Community-Acquired Pneumococcal Pneumonia in Highly Vaccinated Population: Analysis by Serotypes, Vaccination Status, and Underlying Medical Conditions.

BACKGROUND: Targeted risk population has been highly vaccinated against pneumococcal diseases in South Korea. Despite this, the pneumococcal serotype distribution is evolving, which impedes efficient roll-out of vaccines. METHODS: This prospective cohort study included patients aged ≥ 19 years with community-acquired pneumonia (CAP) from five university hospitals in South Korea between September 2018 and July 2021. The outcomes of interest were the demographic and clinical characteristics of patients with CAP, pneumococcal serotype distribution, and risk factors of 30-day mortality in patients with pneumococcal CAP (pCAP). Considering the high seroprevalence, we analyzed the clinical characteristics of serotype 3 pCAP. RESULTS: A total of 5,009 patients hospitalized with CAP was included (mean age ± standard deviation, 70.3 ± 16.0 years; 3,159 [63.1%] men). Streptococcus pneumoniae was the leading causative agent of CAP (11.8% overall, 17.7% in individuals aged < 65 years with chronic medical conditions). Among the 280 serotyped Streptococcus pneumococcus, serotype 3 was the most common (10.0%), followed by serotypes 19A (8.9%), 34 (8.9%), and 35B (8.9%). Non-vaccine serotypes (serotype 35B [13.9%] and 34 [12.0%]) were the most prevalent in 108 individuals vaccinated with 23-valent pneumococcal polysaccharide vaccine (PPSV23). Serotype 3 was prevalent, irrespective of PPSV23 vaccination status, and more common in individuals with chronic lung disease (P = 0.008). Advanced age (adjusted odds ratio [aOR], 1.040; 95% confidence interval [CI], 1.011-1.071), long-term care facility residence (aOR, 2.161; 95% CI, 1.071-4.357), and bacteremia (aOR, 4.193; 95% CI, 1.604-10.962) were independent risk factors for 30-day mortality in patients with pCAP. PPSV23 vaccination reduced the risk of mortality (aOR, 0.507; 95% CI, 0.267-0.961). CONCLUSION: Serotype 3 and 19A were still the most common serotypes of pCAP in South Korea despite the national immunization program of 13-valent pneumococcal conjugated vaccine in children and PPSV23 in old adults. PPSV23 vaccination might reduce the risk of mortality in patients with pCAP.

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.

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.

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.

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.

Significance of Increased Rapid Treatment from HIV Diagnosis to the First Antiretroviral Therapy in the Recent 20 Years and Its Implications: the Korea HIV/AIDS Cohort Study.

From December 2006 to December 2016, 1,429 patients enrolled in the Korea human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) Cohort Study were investigated. Based on the year of diagnosis, the time interval between HIV diagnosis and initiation of antiretroviral therapy (ART) was analyzed by dividing it into 2 years. The more recent the diagnosis, the more likely rapid treatment was initiated (P < 0.001) and the proportion of patients starting ART on the same day of HIV diagnosis was increased in 2016 (6.5%) compared to that in 2006 (1.7%). No significant difference in the median values of CD4+ cell counts according to the diagnosis year was observed. In the past 20 years, the time from the HIV diagnosis to the initiation of ART was significantly reduced. Rapid treatment was being implemented at the HIV diagnosis, regardless of CD4+ cell count. Considering the perspective "treatment is prevention," access to more rapid treatment is necessary at the time of HIV diagnosis.

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.

Metabolic Complications among Korean Patients with HIV Infection: The Korea HIV/AIDS Cohort Study.

Currently, metabolic complications are the most common problem among human immunodeficiency virus (HIV)-infected patients, with a high incidence. However, there have been very few studies regarding metabolic abnormalities published in Asia, especially in Korea. This cross-sectional study was performed to investigate the prevalence of and risk factors for metabolic abnormalities in 1,096 HIV-infected patients of the Korea HIV/AIDS cohort study enrolled from 19 hospitals between 2006 and 2013. Data at entry to cohort were analyzed. As a result, the median age of the 1,096 enrolled subjects was 46 years, and most patients were men (92.8%). The metabolic profiles of the patients were as follows: median weight was 63.8 kg, median body mass index (BMI) was 22.2 kg/m², and 16.4% of the patients had a BMI over 25 kg/m². A total of 5.5% of the patients had abdominal obesity (waist/hip ratio ≥ 1 in men, ≥ 0.85 in women). Increased levels of fasting glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides were present in 10.4%, 6.0%, 5.5%, and 32.1% of the patients. Decreased high-density lipoprotein (HDL) cholesterol levels were observed in 44.2% of the patients. High systolic blood pressure was present in 14.3% of the patients. In multivariate analysis, high BMI and the use of protease inhibitors (PIs) were risk factors for dyslipidemia in HIV-infected patients. In conclusion, proper diagnosis and management should be offered for the prevalent metabolic complications of Korean HIV-infected patients. Further studies on risk factors for metabolic complications are needed.

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.

Multiplex real-time PCR assay for Legionella species.

Legionella pneumophila serogroup 1 (sg1) accounts for the majority of infections in humans, but other Legionella species are also associated with human disease. In this study, a new SYBR Green I-based multiplex real-time PCR assay in a single reaction was developed to allow the rapid detection and differentiation of Legionella species by targeting specific gene sequences. Candidate target genes were selected, and primer sets were designed by referring to comparative genomic hybridization data of Legionella species. The Legionella species-specific groES primer set successfully detected all 30 Legionella strains tested. The xcpX and rfbA primers specifically detected L. pneumophila sg1-15 and L. pneumophila sg1, respectively. In addition, this assay was validated by testing clinical samples and isolates. In conclusion, this novel multiplex real-time PCR assay might be a useful diagnostic tool for the rapid detection and differentiation of Legionella species in both clinical and epidemiological studies.

Anxiety and depressive symptoms among patients infected with human immunodeficiency virus in South Korea.

Patients infected with human immunodeficiency virus (HIV) may develop mental health problems such as anxiety and depression, which negatively impact of disease progression. We investigated factors associated with the prevalence of anxiety and depression symptoms among HIV-infected patients in Korea. A total of 840 HIV-infected patients who participated in the Korea HIV/AIDS Cohort Study from 2006 to 2012 were evaluated. Socio-demographic, epidemiologic, and clinical variables were obtained through standardized questionnaires. The State-Trait Anxiety Inventory and Beck Depression Inventory were used to assess the symptoms of anxiety and depression. Multiple logistic regression analyses were performed to identify factors associated with symptoms of anxiety and depression. The prevalence of anxiety and depressive symptoms among HIV-infected patients was 32% and 36%, respectively. Ex-smoker and persistent symptoms for more than one week within the past six months and diagnosis of HIV infection within one year were associated with increased anxiety symptoms (odds ratio [OR] 1.71, 95% confidence interval [CI] 1.09-2.69; OR 1.52, 95% CI 1.09-2.11; OR 1.49, 95% CI 1.02-2.20) and current smoking and persistent symptoms were also associated with increased depressive symptoms (OR 2.10, 95% CI 1.31-3.30; OR 1.87, 95% CI 1.25-2.79). Marital status, current smoking, current drinking, and persistent symptoms were associated with both increased anxiety and depressive symptoms (OR 1.75, 95% CI 1.07-2.88; OR 1.66, 95% CI 1.06-2.61; OR 1.88, 95% CI 1.18-2.99). The prevalence of anxiety and depressive symptoms among HIV-infected patients is higher than those estimated for the general population. This study shows the necessity to evaluate symptoms of anxiety and depression and suggest psychological support for HIV-infected patients who smoke or have persistent symptoms or have sexual partner or drink.

Nosocomial empyema caused by a rare serotype, serotype 4c, of Listeria monocytogenes in a patient with rheumatoid arthritis and chronic kidney disease: A case report and review of the literature.

The intracellular pathogen Listeria monocytogenes presents characteristically as meningoencephalitis and bacteremia. Herein, we report an extremely rare case of empyema caused by serotype 4c L. monocytogenes in an immunocompromised patient. This case supports the inclusion of L. monocytogenes infection in the differential diagnosis of empyema in an immunocompromised patient.

Multicenter prospective observational study of the comparative efficacy and safety of vancomycin versus teicoplanin in patients with health care-associated methicillin-resistant Staphylococcus aureus bacteremia.

The purpose of this study was to compare the clinical efficacy and safety of vancomycin to those of teicoplanin for the treatment of adult patients with health care-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) bacteremia. A multicenter observational study was prospectively conducted in 15 teaching hospitals in Korea between February 2010 and July 2011. Adult patients (≥18 years old) with HA-MRSA bacteremia who were initially treated with vancomycin (VAN) (n = 134) or teicoplanin (TEC) (n = 56) were enrolled. Clinical and microbiological responses and drug-related adverse events were compared between the two treatment groups using univariate and multivariate logistic regression analyses. The vancomycin and teicoplanin MICs were determined by Etest. The MRSA-related mortality, duration of fever, and duration of MRSA bacteremia in the treatment groups were not significantly different. There was no significant difference in the occurrence of drug-related adverse events. Among the 190 MRSA isolates, the VAN MICs ranged from 0.5 to 2 µg/ml (MIC50 and MIC90, 1.5 µg/ml), and the TEC MIC ranged from 0.5 to 8 µg/ml (MIC50, 3 µg/ml; MIC90, 6 µg/ml). In multivariate analyses, the antibiotic type (vancomycin or teicoplanin) was not associated with treatment outcomes. This study indicates that teicoplanin is an effective and safe alternative to vancomycin for the treatment of HA-MRSA bacteremia.

Predictors of mortality attributable to Clostridium difficile infection in patients with underlying malignancy.

PURPOSE: This study aimed at evaluating the clinical severity and treatment outcomes of Clostridium difficile infections (CDI) and identifying predictors associated with mortality in patients with malignancy. METHODS: A retrospective study was conducted in a teaching hospital from January 2004 to June 2013. The subjects included adult patients (aged ≥ 18 years) receiving treatment for malignancy whose conditions were complicated by CDI. Clinical severity was determined using the guidelines from the Society for Healthcare Epidemiology of America and the Infectious Diseases Society of America (SHEA/IDSA). Multivariate logistic regression analysis was performed to identify predictors independently associated with CDI-related mortality. RESULTS: Of the 5,594 patients treated for malignancy at the Division of Hematology/Oncology during the study period, 61 (1.1%) had CDI complications. CDI-related mortality was 19.7% (12/61). Twenty-seven (44.3%) patients were diagnosed with neutropenia (ANC ≤ 500/mm(3)) at initial CDI presentation. Forty-one patients (67.2%) received antimicrobial therapy for CDI. Based on the SHEA/IDSA guidelines, only 12 patients (19.7%) presented with severe CDI, but 25 (61.0%) patients experienced treatment failure. Multiple logistic regression modeling showed neutropenia to be an independent risk factor for CDI-related mortality (odds ratio, 5.17; 95% confidence interval, 1.24-21.59). CONCLUSIONS: This study tracked poor CDI treatment outcomes in patients with malignancy and identified neutropenia as a previously unrecognized risk factor of CDI-related mortality. Alternative definitions of severe CDI that include neutropenia might be necessary to more accurately determine clinical severity.

An imported case of severe falciparum malaria with prolonged hemolytic anemia clinically mimicking a coinfection with babesiosis.

While imported falciparum malaria has been increasingly reported in recent years in Korea, clinicians have difficulties in making a clinical diagnosis as well as in having accessibility to effective anti-malarial agents. Here we describe an unusual case of imported falciparum malaria with severe hemolytic anemia lasting over 2 weeks, clinically mimicking a coinfection with babesiosis. A 48-year old Korean man was diagnosed with severe falciparum malaria in France after traveling to the Republic of Benin, West Africa. He received a 1-day course of intravenous artesunate and a 7-day course of Malarone (atovaquone/proguanil) with supportive hemodialysis. Coming back to Korea 5 days after discharge, he was readmitted due to recurrent fever, and further treated with Malarone for 3 days. Both the peripheral blood smears and PCR test were positive for Plasmodium falciparum. However, he had prolonged severe hemolytic anemia (Hb 5.6 g/dl). Therefore, 10 days after the hospitalization, Babesia was considered to be potentially coinfected. A 7-day course of Malarone and azithromycin was empirically started. He became afebrile within 3 days of this babesiosis treatment, and hemolytic anemia profiles began to improve at the completion of the treatment. He has remained stable since his discharge. Unexpectedly, the PCR assays failed to detect DNA of Babesia spp. from blood. In addition, during the retrospective review of the case, the artesunate-induced delayed hemolytic anemia was considered as an alternative cause of the unexplained hemolytic anemia.

Clinical impact of time to positivity for Candida species on mortality in patients with candidaemia.

OBJECTIVES: The time to positivity (TTP) of blood cultures is associated with the microbial load in the blood and prognosis in patients with bloodstream infections caused by various bacterial species. However, relevant information about the TTP for Candida species in candidaemia is limited. We investigated the clinical impact of the TTP on mortality in patients with candidaemia. METHODS: All consecutive patients ≥ 18 years of age with candidaemia between January 2006 and July 2012 were included. The demographics, clinical and microbiological characteristics, antifungal treatment and outcomes of the patients were collected retrospectively. RESULTS: A total of 152 patients were identified. The overall mortality rate at 6 weeks was 53%. The median TTP for Candida isolates was 27 h (IQR 19-37 h). A TTP of ≤ 24 h was significantly related to a higher mortality rate (P = 0.021). In a multivariate Cox regression analysis, the Charlson comorbidity index value [adjusted hazard ratio (HR) 1.15, 95% CI 1.02-1.29, P = 0.018], sequential organ failure assessment score (adjusted HR 1.23, 95% CI 1.13-1.34, P < 0.001), TTP ≤ 24 h (adjusted HR 2.74, 95% CI 1.51-4.97, P = 0.001), timing of appropriate antifungal therapy >72 h (adjusted HR 2.38, 95% CI 1.26-4.51, P = 0.008) and persistent candidaemia (adjusted HR 2.50, 95% CI 1.33-4.72, P = 0.005) were independently associated with the 6 week mortality rate. CONCLUSIONS: A short TTP (≤ 24 h) for Candida species was independently associated with increased mortality in patients with candidaemia. Additional studies on the relevance of the TTP to clinical outcome in patients with candidaemia are needed.

Evaluation of Fluconazole versus Echinocandins for Treatment of Candidemia Caused by Susceptible Common Candida Species: A Propensity Score Matching Analysis.

This study aimed to evaluate the effectiveness of fluconazole and echinocandins in the treatment of candidemia caused by both fluconazole- and echinocandin-susceptible common Candida species. A retrospective study which enrolled adult candidemia patients ≥19 years diagnosed at a tertiary care hospital in the Republic of Korea from 2013 to 2018 was conducted. Common Candida species were defined as C. albicans, C. tropicalis, and C. parapsilosis. Cases of candidemia were excluded based on the following exclusion criteria: (1) candidemia showed resistance to either fluconazole or echinocandins, or (2) candidemia was caused by other Candida species than common Candida species. In order to compare the mortality rates between patients who receive fluconazole or echinocandins, the propensity scores on variables of baseline characteristics using the multivariate logistic regression analysis were employed to balance the antifungal treatment groups, and a Kaplan-Meier survival analysis was performed. Fluconazole and echinocandins were used in 40 patients and in 87 patients, respectively. The propensity score matching included 40 patients in each treatment group. After matching, the rates of 60-day mortality after candidemia were 30% in the fluconazole group and 42.5% in the echinocandins group, and a Kaplan-Meier survival analysis showed no significant difference between antifungal treatment groups, p = 0.187. A multivariable analysis demonstrated that septic shock was significantly associated with the 60-day mortality, whereas fluconazole antifungal treatment was not associated with an excess 60-day mortality. In conclusion, our study results suggest that fluconazole use in the treatment of candidemia caused by susceptible common Candida species may be not associated with increased 60-day mortality compared to echinocandins.

Red blood cell transfusions are associated with lower mortality in patients with severe sepsis and septic shock: a propensity-matched analysis*.

OBJECTIVES: To evaluate the effects of transfusions in patients with severe sepsis and septic shock on mortality. DESIGN: Propensity-matched analysis of a prospective observational database (April 2005 to February 2009). SETTING: Twenty-two medical and surgical intensive care units in 12 teaching hospitals in Korea. PATIENTS: One thousand fifty-four patients with community-acquired severe sepsis and septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 1,054 patients, 407 (38.6%) received a blood transfusion. The mean pretransfusion hemoglobin level was 7.7 ± 1.2 g/dL. Transfused patients had higher 28-day and in-hospital mortality rates (32.7% vs. 17.3%; p < .001, 41.3% vs. 20.3%; p < .001, respectively) and a longer duration of hospital stay (21 [interquartile range, 10-35] vs. 13 [interquartile range, 8-24] days; p < .001), but were more severely ill at admission (lower systolic blood pressure, higher Acute Physiology and Chronic Health Evaluation II score, and Sequential Organ Failure Assessment score at admission). In 152 pairs matched according to the propensity score depending on patient transfusion status, transfused patients had a lower risk of 7-day (9.2% vs. 27.0%; p < .001), 28-day (24.3% vs. 38.8%; p = .007), and in-hospital mortality rates (31.6% vs. 42.8%; p = .044). After adjusting for blood transfusion as a time-dependent variable in multivariable analysis, blood transfusion was independently associated with lower risk of 7-day (hazard ratio 0.42, 95% confidence interval 0.19-0.50, p = .026), 28-day (hazard ratio 0.43, 95% confidence interval 0.29-0.62, p < .001), and in-hospital mortality (hazard ratio 0.51, 95% confidence interval 0.39-0.69, p < .001). CONCLUSIONS: In this observational study of patients with community-acquired severe sepsis and septic shock, red blood cell transfusions were associated with lower risk of mortality.