Background: It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia. Methods: This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment. Results: After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. −0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (−55.20% vs. −7.69%, P<0.001) without previously unknown adverse drug events. Conclusion The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin’s preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.

Purpose: With changing fungal epidemiology and azole resistance in Aspergillus species, identifying fungal species and susceptibility patterns is crucial to the management of aspergillosis and mucormycosis. The objectives of this study were to evaluate performance of panfungal polymerase chain reaction (PCR) assays on formalin-fixed paraffin embedded (FFPE) samples in the identification of fungal species and in the detection of azole-resistance mutations in the Aspergillus fumigatus cyp51A gene at a South Korean hospital. Materials and Methods: A total of 75 FFPE specimens with a histopathological diagnosis of aspergillosis or mucormycosis were identified during the 10-year study period (2006–2015). After deparaffinization and DNA extraction, panfungal PCR assays were conducted on FFPE samples for fungal species identification. The identified fungal species were compared with histopathological diagnosis. On samples identified as A. fumigatus, sequencing to identify frequent mutations in the cyp51A gene [tandem repeat 46 (TR46), L98H, and M220 alterations] that confer azole resistance was performed. Results: Specific fungal DNA was identified in 31 (41.3%) FFPE samples, and of these, 16 samples of specific fungal DNA were in accord with a histopathological diagnosis of aspergillosis or mucormycosis; 15 samples had discordant histopathology and PCR results. No azole-mediating cyp51A gene mutation was noted among nine cases of aspergillosis. Moreover, no cyp51A mutations were identified among three cases with history of prior azole use. Conclusion Panfungal PCR assay with FFPE samples may provide additional information of use to fungal species identification. No azole-resistance mediating mutations in the A. fumigatus cyp51A gene were identified among FFPE samples during study period.

Carbapenemase-producing Enterobacteriaceae (CPE) is an important and increasing threat to global health. From July to September 2017, 20 inpatients at a tertiary care hospital in Korea were either colonized or infected with carbapenem-resistant Escherichia coli strains. All of E. coli isolates co-produced bla(NDM-5) and bla(OXA-181) carbapenemase genes and shared ≥88% clonal relatedness on the basis of a cladistic calculation of the distribution of pulsed-field gel electrophoresis patterns. Rapid detection of CPE is one of the most important factors to prevent CPE dissemination because it takes long time for CPE to become negative.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious zoonosis caused by the SFTS virus. Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome associated with excessive immune activation. Cytokine storms are often seen in both SFTS and HLH, resulting in rapid disease progression and poor prognosis. The aim of this study was to identify whether SFTS cases complicated by HLH are related to higher rates of mortality. Descriptive analysis of the frequency of clinical and laboratory data, complications, treatment outcomes, and HLH-2004 criteria was performed. Cases presenting with five or more clinical or laboratory findings corresponding to the HLH-2004 diagnostic criteria were defined as SFTS cases complicated by HLH. Eighteen cases of SFTS were identified during a 2-year study period, with a case-fatality proportion of 22.2% (4 among 18 cases, 95% confidence interval 9%–45.2%). SFTS cases complicated by HLH were identified in 33.3% (6 among 18 cases). A mortality rate of 75% (3 among 4 cases) was recorded among SFTS cases complicated by HLH. Although there were no statistically significant differences in outcomes, fatal cases exhibited more frequent correlation with HLH-2004 criteria than non-fatal cases [3/14 (21.4%) vs. 3/4 (75%), p=0.083]. In conclusion, the present study suggests the possibility that SFTS cases complicated by HLH are at higher risk of poor prognosis.
Disease Progression ; Fatal Outcome ; Fever ; Lymphohistiocytosis, Hemophagocytic ; Mortality ; Prognosis ; Thrombocytopenia

BACKGROUND/AIMS: Providencia species frequently colonize urinary catheters and cause urinary tract infections (UTIs); however, bacteremia is uncommon and not well understood. We investigated the clinical features of Providencia bacteremia and the antibiotic susceptibility of Providencia species. METHODS: We identified cases of Providencia bacteremia from May 2001 to April 2013 at a tertiary care hospital. The medical records of pertinent patients were reviewed. RESULTS: Fourteen cases of Providencia bacteremia occurred; the incidence rate was 0.41 per 10,000 admissions. The median age of the patients was 64.5 years. Eleven cases (78.6%) were nosocomial infections and nine cases (64.3%) were polymicrobial bacteremia. The most common underlying conditions were cerebrovascular/neurologic disease (n = 10) and an indwelling urinary catheter (n = 10, 71.4%). A UTI was the most common source of bacteremia (n = 5, 35.7%). The overall mortality rate was 29% (n = 4); in each case, death occurred within 4 days of the onset of bacteremia. Primary bacteremia was more fatal than other types of bacteremia (mortality rate, 75% [3/4] vs. 10% [1/10], p = 0.041). The underlying disease severity, Acute Physiologic and Chronic Health Evaluation II scores, and Pitt bacteremia scores were significantly higher in nonsurvivors (p = 0.016, p =0.004, and p = 0.002, respectively). Susceptibility to cefepime, imipenem, and piperacillin/tazobactam was noted in 100%, 86%, and 86% of the isolates, respectively. CONCLUSIONS: Providencia bacteremia occurred frequently in elderly patients with cerebrovascular or neurologic disease. Although Providencia bacteremia is uncommon, it can be rapidly fatal and polymicrobial. These characteristics suggest that the selection of appropriate antibiotic therapy could be complicated in Providencia bacteremia.
APACHE ; Adolescent ; Adult ; Aged ; Anti-Bacterial Agents/therapeutic use ; Bacteremia/diagnosis/drug therapy/*microbiology/mortality ; Child ; Cross Infection/diagnosis/drug therapy/*microbiology/mortality ; Cross-Sectional Studies ; Drug Resistance, Bacterial ; Enterobacteriaceae Infections/diagnosis/drug therapy/*microbiology/mortality ; Female ; Hospital Mortality ; Humans ; Incidence ; Male ; Microbial Sensitivity Tests ; Middle Aged ; Predictive Value of Tests ; Providencia/drug effects/*isolation & purification ; Republic of Korea ; Retrospective Studies ; Risk Factors ; *Tertiary Care Centers ; Treatment Outcome ; Young Adult

BACKGROUND: The Korean Society for Nosocomial Infection Control (KOSNIC) ran a surveillance system, called as Korean Nosocomial Infections Surveillance (KONIS), since July 2006. Here, we report the annual data of the intensive care unit (ICU) module of the system from July 2012 through June 2013. METHODS: This is a prospective surveillance of nosocomial urinary tract infections (UTI), bloodstream infections (BSI), and pneumonia (PNEU) at 161 ICUs in 91 hospitals using the KONIS system. The nosocomial infection (NI) rate was calculated as the number of infections per 1,000 patient days or device days. RESULTS: A total of 3,042 NIs were reported during the study period: 877 UTIs (854 cases were urinary catheter-associated), 1,272 BSIs (1,096 were central line-associated), and 893 PNEUs (526 cases were ventilator-associated). The rate of urinary catheter-associated UTIs (CAUTIs) was 1.26 cases per 1,000 device days (95% confidence interval; 1.18-1.34) and urinary catheter utilization ratio was 0.78 (0.779-0.781). The rate of central line-associated BSIs was 2.57 (2.42-2.72) and the utilization ratio was 0.49 (0.489-0.491). The rate of ventilator-associated PNEUs was 1.64 (1.50-1.78) and the utilization ratio was 0.37 (0.369-0.371). The urinary catheter utilization ratio was lower in the ICUs of hospitals with 400-699 beds than in those of hospitals with more than 900 beds; nevertheless, CAUTIs were more common in the hospitals with 400-699 beds. The central line-associated BSI (CLABSI) rate was lower in the study period than in the previous period of July 2011-June 2012 [2.57 (2.42-2.72) vs. 3.01 (2.84-3.19)]. CONCLUSION: The CLABSI rates were lower in the study period than those in the previous years. CAUTIs were more common in the ICUs of hospitals with 400-699 beds than in those of larger hospitals.
Cross Infection* ; Humans ; Intensive Care Units* ; Critical Care* ; Pneumonia ; Prospective Studies ; Urinary Catheters ; Urinary Tract Infections

BACKGROUND: This article reports annual data of intensive care units (ICU) module of the Korean Nosocomial Infections Surveillance (KONIS) system from July 2011 through June 2012. METHODS: We performed a prospective surveillance of nosocomial urinary tract infections (UTI), bloodstream infections (BSI), and pneumonia (PNEU) at 143 ICUs in 81 hospitals using the KONIS system. Nosocomial infection (NI) rates were calculated as the number of infections per 1,000 patient days or device days. Asymptomatic bacteriuria was excluded on or after October 1, 2011. RESULTS: A total of 3,374 NIs were found during the study period: 1,356 UTIs (1,336 cases were urinary catheter-associated), 1,253 BSIs (1,091 were central line-associated), and 765 PNEUs (481 were ventilator-associated). The rate of urinary catheter-associated UTIs (CAUTIs) was 2.26 cases per 1,000 device-days (95% confidence interval, 2.14-2.39) and urinary catheter utilization ratio was 0.85 (0.849-0.851). The rate of central line-associated BSIs was 3.01 (2.84-3.19) and the utilization ratio was 0.52 (0.519-0.521). The rate of ventilator-associated PNEUs (VAPs) was 1.70 (1.56-1.86) and the utilization ratio was 0.40 (0.399-0.401). Ventilator and urinary catheter utilization ratios were lower in the ICUs of hospitals with 400-699 beds than those in hospitals with 700-899 beds or more than 900 beds. Nevertheless, VAPs and CAUTIs were more common in hospitals with 400-699 beds. CONCLUSION: Nosocomial infection rates were similar to the findings of those of the previous period, July 2010-July 2011. Implementation of proven infection-control strategies are needed, especially in the hospitals having fewer than 700 beds.
Bacteriuria ; Cross Infection* ; Humans ; Intensive Care Units* ; Pneumonia ; Prospective Studies ; Urinary Catheters ; Urinary Tract Infections ; Ventilators, Mechanical

PURPOSE: Colistin is used for the treatment of pneumonia associated with multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa. However, the best route of administration and dosage is not known. We report our experience with aerosolized colistin in twelve patients with pneumonia caused by colistin-only-susceptible (COS) A. baumannii. MATERIALS AND METHODS: We retrospectively reviewed patients' medical records who were treated with aerosolized colistin for the treatment of pneumonia. RESULTS: Ten patients were treated only with aerosolized colistin inhalation and two patients received a 3-day course intravenous colistin, and then switched to colistin inhalation therapy. The median duration of aerosolized colistin therapy was 17 days (5-31 days). Four patients were treated only with aerosolized colistin, whereas 4 patients received concomitant glycopeptides, and 4 received concomitant levofloxacin or cefoperazone/sulbactam. At the end of the therapy, the clinical response rate and bacteriological clearance rate was 83% and 50%, respectively. Colistin-resistant strains were isolated from 3 patients after aerosolized colistin therapy; however, all of them showed favorable clinical response. The median interval between inhalation therapy and resistance was 7 days (range 5-19 days). Acute kidney injury developed in 3 patients. Two patients experienced Clostridium difficile associated diarrhea. One patient developed fever and skin rash after aerosolized colistin therapy. No patient developed neurotoxicity or bronchospasm. CONCLUSION: Colistin inhalation therapy is deemed tolerable and safe, and could be beneficial as an adjuctive therapy for the management of pneumonia due to COS A. baumannii. However, the potential development of colistin resistance cannot be overlooked.
Acinetobacter baumannii/drug effects/*pathogenicity ; Administration, Inhalation ; Aged ; Anti-Bacterial Agents/administration & dosage/*therapeutic use ; Colistin/administration & dosage/*therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Pneumonia/*drug therapy ; Retrospective Studies

BACKGROUND: The false positive signals of a continuous monitoring blood culture system (CMBCS) increase the reporting time and laboratory cost. This study aimed to determine the highly relevant variables that discriminate false positive signals from true positive signals in a CMBCS. METHODS: Among 184,363 blood culture sets (aerobic and anaerobic), the signal-positive samples according to a BACTEC FX system (Plus Aerobic/F, BDA; Plus Anaerobic/F, BDN) and BacT/Alert 3D system (Standard Aerobic, BSA; Standard Anaerobic, BSN) between April 2010 and November 2013 were classified into two groups: false positive or true positive signals. The data of 15 parameters between the two groups were then statistically compared. RESULTS: Among total blood cultures, the positive rates of CMBCS signals according to BDA, BDN, BSA, and BSN were 4.9%, 2.8%, 3.8%, and 3.2%, respectively. The false positive rates of CMBCS signals according to BDA, BDN, BSA, and BSN were 0.6%, 0.1%, 0.1%, and 0.1%, respectively. The blood volume, detection time, time interval between admission and test, C-reactive protein concentration, leukocyte count, delta neutrophil index, and mean peroxidase index showed statistically significant differences between the two groups. CONCLUSION: There were no variables with diagnostic sensitivity and specificity for discriminating the two groups. Therefore, analysis of bacterial growth curves produced by CMBCS is needed for early and effective detection of false positive signals.
Blood Volume ; C-Reactive Protein ; Leukocyte Count ; Neutrophils ; Peroxidase

BACKGROUND: The aim of this study was to evaluate a newly developed PCR-based reverse blot hybridization assay (PCR-REBA), REBA Sepsis-ID (M&D, Wonju, Korea), to rapidly detect the presence of bacteremia and antimicrobial resistance gene in blood culture samples. METHODS: One thousand four hundred consecutive blood culture samples from patients with a delta neutrophil index greater than 2.7% were selected from March to July in 2013. Three hundred positive and 1,100 negative for bacterial growth in blood culture bottles samples were tested by conventional and real-time PCR-REBA, respectively. RESULTS: The overall agreement between the conventional identification test and the REBA Sepsis-ID test was 95.3% (286/300). Agreement for gram-positive bacteria, gram-negative bacteria, fungi, and polymicrobials was 94.5% (190/201), 97.3% (71/73), 100% (14/14), and 91.7% (11/12), respectively. The detection rate of the mecA gene from methicillin-resistant Staphylococcus isolates was 97.8% (90/92). The vanA gene was detected in one blood culture sample from which vancomycin-resistant Enterococcus was isolated. When the cycle threshold for real-time PCR was defined as 30.0, 2.4% (26/1,100) of negative blood culture samples tested positive by real-time PCR. CONCLUSIONS: The REBA Sepsis-ID test is capable of simultaneously and quickly detecting both causative agents and antimicrobial resistance genes, such as mecA and van, in blood culture positive samples.
Bacteremia/microbiology ; Bacterial Proteins/*genetics ; Bacteriological Techniques/*methods ; Carbon-Oxygen Ligases/*genetics ; Drug Resistance, Bacterial/genetics ; Enterococcus/*genetics/isolation & purification ; Humans ; Methicillin-Resistant Staphylococcus aureus/*genetics/isolation & purification ; *Nucleic Acid Hybridization ; RNA, Ribosomal, 16S/analysis ; Reagent Kits, Diagnostic ; *Real-Time Polymerase Chain Reaction