Association between Pneumonia Development and Virulence Gene Expression in Carbapenem-Resistant Acinetobacter baumannii Isolated from Clinical Specimens.

We investigated the virulence gene expression of carbapenem-resistant Acinetobacter baumanii (CRAB) isolated from the respiratory samples of patients with CRAB pneumonia and those with CRAB colonization to identify the virulence genes contributing to CRAB pneumonia's development and mortality. Patients with CRAB identified from respiratory specimens were screened at a tertiary university hospital between January 2018 and January 2019. Patients were classified into CRAB pneumonia or CRAB colonization groups according to predefined clinical criteria. A. baumannii isolated from respiratory specimens was examined for the expression levels of ompA, uspA, hfq, hisF, feoA, and bfnL by quantitative reverse-transcription polymerase chain reaction. Among 156 patients with CRAB from respiratory specimens, 17 and 24 met the criteria for inclusion in the pneumonia and colonization groups, respectively. The expression level of ompA was significantly higher in the pneumonia group than in the colonization group (1.45 vs. 0.63, P=0.03). The expression levels of ompA (1.97 vs. 0.86, P=0.02), hisF (1.06 vs. 0.10, P < 0.01), uspA (1.62 vs. 1.01, P < 0.01), and bfnL (3.14 vs. 2.14, P=0.03) were significantly higher in patients with 30-day mortality than in the surviving patients. Elevated expression of hisF (adjusted odds ratio = 5.93, P=0.03) and uspA (adjusted odds ratio = 7.36, P=0.02) were associated with 30-day mortality after adjusting for age and the Charlson score. uspA and hisF may serve as putative targets for novel therapeutic strategies.

Interim analysis from a phase 2 randomized trial of EuCorVac-19: a recombinant protein SARS-CoV-2 RBD nanoliposome vaccine.

BACKGROUND: Numerous vaccine strategies are being advanced to control SARS-CoV-2, the cause of the COVID-19 pandemic. EuCorVac-19 (ECV19) is a recombinant protein nanoparticle vaccine that displays the SARS-CoV-2 receptor-binding domain (RBD) on immunogenic nanoliposomes. METHODS: Initial study of a phase 2 randomized, observer-blind, placebo-controlled trial to assess the immunogenicity, safety, and tolerance of ECV19 was carried out between July and October 2021. Two hundred twenty-nine participants were enrolled at 5 hospital sites in South Korea. Healthy adults aged 19-75 without prior known exposure to COVID-19 were vaccinated intramuscularly on day 0 and day 21. Of the participants who received two vaccine doses according to protocol, 100 received high-dose ECV19 (20 µg RBD), 96 received low-dose ECV19 (10 µg RBD), and 27 received placebo. Local and systemic adverse events were monitored. Serum was assessed on days 0, 21, and 42 for immunogenicity analysis by ELISA and neutralizing antibody response by focus reduction neutralization test (FRNT). RESULTS: Low-grade injection site tenderness and pain were observed in most participants. Solicited systemic adverse events were less frequent, and mostly involved low-grade fatigue/malaise, myalgia, and headache. No clinical laboratory abnormalities were observed. Adverse events did not increase with the second injection and no serious adverse events were solicited by ECV19. On day 42, Spike IgG geometric mean ELISA titers were 0.8, 211, and 590 Spike binding antibody units (BAU/mL) for placebo, low-dose and high-dose ECV19, respectively (p < 0.001 between groups). Neutralizing antibodies levels of the low-dose and high-dose ECV19 groups had FRNT50 geometric mean values of 129 and 316, respectively. Boosting responses and dose responses were observed. Antibodies against the RBD correlated with antibodies against the Spike and with virus neutralization. CONCLUSIONS: ECV19 was generally well-tolerated and induced antibodies in a dose-dependent manner that neutralized SARS-CoV-2. The unique liposome display approach of ECV19, which lacks any immunogenic protein components besides the antigen itself, coupled with the lack of increased adverse events during boosting suggest the vaccine platform may be amenable to multiple boosting regimes in the future. Taken together, these findings motivate further investigation of ECV19 in larger scale clinical testing that is underway. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov as # NCT04783311.

Toll-like receptor 2 downregulation and cytokine dysregulation predict mortality in patients with Staphylococcus aureus bacteremia.

BACKGROUND: Staphylococcus aureus bacteremia (SAB) presents heterogeneously, owing to the differences in underlying host conditions and immune responses. Although Toll-like receptor 2 (TLR2) is important in recognizing S. aureus, its function during S. aureus infection remains controversial. We aimed to examine the association of TLR2 expression and associated cytokine responses with clinical SAB outcomes. METHODS: Patients from a prospective SAB cohort at two tertiary-care medical centers were enrolled. Blood was sampled at several timepoints (≤5 d, 6-9 d, 10-13 d, 14-19 d, and ≥ 20 d) after SAB onset. TLR2 mRNA levels were determined via real-time PCR and serum tumor necrosis factor [TNF]-α, interleukin [IL]-6, and IL-10 levels were analyzed with multiplex-high-sensitivity electrochemiluminescent ELISA. RESULTS: TLR2 levels varied among 59 SAB patients. On days 2-5, TLR2 levels were significantly higher in SAB survivors than in healthy controls (p = 0.040) and slightly but not significantly higher than non-survivors (p = 0.120), and SAB patients dying within 7 d had lower TLR2 levels than survivors (P = 0.077) although statistically insignificant. IL-6 and IL-10 levels were significantly higher in non-survivors than in survivors on days 2-5 post-bacteremia (P = 0.010 and P = 0.021, respectively), and those dying within 7 d of SAB (n = 3) displayed significantly higher IL-10/TNF-α ratios than the survivors did (P = 0.007). CONCLUSION: TLR2 downregulation and IL-6 and IL-10 concentrations suggestive of immune dysregulation during early bacteremia may be associated with mortality from SAB. TLR2 expression levels and associated cytokine reactions during early-phase SAB may be potential prognostic factors in SAB, although larger studies are warranted.

A Prospective Cohort Study of Durations of Staphylococcus aureus Bacteremia According to Different Phenotypes and a New Concept of Persistent Bacteremia.

The purpose of this study was to describe and compare the duration of Staphylococcus aureus bacteremia (SAB) according to methicillin resistance and the primary foci of infection. We also aimed to newly define persistent SAB considering these results. Nonduplicated episodes of SAB in patients aged ≥15 years from 14 hospitals in the Republic of Korea were analyzed between January 2009 and February 2018. The duration of SAB was defined as the number of days from the time of administration of an antibiotic to which the isolate was susceptible after the onset of SAB to the last day of a positive blood culture for S. aureus SAB durations were described and compared based on methicillin resistance and the primary foci of infection. Cases in the top quartile for the duration of bacteremia in the respective clinical context were classified as newly defined persistent SAB, and its association with in-hospital mortality was evaluated. A total of 1,917 cases were analyzed. The duration of SAB was longer in patients with methicillin-resistant SAB (MRSAB; n = 995) than in patients with methicillin-susceptible SAB (MSSAB; n = 922) (median duration, 1 day [interquartile range, 1 to 3 days] for MSSAB and 1 day [interquartile range, 0 to 5 days] for MRSAB; P < 0.001). The duration of bacteremia was longer in patients with endocarditis and bone and joint, endovascular, and surgical site infections and was shorter in patients with skin and soft tissue infections. Newly defined persistent SAB was independently associated with in-hospital mortality (adjusted odds ratio, 1.97; 95% confidence interval, 1.54 to 2.53; P < 0.001). The durations of SAB were dependent on methicillin resistance and the primary foci of infection, and considering these contexts, persistent SAB was significantly associated with in-hospital mortality.

Clinical Prediction Score for Community-Onset Bloodstream Infections Caused by Extended-Spectrum Beta-Lactamase-Producing Escherichia coli and Klebsiella Species.

BACKGROUND: This study aimed to identify the predictors and build a prediction score for community-onset bloodstream infections (CO-BSIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella species. METHODS: All CO-BSIs caused by E. coli and Klebsiella species from 2012 to 2015 were grouped into derivation (BSIs from 2012 to 2014) and validation (BSIs in 2015) cohorts. A prediction score was built using the coefficients of the multivariate logistic regression model from the derivation cohort. RESULTS: The study included 886 CO-BSIs (594 and 292 in the derivation and validation cohorts, respectively). The independent predictors of CO-BSIs caused by ESBL-producing E. coli and Klebsiella species included: 1) identification of ESBL-producing microorganisms from any clinical culture within one year of admission, 2) beta-lactam or fluoroquinolone treatment within 30 days (with 2 or more courses within 90 days; with 1 course within 90 days), 3) hospitalization within one year, 4) the presence of an indwelling urinary catheter at the time of admission. The area under the curve (AUC) of the clinical prediction score was 0.72 (95% confidence interval [CI], 0.68-0.77). In the validation cohort, the AUC was 0.70 (95% CI, 0.63-0.77). CONCLUSIONS: The results of this study suggest a simple and easy-to-use scoring system to predict CO-BSIs caused by ESBL-producing E. coli and Klebsiella species.

Gender affects prognosis of methicillin-resistant Staphylococcus aureus bacteremia differently depending on the severity of underlying disease.

We aimed to elucidate the potential impact of gender on prognosis of Staphylococcus aureus bacteremia (SAB). We analyzed SAB cases prospectively collected over an 8-year period at 11 hospitals in Korea. SAB-related mortality was pre-defined as a death within 30 days from the onset of SAB without other apparent cause of death. The effect of gender on SAB-related mortality was examined in the entire cohort and in subgroups stratified according to methicillin resistance and Charlson's comorbidity-weighted index (CCWI) score. Those factors independently associated to SAB-related mortality were explored. Among 1974 eligible cases, SAB-related mortality rates in male and female were 21.2% (259/1224) and 21.9% (164/750), respectively (P = 0.786). The SAB-related mortality rate was independently higher in male than that in female in CCWI score ≤ 3 methicillin-resistant SAB (MRSAB) group (15.9 vs. 6.2%; aOR 3.65, 95% CI 1.46-9.13; P = 0.006) while the association tended to be inverse when CCWI score rises. Interaction between CCWI score and gender to MRSAB-related mortality was significant in multivariate analysis (aOR 0.85, 95% CI 0.74-0.96; P = 0.011). There was no significant interaction between gender and CCWI in entire SAB or methicillin-susceptible SAB cohorts. Gender may affect clinical outcomes of MRSAB differently depending on the severity of underlying disease.

Impact of Vancomycin MIC on Treatment Outcomes in Invasive Staphylococcus aureus Infections.

There are conflicting data on the association of vancomycin MIC (VAN-MIC) with treatment outcomes in Staphylococcus aureus infections. We investigated the relationship between high VAN-MIC and 30-day mortality and identified the risk factors for mortality in a large cohort of patients with invasive S. aureus (ISA) infections, defined as the isolation of S. aureus from a normally sterile site. Over a 2-year period, 1,027 adult patients with ISA infections were enrolled in 10 hospitals, including 673 (66%) patients with methicillin-resistant S. aureus (MRSA) infections. There were 200 (19.5%) isolates with high VAN-MIC (≥1.5 mg/liter) by Etest and 87 (8.5%) by broth microdilution (BMD). The all-cause 30-day mortality rate was 27.4%. High VAN-MIC by either method was not associated with all-cause 30-day mortality, and this finding was consistent across MIC methodologies and methicillin susceptibilities. We conclude that high VAN-MIC is not associated with increased risk of all-cause 30-day mortality in ISA infections. Our data support the view that VAN-MIC alone is not sufficient evidence to change current clinical practice.

Comparison of characteristics of culture-negative pyogenic spondylitis and tuberculous spondylitis: a retrospective study.

BACKGROUND: Differences between the characteristics of culture positive pyogenic spondylitis (CPPS) and tuberculous spondylitis (TS) are well known. However, differences between the characteristics of culture negative pyogenic spondylitis (CNPS) and TS have not been reported; these would be more helpful in clinical practice especially when initial microbiologic examination of blood and/or biopsy tissue did not reveal the causative bacteria in patients with infectious spondylitis. METHODS: We performed a retrospective review of the medical records of patients with CNPS and TS. We compared the characteristics of 71 patients with CNPS with those of 94 patients with TS. RESULTS: Patients with TS had more previous histories of tuberculosis (9.9 vs 22.3 %, p = 0.034), simultaneous tuberculosis other than of the spine (0 vs 47.9 %, p < 0.001), and positive results in the interferon-gamma release assay (27.6 vs 79.2 %, p < 0.001). Fever (15.5 vs. 31.8 %, p = 0.018), psoas abscesses (15.5 vs 33.0 %, p = 0.011), and paravertebral abscesses (49.3 vs. 74.5 %, p = 0.011) were also more prevalent in TS than CNPS. CONCLUSIONS: Different from or contrary to the previous comparisons between CPPS and TS, fever, psoas abscesses, and paravertebral abscesses are more common in patients with TS than in those with CNPS.

Serotype Distribution and Antimicrobial Susceptibilities of Invasive Streptococcus pneumoniae Isolates from Adults in Korea from 1997 to 2012.

In Republic of Korea, a 7-valent pneumococcal conjugated vaccine (PCV7) was licensed for use in infants in 2003, and 13-valent PCV (PCV13) replaced it since 2010. We investigated trends in serotype distribution and antibiotic susceptibility of pneumococcal isolates from adult patients with invasive pneumococcal diseases (IPD). Invasive pneumococcal isolates from adult patients of ≥ 16 years of age were collected from 1997 to 2012. Serotypes of the isolates were determined by the Quellung reaction. Distribution of serotypes was analyzed according to the vaccine types. Antibiotic susceptibility was tested by using E-test strips. A total of 272 invasive pneumococcal isolates were included. The most common serotypes were serotype 19F (8.5%, 23/272), and serotype 3 (8.1%, 22/272), and 24.6% (67/272) of the isolates were of non-vaccine serotypes. Of the 272 isolates, 2.6% (7/272) were penicillin MICs of ≥ 4 µg/mL. The proportion of the PCV13 serotypes decreased from 63.3% (50/79) in 1997-2003 to 48.6% (17/35) in 2011-2012, whereas that of non-vaccine serotypes was 26.6% (21/79) and 25.7% (9/35), respectively, for the same periods. The proportion of the PCV13 serotypes showed a decreasing trend among adult patients with IPD over the study period.

Factors influencing culture positivity in pyogenic vertebral osteomyelitis patients with prior antibiotic exposure.

We conducted a retrospective cohort study to evaluate factors influencing tissue culture positivity in patients with pyogenic vertebral osteomyelitis exposed to antibiotics before diagnosis. Tissue culture was positive in 48.3% (28/58) of the patients, and the median antibiotic-free period was 1.5 days (range, 0.7 to 5.7 days). In a multivariate analysis, a higher C-reactive protein (CRP) level (adjusted odds ratio [aOR], 1.18; 95% confidence interval, 1.07 to 1.29) and open surgical biopsy (aOR, 6.33; 95% confidence interval, 1.12 to 35.86) were associated with tissue culture positivity.

agr dysfunction affects staphylococcal cassette chromosome mec type-dependent clinical outcomes in methicillin-resistant Staphylococcus aureus bacteremia.

Staphylococcal cassette chromosome mec element (SCCmec) type-dependent clinical outcomes may vary due to geographical variation in the presence of virulence determinants. We compared the microbiological factors and mortality attributed to methicillin-resistant Staphylococcus aureus (MRSA) bacteremia between SCCmec types II/III and type IV. All episodes of MRSA bacteremia in a tertiary-care hospital (South Korea) over a 4.5-year period were reviewed. We studied the microbiological factors associated with all blood MRSA isolates, including spa type, agr type, agr dysfunction, and the genes for Panton-Valentine leukocidin (PVL) and phenol-soluble modulin (PSM)-mec, in addition to SCCmec type. Of 195 cases, 137 involved SCCmec types II/III, and 58 involved type IV. The mortality attributed to MRSA bacteremia was less frequent among the SCCmec type IV (5/58) than that among types II/III (39/137, P = 0.002). This difference remained significant when adjusted for clinical factors (adjusted odds ratio [aOR], 0.14; 95% confidence interval [CI], 0.04 to 0.49; P = 0.002). Of the microbiological factors tested, agr dysfunction was the only significant factor that showed different positivity between the SCCmec types, and it was independently associated with MRSA bacteremia-attributed mortality (aOR, 4.71; 95% CI, 1.72 to 12.92; P = 0.003). SCCmec type IV is associated with lower MRSA bacteremia-attributed mortality than are types II/III, which might be explained by the high rate of agr dysfunction in SCCmec types II/III in South Korea.

Why is asymptomatic bacteriuria overtreated?: A tertiary care institutional survey of resident physicians.

BACKGROUND: Asymptomatic bacteriuria (ABU) is common and often leads to unnecessary antimicrobial use. Reducing antibiotic overuse for ABU is therefore an important issue for antimicrobial stewardship. We performed this study to investigate the appropriateness of ABU management and to evaluate physicians' knowledge and practice regarding ABU. METHODS: We reviewed all urine cultures of ≥10(5) cfu/mL of bacteria among inpatients in a 900-bed hospital in 2011. Each episode of bacteriuria was classified into ABU or urinary tract infection (UTI). ABU was defined as a positive urine culture (≥10(5) cfu/mL) without symptoms or signs suggesting UTI. In October 2012 a cross-sectional survey of resident physicians was undertaken using an anonymous, self-administered questionnaire. RESULTS: We identified 219 ABU cases among 1167 positive urine cultures, of which 70 (32.0 %) were inappropriately treated. Female gender, old age, pyuria, hematuria, and positive nitrite on urinalysis were associated with inappropriate ABU treatment in a multivariate analysis (P < 0.05). The response rate to the survey was 74.2 % (95/128). The mean knowledge score was 37.3 %, and 33.7 % of respondents were able to distinguish ABU from UTI, but less than half knew the indications for treating ABU. Even after ABU was correctly diagnosed, concerns about postoperative infections (38.6 %), UTI (9.1 %), and abnormal urinalysis (29.5 %) prevented proper management. About half of the respondents reported to prescribing antibiotics for ABU despite knowing they were not indicated. CONCLUSIONS: About one third of ABUs were inappropriately managed. Lack of knowledge and discrepancies between knowledge and practice, contributed to antimicrobial overuse for ABU. Our findings highlight the importance of developing interventions, including education, audit and feedback, to tackle the problem of inappropriate treatment of ABU.

Disseminated Aspergillosis in the Immunocompetent Host: A Case Report and Literature Review.

Disseminated aspergillosis is very rare in immunocompetent hosts and is typically associated with a poor prognosis. We describe the case of a 66-year-old, immunocompetent man who developed pneumonia, endophthalmitis and probable spondylitis caused by Aspergillus species. The patient was successfully treated with antifungal drugs. We reviewed the English-language literature between 1980 and 2012 for disseminated aspergillosis cases in immunocompetent hosts, using the keywords "dissemin*" and "aspergillo*." Disseminated aspergillosis in immunocompetent hosts is very rare in the literature. However, awareness of possible dissemination of Aspergillus spp. is necessary in patients who have a probable lung lesion and in cases with unusual presentation of a disseminated infection, even if the patient has no risk factors.

The burden of nosocomial staphylococcus aureus bloodstream infection in South Korea: a prospective hospital-based nationwide study.

BACKGROUND: We estimated the nationwide burden of nosocomial S. aureus bloodstream infection (SA-BSI), a major cause of nosocomial infection, in South Korea. METHODS: To evaluate the nationwide incidence of nosocomial SA-BSI, cases of SA-BSI were prospectively collected from 22 hospitals with over 500 beds over 4?months. Data on patient-days were obtained from a national health insurance database containing the claims data for all healthcare facilities in South Korea. The additional cost of SA-BSI was estimated through a matched case?control study. The economic burden was calculated from the sum of the medical costs, the costs of caregiving and loss of productivity. RESULTS: Three hundred and thirty nine cases of nosocomial SA-BSI were included in the study: 254 cases of methicillin-resistant SA-BSI (MRSA-BSI) and 85 cases of methicillin-susceptible SA-BSI (MSSA-BSI). Death related to BSI occurred in 81 cases (31.9%) of MRSA-BSI and 12 cases (14.1%) of MSSA-BSI. The estimated incidence of nosocomial MRSA-BSI was 0.12/1,000 patient-days and that of nosocomial MSSA-BSI, 0.04/1,000 patient-days. The estimated annual cases of nosocomial BSI were 2,946 for MRSA and 986 for MSSA in South Korea. The additional economic burden per case of nosocomial SA-BSI was US $20,494 for MRSA-BSI and $6,914 for MSSA-BSI. Total additional annual cost of nosocomial SA-BSI was $67,192,559. CONCLUSION: In view of the burden of nosocomial SA-BSI, a national strategy for reducing nosocomial SA-BSI is urgently needed in South Korea.

Virtual Reality Simulation-Based Clinical Procedure Skills Training for Nursing College Students: A Quasi-Experimental Study.

Core nursing skills are emphasized in nursing education, given their vital role in nurses' competence; however, invasive nursing procedures like catheterization and enemas are infrequently performed in actual clinical practice, primarily being observed rather than executed. Virtual reality simulation training involves performing core nursing skills on virtual patients in a three-dimensional virtual reality environment, following the correct procedures. The purpose of this study is to examine the effects of VR simulation on nursing students' confidence, proficiency, task engagement, and satisfaction. The study participants included 76 second-year nursing students, with 37 in the VR group and 39 in the control group. The VR group engaged in immersive VR (IVR) training sessions including enemas, nasogastric feeding, and nelaton catheterization. Conversely, the control group practiced these skills using mannequins. Assessments evaluated confidence, proficiency, learning satisfaction, and task engagement before and after the intervention. The average age of the study participants was 21.07 years, with 78.95% being female and 21.05% being male. The study findings revealed no significant differences between the VR and control groups regarding confidence (F = 3.878, p = 0.053), task engagement (F = 0.164, p = 0.687), and learning satisfaction (F = 0.668, p = 0.416). However, the VR group demonstrated significantly higher proficiency in the overall assessment of nasogastric feeding (F = 5.389, p = 0.023) and core components of nelaton catheterization (F = 4.046, p = 0.048). The IVR program emerged as an effective and valuable teaching tool, particularly well-suited for second-year nursing students, significantly enhancing proficiency.

Effectiveness of COVID-19 vaccines against severe outcomes in cancer patients: Real-world evidence from self-controlled risk interval and retrospective cohort studies.

BACKGROUND: The effectiveness of COVID-19 vaccines is generally reduced in cancer patients compared to the general population. However, there are only a few studies that compare the relative risk of breakthrough infections and severe COVID-19 outcomes in fully vaccinated cancer patients versus their unvaccinated counterparts. METHODS: To assess the effectiveness of COVID-19 vaccines in cancer patients, we employed (1) a self-controlled risk interval (SCRI) design, and (2) a retrospective matched cohort design. A SCRI design was used to compare the risk of breakthrough infection in vaccinated cancer patients during the period immediately following vaccination ("control window") and the period in which immunity is achieved ("exposure windows"). The retrospective matched cohort design was used to compare the risk of severe COVID-19 outcomes between vaccinated and unvaccinated cancer patients. For both studies, data were extracted from the Korea Disease Control and Prevention Agency-COVID-19-National Health Insurance Service cohort, including demographics, medical history, and vaccination records of all individuals confirmed with COVID-19. We used conditional Poisson regression to calculate the incidence rate ratio (IRR) for breakthrough infection and Cox regression to estimate the hazard ratio (HR) for severe outcomes. RESULTS: Of 14,448 cancer patients diagnosed with COVID-19 between October 2020 and December 2021, a total of 217 and 3996 cancer patients were included in the SCRI and cohort study respectively. While the risk of breakthrough infections, measured by the incidence rate in the control and exposure windows, did not show statistically significant difference in vaccinated cancer patients (IRR=0.88, 95% CI: 0.64-1.22), the risk of severe COVID-19 outcomes was significantly lower in vaccinated cancer patients compared to those unvaccinated (HR=0.27, 95% CI: 0.22-0.34). CONCLUSION: COVID-19 vaccines significantly reduce the risk of severe outcomes in cancer patients, though their efficacy against breakthrough infections is less evident.

Prospective Audit and Feedback for Antimicrobial Treatment of Patients Receiving Renal Replacement Therapy in Community-Based University Hospitals: A before-and-after Study.

In South Korea, because of manpower and budgetary limitations, antimicrobial stewardship programs have relied on preauthorization. This study analyzed the impact of a prospective audit and feedback (PAF) program targeting inpatients undergoing intermittent hemodialysis or continuous renal replacement therapy, which was implemented at two community-based university hospitals. During three years of PAF, 27,906 antimicrobial prescriptions were reviewed, with 622 (2.2%) interventions. The mean incidence density per 1000 patient days of multidrug-resistant organisms, except for carbapenem-resistant Acinetobacter baumannii, decreased in the study population, whereas it increased among inpatients. Multivariable Poisson regression analysis revealed that after PAF, the incidences of vancomycin-resistant Enterococcus and mortality decreased (incidence risk ratio, 95% confidence interval: 0.53, 0.31-0.93 and 0.70, 0.55-0.90, respectively). Notably, after PAF, incorrect antimicrobial dosing rates significantly decreased (tau -0.244; p = 0.02). However, the incidences of other multidrug-resistant organisms, Clostridioides difficile, length of stay, and readmission did not significantly change. This study shows that in patients undergoing intermittent hemodialysis or continuous renal replacement, targeted PAF can significantly reduce multidrug-resistant organism rates and all-cause hospital mortality, despite limited resources. Furthermore, it can improve antimicrobial dosage accuracy.

One-year antibody durability induced by EuCorVac-19, a liposome-displayed COVID-19 receptor binding domain subunit vaccine, in healthy Korean subjects.

OBJECTIVE: EuCorVac-19 (ECV-19), an adjuvanted liposome-displayed receptor binding domain (RBD) COVID-19 vaccine, previously reported interim Phase 2 trial results showing induction of neutralizing antibodies 3 weeks after prime-boost immunization. The objective of this study was to determine the longer-term antibody response of the vaccine. METHODS: To assess immunogenicity 6 and 12 months after vaccination, participants in the Phase 2 trial (NCT04783311) were excluded if they: 1) withdrew, 2) reported COVID-19 infection or additional vaccination, or 3) exhibited increasing Spike (S) antibodies (representing possible non-reported infection). Following exclusions, of the 197 initial subjects, anti-S IgG antibodies and neutralizing antibodies were further assessed in 124 subjects at the 6-month timepoint, and 36 subjects at the 12-month timepoint. RESULTS: Median anti-S antibody half-life was 52 days (interquartile range [IQR]:42-70), in the "early" period from 3 weeks to 6 months, and 130 days (IQR:97-169) in the "late" period from 6 to 12 months. There was a negative correlation between initial antibody titer and half-life. Anti-S and neutralizing antibody responses were correlated. Neutralizing antibody responses showed longer half-lives; the early period had a median half-life of 120 days (IQR:81-207), and the late period had a median half-life of 214 days (IQR:140-550). CONCLUSION: These data establish antibody durability of ECV-19, using a framework to analyze COVID-19 vaccine-induced antibodies during periods of high infection.

Subcutaneous tunneling versus conventional insertion of peripherally inserted central catheters in hospitalized patients (TUNNEL-PICC): a multicentre, open-label, randomized, controlled trial.

OBJECTIVE: We aimed to evaluate whether subcutaneous tunneling in peripherally inserted central catheters (PICC) placement could reduce the occurrence of central-line associated blood stream infection (CLABSI). METHODS: We conducted an open-label, multicentre, randomized, controlled trial in five tertiary hospitals. Adult hospitalized patients requiring a PICC were randomized in a one-to-one ratio to conventional (cPICC) or tunneled PICC (tPICC) arms using a centralized web-based computer-generated stratified randomization. CLABSI rates between groups were compared in a modified intention-to-treat population. Safety including the incidence of exit-site infection or hemorrhage-associated catheter removal were also compared. This trial was registered with Clinical Research Information Service of Republic of Korea (KCT0005521). RESULTS: From November 2020 to March 2023, 1,324 participants were enrolled and randomly assigned to tPICC (n=662) and cPICC (n=662). This study was terminated early due to the cohort CLABSI rate being lower than estimated, therefore, the original sample size of 1,694 would render the study underpowered to detect a difference in CLABSI rates. In the tPICC, CLABSI occurred in 13 of 651 participants over 11,071 catheter-days (1.2/1,000 catheter-days), compared with 20 among 650 patients with cPICC over 11,141 catheter-days (1.8/1,000 catheter-days, rate ratio 0.65, 95% CI 0.30-1.38, p=0.30). The incidence of exit-site infection (29 tPICC, 36 cPICC, p=0.5) and hemorrhage-associated catheter removal (11 tPICC, 11 cPICC, p=0.99) was not different between both groups. CONCLUSION: Due to insufficient sample size, this study could not demonstrate a statistically significant CLABSI risk reduction in the tPICC group compared to the cPICC group. Both groups had similar rates of exit site infection and bleeding.

Pseudomonas aeruginosa bacteremia in patients with liver cirrhosis: a comparison with bacteremia caused by Enterobacteriaceae.

BACKGROUND: This study was performed to detect risk factors for Pseudomonas aeruginosa bacteremia in patients with liver cirrhosis. METHODS: A retrospective case-control study was designed to identify risk factors for P. aeruginosa bacteremia in cirrhotic patients. The cases were cirrhotic patients with P. aeruginosa bacteremia and the controls were cirrhotic patients with Enterobacteriaceae bacteremia. RESULTS: Sixty-one cases and the same number of controls were enrolled. In a multivariate analysis, younger age {adjusted odds ratio (aOR) per one year: 0.96, 95% confidence interval: 0.93 - 0.99}, nosocomial acquisition (aOR 3.87, 95% confidence interval: 1.50 - 9.94), preexisting biliary disease (aOR 4.79, 95% confidence interval: 1.92 - 10.47), and recent exposure to immunosuppressive agent (aOR 3.10, 95% confidence interval: 1.23 - 7.82) were associated with P. aeruginosa bacteremia. In the case group the frequency of appropriate initial antibiotic regimens was considerably lower than in the control group: 29.5% vs. 65.6% (P <0.01). However, thirty day mortality did not differ significantly between cases and controls (19.7% vs. 24.6%). CONCLUSIONS: Nosocomial acquisition, preexisting biliary disease, and recent use of immunosuppressive agents are strong predictive factors for P. aeruginosa bacteremia in cirrhotic patients.