Effects of sub-inhibitory concentrations of nafcillin, vancomycin, ciprofloxacin, and rifampin on biofilm formation of clinical methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) infections are often difficult to treat because of their biofilm-forming ability and antimicrobial resistance. We investigated the effects of sub-minimal inhibitory concentrations (MICs) of antibiotics on MRSA biofilm formation. Clinical MRSA isolates were grown with sub-MICs (1/256-1/2 × MICs) of nafcillin, vancomycin, ciprofloxacin, and rifampin. The biofilm biomass was measured using crystal violet staining. Of the 107 MRSA isolates tested, 63 (58.9%) belonged to sequence type 5 (ST5), and 44 (41.1%) belonged to ST72. The MIC50/MIC90 values of nafcillin, vancomycin, ciprofloxacin, and rifampin were 256/512, 1/2, 64/512, and 0.008/0.03 mg/L, respectively. The sub-MICs of nafcillin, vancomycin, ciprofloxacin, and rifampin promoted biofilm formation in 75 (70.1%), 49 (45.8%), 89 (83.2%), and 89 (83.2%) isolates, respectively. At sub-MICs of nafcillin, the factors associated with strong biofilm induction were the ST5 strain (P = 0.001) and agr dysfunction (P = 0.005). For the sub-MICs of ciprofloxacin, the associated factors were the ST5 strain (P = 0.002), staphylococcal protein A type t002 strain (P < 0.001), and ciprofloxacin resistance (P < 0.001). Among the sub-MICs of rifampin, only ST5 was associated with strong biofilm induction (P = 0.006). Because the sub-MICs of rifampin were much lower than clinically relevant concentrations, we further tested the capability of biofilm induction in 0.03[Formula: see text]32 mg/L of rifampin. At these concentrations, rifampin-induced biofilm formation was rare in rifampin-susceptible MRSA [1.0% (1 of 100)] but common in rifampin-resistant MRSA [71.4% (5 of 7), P < 0.001]. Induction of biofilm biomass at sub-MICs of antibiotics is common in clinical MRSA isolates and is differentially affected by the MRSA strain and antibiotic class. IMPORTANCE: Bacteria can be exposed to sub-MICs of antibiotics at the beginning and end of a dosing regimen, between doses, or during low-dose therapies. Growing evidence suggests that sub-MICs of antimicrobials can stimulate MRSA biofilm formation and alter the composition of the biofilm matrix. Pevious studies have found that sub-MICs of oxacillin, methicillin, and amoxicillin promote biofilm formation in some community-acquired MRSA (CA-MRSA). We evaluated biofilm induction by sub-MICs of four different classes of antibiotics in 44 CA-MRSA and 63 healthcare-associated MRSA (HA-MRSA) strains. Our study indicated that sub-MICs of nafcillin, vancomycin, ciprofloxacin, and rifampin frequently promote biofilm induction in clinical MRSA isolates. Strong biofilm induction in sub-MICs of nafcillin, ciprofloxacin, and rifampin was more frequent in HA-MRSA than in CA-MRSA. Antibiotic-induced biofilm formation depends on the antibiotic class, MRSA strain, and antibiotic resistance. Our results emphasize the importance of maintaining effective bactericidal concentrations of antibiotics to treat biofilm-related infections.

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.

Abnormal accumulation of extracellular vesicles in hippocampal dystrophic axons and regulation by the primary cilia in Alzheimer's disease.

Dystrophic neurites (DNs) are abnormal axons and dendrites that are swollen or deformed in various neuropathological conditions. In Alzheimer's disease (AD), DNs play a crucial role in impairing neuronal communication and function, and they may also contribute to the accumulation and spread of amyloid beta (Aß) in the brain of AD patients. However, it is still a challenge to understand the DNs of specific neurons that are vulnerable to Aß in the pathogenesis of AD. To shed light on the development of radiating DNs, we examined enriched dystrophic hippocampal axons in a mouse model of AD using a three-dimensional rendering of projecting neurons. We employed the anterograde spread of adeno-associated virus (AAV)1 and conducted proteomic analysis of synaptic compartments obtained from hippocampo-septal regions. Our findings revealed that DNs were formed due to synaptic loss at the axon terminals caused by the accumulation of extracellular vesicle (EV). Abnormal EV-mediated transport and exocytosis were identified in association with primary cilia, indicating their involvement in the accumulation of EVs at presynaptic terminals. To further address the regulation of DNs by primary cilia, we conducted knockdown of the Ift88 gene in hippocampal neurons, which impaired EV-mediated secretion of Aß and promoted accumulation of axonal spheroids. Using single-cell RNA sequencing, we identified the septal projecting hippocampal somatostatin neurons (SOM) as selectively vulnerable to Aß with primary cilia dysfunction and vesicle accumulation. Our study suggests that DNs in AD are initiated by the ectopic accumulation of EVs at the neuronal axon terminals, which is affected by neuronal primary cilia.

Carbapenem Use in the Last Days of Life: A Nationwide Korean Study.

The appropriate use of carbapenem is a critical concern for patient safety and public health, and is a national priority. We investigated the nationwide status of carbapenem prescription in patients within their last 14 days of life to guide judicious-use protocols from the previous study comprised of 1350 decedents. Carbapenem use was universally controlled through computerised authorisation system at all centres during the study period. Carbapenem prescribing patterns and their optimality were evaluated. A total of 1201 patients received antimicrobial agents within the last two weeks of their lives, of whom 533 (44.4%) received at least one carbapenem. The median carbapenem treatment duration was seven days. Of the 533 patients receiving carbapenems, 510 (95.7%) patients had microbiological samples drawn and 196 (36.8%) yielded carbapenem-resistant pathogens. A total of 200 (37.5%) patients were referred to infectious disease (ID) specialists. Of the 333 patients (62.5%) who did not have ID consultations, 194 (58.2%) were assessed as "not optimal", 79 (23.7%) required escalation, 100 (30.0%) required de-escalation, and 15 (4.5%) were discontinued. Notwithstanding the existing antibiotic restriction program system, carbapenems are commonly prescribed to patients in their last days of life.

Use of Antibiotics Within the Last 14 Days of Life in Korean Patients: A Nationwide Study.

BACKGROUND: Antimicrobial prescriptions for serious chronic or acute illness nearing its end stages raise concerns about the potential for futile use, adverse events, increased multidrug-resistant organisms, and significant patient and social cost burdens. This study investigated the nationwide situation of how antibiotics are prescribed to patients during the last 14 days of life to guide future actions. METHODS: This nationwide multicenter retrospective cohort study was conducted at 13 hospitals in South Korea from November 1 to December 31, 2018. All decedents were included in the study. Antibiotic use during the last two weeks of their lives was investigated. RESULTS: A total of 1,201 (88.9%) patients received a median of two antimicrobial agents during the last two weeks of their lives. Carbapenems were prescribed to approximately half of the patients (44.4%) in the highest amount (301.2 days of therapy per 1,000 patient-days). Among the patients receiving antimicrobial agents, 63.6% were inappropriate and only 327 patients (27.2%) were referred by infectious disease specialists. The use of carbapenem (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.13-2.03; P = 0.006), underlying cancer (OR, 1.56; 95% CI, 1.20-2.01, P = 0.047), underlying cerebrovascular disease (OR, 1.88; 95% CI, 1.23-2.89, P = 0.004), and no microbiological testing (OR, 1.79; 95% CI, 1.15-2.73; P = 0.010) were independent predictors for inappropriate antibiotic prescribing. CONCLUSION: A considerable number of antimicrobial agents are administered to patients with chronic or acute illnesses nearing their end-of-life, a high proportion of which are prescribed inappropriately. Consultation with an infectious disease specialist, in addition to an antimicrobial stewardship program, may be necessary to induce the optimal use of antibiotics.

Developing Core Elements and Checklist Items for Implementing Antimicrobial Stewardship Programs in Korean General Hospitals: A Modified Delphi Survey.

BACKGROUND: Antimicrobial stewardship programs (ASPs) aim to optimize antimicrobial use by minimizing the spread of antimicrobial resistance. The core elements for implementing ASPs in healthcare facilities have been developed by the World Health Organization, international research group and government agencies of various countries. However, to date, there is no documented core elements for implementation of ASP in Korea. This survey aimed to establish a national consensus on a set of core elements and their related checklist items for the implementation of ASPs in Korean general hospitals. MATERIALS AND METHODS: The survey was conducted from July 2022 to August 2022 by the Korean Society for Antimicrobial Therapy with support from the Korea Disease Control and Prevention Agency. A literature review was conducted by searching Medline and relevant websites to retrieve a list of core elements and checklist items. These core elements and checklist items were evaluated by a multidisciplinary panel of experts using a structured modified Delphi consensus procedure, using two-step survey included online in-depth questionnaires and in-person meeting. RESULTS: The literature review identified 6 core elements (Leadership commitment, Operating system, Action, Tracking, Reporting, and Education) and 37 related checklist items. Fifteen experts participated in the consensus procedures. Ultimately, all 6 core elements were retained, and 28 checklist items were proposed, all with ≥80% agreement; in addition 9 items were merged into 2 items, 2 items were deleted, and 15 items were rephrased. CONCLUSION: This Delphi survey provides useful indicators for the implementation of ASP in Korea and suggests national policy improvement about the barriers (e.g., shortage of staffing and financial support) existing in Korea for optimal implementation of ASPs.

A study on changes in lung function, neutralizing antibodies, and symptoms of adult patients hospitalized with COVID-19.

BACKGROUND/AIMS: To identify changes in symptoms and pulmonary sequelae in patients with coronavirus disease 2019 (COVID-19). METHODS: Patients with COVID-19 hospitalized at seven university hospitals in Korea between February 2020 and February 2021 were enrolled, provided they had ≥ 1 outpatient follow-up visit. Between January 11 and March 9, 2021 (study period), residual symptom investigations, chest computed tomography (CT) scans, pulmonary function tests (PFT), and neutralizing antibody tests (NAb) were performed at the outpatient visit (cross-sectional design). Additionally, data from patients who already had follow-up outpatient visits before the study period were collected retrospectively. RESULTS: Investigation of residual symptoms, chest CT scans, PFT, and NAb were performed in 84, 35, 31, and 27 patients, respectively. After 6 months, chest discomfort and dyspnea persisted in 26.7% (4/15) and 33.3% (5/15) patients, respectively, and 40.0% (6/15) and 26.7% (4/15) patients experienced financial loss and emotional distress, respectively. When the ratio of later CT score to previous ones was calculated for each patient between three different time intervals (1-14, 15-60, and 61-365 days), the median values were 0.65 (the second interval to the first), 0.39 (the third to the second), and 0.20 (the third to the first), indicating that CT score decreases with time. In the high-severity group, the ratio was lower than in the low-severity group. CONCLUSION: In COVID-19 survivors, chest CT score recovers over time, but recovery is slower in severely ill patients. Subjects complained of various ongoing symptoms and socioeconomic problems for several months after recovery.

Invasive Pneumococcal Diseases in Korean Adults After the Introduction of Pneumococcal Vaccine into the National Immunization Program.

Although Streptococcus pneumoniae has been one of the most common bacterial causes of disease in humans, its impact has been blunted by the broad use of vaccines. Since 2018, the incidence of invasive pneumococcal disease in Korea decreased with effective pneumococcal vaccines but is on the rise again recently. In this paper I will review the epidemiology, risk factors, and antibiotic resistance of invasive pneumococcal disease after the introduction of the pneumococcal vaccine in Korean adults.

Development of a Roadmap for the Antimicrobial Usage Monitoring System for Medical Institutions in Korea: a Delphi Study.

BACKGROUND: It is necessary to develop a roadmap for antimicrobial usage monitoring in order to perform monitoring of antimicrobial use at the national level properly. Therefore, this study aimed to develop a roadmap for establishing surveillance and monitoring of antimicrobial use in medical institutions at the national level. MATERIALS AND METHODS: A modified Delphi study was conducted, including 3 rounds of an online survey and a virtual meeting with 16 expert panels. The survey items were developed based on a literature review of the surveillance systems for antimicrobial use in 12 countries and interviews with experts. The questionnaire was designed to include both the surveillance and benchmarking systems. RESULTS: Regarding the scope of target institutions to be included in the surveillance system, medical institutions for sentinel surveillance had the highest proportion of agreement among the panels (75.0%, 9/12). For the benchmarking system, "tertiary- and secondary-care hospitals" were accepted as the scope of target institutions at the current moment. Furthermore, the National Health Insurance claims and prescription data of individual hospitals were considered appropriate data sources for the surveillance system. As for the measures to promote the participation of hospitals in the benchmarking system, "compensation through the establishment of antimicrobial management fees" and "set the participation in the program as a quality evaluation or accreditation index for hospital evaluation" were accepted. CONCLUSION: This study provides a roadmap for establishing an antimicrobial use monitoring and benchmarking system for medical institutions at a national level in Korea.

Core Elements for Implementing Antimicrobial Stewardship Programs in Korean General Hospitals.

Currently, antimicrobial resistance (AMR) is a major threat to global public health. The antimicrobial stewardship program (ASP) has been proposed as an important approach to overcome this crisis. ASP supports the optimal use of antimicrobials, including appropriate dosing decisions, administration duration, and administration routes. In Korea, efforts are being made to overcome AMR using ASPs as a national policy. The current study aimed to develop core elements of ASP that could be introduced in domestic medical facilities. A Delphi survey was conducted twice to select the core elements through expert consensus. The core elements for implementing the ASP included (1) leadership commitment, (2) operating system, (3) action, (4) tracking, (5) reporting, and (6) education. To ensure these core elements are present at medical facilities, multiple departments must collaborate as teams for ASP operations. Establishing a reimbursement system and a workforce for ASPs are prerequisites for implementing ASPs. To ensure that ASP core elements are actively implemented in medical facilities, it is necessary to provide financial support for ASPs in medical facilities, nurture the healthcare workforce in performing ASPs, apply the core elements to healthcare accreditation, and provide incentives to medical facilities by quality evaluation criteria.

Korean Guidelines for Use of Antibiotics for Intra-abdominal Infections in Adults.

The guidelines are intended to provide practical information for the correct use of antibiotics for intra-abdominal infections in Korea. With the aim of realizing evidence-based treatment, these guidelines for the use of antibiotics were written to help clinicians find answers to key clinical questions that arise in the course of patient care, using the latest research results based on systematic literature review. The guidelines were prepared in consideration of the data on the causative pathogens of intra-abdominal infections in Korea, the antibiotic susceptibility of the causative pathogens, and the antibiotics available in Korea.

Clostridium difficile infection after orthopedic surgery: Incidence, associated factors, and impact on outcome.

BACKGROUND: To identify the incidence, associated factors, and impact of hospital-acquired Clostridium difficile infection (CDI) among patients who have undergone orthopedic surgery. METHODS: We retrospectively reviewed the charts of all adults patients who underwent orthopedic surgery from January 2016 through December 2017 at a tertiary hospital. RESULTS: Of 7,363 patients who underwent orthopedic surgical procedures, 52 (0.7%) developed hospital-acquired CDI. The independent factors associated with CDI were age ≥65 years (adjusted odds ratio [aOR], 3.4; P < .001), preoperative hospital stay ≥3 days (aOR, 3.7; P < .001), operating time ≥3 hours (aOR, 2.5; P < .005), and antibiotic use for infection treatment (aOR, 4.3; P < .001). After adjusting for the timing of CDI using a multistate model, the mean excess LOS attributable to CDI was 2.8 days (95% confidence interval [CI], 0.4-5.3). The impact of CDI on excess LOS was more evident among patients aged ≥65 years (4.4 days; 95% CI, 1.8-7.0) and those with any comorbidity (5.6 days; 95% CI, 3.0-8.1). CONCLUSIONS: The overall incidence of CDI after orthopedic surgery was 0.7%. The occurrence of CDI after orthopedic surgery contributes to increased LOS. The greatest impact of CDI on LOS occurs among elderly patients and patients with comorbidities.

Report of the Korean Society of Infectious Diseases Roundtable Discussion on Responses to the Measles Outbreaks in Korea in 2019.

During the 2019 domestic measles outbreak in Korea, measles occurred in healthcare workers with two doses of the measles, mumps and rubella vaccine, and the strict application of the Occupational Safety and Health Act required medical institutions to identify healthcare workers' immunity to measles and vaccinate the susceptible pockets. In response to the frontline medical institutions' request to review the measles recommendations and guidelines, the Korean Society of Infectious Diseases held a roundtable discussion on the causes of measles outbreak, timing of vaccinations, antibody tests, and booster vaccinations for healthcare workers, and financial support from the government and municipality as well as response strategies against the outbreak in healthcare settings. In Korea, the seroprevalence of measles is decreasing in the vaccine-induced immunity group during the maintenance of measles elimination over several years. The susceptible group against measles is in their 20s and 30s, and this may be because of waning immunity rather than non-response considering Korea's vaccine policy. The risk of measles nosocomial infection from community increases as these susceptible pockets actively engage in medical institutions. Thus, data on the immunity of low seroprevalence group in Korea are needed, further discussion is needed on the booster vaccination based on the data. Especially, antibody testing and vaccination in healthcare workers may be necessary to prevent the spread of measles in medical insutitutions, and further discussion is needed regarding specific testing methods, and the timing and frequency of test and vaccination.

Dual respiratory virus detection in adult patients with acute respiratory illness.

BACKGROUND: Nonrandom multiple respiratory virus (RV) detection provides evidence for viral interference among respiratory viruses. However, little is known as to whether it occurs randomly. METHODS: The prevalence of dual RV detection (DRVD) in patients with acute respiratory illnesses (ARIs) at 4 academic medical centers was investigated; data about the prevalence of 8 RVs were collected from the Korean national RV surveillance dataset. Linear regression analysis was performed to assess the correlation between observed and estimated prevalence of each type of DRVD. RESULTS: In total, 108 patients with ARIs showing DRVD were included in this study between 2011 and 2017. In several types of regression analysis, a strong correlation was observed between the observed and estimated prevalence of each type of DRVD. Excluding three DRVD types (influenza/picornavirus, influenza/human metapneumovirus, and adenovirus/respiratory syncytial virus), the slope of the regression line was higher than that of the line of random occurrence (1.231 > 1.000) and the 95% confidence interval of the regression line was located above the line of random occurrence. CONCLUSIONS: Contrary to the results of previous epidemiologic studies, most types of DRVD occur more frequently than expected from the prevalence rates of individual RV, except for three underrepresented pairs above.

Status of antimicrobial stewardship programmes in Korean hospitals including small to medium-sized hospitals and the awareness and demands of physicians: a nationwide survey in 2020.

OBJECTIVES: This study aimed to identify the status of antimicrobial stewardship programmes (ASPs) in small to medium-sized Korean hospitals as well as the awareness and demands about ASPs of physicians. METHODS: A questionnaire was designed based on a questionnaire from a previous nationwide survey in 2018 targeting large hospitals in Korea and modified to reflect the results of in-depth interviews with non-infectious diseases (IDs) physicians at secondary care hospitals. The survey targeted all hospitals with ≥150 beds in South Korea and was performed in May-June 2020. Only one ASP-associated physician per hospital participated in the survey. RESULTS: The survey response rate was 31.9% (217/680). ID specialists comprised the majority of medical personnel participating in ASPs in tertiary care hospitals. Conversely, in secondary and primary care hospitals there was no predominant medical personnel for ASPs and the median full-time equivalent was 0 for all types of medical personnel. Tertiary care hospitals, more than secondary and primary care hospitals, tended to perform ASP activities more actively. 'Workforce for ASPs', 'Establishment of healthcare fees for ASPs' and 'Development of tools for ASPs' were the most important required support for ASP improvement. CONCLUSION: The level of ASP establishment was more limited in primary care hospitals than in secondary and tertiary care hospitals in Korea. To improve ASPs in Korean hospitals, a supporting workforce and the establishment of a healthcare fee for ASPs appear to be necessary.

Safety and immunogenicity of a seasonal quadrivalent influenza vaccine (GC3110A) in healthy participants aged ≥ 65 years.

BACKGROUND: Seasonal Influenza is still considered associated with seasonal morbidity and hospitalization in the elderly population. The World Health Organization (WHO) recommended seasonal quadrivalent influenza vaccine (QIV) to reduce burden of two currently circulating influenza B lineages. Until 2019 Korean National Immunization Program (NIP) recommended trivalent influenza vaccine (TIV) after ongoing debates on cost effectiveness of QIV for elderly population. Although influenza vaccine only showed modest effect on reducing influenza in elderly, this study aimed to evaluate the immunogenicity and safety of inactivated QIV in healthy participants ≥ 65 years of age. METHODS: A total of 274 healthy participants aged ≥ 65 years received a QIV. Seroconversion-based vaccine efficacy of 4 strains of seasonal influenza was assessed 21 days after vaccination and adverse events were monitored until 180 days after vaccination. RESULTS: The percentages of participants seroconverted after vaccination on HI antibody against each strain were 36.5% (99/271) to A/H1N1, 47.6% (129/271) to A/H3N2, 40.6% (110/271) to B Yamagata, and 49.1% (133/271) to B Victoria. The percentages of participants seroprotected after vaccination on HI antibody against each strain were 81.2% (220/271) to A/H1N1, 98.5% (267/271) to A/H3N2, 95.2% (258/271) to B Yamagata, and 93.7% (254/271) to B Victoria. There was no serious adverse event (SAE) related with the study vaccine. CONCLUSION: The quadrivalent split influenza vaccine is expected to offer seroprotection against influenza A and both influenza B lineages even in the elderly population.

Clinical implications of multidrug-resistant microorganisms and fungi isolated from patients with intra-abdominal infections in the Republic of Korea: a multicenter study.

The purpose of this study was to evaluate the clinical significance of fungi and multidrug-resistant organisms (MDROs) isolated from patients with intra-abdominal infections (IAIs). This multicenter study included consecutive patients admitted for microbiologically proven IAIs at 6 university-affiliated hospitals in South Korea between 2016 and 2018. A total of 1571 patients were enrolled. Multivariable logistic regression analysis revealed that the isolation of MDROs, isolation of Candida spp., underlying renal diseases, Charlson comorbidity score ≥ 3, septic shock, failure to receive a required surgery or invasive intervention, secondary bacteremia due to IAIs, and lower body mass index were found to be independent predictors for 28-day mortality. However, the isolation of Enterococcus spp. was not identified as a significant risk factor. MDROs and Candida spp. were found in 42 (2.7%) and 395 (25.1%), patients respectively. The isolation of MDROs or Candida spp. was a surrogate marker of 28-day mortality.

Predictors of Acute Kidney Injury and 28-Day Mortality in Carbapenem-Resistant Acinetobacter baumannii Complex Bacteremia.

Colistin is an, antibiotic used to treat carbapenem-resistant Acinetobacter baumannii complex (CRABC) infection. However, colistin is well known for its nephrotoxicity. To accurately assess the effects of colistin on acute kidney injury (AKI) and 28-day mortality, we investigated the risk factors associated with AKI and mortality in patients with CRABC bacteremia who received or never received colistin. Patients with CRABC bacteremia aged ≥18 years were retrospectively identified for 3 years at five tertiary teaching hospitals. AKI was defined by using the Kidney Disease Improving Global Outcomes criteria. AKI developed in 103 (34.9%) of the 295 patients enrolled patients. AKI developed more frequently in patients who received colistin than in patients who did not (46.7% vs. 29.5%, p = 0.004). Multivariate analysis showed that intravenous colistin usage was an independent risk factor for AKI in these patients. Nonfatal disease, catheter-related bloodstream infection, and administration of colistin were protective factors for 28-day mortality. However, the sequential organ failure assessment score and AKI were associated with poor outcomes. In conclusion, colistin may be a double-edged sword; although it causes AKI, it also reduces 28-day mortality in patients with CRABC bacteremia. Therefore, colistin administration as an appropriate antibiotic may improve CRABC bacteremia prognosis, despite its nephrotoxicity.

IOX1 activity as sepsis therapy and an antibiotic against multidrug-resistant bacteria.

Sepsis is caused by organ dysfunction initiated by an unrestrained host immune response to infection. The emergence of antibiotic-resistant bacteria has rapidly increased in the last decades and has stimulated a firm research platform to combat infections caused by antibiotic-resistant bacteria that cannot be eradicated with conventional antibiotics. Strategies like epigenetic regulators such as lysine demethylase (Kdm) has received attention as a new target. Thus, we sought to investigate the epigenetic mechanisms in sepsis pathophysiology with the aim of discovering new concepts for treatment. A transcriptome analysis of dendritic cells during their inflammatory state identified Kdm as a critical molecule in sepsis regulation. Next, 8-hydroxyquinoline-5-carboxylic acid (IOX1) ability to control endotoxemia induced by Lipopolysaccharide and bacterial sepsis was demonstrated. IOX1 has been shown to regulate endotoxemia and sepsis caused by Escherichia coli and carbapenem-resistant Acinetobacter baumannii and has also contributed to the suppression of multidrug-resistant bacterial growth through the inhibition of DNA Gyrase. These findings show that IOX1 could be a component agent against bacterial sepsis by functioning as a broad-spectrum antibiotic with dual effects.

Machine-Learning-Based Approach to Differential Diagnosis in Tuberculous and Viral Meningitis.

BACKGROUND: Tuberculous meningitis (TBM) is the most severe form of tuberculosis, but differentiating between the diagnosis of TBM and viral meningitis (VM) is difficult. Thus, we have developed machine-learning modules for differentiating TBM from VM. MATERIAL AND METHODS: For the training data, confirmed or probable TBM and confirmed VM cases were retrospectively collected from five teaching hospitals in Korea between January 2000 - July 2018. Various machine-learning algorithms were used for training. The machine-learning algorithms were tested by the leave-one-out cross-validation. Four residents and two infectious disease specialists were tested using the summarized medical information. RESULTS: The training study comprised data from 60 patients with confirmed or probable TBM and 143 patients with confirmed VM. Older age, longer symptom duration before the visit, lower serum sodium, lower cerebrospinal fluid (CSF) glucose, higher CSF protein, and CSF adenosine deaminase were found in the TBM patients. Among the various machine-learning algorithms, the area under the curve (AUC) of the receiver operating characteristics of artificial neural network (ANN) with ImperativeImputer for matrix completion (0.85; 95% confidence interval 0.79 - 0.89) was found to be the highest. The AUC of the ANN model was statistically higher than those of all the residents (range 0.67 - 0.72, P <0.001) and an infectious disease specialist (AUC 0.76; P = 0.03). CONCLUSION: The machine-learning techniques may play a role in differentiating between TBM and VM. Specifically, the ANN model seems to have better diagnostic performance than the non-expert clinician.