk of death in elderly patients with moderate to severe traumatic brain injury is increased. However, the relationship between mild traumatic brain injury and death has never been established. We investigated the mortality rates of older patients with mild traumatic brain injury in Taiwan to evaluate if there is a higher risk of death compared with the general population.

Background: Bloodstream infections are associated with high morbidity and mortality, both of which contribute substantially to healthcare costs. The effects of early administration of appropriate antimicrobials on the prognosis and timing of defervescence of bacteremic patients remain under debate. Methods: In a 6-year retrospective, multicenter cohort, adults with community-onset bacteremia at the emergency departments (EDs) were analyzed. The period from ED arrival to appropriate antimicrobial administration and that from appropriate antimicrobial administration to defervescence was regarded as the time-to-appropriate antibiotic (TtAa) and time-to-defervescence (TtD), respectively. The primary study outcome was 30-day mortality after ED arrival. The effects of TtAa on 30-day mortality and delayed defervescence were examined after adjustment for independent predictors of mortality, which were recognized by a multivariate regression analysis. Results: Of the total 3194 patients, a TtAa-related trend in the 30-day crude (γ = 0.919, P = 0.01) and sepsis-related (γ = 0.909, P = 0.01) mortality rate was evidenced. Each hour of TtAa delay was associated with an average increase in the 30-day crude mortality rate of 0.3% (adjusted odds ratio [AOR], 1.003; P < 0.001) in the entire cohort and 0.4% (AOR, 1.004; P < 0.001) in critically ill patients, respectively, after adjustment of independent predictors of 30-day crude mortality. Of 2469 febrile patients, a TtAa-related trend in the TtD (γ = 0.965, P = 0.002) was exhibited. Each hour of TtAa delay was associated with an average 0.7% increase (AOR, 1.007; P < 0.001) in delayed defervescence (TtD of ≥ 7 days) after adjustment of independent determinants of delayed defervescence. Notably, the adverse impact of the inappropriateness of empirical antimicrobial therapy (TtAa > 24 h) on the TtD was noted, regardless of bacteremia severity, bacteremia sources, or causative microorganisms. Conclusions: The delay in the TtAa was associated with an increasing risk of delayed defervescence and 30-day mortality for adults with community-onset bacteremia, especially for critically ill patients. Thus, for severe bacteremia episodes, early administration of appropriate empirical antimicrobials should be recommended.