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.

With the rapid development of the COVID-19 pandemic, countries are trying to cope with increasing medical demands, and, at the same time, to reduce the increase of infected numbers by implementing a number of public health measures, namely non-pharmaceutical interventions (NPIs). These public health measures can include social distancing, frequent handwashing, and personal protective equipment (PPE) at the personal level; at the community and the government level, these measures can range from canceling activities, avoiding mass gatherings, closing facilities, and, at the extreme, enacting national or provincial lockdowns. Rather than completely stopping the infectious disease, the major purpose of these NPIs in facing an emerging infectious disease is to reduce the contact rate within the population, and reduce the spread of the virus until the time a vaccine or reliable medications become available. The idea is to avoid a surge of patients with severe symptoms beyond the capacity of the hospitals’ medical resources, which would lead to more mortality and morbidity. While many countries have experienced steep curves in new cases, some, including Hong Kong, Vietnam, South Korea, New Zealand, and Taiwan, seem to have controlled or even eliminated the infection locally. From its first case of COVID-19 on the 21 January until the 12 May, Taiwan had 440 cases, including just 55 local infections, and seven deaths in total, representing 1.85 cases per 100,000 population and a 1.5% death rate (based on the Worldometer 2020 statistics of Taiwan’s population of 23.8 million). This paper presents evidence that spread prevention involving mass masking and universal hygiene at the early stage of the COVID-19 pandemic resulted in a 50% decline of infectious respiratory diseases, based on historical data during the influenza season in Taiwan. These outcomes provide potential support for the effectiveness of widely implementing public health precaution measures in controlling COVID-19 without a lockdown policy.

Introduction: Bacteremia is a common but life-threatening infectious disease. However, a well-defined rule to assess patient risk of bacteremia and the urgency of blood culture is lacking. The aim of this study is to establish a predictive model for bacteremia in septic patients using available big data in the emergency department (ED) through logistic regression and other machine learning (ML) methods. Material and Methods: We conducted a retrospective cohort study at the ED of National Cheng Kung University Hospital in Taiwan from January 2015 to December 2019. ED adults (≥18 years old) with systemic inflammatory response syndrome and receiving blood cultures during the ED stay were included. Models I and II were established based on logistic regression, both of which were derived from support vector machine (SVM) and random forest (RF). Net reclassification index was used to determine which model was superior. Results: During the study period, 437,969 patients visited the study ED, and 40,395 patients were enrolled. Patients diagnosed with bacteremia accounted for 7.7% of the cohort. The area under the receiver operating curve (AUROC) in models I and II was 0.729 (95% CI, 0.718–0.740) and 0.731 (95% CI, 0.721–0.742), with Akaike information criterion (AIC) of 16,840 and 16,803, respectively. The performance of model II was superior to that of model I. The AUROC values of models III and IV in the validation dataset were 0.730 (95% CI, 0.713–0.747) and 0.705 (0.688–0.722), respectively. There is no statistical evidence to support that the performance of the model created with logistic regression is superior to those created by SVM and RF. Discussion: The advantage of the SVM or RF model is that the prediction model is more elastic and not limited to a linear relationship. The advantage of the LR model is that it is easy to explain the influence of the independent variable on the response variable. These models could help medical staff identify high-risk patients and prevent unnecessary antibiotic use. The performance of SVM and RF was not inferior to that of logistic regression. Conclusions: We established models that provide discrimination in predicting bacteremia among patients with sepsis. The reported results could inspire researchers to adopt ML in their development of prediction algorithms.

Background: The clinical impact of ST (sequence type) 131 in adults with community-onset Escherichia coli bacteremia remains controversial. Methods: Clinical data of 843 adults presenting with community-onset monomicrobial E. coli bacteremia at a medical center between 2008 and 2013 were collected. E. coli isolates were genotyped by a multiplex polymerase chain reaction to detect ST131 and non-ST131 clones. Results: Of 843 isolates from 843 patients with a mean age of 69 years, there were 102 (12.1%) isolates of ST131. The ST131 clone was more likely to be found in the elderly (76.5% vs. 64.0%; p = 0.01) and in nursing-home residents (12.7% vs. 3.8%; p < 0.001) than non-ST131 clones. Furthermore, the ST131 clone was associated with a longer time to appropriate antibiotic therapy (2.6 vs. 0.8 days; p = 0.004) and a higher 28-day mortality rate (14.7% vs. 6.5%, p = 0.003). In the Cox regression analysis with an adjustment of independent predictors, the ST131 clone exhibited a significant adverse impact on 28-day mortality (adjusted odds ratio (aOR), 2.18; p = 0.02). The different impact of the ST131 clone on 28-day mortality was disclosed in the non-ESBL (aOR 1.27; p = 0.70) and ESBL (aOR 10.19; p = 0.048) subgroups. Conclusions: Among adults with community-onset E. coli bacteremia, the ST131 clone was associated with higher 28-day mortality, particularly in those infected by ESBL producers.

Background: Cefazolin is in vitro active against wild isolates of Escherichia coli, Klebsiella species, and Proteus mirabilis (EKP), but clinical evidence supporting the contemporary susceptibility breakpoint issued by the Clinical and Laboratory Standards Institute (CLSI) are limited. Methods: Between 2010 and 2015, adults with monomicrobial community-onset EKP bacteremia with definitive cefazolin treatment (DCT) at two hospitals were analyzed. Cefazolin minimum inhibitory concentrations (MICs) were correlated with clinical outcomes, including primary (treatment failure of DCT) and secondary (30-day mortality after bacteremia onset, recurrent bacteremia, and mortality within 90 days after the end of DCT) outcomes. Results: Overall, 466 bacteremic episodes, including 340 (76.2%) episodes due to E. coli, 90 (20.2%) Klebsiella species, and 16 (3.6%) P. mirabilis isolates, were analyzed. The mean age of these patients was 67.8 years and female-predominated (68.4%). A crude 15- and 30-day mortality rate was 0.7% and 2.2%, respectively, and 11.2% experienced treatment failure of DCT. A significant linear-by-linear association of cefazolin MICs, with the rate of treatment failure, 30-day crude mortality, recurrent bacteremia or 90-day mortality after the DCT was present (all γ = 1.00, p = 0.01). After adjustment, the significant impact of cefazolin MIC breakpoint on treatment failure and 30-day crude mortality was most evident in 2 mg/L (>2 mg/L vs. ≤2 mg/L; adjusted hazard ratio, 3.69 and 4.79; p < 0.001 and 0.02, respectively). Conclusion: For stabilized patients with community-onset EKP bacteremia after appropriate empirical antimicrobial therapy, cefazolin might be recommended as a definitive therapy for cefazolin-susceptible EKP bacteremia, based on the contemporary CLSI breakpoint.

Cefazolin is traditionally active against Escherichia coli, Klebsiella species, and Proteus mirabilis (EKP) isolates. The Clinical and Laboratory Standards Institute (CLSI) has twice updated cefazolin susceptibility breakpoints for EKP since 2010, but its role in the definitive treatment of cefazolin-susceptible EKP bacteremia remains debated. To assess its efficacy as a definitive agent, the 8-year cohort study consisted of 941 adults with monomicrobial cefazolin-susceptible EKP bacteremia, based on the CLSI criteria issued in 2019, was retrospectively established in a medical center. Based on the definitive antimicrobial prescription, eligible patients were categorized into the cefazolin (399 patients, 42.4%) and broader-spectrum antibiotic (BSA) (542, 57.6%) groups. Initially, fewer proportions of patients with fatal comorbidities (the McCabe classification) and the critical illness (a Pitt bacteremia score ≥4) at the onset and day 3 of the bacteremia episode were found in the cefazolin group, compared to the BSA group. After propensity-score matching, no significant difference of patient proportions between the cefazolin (345 patients) and BSA (345) groups was observed, in terms of the elderly, types and severity of comorbidities, bacteremia severity at the onset and day 3, major bacteremia sources, and the 15-day and 30-day crude mortality. In early outcomes, lengths of time to defervescence, intravenous (IV) antimicrobial administration, and hospitalization were similar in the two matched groups; lower costs of IV antimicrobial administration were observed in the cefazolin group. Notably, for late outcomes, lower proportions of post-treatment infections caused by antimicrobial-resistant pathogens (ARPs) and post-treatment mortality rates were evidenced in the cefazolin group. Conclusively, cefazolin is definitively efficacious and cost-effective for adults with community-onset cefazolin-susceptible EKP bacteremia in this one-center study, compared to BSAs. However, a prospective multicenter study should be conducted for external validation with other communities.