Optimizing Treatment for Carbapenem-Resistant Acinetobacter baumannii Complex Infections: A Review of Current Evidence.

Carbapenem-resistant Acinetobacter baumannii complex (CRAB) poses a significant global health challenge owing to its resistance to multiple antibiotics and limited treatment options. Polymyxin-based therapies have been widely used to treat CRAB infections; however, they are associated with high mortality rates and common adverse events such as nephrotoxicity. Recent developments include numerous observational studies and randomized clinical trials investigating antibiotic combinations, repurposing existing antibiotics, and the development of novel agents. Consequently, recommendations for treating CRAB are undergoing significant changes. The importance of colistin is decreasing, and the role of sulbactam, which exhibits direct antibacterial activity against A. baumannii complex, is being reassessed. High-dose ampicillin-sulbactam-based combination therapies, as well as combinations of sulbactam and durlobactam, which prevent the hydrolysis of sulbactam and binds to penicillin-binding protein 2, have shown promising results. This review introduces recent advancements in CRAB infection treatment based on clinical trial data, highlighting the need for optimized treatment protocols and comprehensive clinical trials to combat the evolving threat of CRAB effectively.

The Microbiological Characteristics of Acinetobacter Baumannii Associated With Early Mortality in Patients With Bloodstream Infection.

Background: Despite rapid deaths resulting from Acinetobacter baumannii bacteremia, the clinical impact of the microbiological characteristics of A baumannii strains on early mortality (EM) is unclear. We aimed to identify the microbiological characteristics of A baumannii strains associated with EM. Methods: Clinical information and isolates from patients with A baumannii bacteremia from January 2015 to December 2021 were collected. EM was defined as death within 3 days of the initial positive blood culture, whereas late mortality meant death within 5-30 days. The microbiological characteristics of A baumannii were analyzed using multilocus sequence typing, polymerase chain reactions, and a Galleria mellonella in vivo infection model. Results: Among 130 patients, 69 (53.1%) died within 30 days and EM occurred in 38 (55.1% of 30-day deaths). Sequence type 191 (ST191) strain was more prevalent in patients with EM than in 30-day survivors (31.6% vs 6.6%). Regarding virulence genes, bfmS was more frequent (92.1% vs 47.5%), whereas bauA was less frequent (13.2% vs 52.5%) in patients with EM than in 30-day survivors. Higher clinical severity, pneumonia, and ST191 infection were identified as independent risk factors for EM. In the G mellonella infection model, ST191, bfmS+, and bauA- isolates showed higher virulence than non-ST191, bfmS-, and bauA+ isolates, respectively. Conclusions: ST191 and bfmS were more frequently found in the EM group. ST191 infection was also an independent risk factor for EM and highly virulent in the in vivo model. Tailored infection control measures based on these characteristics are necessary for A baumannii bacteremia management.

Overcoming the age-dependent SARS-CoV-2 vaccine response through hybrid immunity: analysis of humoral and cellular immunity with mass cytometry profiling.

BACKGROUND: Age-dependent immune responses to coronavirus disease 2019 (COVID-19) vaccinations and breakthrough infections (BIs) in young and middle-aged individuals are unclear. METHODS: This nationwide multicenter prospective cohort study analyzed immune responses in participants of the ChAdOx1 (ChAd)-ChAd-mRNA vaccine group using cytometry by time-of-flight, anti-spike protein antibody (Sab) and anti-nucleocapsid antibody (Nab) titers, plaque reduction neutralization tests (PRNTs), and interferon-gamma (IFN-γ) release assays at various time points. RESULTS: We evaluated 347 participants with an average age of 38.9 ± 9.4 years (range: 21-63). There was a significant inverse correlation between age and Sab levels after the second dose (slope - 14.96, P = 0.032), and this was more pronounced after the third dose (slope - 208.9, P < 0.001). After BIs, older participants showed significantly higher Sab titers (slope 398.8, P = 0.001), reversing the age-related decline observed post-vaccination. This reversal was also observed in PRNTs against wild-type SARS-CoV-2 and the BA.1 and BA.5 variants. IFN-γ responses increased markedly after the third dose and Bis, but showed a weak positive correlation with age, without statistical significance. Immune cell profiling revealed an age-dependent decrease in the proportions of B-cell lineage cells. The proportions of naive CD4+ and CD8+ T cells were inversely correlated with age, whereas the proportions of mature T cell subsets with memory function, including memory CD4+ T, CD8+ TEM, CD8+ TEMRA, and TFH cells, increased with age. CONCLUSIONS: Age-dependent waning of the serologic response to COVID-19 vaccines occurred even in middle-aged individuals, but was reversed after BIs. IFN-γ responses were preserved, compensating for the decrease in naive T cell populations, with an increase in memory T cell populations.

Limited impact of bacterial virulence on early mortality risk factors in Acinetobacter baumannii bacteremia observed in a Galleria mellonella model.

Acinetobacter baumannii (AB) has emerged as a major pathogen in vulnerable and severely ill patients. It remains unclear whether early mortality (EM) due to AB bacteremia is because of worse clinical characteristics of the infected patients or the virulence of the pathogen. In this study, we aimed to investigate the effect of AB virulence on EM due to bacteremia. This retrospective study included 138 patients with AB bacteremia (age: ≥ 18 years) who were admitted to a tertiary care teaching hospital in South Korea between 2015 and 2019. EM was defined as death occurring within 7 days of bacteremia onset. The AB clinical isolates obtained from the patients' blood cultures were injected into 15 Galleria mellonella larvae each, which were incubated for 5 days. Clinical isolates were classified into high- and low-virulence groups based on the number of dead larvae. Patients' clinical data were combined and subjected to multivariate Cox regression analyses to identify the risk factors for EM. In total, 48/138 (34.8%) patients died within 7 days of bacteremia onset. The Pitt bacteremia score was the only risk factor associated with EM. In conclusion, AB virulence had no independent effect on EM in patients with AB bacteremia.

Persistent differences in the immunogenicity of the two COVID-19 primary vaccines series, modulated by booster mRNA vaccination and breakthrough infection.

INTRODUCTION: The long-term impact of initial immunogenicity induced by different primary COVID-19 vaccine series remains unclear. METHODS: A prospective cohort study was conducted at 10 tertiary hospitals in Korea from March 2021 to September 2022. Immunogenicity assessments included anti-spike protein antibody (Sab), SARS-CoV-2-specific interferon-gamma releasing assay (IGRA), and multiplex cytokine assays for spike protein-stimulated plasma. Spike proteins derived from wild-type SARS-CoV-2 and alpha variant (Spike1) and beta and gamma variant (Spike2) were utilized. RESULTS: A total of 235 healthcare workers who had received a two-dose primary vaccine series of either ChAdOx1 or BNT162b2, followed by a third booster dose of BNT162b2 (166 in the ChAdOx1/ChAdOx1/BNT162b2 (CCB) group and 69 in the BNT162b2/BNT162b2/BNT162b2 (BBB) group, based on the vaccine series) were included. Following the primary vaccine series, the BBB group exhibited significantly higher increases in Sab levels, IGRA responses, and multiple cytokines (CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1ß, interleukin (IL)-1ra, IFN-γ, IL-2, IL-4, and IL-10) compared to the CCB group (all P < 0.05). One month after the third BNT162b2 booster, the CCB group showed Sab levels comparable to those of the BBB group, and both groups exhibited lower levels after six months without breakthrough infections (BIs). However, among those who experienced BA.1/2 BIs after the third booster, Sab levels increased significantly more in the BBB group than in the CCB group (P < 0.001). IGRA responses to both Spike1 and Spike2 proteins were significantly stronger in the BBB group than the CCB group after the third booster, while only the Spike2 response were higher after BIs (P = 0.007). The BBB group exhibited stronger enhancement of T-cell cytokines (IL-2, IL-4, and IL-17A) after BIs than in the CCB group (P < 0.05). CONCLUSION: Differences in immunogenicity induced by the two primary vaccine series persisted, modulated by subsequent booster vaccinations and BIs.

Trends of antibiotic use at the end-of-life of cancer and non-cancer decedents: a nationwide population-based longitudinal study (2006-2018).

Objective: This study aimed to assess the actual burden of antibiotic use among end-of-life (EOL) patients in South Korea and to compare trends between cancer and non-cancer decedents. Design: Population-based mortality follow-back study. Setting: Data from the Korean National Health Insurance Database, covering the period from January1, 2006, to December 31, 2018, provided for research by the National Health Insurance Service (NHIS), were used. Participants: All decedents from 2006 to 2018 were included and categorized as cancer decedents or non-cancer decedents. Methods: Annual antibiotic consumption rates and prescription rates were calculated, and Poisson regression was used to estimate their trends. Results: Overall antibiotic consumption rates decreased slightly among decedents in their final month with a less pronounced annual decrease rate among cancer decedents compared to non-cancer decedents (0.4% vs 2.3% per year, P <.001). Over the study period, although narrow spectrum antibiotics were used less, utilization and prescription of broad-spectrum antibiotics steadily increased, and prescription rates were higher in cancer decedents compared to non-cancer controls. Specifically, carbapenem prescription rates increased from 5.6% to 18.5%, (RR 1.087, 95% CI 1.085-1.088, P <.001) in cancer decedents and from 2.9% to 13.2% (RR 1.115, 95% CI 1.113-1.116, P <.001) in non-cancer decedents. Conclusions: Our findings show that patients at the EOL, especially those with cancer, are increasingly and highly exposed to broad-spectrum antibiotics. Measures of antibiotic stewardship are required among this population.

Incidence of Clostridioides difficile Infections in Republic of Korea: A Prospective Study With Active Surveillance vs. National Data From Health Insurance Review & Assessment Service.

BACKGROUND: Since the emergence of hypervirulent strains of Clostridioides difficile, the incidence of C. difficile infections (CDI) has increased significantly. METHODS: To assess the incidence of CDI in Korea, we conducted a prospective multicentre observational study from October 2020 to October 2021. Additionally, we calculated the incidence of CDI from mass data obtained from the Health Insurance Review and Assessment Service (HIRA) from 2008 to 2020. RESULTS: In the prospective study with active surveillance, 30,212 patients had diarrhoea and 907 patients were diagnosed with CDI over 1,288,571 patient-days and 193,264 admissions in 18 participating hospitals during 3 months of study period; the CDI per 10,000 patient-days was 7.04 and the CDI per 1,000 admission was 4.69. The incidence of CDI was higher in general hospitals than in tertiary hospitals: 6.38 per 10,000 patient-days (range: 3.25-12.05) and 4.18 per 1,000 admissions (range: 1.92-8.59) in 11 tertiary hospitals, vs. 9.45 per 10,000 patient-days (range: 5.68-13.90) and 6.73 per 1,000 admissions (range: 3.18-15.85) in seven general hospitals. With regard to HIRA data, the incidence of CDI in all hospitals has been increasing over the 13-year-period: from 0.3 to 1.8 per 10,000 patient-days, 0.3 to 1.6 per 1,000 admissions, and 6.9 to 56.9 per 100,000 population, respectively. CONCLUSION: The incidence of CDI in Korea has been gradually increasing, and its recent value is as high as that in the United State and Europe. CDI is underestimated, particularly in general hospitals in Korea.

Clinical Features of Mpox Patients in Korea: A Multicenter Retrospective Study.

BACKGROUND: Mpox is a viral illness with a characteristic skin rash caused by the monkeypox virus. In 2022, Mpox spread throughout the world, and an epidemic through domestic transmission started in South Korea in early 2023. This study aimed to summarize the clinical features of Mpox patients in South Korea. METHODS: This is a multicenter retrospective study conducted at four hospitals in South Korea. All adult patients diagnosed with Mpox who were admitted to the study hospitals between June 1, 2022 and May 26, 2023 and were discharged by June 30, 2023 were reviewed. RESULTS: Sixty patients were included, accounting for 65.9% of Mpox cases reported in South Korea during the study period. Median age was 32 years and 97% (58/60) of patients were male. In total, 85% (51/60) of patients reported their sexual orientation as homosexual or bisexual. The most common route of transmission was sexual or close contact (55/60). Every patient had a skin rash and 88% (53/60) had constitutional symptoms. In total, 42% (25/60) of patients had human immunodeficiency virus and 25% (15/60) had concomitant sexually transmitted infections. Severe manifestations of Mpox were identified in only two patients. CONCLUSION: Mpox patients in South Korea were mainly young adult males and were infected through sexual contact. The clinical outcomes were favorable.

False-positive results of galactomannan assays in patients administered glucose-containing solutions.

Galactomannan (GM) is a polysaccharide cell wall component released by Aspergillus spp., and an immunoenzymatic GM assay is used for the diagnosis of invasive pulmonary aspergillosis. We evaluated the cause of strong positivity for GM in patients with no typical signs of aspergillosis. Repeat assays were performed using different instruments and reagent lots, but there were no differences in results among the assays. Patients with strongly positive GM results were investigated. Medication histories revealed that 14 of 23 patients had been administered total parenteral nutrition solution from one manufacturer and 4 patients had been administered dextrose solution from a different manufacturer before being tested. The results of GM assays conducted on samples of dextrose solution and the glucose fraction of the total parenteral nutrition solution were strongly positive, confirming the causes of the false-positive reactions. We hypothesize that a trace amount of GM was introduced into the glucose-containing solutions because glucoamylase, which is necessary for the saccharification step of glucose synthesis, was derived from Aspergillus niger. To enhance patient care and prevent unnecessary antifungal prescriptions, healthcare providers and manufacturers of healthcare products need to be aware of the possibility of false-positive reactions for GM.

Staphylococcus argenteus bacteremia in the Republic of Korea.

In 2015, Staphylococcus argenteus and Staphylococcus schweitzeri were proposed as new species, distinct from Staphylococcus aureus and collectively referred to as the S. aureus complex. However, no clinical reports of these new species exist in Korea. Upon the application of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for all bloodstream isolates since September 2022, S. argenteus was identified in one patient. Therefore, we aimed to search for new species among the archives of the S. aureus bacteremia cohort and describe their clinical and microbiological characteristics. Among the 691 archived S. aureus isolates between 2012 and 2018, one was identified as S. argenteus via MALDI-TOF MS. Both S. argenteus isolates (one in 2022) were obtained from patients with extensive pneumonia accompanied by bacteremia and both cases had fatal outcomes. They harbored multiple virulence genes (clfA, clfB, fnbpA, sdrC, sdrD, sdrE, bbp, cna, see, seg, sei, blaZ, fnbpB, and map) but did not harbor mecA and pvl. No matched sequence type (ST) was found in either isolate, and both S. argenteus isolates were closely related to ST1594, ST1593, ST1793, and ST1303, which belonged to S. argenteus. S. argenteus accounted for <1% of the S. aureus complex but had clinical characteristics similar to S. aureus. Therefore, clinicians should be aware of these factors to avoid misidentifying these strains as coagulase-negative staphylococci, and appropriate reporting is required to minimize confusion.IMPORTANCEStaphylococcus argenteus, a member of Staphylococcus aureus complex, has been reported as an important pathogen that causes clinically invasive infections in humans similar to S. aureus. Clinical isolates of S. argenteus have been reported across the world, showing a large geographical difference in prevalence and genomic profile. However, there have been no clinical reports regarding this new species in Korea. This is the first report to investigate the clinical and genetic characteristics of S. argenteus identified in patients with bacteremia, and the proportion of S. argenteus bacteremia among S. aureus bacteremia cohort in Korea.

Development of machine learning algorithms for scaling-up antibiotic stewardship.

BACKGROUND: Antibiotic stewardship programs (ASP) aim to reduce inappropriate use of antibiotics, but their labor-intensive nature impedes their wide adoption. The present study introduces explainable machine learning (ML) models designed to prioritize inpatients who would benefit most from stewardship interventions. METHODS: A cohort of inpatients who received systemic antibiotics and were monitored by a multidisciplinary ASP team at a tertiary hospital in the Republic of Korea was assembled. Data encompassing over 130,000 patient-days and comprising more than 160 features from multiple domains, including prescription records, laboratory, microbiology results, and patient conditions was collected.Outcome labels were generated using medication administration history: discontinuation, switching from intravenous to oral medication (IV to PO), and early or late de-escalation. The models were trained using Extreme Gradient Boosting (XGB) and light Gradient Boosting Machine (LGBM), with SHapley Additive exPlanations (SHAP) analysis used to explain the model's predictions. RESULTS: The models demonstrated strong discrimination when evaluated on a hold-out test set(AUROC - IV to PO: 0.81, Early de-escalation: 0.78, Late de-escalation: 0.72, Discontinue: 0.80). The models identified 41%, 16%, 22%, and 17% more cases requiring discontinuation, IV to PO, early and late de-escalation, respectively, compared to the conventional length of therapy strategy, given that the same number of patients were reviewed by the ASP team. The SHAP results explain how each model makes their predictions, highlighting a unique set of important features that are well-aligned with the clinical intuitions of the ASP team. CONCLUSIONS: The models are expected to improve the efficiency of ASP activities by prioritizing cases that would benefit from different types of ASP interventions along with detailed explanations.

Clinical utility of quantitative immunoassays and surrogate virus neutralization tests for predicting neutralizing activity against the SARS-CoV-2 Omicron BA.1 and BA.5 variants.

Developing new antibody assays for emerging SARS-CoV-2 variants is challenging. SARS-CoV-2 surrogate virus neutralization tests (sVNT) targeting Omicron BA.1 and BA.5 have been devised, but their performance needs to be validated in comparison with quantitative immunoassays. First, using 1749 PRNT-positive sera, we noticed that log-transformed optical density (OD) ratio of wild-type (WT) sVNT exhibited better titer-correlation with plaque reduction neutralization test (PRNT) than % inhibition value. Second, we tried 798 dilutional titration tests with 103 sera, but nonlinear correlation between OD ratio and antibody concentration limited titration of sVNT. Third, the titer-correlations of two sVNT kits for BA.1 and two quantitative immunoassays for WT were evaluated with BA.1 and BA.5 PRNT. All tested kits exhibited a linear correlation with PRNT titers, but the sVNT kits exhibited high false-negative rates (cPass-BA.1 kit, 45.4% for BA.1 and 44.2% for BA.5; STANDARD F-BA.1 kit, 1.9% for BA.1 and 2.2% for BA.5), while quantitative immunoassays showed 100% sensitivity. Linear mixed-effects model suggested superior titer-correlation with PRNT for quantitative immunoassays compared to sVNT kits. Taken together, the use of quantitative immunoassays for WT, rather than rapid development of new kits, would be practical for predicting neutralizing activities against emerging new variants.

Tracking antigen-specific TCR clonotypes in SARS-CoV-2 infection reveals distinct severity trajectories.

Despite the importance of antigen-specific T cells in infectious disease, characterizing and tracking clonally amplified T cells during the progression of a patient's symptoms remain unclear. Here, we performed a longitudinal, in-depth single-cell multiomics analysis of samples from asymptomatic, mild, usual severe, and delayed severe patients of SARS-CoV-2 infection. Our in-depth analysis revealed that hyperactive or improper T-cell responses were more aggressive in delayed severe patients. Interestingly, tracking of antigen-specific T-cell receptor (TCR) clonotypes along the developmental trajectory indicated an attenuation in functional T cells upon severity. In addition, increased glycolysis and interleukin-6 signaling in the cytotoxic T cells were markedly distinct in delayed severe patients compared to usual severe patients, particularly in the middle and late stages of infection. Tracking B-cell receptor clonotypes also revealed distinct transitions and somatic hypermutations within B cells across different levels of disease severity. Our results suggest that single-cell TCR clonotype tracking can distinguish the severity of patients through immunological hallmarks, leading to a better understanding of the severity differences in and improving the management of infectious diseases by analyzing the dynamics of immune responses over time.

Coinfection With Severe Fever With Thrombocytopenia Syndrome and Scrub Typhus in Korea.

Background: Scrub typhus and severe fever with thrombocytopenia syndrome (SFTS) are the 2 most common tick-borne infectious diseases in Korea. Every year, an increasing number of cases are reported, which is a public health concern. Therefore, we aimed to investigate the prevalence of SFTS-scrub typhus coinfection in patients with SFTS. Methods: Clinical samples were collected from 129 patients with SFTS. One-step reverse-transcription polymerase chain reaction (PCR) was performed to identify the SFTS virus (SFTSV), and real-time PCR followed by nested PCR was performed to detect the Orientia tsutsugamushi gene for scrub typhus. Phylogenetic analysis was conducted to confirm the evolutionary relationships among different species. Results: Among 129 SFTS cases, 2 patients with SFTSV were positive for O. tsutsugamushi with a prevalence of coinfection of 1.6% (95% confidence interval, .001-.06). Phylogenetic analysis confirmed these as O. tsutsugamushi strain Boryong. Conclusions: Our study found that 1.6% of patients were coinfected with SFTS and scrub typhus infection. We believe that this information will add a new dimension to clinical diagnosis, which should be considered for better public health management. Further research is needed to better understand the ecological transmission dynamics and geographical distribution of SFTSV and O. tsutsugamushi in endemic countries.

Possibility of Decreasing Incidence of Human Immunodeficiency Virus Infection in Korea.

BACKGROUND: The number of newly diagnosed cases of human immunodeficiency virus (HIV) infection in Korea, which had increased until 2019, has markedly decreased since the coronavirus disease 2019 pandemic started. This study evaluated whether the decrease is due to a reduction in the incidence of HIV infection and/or delayed diagnosis during the pandemic. MATERIALS AND METHODS: We reviewed the medical records of 587 newly diagnosed patients with HIV infection between February 2018 and January 2022 from four general hospitals, and their characteristics were compared between the pre-pandemic and pandemic periods. The lapse time from infection to diagnosis was estimated using an HIV modeling tool. RESULTS: The estimated mean times to diagnosis were 5.68 years (95% confidence interval [CI]: 4.45 - 6.51 years) and 5.41 years (95% CI: 4.09 - 7.03 years) before and during the pandemic, respectively (P = 0.016). The proportion of patients with acquired immunodeficiency syndrome-defining illnesses, expected to visit hospitals regardless of the pandemic, decreased from 17.2% before the pandemic to 11.9% during the pandemic (P = 0.086). CONCLUSION: The decrease in the number of newly diagnosed cases of HIV infection in Korea might have resulted from an actual decrease in the incidence of HIV infection rather than a worsening of underdiagnosis or delayed diagnosis.

Immune Response Kinetics Following a Third Heterologous BNT162b2 Booster Dose After Primary 2-Dose ChAdOx1 Vaccination in Relation to Omicron Breakthrough Infection: A Prospective Nationwide Cohort Study in South Korea.

Background: Immune responses to each vaccine must be investigated to establish effective vaccination strategies for the ongoing coronavirus disease (COVID-19) pandemic. We investigated the long-term kinetics of immune responses after heterologous booster vaccination in relation to Omicron breakthrough infection (BI). Methods: Our study included 373 healthcare workers who received primary ChAdOx1 vaccine doses and a third BNT162b2 vaccine dose. BIs that occurred after the third vaccine were investigated. Blood specimens were collected before and 3 months after the booster dose from participants without BI and 1, 4, and 6 months after BI from participants who experienced BI. Spike-specific binding and neutralizing antibody levels against the wild-type virus, Omicron BA.1, and Omicron BA.5, as well as cellular responses, were analyzed. Results: A total of 346 participants (82 in the no BI group; 192 in the BI group during the BA.1/BA.2 period; 72 in the BI group during the BA.5 period) were included in the analysis. Participants without BI exhibited the highest binding and neutralizing antibody concentrations and greatest cellular response 1 month after the third vaccination, which reached a nadir by the ninth month. Antibody and cellular responses in participants who experienced BI substantially increased postinfection. Neutralizing antibody titers in individuals who experienced BI during the BA.1/BA.2 period showed more robust increase against wild-type virus than against BA.1 and BA.5. Conclusions: Our findings provide evidence of antigenic imprinting in participants who received a heterologous booster vaccination, thereby serving as a foundation for further studies on the impact of BIs on immune responses.

Antibiotic Prescription in Patients With Coronavirus Disease 2019: Analysis of National Health Insurance System Data in the Republic of Korea.

BACKGROUND: Although coronavirus disease 2019 (COVID-19) is a viral infection, antibiotics are often prescribed due to concerns about accompanying bacterial infection. Therefore, we aimed to analyze the number of patients with COVID-19 who received antibiotic prescriptions, as well as factors that influenced antibiotics prescription, using the National Health Insurance System database. METHODS: We retrospectively reviewed claims data for adults aged ≥ 19 years hospitalized for COVID-19 from December 1, 2019 to December 31, 2020. According to the National Institutes of Health guidelines for severity classification, we calculated the proportion of patients who received antibiotics and the number of days of therapy per 1,000 patient-days. Factors contributing to antibiotic use were determined using linear regression analysis. In addition, antibiotic prescription data for patients with influenza hospitalized from 2018 to 2021 were compared with those for patients with COVID-19, using an integrated database from Korea Disease Control and Prevention Agency-COVID19-National Health Insurance Service cohort (K-COV-N cohort), which was partially adjusted and obtained from October 2020 to December 2021. RESULTS: Of the 55,228 patients, 46.6% were males, 55.9% were aged ≥ 50 years, and most patients (88.7%) had no underlying diseases. The majority (84.3%; n = 46,576) were classified as having mild-to-moderate illness, with 11.2% (n = 6,168) and 4.5% (n = 2,484) having severe and critical illness, respectively. Antibiotics were prescribed to 27.3% (n = 15,081) of the total study population, and to 73.8%, 87.6%, and 17.9% of patients with severe, critical, and mild-to-moderate illness, respectively. Fluoroquinolones were the most commonly prescribed antibiotics (15.1%; n = 8,348), followed by third-generation cephalosporins (10.4%; n = 5,729) and beta-lactam/beta-lactamase inhibitors (6.9%; n = 3,822). Older age, COVID-19 severity, and underlying medical conditions contributed significantly to antibiotic prescription requirement. The antibiotic use rate was higher in the influenza group (57.1%) than in the total COVID-19 patient group (21.2%), and higher in severe-to-critical COVID-19 cases (66.6%) than in influenza cases. CONCLUSION: Although most patients with COVID-19 had mild to moderate illness, more than a quarter were prescribed antibiotics. Judicious use of antibiotics is necessary for patients with COVID-19, considering the severity of disease and risk of bacterial co-infection.

Exercise With a Novel Digital Device Increased Serum Anti-influenza Antibody Titers After Influenza Vaccination.

It has been reported that some exercise could enhance the anti-viral antibody titers after vaccination including influenza and coronavirus disease 2019 vaccines. We developed SAT-008, a novel digital device, consists of physical activities and activities related to the autonomic nervous system. We assessed the feasibility of SAT-008 to boost host immunity after an influenza vaccination by a randomized, open-label, and controlled study on adults administered influenza vaccines in the previous year. Among 32 participants, the SAT-008 showed a significant increase in the anti-influenza antibody titers assessed by hemagglutination-inhibition test against antigen subtype B Yamagata lineage after 4 wk of vaccination and subtype B Victoria lineage after 12 wk (p<0.05). There was no difference in the antibody titers against subtype "A." The SAT-008 also showed significant increase in the plasma cytokine levels of IL-10, IL-1ß, and IL-6 at weeks 4 and 12 after the vaccination (p<0.05). A new approach using the digital device may boost host immunity against virus via vaccine adjuvant-like effects. Trial Registration: ClinicalTrials.gov Identifier: NCT04916145.

Low humoral and cellular immune responses early after breakthrough infection may contribute to severe COVID-19.

Background: Little is known about the immune determinants for severe coronavirus disease 2019 (COVID-19) in individuals vaccinated against severe acute respiratory syndrome coronavirus 2. We therefore attempted to identify differences in humoral and cellular immune responses between patients with non-severe and severe breakthrough COVID-19. Methods: We prospectively enrolled hospitalized patients with breakthrough COVID-19 (severe and non-severe groups) and uninfected individuals who were vaccinated at a similar time (control group). Severe cases were defined as those who required oxygen therapy while hospitalized. Enzyme-linked immunosorbent assays and flow cytometry were used to evaluate humoral and cellular immune responses, respectively. Results: Anti-S1 IgG titers were significantly lower in the severe group than in the non-severe group within 1 week of symptom onset and higher in the non-severe group than in the control group. Compared with the control group, the cellular immune response tended to be diminished in breakthrough cases, particularly in the severe group. In multivariate analysis, advanced age and low anti-S1 IgG titer were associated with severe breakthrough COVID-19. Conclusions: Severe breakthrough COVID-19 might be attributed by low humoral and cellular immune responses early after infection. In the vaccinated population, delayed humoral and cellular immune responses may contribute to severe breakthrough COVID-19.

Evaluation of Vancomycin TDM Strategies: Prediction and Prevention of Kidney Injuries Based on Vancomycin TDM Results.

The current guidelines for therapeutic drug monitoring (TDM) of vancomycin suggest a target 24-hour area under the curve (AUC0-24) of 400 to 600 mg*h/L for serious methicillin-resistant Staphylococcus aureus infections. In this study, the predictabilities of acute kidney injury (AKI) of various TDM target parameters, target levels, and sampling methods were evaluated in patients who underwent TDM from January 2020 to December 2020. The AUC0-24 and trough values were calculated by both one- and two-point sampling methods, and were evaluated for the predictability of AKI. Among the AUC0-24 cutoff comparisons, the threshold value of 500 mg*h/L in the two sampling methods was statistically significant (P = 0.042) when evaluated for the predictability of AKI. Analysis by an receiver operating characteristic curve estimated an AUC0-24 cutoff value of 563.45 mg*h/L as a predictor of AKI, and was proposed as the upper limit of TDM target.