Clinical impact of COVID-19 in patients with carbapenem-resistant Acinetobacter baumannii bacteraemia.

The aim of this study was to evaluate the impact of coronavirus disease 2019 (COVID-19) on treatment outcomes in critically ill patients with carbapenem-resistant Acinetobacter baumannii (CRAB) bloodstream infection (BSI). This single-centre, retrospective cohort study was conducted in a 1,048-bed university-affiliated tertiary hospital in the Republic of Korea from January 2021 to March 2022. The study participants included consecutive hospitalised adult patients (aged ≥18 years) in the intensive care unit with CRAB monomicrobial BSI. During the study period, a total of 70 patients were included in our study, and 24 (34.3%) were diagnosed with COVID-19. The 28-day mortality rate was 64.3%. In the multivariate Cox proportional hazard regression analysis, diagnosis of COVID-19 (hazard ratio (HR), 2.91; 95% confidence interval (CI): 1.45-5.87), neutropenia (HR, 2.76; 95% CI: 1.04-7.29), Pitt bacteraemia score (per point; HR, 1.30; 95% CI: 1.19-1.41), and appropriate definite antibiotic therapy (HR, 0.31; 95% CI: 0.15-0.62) were independent predictors of 28-day mortality in patients with CRAB BSI. In conclusion, our findings suggested that COVID-19 has a negative prognostic impact on patients with CRAB BSI. Further study is needed to investigate the specific mechanisms of how COVID-19 worsens the prognosis of CRAB infection.

Clinical prediction rule for identifying older patients with toxigenic clostridioides difficile at the time of hospital admission.

BACKGROUND: This study aimed to develop and validate a clinical prediction rule to screen older patients at risk of being toxigenic Clostridioides difficile carriers at the time of hospital admission. METHODS: This retrospective case-control study was performed at a university-affiliated hospital. Active surveillance using a real-time polymerase chain reaction (PCR) assay for the toxin genes of C. difficile was conducted among older patients (≥ 65 years) upon admission to the Division of Infectious Diseases of our institution. This rule was drawn from a derivative cohort between October 2019 and April 2021 using a multivariable logistic regression model. Clinical predictability was evaluated in the validation cohort between May 2021 and October 2021. RESULTS: Of 628 PCR screenings for toxigenic C. difficile carriage, 101 (16.1%) yielded positive findings. To establish clinical prediction rules in the derivation cohort, the formula was derived using significant predictors for toxigenic C. difficile carriage at admission, such as septic shock, connective tissue diseases, anemia, recent use of antibiotics, and recent use of proton-pump inhibitors. In the validation cohort, the sensitivity, specificity, and positive and negative predictive values of the prediction rule, based on a cut-off value of ≥ 0.45, were 78.3%, 70.8%, 29.5%, and 95.4%, respectively. CONCLUSION: This clinical prediction rule for identifying toxigenic C. difficile carriage at admission may facilitate the selective screening of high-risk groups. To implement it in a clinical setting, more patients from other medical institutions need to be prospectively examined.

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.

Two Years of Experience and Methodology of Korean COVID-19 Living Clinical Practice Guideline Development.

BACKGROUND: In Korea, during the early phase of the coronavirus disease 2019 (COVID-19) pandemic, we responded to the uncertainty of treatments under various conditions, consistently playing catch up with the speed of evidence updates. Therefore, there was high demand for national-level evidence-based clinical practice guidelines for clinicians in a timely manner. We developed evidence-based and updated living recommendations for clinicians through a transparent development process and multidisciplinary expert collaboration. METHODS: The National Evidence-based Healthcare Collaborating Agency (NECA) and the Korean Academy of Medical Sciences (KAMS) collaborated to develop trustworthy Korean living guidelines. The NECA-supported methodological sections and 8 professional medical societies of the KAMS worked with clinical experts, and 31 clinicians were involved annually. We developed a total of 35 clinical questions, including medications, respiratory/critical care, pediatric care, emergency care, diagnostic tests, and radiological examinations. RESULTS: An evidence-based search for treatments began in March 2021 and monthly updates were performed. It was expanded to other areas, and the search interval was organized by a steering committee owing to priority changes. Evidence synthesis and recommendation review was performed by researchers, and living recommendations were updated within 3-4 months. CONCLUSION: We provided timely recommendations on living schemes and disseminated them to the public, policymakers and various stakeholders using webpages and social media. Although the output was successful, there were some limitations. The rigor of development issues, urgent timelines for public dissemination, education for new developers, and spread of several new COVID-19 variants have worked as barriers. Therefore, we must prepare systematic processes and funding for future pandemics.

Maternal and Neonatal Outcomes in Pregnant Women With Coronavirus Disease 2019 in Korea.

BACKGROUND: This study aimed to describe the maternal, obstetrical, and neonatal outcomes in pregnant women with coronavirus disease 2019 (COVID-19) and identify the predictors associated with the severity of COVID-19. METHODS: This multicenter observational study included consecutive pregnant women admitted because of COVID-19 confirmed using reverse transcriptase-polymerase chain reaction (RT-PCR) test at 15 hospitals in the Republic of Korea between January 2020 and December 2021. RESULTS: A total of 257 women with COVID-19 and 62 newborns were included in this study. Most of the patients developed this disease during the third trimester. Nine patients (7.4%) developed pregnancy-related complications. All pregnant women received inpatient treatment, of whom 9 (3.5%) required intensive care, but none of them died. The gestational age at COVID-19 diagnosis (odds ratio [OR], 1.096, 95% confidence interval [CI], 1.04-1.15) and parity (OR, 1.703, 95% CI, 1.13-2.57) were identified as significant risk factors of severe diseases. Among women who delivered, 78.5% underwent cesarean section. Preterm birth (38.5%), premature rupture of membranes (7.7%), and miscarriage (4.6%) occurred, but there was no stillbirth or neonatal death. The RT-PCR test of newborns' amniotic fluid and umbilical cord blood samples was negative for severe acute respiratory syndrome coronavirus 2. CONCLUSION: At the time of COVID-19 diagnosis, gestational age and parity of pregnant women were the risk factors of disease severity. Vertical transmission of COVID-19 was not observed, and maternal severity did not significantly affect the neonatal prognosis.

Rhamnetin, a Natural Flavonoid, Ameliorates Organ Damage in a Mouse Model of Carbapenem-Resistant Acinetobacter baumannii-Induced Sepsis.

In sepsis, the persistence of uncontrolled inflammatory response of infected host cells eventually leads to severe lung and organ failure and, ultimately, death. Carbapenem-resistant Acinetobacter baumannii (CRAB), causative bacteria of sepsis and lung failure in acute cases, belongs to a group of critical pathogens that cannot be eradicated using the currently available antibiotics. This underlines the necessity of developing new modes of therapeutics that can control sepsis at the initial stages. In this study, we investigated the anti-inflammatory activities in vitro and in vivo and the antiseptic effects of rhamnetin, a naturally occurring flavonoid. We found that among its isoforms, the potency of rhamnetin was less explored but rhamnetin possessed superior anti-inflammatory activity with least cytotoxicity. Rhamnetin showed significant anti-inflammatory effects in lipopolysaccharide-, CRAB-, and Escherichia coli (E. coli)-stimulated mouse macrophages by inhibiting the release of interleukin-6 and nitric oxide. In a mouse model of sepsis infected with clinically isolated CRAB or E. coli, rhamnetin significantly reduced the bacterial burden in the organs. In addition, normalized pro-inflammatory cytokine levels in lung lysates and histological analysis of lung tissue indicated alleviation of lung damage. This study implies that a potent natural product such as rhamnetin could be a future therapeutic for treating carbapenem-resistant gram-negative sepsis.

The role of smart monitoring digital health care system based on smartphone application and personal health record platform for patients diagnosed with coronavirus disease 2019.

BACKGROUND: The massive outbreak of the novel coronavirus disease 2019 (COVID-19) in Daegu city and Gyeongsangbuk-do, Republic of Korea (ROK), caused the exponential increase in new cases exceeding 5000 within 6 weeks. Therefore, the community treatment center (CTC) with a digital health care monitoring system based on the smartphone application and personal health record platform (PHR) was implemented. Thus, we report our experience in one of the CTCs to investigate the role of CTC and the feasibility of the digital health care monitoring system in the COVID-19 pandemic. METHODS: The Gyeongbuk-Daegu 2 CTC was set up at the private residential facility. Admission criteria were 1) patients < 65 years with COVID-19, 2) patients without underlying medical comorbidities, and 3) COVID-19 disease severity of mild class. Admitted patients were placed under monitoring of vital signs and symptoms. Clinical information was collected using the smartphone application or telephone communication. Collected information was displayed on the PHR platform in a real-time fashion for close monitoring. RESULTS: From Mar 3, 2020, to Mar 26, 2020, there was a total of 290 patients admitted to the facility. Males were 104 (35.9%). The median age was 37 years. The median time between the COVID-19 diagnosis and admission was 7 days. Five patients were identified and were transferred to the designed COVID-19 treatment hospital for their urgent medical needs. The smartphone application usage to report vital signs and symptoms was noted in 96% of the patients. There were no deaths of the patients. CONCLUSIONS: Our results suggest that implementation of the CTC using a commercial residence facility and digital health care technology may offer valuable solutions to the challenges posed by the COVID-19 outbreak.

Maternal Outcomes and Clinical Characteristics of COVID-19 in Korean Pregnant Women during the Early Period of the Pandemic.

The present study aimed to compare the clinical characteristics and outcomes between pregnant women and non-pregnant women of childbearing age (20-49 years old) diagnosed with coronavirus disease 2019 (COVID-19) during the initial stage of the COVID-19 pandemic in the Republic of Korea. This nationwide observational study included the information of COVID-19 patients collected by the Korea Disease Control and Prevention Agency from January 2020 to April 2021. Among 5,647 COVID-19 patients, 2,444 (43.3%) were women of childbearing age and 19 were pregnant. None of the pregnant women died. However, 4 deaths occurred among non-pregnant women aged 20-49 years. None of the 19 pregnant women with COVID-19 were admitted to the intensive care unit: they were admitted to the general ward, and none of them required supplemental oxygen. In conclusion, none of the pregnant women with COVID-19 experienced severe infection or death, unlike non-pregnant women of childbearing age.

Early Safety Monitoring of COVID-19 Vaccines in Healthcare Workers.

Hospital-based surveillance for adverse events was conducted on healthcare workers after they received the first dose of coronavirus disease 2019 (COVID-19) vaccine. Among the two new platform vaccines (messenger RNA- and adenoviral vector-based vaccines), the rates of systemic adverse events were significantly higher among adenovirus-vectored vaccine recipients. Fatigue (87.6% vs. 53.8%), myalgia (80.8% vs. 50.0%), headache (72.0% vs. 28.8%), and fever (≥ 38.0°C, 38.7% vs. 0%) were the most common adverse events among adenovirus-vectored vaccine recipients, but most symptoms resolved within 2 days. Both types of COVID-19 vaccines were generally safe, and serious adverse events rarely occurred.

Antiseptic 9-Meric Peptide with Potency against Carbapenem-Resistant Acinetobacter baumannii Infection.

Carbapenem-resistant A. baumannii (CRAB) infection can cause acute host reactions that lead to high-fatality sepsis, making it important to develop new therapeutic options. Previously, we developed a short 9-meric peptide, Pro9-3D, with significant antibacterial and cytotoxic effects. In this study, we attempted to produce safer peptide antibiotics against CRAB by reversing the parent sequence to generate R-Pro9-3 and R-Pro9-3D. Among the tested peptides, R-Pro9-3D had the most rapid and effective antibacterial activity against Gram-negative bacteria, particularly clinical CRAB isolates. Analyses of antimicrobial mechanisms based on lipopolysaccharide (LPS)-neutralization, LPS binding, and membrane depolarization, as well as SEM ultrastructural investigations, revealed that R-Pro9-3D binds strongly to LPS and impairs the membrane integrity of CRAB by effectively permeabilizing its outer membrane. R-Pro9-3D was also less cytotoxic and had better proteolytic stability than Pro9-3D and killed biofilm forming CRAB. As an LPS-neutralizing peptide, R-Pro9-3D effectively reduced LPS-induced pro-inflammatory cytokine levels in RAW 264.7 cells. The antiseptic abilities of R-Pro9-3D were also investigated using a mouse model of CRAB-induced sepsis, which revealed that R-Pro9-3D reduced multiple organ damage and attenuated systemic infection by acting as an antibacterial and immunosuppressive agent. Thus, R-Pro9-3D displays potential as a novel antiseptic peptide for treating Gram-negative CRAB infections.

A Systematic Narrative Review of Comprehensive Preparedness Strategies of Healthcare Resources for a Large Resurgence of COVID-19 Nationally, with Local or Regional Epidemics: Present Era and Beyond.

Coronavirus disease 2019 (COVID-19) has penetrated our daily lives, leading us to a new normal era. The unexpected impact of COVID-19 has posed a unique challenge for the health care system, bringing innovation around the world. Considering the current pandemic pattern, comprehensive preparedness strategies of healthcare resources need to be implemented to prepare for a large resurgence of COVID-19 within a short time. With the unprecedented spread of the new pandemic and the impending influenza season, scientific evidence-based schemes need to be developed through cooperation, coordination, and solidarity. Based on the early experience with the current pandemic, this narrative interpretive review of qualitative studies suggests a 6-domain plan to establish a better health care system that is prepared to deal with the current and future public health crises. The 6 domains are medical institutions, medical workforce, medical equipment, COVID-19 surveillance, data and information application, and governance structure.

Characteristics of Klebsiella pneumoniae Isolates from Stool Samples of Patients with Liver Abscess Caused by Hypervirulent K. pneumoniae.

BACKGROUND: Hypervirulent Klebsiella pneumoniae (hvKP) has been the most significant pathogen for liver abscesses in East Asia including the Republic of Korea (ROK). Although gastrointestinal colonization of K. pneumoniae may cross the intestinal barrier to invade the liver, characteristics of gastrointestinal carriage K. pneumoniae of hvKP liver abscess patients in the ROK are not well known. METHODS: Characteristics of K. pneumoniae isolated from stool samples and liver aspirate samples of patients with hvKP liver abscess at a tertiary care hospital in the ROK between 2017 and 2018 were evaluated. RESULTS: Out of 37 patients with hvKP liver abscess, 11 patients were noted to have K. pneumoniae isolated from stool samples and were enrolled for analysis. The median age was 71 years. For hvKP isolates from the liver aspirate samples, the most common serotype was K1 (72.7%) followed by K2 (27.3%). For K. pneumoniae isolates from the stool sample, the majority was non-K1/K2 serotype (72.7%). Among non-K1/K2 serotype isolates, high variability of sequence type (ST; ST15, ST307, ST37, ST273, ST2622, and ST42) with high rate of presence of extended-spectrum beta-lactamase (100.0%) was noted. The concordance rate of the K. pneumoniae isolates between the liver aspirate samples and the stool samples from the primary hvKP liver abscess was low (27.3%). CONCLUSION: This study suggests that significant heterogeneity of K. pneumoniae colonizing intestinal tract of the hvKP liver abscess patients. Further studies involving a larger number of hvKP liver abscess patients with continuing surveillance are needed to define the changing epidemiology and the role of gastrointestinal K. pneumoniae in the hvKP liver abscess patients in the ROK.

Development of Antibiotic Classification for Measuring Antibiotic Usage in Korean Hospitals Using a Modified Delphi Method.

In 2019, a project designed to develop a system for measuring and comparing antibiotic usage in hospitals was launched in Korea. As part of this project, we developed a means to classify antibiotic usage in Korean hospitals using a modified Delphi method. In results, the following categories of antibiotic classification were accepted for use in Korean hospitals: 1) broad-spectrum antibacterial agents predominantly used for hospital-onset infections in adults, 2) broad-spectrum antibacterial agents predominantly used for community-acquired infections in adults, 3) antibacterial agents predominantly used for resistant gram-positive infections in adults, 4) narrow-spectrum beta-lactam agents in adults, 5) antibacterial agents predominantly used for extensive antibiotic resistant gram-negative bacteria in adults, and 6) total antibacterial agents.

Anidulafungin Versus Micafungin in the Treatment of Candidemia in Adult Patients.

BACKGROUND: Echinocandins are recommended for the treatment of invasive candidiasis and candidemia. However, there are few studies comparing anidulafungin and micafungin in terms of efficacy and safety. The objective of this study was to evaluate the clinical efficacy and safety between anidulafungin and micafungin treatment for adult patients with candidemia. METHODS: This retrospective cohort study performed on adult candidemia patients diagnosed from January 2006 through December 2018 at a tertiary medical center. The study subjects included adult patients ≥ 19 years with candidemia who were only treated with anidulafungin or micafungin for ≥ 3 days. Clinical characteristics were collected and analyzed. Hepatotoxicity was assessed according to the Common Terminology Criteria for Adverse Events Version 5.0. RESULTS: A total of 98 patients with candidemia were treated with anidulafungin (n = 52, 53.1%) or micafungin (n = 46, 46.9%). There were no significant differences in age, sex, source of candidemia, and comorbidities between the anidulafungin and micafungin groups. Although there were more patients with abnormal baseline liver function test (LFT) in the anidulafungin group, the rate of clinical response (51.9% vs. 46.7%), mycological response (76.9% vs. 67.4%), and mortality (30-day mortality 26.9% vs. 21.7% and 90-day mortality 78.8% vs. 73.9%) was similar between the anidulafungin and micafungin groups. Also, there was no significant difference in terms of hepatotoxicity, even among the patients with abnormal baseline LFT between the two groups. CONCLUSIONS: Our results suggest that clinical efficacy and safety may be similar between anidulafungin and micafungin treatment for adult patients with candidemia.

Development for Clinical Use of a Multiplexed Immunoassay Using Sputum Samples for Streptococcus pneumoniae: a Non-Culture-Based Approach for Serotype-Specific Detection.

The multiplexed immunoassay (MIA) is an automated, monoclonal antibody-based serotyping assay that uses culture lysates of Streptococcus pneumoniae This study describes the development and validation of applying MIA directly to sputum samples for the serotype-specific detection of S. pneumoniae Sputum optimization involved liquefaction and fractionation. The subjects included 173 adult patients from whom both pneumococcal isolates cultured from sputum samples and the corresponding sputum samples were available at the Korea University Hospital from March 2012 to June 2015. Pneumococcal lysates and the sputum fraction were separately evaluated by MIA with a set A reaction to identify 27 serotypes (24 vaccine serotypes and serotypes 6C, 6D, and 11E). MIA results were validated by multiplex PCR (mPCR). Among the 173 patients analyzed, the pneumococcal isolate MIA detected a single set A serotype in 104 patients, and the corresponding sputum MIA showed concordant results with additional multiple serotypes in 21 patients. For the remaining 69 patients whose pneumococcal isolates were not determined to be set A serotypes by the pneumococcal isolate MIA, the corresponding sputum MIA identified additional set A serotypes (single serotypes, n = 17; multiple serotypes, n = 4). Serotypes 3 and 11A/D/F were the most commonly detected serotypes in both the pneumococcal isolate and sputum MIA analyses. However, serotype 8 was the most prevalent serotype detected only by the sputum MIA. The results of mPCR, performed for validation, showed a high concordance with the results of the sputum MIA. In conclusion, MIA using sputum samples enables the accurate, rapid, direct, and serotype-specific detection of S. pneumoniae, which may improve postvaccination serotype surveillance.

Determining the clinical significance of co-colonization of vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus in the intestinal tracts of patients in intensive care units: a case-control study.

BACKGROUND: The emergence of vancomycin-resistant Staphylococcus aureus (VRSA) has become a global concern for public health. The proximity of vancomycin-resistant enterococcus (VRE) and methicillin-resistant S. aureus (MRSA) is considered to be one of the foremost risk factors for the development of VRSA. This study aimed to determine the incidence, risk factors, and clinical outcomes of intestinal co-colonization with VRE and MRSA. METHODS: A case-control study was conducted in 52-bed intensive care units (ICUs) of a university-affiliated hospital from September 2012 to October 2017. Active surveillance using rectal cultures for VRE were conducted at ICU admission and on a weekly basis. Weekly surveillance cultures for detection of rectal MRSA were also conducted in patients with VRE carriage. Patients with intestinal co-colonization of VRE and MRSA were compared with randomly selected control patients with VRE colonization alone (1:1). Vancomycin minimum inhibitory concentrations (MICs) for MRSA isolates were determined by the Etest. RESULTS: Of the 4679 consecutive patients, 195 cases and 924 controls were detected. The median monthly incidence and duration of intestinal co-colonization with VRE and MRSA were 2.3/1000 patient-days and 7 days, respectively. The frequency of both MRSA infections and mortality attributable to MRSA were higher in the case group than in the control group: 56.9% vs. 44.1% (P = 0.011) and 8.2% vs. 1.0% (P = 0.002), respectively. Independent risk factors for intestinal co-colonization were enteral tube feeding (odds ratio [OR], 2.09; 95% confidence interval [CI] 1.32-3.32), metabolic diseases (OR, 1.75; 95% CI 1.05-2.93), male gender (OR, 1.62; 95% CI 1.06-2.50), and Charlson comorbidity index < 3 (OR, 3.61; 95% CI 1.88-6.94). All MRSA isolates from case patients were susceptible to vancomycin (MIC ≤ 2 mg/L). CONCLUSIONS: Our study indicates that intestinal co-colonization of VRE and MRSA occurs commonly among patients in the ICU with MRSA endemicity, which might be associated with poor clinical outcomes.

Antimicrobial Susceptibility of Microorganisms Isolated from Patients with Intraabdominal Infection in Korea: a Multicenter Study.

BACKGROUND: This study evaluated the antimicrobial susceptibility of pathogens isolated from Korean patients with intraabdominal infections (IAIs). METHODS: This multicenter study was conducted at 6 university-affiliated hospitals in Korea between 2016 and 2018. All patients with microbiologically proven IAIs were retrospectively included, while patients with spontaneous bacterial peritonitis or continuous ambulatory peritoneal dialysis peritonitis were excluded. Identification and antimicrobial susceptibility testing were performed using automated microbiology systems. RESULTS: A total of 2,114 non-duplicated clinical isolates were collected from 1,571 patients. Among these pathogens, 510 (24.1%) were isolated from nosocomial infections, and 848 isolates (40.1%) were associated with complicated IAIs. The distribution of the microorganisms included aerobic gram-negative (62.6% of isolates), aerobic gram-positive (33.7%), anaerobic (0.9%), and fungal (2.8%) pathogens. The most common pathogens were Escherichia coli (23.8%), followed by Enterococcus spp. (23.1%) and Klebsiella spp. (19.8%). The susceptibility rates of E. coli and Klebsiella spp. to major antibiotics were as follows: amoxicillin/clavulanate (62.5%, 83.0%), cefotaxime (61.4%, 80.7%), ceftazidime (63.7%, 83.1%), cefepime (65.3%, 84.3%), ciprofloxacin (56.4%, 86.3%), piperacillin/tazobactam (99.0%, 84.8%), amikacin (97.4%, 98.3%), and imipenem (99.8%, 98.8%). The susceptibility rates of Enterococcus spp. to ampicillin were 61.0%, amoxicillin/clavulanate, 63.6%; ciprofloxacin, 49.7%; imipenem, 65.2%; and vancomycin, 78.2%. The susceptibility rates of Pseudomonas aeruginosa and Acinetobacter spp. to imipenem were 77.4% and 36.7%, respectively. CONCLUSION: Enterococcus spp. with susceptibility to limited antibiotics was one of the main pathogens in Korean IAIs, along with E. coli and Klebsiella spp., which were highly susceptible to imipenem, amikacin, and piperacillin/tazobactam. Meanwhile, the low susceptibilities of E. coli or Klebsiella spp. to amoxicillin/clavulanate, advanced-generation cephalosporins, and ciprofloxacin should be considered when determining empirical antibiotic therapy in clinical practice.

Prosthetic Joint Infections Caused by Candida Species: A Systematic Review and a Case Series.

The purpose of this study was to evaluate the efficacy of echinocandins in the treatment of Candida prosthetic joint infection (PJI) based on published literature and on patients we examined. A structured literature review of multiple databases was conducted to identify patients who received echinocandins for Candida PJIs. Additionally, we describe here the first cases of PJIs due to C. parapsilosis, successfully treated with prolonged anidulafungin therapy. Out of 17 patients, 12 were female and the mean age at diagnosis was 66.0 years. No risk factors associated with Candida PJIs were found in four patients (23.5%). Infection sites included the knee (n = 10, 62.5%), the hip (n = 6, 35.3%) and the shoulder (n = 1, 5.9%). The most frequently isolated Candida species were C. albicans (n = 7, 41.2%) and C. glabrata (n = 7, 41.2%), followed by C. parapsilosis (n = 2, 11.8%) and C. freyschussii (n = 1, 5.9%). All patients were cured with the combination of systemic antifungal therapy and surgical interventions. Two-stage exchange arthroplasty and resection arthroplasty were performed in five and nine patients, respectively. The most frequently used echinocandins were caspofungin (n = 11, 64.7%), followed by anidulafungin (n = 4, 23.5%) and micafungin (n = 2, 11.8%). The median duration (days) of echinocandin therapy was as follows: caspofungin (25.5, range 8-56), micafungin (14.0, range 4-56) and anidulafungin (58, range 14-90). This study supports the effective role of echinocandins, as well as the potential advantage of surgical intervention in the treatment of Candida PJIs. Furthermore, it provides fundamental data on the safety of long-term echinocandin therapy.

Neoagarooligosaccharides prevent septic shock by modulating A20-and cyclooxygenase-2-mediated interleukin-10 secretion in a septic-shock mouse model.

Analysis of the signaling mechanism triggered by endotoxin-mediated toll-like receptor-4 activation using immune cell systems or rodent models may help identify potential agents for the prevention of Gram-negative bacteria infection. ß-agarase cleaves the ß-1,4-linkages of agar to produce neoagarooligosaccharides (NAOs), which have various physiological functions. The aim of this study was to investigate the efficacy of NAOs in preventing experimental sepsis caused by the administration of endotoxin or Gram-negative bacteria. Organ damage and neutrophil infiltration in an endotoxemia and septic-shock mouse model were suppressed by NAOs. Pro-inflammatory cytokine level was decreased, but IL-10 level was increased by NAO-treatment. Further induction by NAOs in the presence of endotoxin was associated with a significant induction of A20 and cyclooxygenase (COX)-2 expressions. Our data suggest that NAOs have a beneficial preventive effect in septic shock correlated with the enhancement of IL-10 via the induction of A20 and COX-2.

Effects of inappropriate empirical antibiotic therapy on mortality in patients with healthcare-associated methicillin-resistant Staphylococcus aureus bacteremia: a propensity-matched analysis.

BACKGROUND: The purported value of empirical therapy to cover methicillin-resistant Staphylococcus aureus (MRSA) has been debated for decades. The purpose of this study was to evaluate the effects of inappropriate empirical antibiotic therapy on clinical outcomes in patients with healthcare-associated MRSA bacteremia (HA-MRSAB). METHODS: A prospective, multicenter, observational study was conducted in 15 teaching hospitals in the Republic of Korea from February 2010 to July 2011. The study subjects included adult patients with HA-MRSAB. Covariate adjustment using the propensity score was performed to control for bias in treatment assignment. The predictors of in-hospital mortality were determined by multivariate logistic regression analyses. RESULTS: In total, 345 patients with HA-MRSAB were analyzed. The overall in-hospital mortality rate was 33.0 %. Appropriate empirical antibiotic therapy was given to 154 (44.6 %) patients. The vancomycin minimum inhibitory concentrations of the MRSA isolates ranged from 0.5 to 2 mg/L by E-test. There was no significant difference in mortality between propensity-matched patient pairs receiving inappropriate or appropriate empirical antibiotics (odds ratio [OR] = 1.20; 95 % confidence interval [CI] = 0.71-2.03). Among patients with severe sepsis or septic shock, there was no significant difference in mortality between the treatment groups. In multivariate analyses, severe sepsis or septic shock (OR = 5.45; 95 % CI = 2.14-13.87), Charlson's comorbidity index (per 1-point increment; OR = 1.52; 95 % CI = 1.27-1.83), and prior receipt of glycopeptides (OR = 3.24; 95 % CI = 1.08-9.67) were independent risk factors for mortality. CONCLUSION: Inappropriate empirical antibiotic therapy was not associated with clinical outcome in patients with HA-MRSAB. Prudent use of empirical glycopeptide therapy should be justified even in hospitals with high MRSA prevalence.