Clinical and economic burden of bacteremia due to multidrug-resistant organisms in Korea: a prospective case control study.

OBJECTIVES: The socioeconomic and clinical burden of multidrug-resistant organisms (MDRO), including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), multidrug-resistant Acinetobacter baumannii (MRAB), multidrug-resistant Pseudomonas aeruginosa (MRPA), and carbapenem-resistant Enterobacteriaceae (CRE) have not yet been adequately addressed. METHODS: We prospectively searched for MDRO bacteremia cases with matched controls from 10 hospitals across Korea during a 6-month period in 2017. Patients were classified into the MDRO, susceptible organism, and no-infection groups. The corresponding susceptible or no-infection controls had been selected according to predefined criteria. We collected clinical information and estimated the total additional medical cost due to MDRO infections using the multistate model. RESULTS: During the 6-month period, a total of 486 MDRO bacteremia cases (260, 87, 18, 20, and 101 cases of MRSA, MRAB, MRPA, CRE, and VRE, respectively) were identified. The 90-d mortality rates were 30.4%, 63.2%, 16.7%, 55.0%, and 47.5%, respectively. The additional costs caused by bacteremia were $15 768, $35 682, $39 908, $72 051, and $33 662 per MDRO type, respectively. Based on these 6-month data, the estimated annual number of bacteremia cases due to these five MDRO in Korea were 7979 (4070, 1396, 218, 461, and 1834 cases, respectively). Overall, this caused an estimated 3280 (1237, 882, 36, 254, and 871, respectively) deaths and cost $294 505 002 ($84 707 359, $74 387 364, $10 344 370, $45 850 215, and $79 215 694, respectively) (range $170,627,020-$416,094,679) in socioeconomic loss. CONCLUSIONS: A tremendous clinical and economic burden is caused by MDRO bacteremia compared with antibiotic-susceptible and no-infection groups. Substantial investment and efforts by related government agencies and medical staffs are needed.

Socioeconomic burden of pneumonia due to multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa in Korea.

We aimed to estimate the socioeconomic burden of pneumonia due to multidrug-resistant Acinetobacter baumannii (MRAB) and Pseudomonas aeruginosa (MRPA). We prospectively searched for MRAB and MRPA pneumonia cases and matched them with susceptible-organism pneumonia and non-infected patients from 10 hospitals. The matching criteria were: same principal diagnosis, same surgery or intervention during hospitalisation, age, sex, and admission date within 60 days. We calculated the economic burden by using the difference in hospital costs, the difference in caregiver costs, and the sum of productivity loss from an unexpected death. We identified 108 MRAB pneumonia [MRAB-P] and 28 MRPA pneumonia [MRPA-P] cases. The estimated number of annual MRAB-P and MRPA-P cases in South Korea were 1309-2483 and 339-644, with 485-920 and 133-253 deaths, respectively. The annual socioeconomic burden of MRAB-P and MRPA-P in South Korea was $64,549,723-122,533,585 and $15,241,883-28,994,008, respectively. The results revealed that MRAB-P and MRPA-P occurred in 1648-3127 patients, resulted in 618-1173 deaths, and caused a nationwide socioeconomic burden of $79,791,606-151,527,593. Multidrug-resistant organisms (MDRO) impose a great clinical and economic burden at a national level. Therefore, controlling the spread of MDRO will be an effective measure to reduce this burden.

Risk factors for early mortality in patients with carbapenem-resistant Acinetobacter baumannii bacteraemia.

OBJECTIVES: Although many deaths due to carbapenem-resistant Acinetobacter baumannii (CRAB) bacteraemia occur within a few days after the onset of bacteraemia, risk factors for early mortality (EM) have not been deeply investigated. We aimed to determine the risk factors for EM and the difference between risk factors associated with EM and late mortality (LM) in CRAB bacteraemia. METHODS: Clinical information on all patients with CRAB bacteraemia in 10 hospitals during a 1-year period was collected. Among the cases with mortality within 30 days, EM and LM were defined as death within 3 and more than 5 calendar days from the first positive blood culture, respectively. RESULTS: In total, 212 CRAB bacteraemia cases were included in the analysis. Of 122 (57.5%) patients with 30-day mortality, EM was observed in 75 (61.5%) patients and LM in 39 (32.0%) patients. The proportion of severe sepsis or septic shock, Pitt score, and Sequential Organ Failure Assessment (SOFA) score was significantly higher in patients with EM than those with LM. Although urinary tract infection as the site of infection and the severity of illness were independent predictors of LM, only factors representing the severity of illness were independent risk factors for EM. CONCLUSION: Our results suggest that a large proportion of CRAB bacteraemia with high severity progresses to a rapidly fatal course, regardless of the underlying diseases or source of infection. Further studies might be needed to investigate the microbiological factors associated with CRAB and pathogen-host interaction in patients with EM.

Thirty-Day Mortality Rates in Patients with Extended-Spectrum ß-Lactamase-Producing Enterobacterales Bacteremia Receiving Ertapenem versus Other Carbapenems.

Ertapenem is one of the carbapenems recommended for treating extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales. However, efficacy data are limited. We compared 30-day mortality rates for patients receiving ertapenem and other carbapenems for treatment of ESBL-producing Enterobacterales bacteremia. A multicenter, retrospective study was performed from January 2013 to December 2020 at three hospitals. Patients who received only members of one group of carbapenems (group 1 or group 2) throughout their treatment for ESBL-producing Escherichia coli or Klebsiella pneumoniae bacteremia were enrolled. To compare 30-day all-cause mortality rates in the two groups, propensity score matching was used to control for selection bias. Subgroup analyses were performed for several subgroups. Secondary outcomes included Clostridioides difficile infection (CDI) and the emergence of multidrug-resistant Gram-negative bacteria within 90 days after initiation of carbapenem treatment. One-to-one propensity score matching yielded 162 pairs of patients from the total of 603 patients included. There was no difference in 30-day mortality rates between ertapenem and the other carbapenems in adjusted analyses (hazard ratio, 0.60 [95% confidence interval [CI], 0.29 to 1.22]) of the propensity score-matched cohorts. A similar result was obtained in a subgroup analysis of patients who suffered severe sepsis or septic shock and those who did not (P = 0.54 for interaction). Emergence of CDI (odds ratio [OR], 0.99 [95% CI, 0.44 to 2.20]) and carbapenem-resistant Enterobacterales (OR, 1.31 [95% CI, 0.51 to 3.53]) did not differ between the two groups. Our study suggests that the efficacy of ertapenem may be comparable to that of the other carbapenems in treatment of ESBL-producing E. coli and K. pneumoniae bacteremia.

Different clinical characteristics and impact of carbapenem-resistance on outcomes between Acinetobacter baumannii and Pseudomonas aeruginosa bacteraemia: a prospective observational study.

This study aimed to evaluate the differences in clinical characteristics and impact of carbapenem resistance (CR) on outcomes between Acinetobacter baumannii (Ab) and Pseudomonas aeruginosa (Pa) bacteraemia. We prospectively identified all patients with Ab and Pa bacteraemia in 10 hospitals over 1 year. Treatment failure was defined as all-cause 30-day mortality, persistent bacteraemia, or recurrent bacteraemia within 30 days. We included 304 Ab and 241 Pa bacteraemia cases. CR was detected in 216 patients (71%) with Ab bacteraemia and 55 patients (23%) with Pa bacteraemia. Treatment failure was significantly higher in CR-Ab than in CR-Pa (60.6% vs. 34.5%, P = 0.001). In Ab, severe sepsis or septic shock and high Pitt bacteraemia score were independent risk factors for treatment failure in the inappropriate empirical antibiotics group. In Pa, hospital-acquired infection and high Pitt bacteraemia score were independent risk factors for treatment failure in both groups. CR was an independent risk factor in Ab for treatment failure in both groups, but not in Pa bacteraemia. We demonstrated significant differences in clinical characteristics and impact of CR on clinical outcomes between Ab and Pa bacteraemia, suggesting that different treatment approaches may be needed.

A comparative study of adult and adolescent maternal care continuum following community-oriented interventions in Cambodia, Guatemala, Kenya, and Zambia.

BACKGROUND: The coverage for reproductive care continuum is a growing concern for communities in low- income economies. Adolescents (15-19 years) are often at higher odds of maternal morbidity and mortality due to other underlying factors including biological immaturity, social, and economic differences. The aim of the study was to examine a) differences in care-seeking and continuum of care (4 antenatal care (ANC4+), skilled birth attendance (SBA) and postnatal care (PNC) within 24h) between adult (20-49 Years) and adolescents and b) the effect of multilevel community-oriented interventions on adolescent and adult reproductive care-seeking in Cambodia, Guatemala, Kenya, and Zambia using a quasi-experimental study design. METHODS: In each country, communities in two districts/sub-districts received timed community health worker (CHW) household health promotion and social accountability interventions with community scorecards. Two matched districts/sub-districts were selected for comparison and received routine healthcare services. RESULTS: Results from the final evaluation showed that there were no significant differences in the care continuum for adolescents and adults except for Kenya (26.1% vs 18.8%, p<0.05). SBA was significantly higher for adolescents compared to adult women for Guatemala (64% vs 55.5%, p<0.05). Adolescents in the intervention sites showed significantly higher ANC utilization for Kenya (95.3% vs 84.8%, p<0.01) and Zambia (87% vs 72.7%, p<0.05), ANC4 for Cambodia (83.7% vs 43.2%, p<0.001) and Kenya (65.9% vs 48.1%, p<0.05), SBA for Cambodia (100% vs 88.9%, p<0.05), early PNC for Cambodia (91.8% vs 72.8%, p<0.01) and Zambia (56.5% vs 16.9%, p<0.001) compared to the comparison sites. However, the findings from Guatemala illustrated significantly lower care continuum for intervention sites (aOR:0.34, 95% CI 0.28-0.42, p<0.001). The study provides some evidence on the potential of multilevel community-oriented interventions to improve adolescent healthcare seeking in rural contexts. The predictors of care continuum varied across countries, indicating the importance of contextual factors in designing interventions.

The associations of previous influenza/upper respiratory infection with COVID-19 susceptibility/morbidity/mortality: a nationwide cohort study in South Korea.

We aimed to investigate the associations of previous influenza/URI with the susceptibility of COVID-19 patients compared to that of non-COVID-19 participants. A nationwide COVID-19 cohort database was collected by the Korea National Health Insurance Corporation. A total of 8,070 COVID-19 patients (1 January 2020 through 4 June 2020) were matched with 32,280 control participants. Severe COVID-19 morbidity was defined based on the treatment histories of the intensive care unit, invasive ventilation, and extracorporeal membrane oxygenation and death. The susceptibility/morbidity/mortality associated with prior histories of 1-14, 1-30, 1-90, 15-45, 15-90, and 31-90 days before COVID-19 onset were analyzed using conditional/unconditional logistic regression. Prior influenza infection was related to increased susceptibility to COVID-19 (adjusted odds ratio [95% confidence interval] = 3.07 [1.61-5.85] for 1-14 days and 1.91 [1.54-2.37] for 1-90 days). Prior URI was also associated with increased susceptibility to COVID-19 (6.95 [6.38-7.58] for 1-14 days, 4.99 [4.64-5.37] for 1-30 days, and 2.70 [2.55-2.86] for 1-90 days). COVID-19 morbidity was positively associated with influenza (3.64 [1.55-9.21] and 3.59 [1.42-9.05]) and URI (1.40 [1.11-1.78] and 1.28 [1.02-1.61]) at 1-14 days and 1-30 days, respectively. Overall, previous influenza/URI did not show an association with COVID-19 mortality. Previous influenza/URI histories were associated with increased COVID-19 susceptibility and morbidity. Our findings indicate why controlling influenza/URI is important during the COVID-19 pandemic.

The Effects of Previous Asthma and COPD on the Susceptibility to and Severity of COVID-19: A Nationwide Cohort Study in South Korea.

BACKGROUND: There is controversial evidence of the associations of asthma and chronic obstructive pulmonary disease (COPD) with the risk and outcomes of Coronavirus Disease 2019 (COVID-19). We aimed to evaluate the effects of asthma and COPD on the susceptibility to and severity of COVID-19. METHODS: Data from a nationwide COVID-19 cohort database by the Korea National Health Insurance Corporation were utilized. A total of 4066 COVID-19 patients (1 January 2020 through 4 June 2020) were 1:4 matched with 16,264 controls with regard to age, sex, and income. Asthma and COPD were defined as diagnostic codes (ICD-10) and medication claim codes. Conditional and unconditional multivariate logistic regression were applied to analyze the susceptibility to and severity of COVID-19 associated with asthma and COPD. RESULTS: The prevalence of mild and severe asthma/COPD did not differ between the COVID-19 and control patients in the multivariate analyses. Among the total 4066 COVID-19 patients, 343 (8.4%) had severe COVID-19, of whom 132 (3.2% of the total COVID-19 patients) died. Regarding the outcomes of COVID-19, neither mild nor severe asthma were associated with the severity or mortality of COVID-19 after adjusting for other variables. However, severe COPD was a significant risk factor for severe COVID-19 (odds ratio (OR) = 2.23, 95% confidence intervals (CI): 1.08-4.60, p = 0.030) and the mortality of COVID-19 in the multivariate analyses (OR = 3.06, 95% CI: 1.14-8.2, p = 0.026). CONCLUSIONS: In a Korean nationwide cohort, neither asthma nor COPD were associated with COVID-19, but severe COPD was associated with the severity and mortality of COVID-19.

Association between previous rheumatoid arthritis and COVID-19 and its severity: a nationwide cohort study in South Korea.

OBJECTIVES: The prevalence of rheumatoid arthritis (RA) among patients with COVID-19 and the association between RA and the outcome of COVID-19 remain unclear. We aimed to compare the prevalence of RA between participants with and without COVID-19; we then analysed the association between the presence of RA and the severity of COVID-19. DESIGN: A cross-sectional study. SETTING: Data from a nationwide COVID-19 cohort database by the Korea National Health Insurance Corporation were used. PARTICIPANTS AND INTERVENTIONS: A total of 8070 patients with COVID-19 (1 January 2020 through 4 June 2020) were matched with 32 280 control participants with regard to age, sex and income. Patients with COVID-19 were confirmed by SARS-CoV-2 PCR and controls were collected from the database. RA was confirmed using the diagnostic code (International Classification of Disease, Tenth Revision) and medication claim codes. Conditional/unconditional logistic regression was applied to analyse the association between RA and COVID-19. PRIMARY OUTCOME AND SECONDARY OUTCOME: Laboratory confirmation of SARS-CoV-2 infection was defined as the primary outcome. The secondary outcome was severe COVID-19 defined as a history of intensive care unit admission, invasive ventilation or death. RESULTS: The prevalence of RA in the COVID-19 (0.4%, 35/8070) and control (0.4%, 121/32,280) groups did not differ (p=0.446). After adjusting for underlying diseases, no association between RA and COVID-19 was observed (adjusted OR=1.14, 95% CI: 0.78 to 1.67) and COVID-19 severity was not associated with RA (adjusted OR=0.62, 95% CI: 0.14 to 7.29). The overall mortality rate was 2.9% (237/8070) and RA was not significantly associated with mortality (adjusted OR=1.64, 95% CI: 0.33 to 8.15). CONCLUSION: We did not find an association between the presence of RA and COVID-19. In addition, RA was not associated with the severity of COVID-19.

Characterization of oxazolidinone and phenicol resistance genes in non-clinical enterococcal isolates from Korea.

OBJECTIVES: To investigate the distribution and genetic characteristics of linezolid-resistant enterococci. METHODS: Enterococcus faecalis and Enterococcus faecium strains were isolated from pigs, equipment, grounds, and employees of 19 Korean swine farms in 2017. Antimicrobial susceptibility testing was then performed and linezolid resistance genes were detected via PCR. For genetic epidemiological characterization, multilocus sequence typing and whole-genome sequencing data were analysed. RESULTS: Twenty-eightE. faecalis and five E. faecium strains were isolated from 1026 samples obtained from the 19 farms. Ten sequence types were identified among the E. faecalis strains, of which ST256 (42.9%) and ST86 (25%) were the most abundant. The oxazolidinone and phenicol resistance genes poxtA, optrA, and fexA were detected in isolates of E. faecalis (100%, 85.7%, and 67.9%, respectively) and E. faecium (100%, 60%, and 80%, respectively). The minimum inhibitory concentrations of linezolid in these isolates ranged from 2 mg/L to 12 mg/L. The whole-genome sequencing data indicated that fexA was located upstream of poxtA. CONCLUSIONS: This is the first study to report the detection of poxtA in isolates that were both susceptible and resistant to linezolid in Korea. These results demonstrate the importance of antimicrobial resistance monitoring programmes, including regular antimicrobial susceptibility testing and resistance gene expression analysis, to facilitate the control of the spread of antibiotic resistance in non-clinical settings in Korea.

Prospective Cohort Study of Population Pharmacokinetics and Pharmacodynamic Target Attainment of Vancomycin in Adults on Extracorporeal Membrane Oxygenation.

The aim of this study was to develop a population pharmacokinetics (PK) model for vancomycin and to evaluate its pharmacodynamic target attainment in adults on extracorporeal membrane oxygenation (ECMO). After a single 1,000-mg dose of vancomycin, samples were collected 9 times per patient prospectively. A population PK model was developed using a nonlinear mixed-effect model. The probability of target attainment (PTA) of vancomycin was evaluated for various dosing strategies using Monte Carlo simulation. The ratio of the area under the vancomycin concentration-time curve at steady state over 24 h to the MIC (AUC/MIC ratio) was investigated by applying the vancomycin breakpoint distribution of MICs for methicillin-resistant Staphylococcus aureus A total of 22 adult patients with 194 concentration measurements were included. The population PK was best described by a three-compartment model with a proportional residual error model. Vancomycin clearance and steady-state volume of distribution were 4.01 liters/h (0.0542 liters/h/kg) and 29.6 liters (0.400 liters/kg), respectively. If the treatment target AUC/MIC value was only ≥400, a total daily dose of 3 to 4 g would be optimal (PTA of ≥90%) for patients with normal renal function (estimated glomerular filtration rate [eGFR] = 60 to 120 ml/min/1.73 m2) when the MIC was presumed to be 1 mg/liter. However, AUC/MIC values of 400 to 600 were difficult to attain with any dosing strategy regardless of MIC and eGFR. Thus, it is hard to achieve efficacy and safety targets in patients on ECMO using the population dosing approach with Monte Carlo simulations, and therapeutic drug monitoring should be implemented in these patients.

Can people-centered community-oriented interventions improve skilled birth attendance? Evidence from a quasi-experimental study in rural communities of Cambodia, Kenya, and Zambia.

BACKGROUND: Skilled attendance at delivery is a key marker for reducing maternal mortality. Effective community engagement strategies complemented by community health worker (CHW) services can improve access to maternal health services in areas with limited health infrastructure or workforce. METHODS: A quasi-experimental study with matched comparison groups was conducted in Cambodia, Kenya and Zambia to determine the effect of integrated community investments on skilled birth attendance (SBA). In each country, communities in two districts/sub-districts received a package of community-oriented interventions comprised of timed CHW household health promotion for maternal, newborn and child health complemented by social accountability mechanisms using community scorecards. Two matched comparison districts/sub-districts received ongoing routine interventions. Data from the final evaluation were examined to determine the effect of timed CHW services and community-oriented interventions on SBA. RESULTS: Over 80% of the 3037 women in Cambodia, 2805 women in Kenya and 1171 women in Zambia reported SBA. Women in intervention sites who received timely CHW health promotion and social accountability mechanisms in Cambodia showed significantly higher odds of SBA (aOR = 7.48; 95% CI: 3.87, 14.5). The findings also indicated that women over the age of 24 in Cambodia, women with primary or secondary education in Cambodia and secondary education in Kenya, women from higher wealth quintiles in Cambodia, and women with four or more antenatal care (ANC) visits in all countries reported significantly higher odds of SBA. Inclusion of family members in pregnancy-related discussions in Kenya (aOR = 2.12; 95% CI: 1.06, 4.26) and Zambia (aOR = 6.78; 95% CI: 1.15, 13.9) and follow up CHW visits after a referral or health facility visit (aOR = 2.44; 95% CI: 1.30, 4.60 in Cambodia; aOR = 2.17; 95% CI 1.25, 3.75 in Kenya; aOR = 1.89; 95% CI: 1.05, 2.02 in Zambia) also showed significantly greater odds of SBA. CONCLUSIONS: Enhancing people-centered care through culturally appropriate community-oriented strategies integrating timely CHW health promotion and social accountability mechanisms shows some evidence for improving SBA during delivery. These strategies can accelerate the achievement of the sustainable development goals for maternal child and newborn health.

Can social accountability mechanisms using community scorecards improve quality of pediatric care in rural Cambodia?

OBJECTIVE: To determine the effect of social accountability strategies on pediatric quality of care. DESIGN AND SETTING: A non-randomized quasi experimental study was conducted in four districts in Cambodia and all operational public health facilities were included. PARTICIPANTS: Five patients under 5 years and their caretakers were randomly selected in each facility. INTERVENTIONS: To determine the effect of maternal and child health interventions integrating citizen voice and action using community scorecards on quality of pediatric care. OUTCOME MEASURES: Patient observations were conducted to determine quality of screening and counseling, followed by exit interviews with caretakers. RESULTS: Results indicated significant differences between intervention and comparison facilities; screening by Integrated Management of Childhood Illness (IMCI) trained providers (100% vs 67%, P < 0.019), screening for danger signs; ability to drink/breastfeed (100% vs 86.7%, P < 0.041), lethargy (86.7% vs 40%, P < 0.004) and convulsions (83.3 vs 46.7%, P < 0.023). Screening was significantly higher for patients in the intervention facilities for edema (56.7% vs 6.7%, P < 0.000), immunization card (90% vs 40%, P < 0.002), child weight (100 vs 86.7, P < 0.041) and checking growth chart (96.7% vs 66.7%, P < 0.035). The IMCI index, constructed from key performance indicators, was significantly higher for patients in the intervention facilities than comparison facilities (screening index 8.8 vs 7.0, P < 0.018, counseling index 2.7 vs 1.5, P < 0.001). Predictors of screening quality were child age, screening by IMCI trained provider, wealthier quintiles and intervention facilities. CONCLUSION: The institution of social accountability mechanisms to engage communities and facility providers showed some improvements in quality of care for common pediatric conditions, but socioeconomic disparities were evident.

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

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

Severe fever with thrombocytopenia syndrome: comparison with scrub typhus and clinical diagnostic prediction.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is emerging in Asian 3 countries, China, Japan and Korea, which are scrub typhus endemic areas, and its incidence is increasing. As the two infections overlap epidemiologically and clinically and the accessibility or sensitivity of diagnostic tests is limited, early clinical prediction may be useful for diagnostic and therapeutic purposes. METHODS: Patients aged ≥16 years who were clinically suspected and laboratory-confirmed to be infected with Orientia tsutsugamushi or the SFTS virus in South Korea were enrolled. Clinical and laboratory parameters were compared. Scrub typhus was further subclassified according to the status of eschar and skin rash. An SFTS prediction scoring tool was generated based on a logistic regression analysis of SFTS compared with scrub typhus. RESULTS: The analysis was performed on 255 patients with scrub typhus and 107 patients with SFTS. At initial presentation, subjective symptoms except for gastrointestinal symptoms, were more prominent in scrub typhus patients. In addition to the characteristic eschar and skin rash, headache was significantly more prominent in scrub typhus, while laboratory abnormalities were more prominent in SFTS. Leukopenia (white blood cell count < 4000/mm3; odds ratio [OR] 30.13), thrombocytopenia (platelet count < 80,000 /mm3; OR 19.73) and low C-reactive protein (< 1 mg/dL; OR 67.46) were consistent risk factors for SFTS (all P < 0.001). A prediction score was generated using these 3 variables, and a score ≥ 2 had a sensitivity of 93.1% (95% confidence interval [CI], 87.9-96.4%) and a specificity of 96.1% (95% CI, 93.8-97.6%) for SFTS. CONCLUSION: This prediction scoring tool may be useful for differentiating SFTS from eschar- or skin rash-negative scrub typhus. It is a simple and readily applicable tool with potential for use in primary care settings.

In vitro activity of flomoxef against extended-spectrum ß-lactamase-producing Escherichia coli and Klebsiella pneumoniae in Korea.

To find an alternative regimen for the treatment of extended-spectrum ß-lactamase (EBSL)-producing Enterobacteriaceae infections, we examined the in vitro activity of flomoxef against Escherichia coli and Klebsiella pneumoniae having CTX-M-1 group and/or CTX-M-9 group ESBLs. Boronic acid disk methods and polymerase chain reaction amplification were used to detect for ESBL, and AmpC ß-lactamase and AmpC ß-lactamase co-producers were excluded. Minimum inhibitory concentrations (MICs) were determined for flomoxef by broth microdilution. One hundred seventy-six isolates (E. coli, n = 93 and K. pneumoniae, n = 83) were analyzed for susceptibility test. A total of 94.3% (166/176) of isolates were susceptible to flomoxef (MIC50/MIC90 were 0.5/8 µg/mL); 98.9% of the ESBL-producing E. coli (MIC50/MIC90 were 1/4 µg/mL) and 89.2% of the ESBL-producing K. pneumoniae (MIC50/MIC90 were 0.5/16 µg/mL) were susceptible to flomoxef. Flomoxef has good in vitro activity against ESBL-producing E. coli and K. pneumoniae and could be considered as an alternative for infections caused by these organisms.

Economic and epidemiologic impact of guidelines for early ART initiation irrespective of CD4 count in Spain.

INTRODUCTION: Emerging data suggest that early antiretroviral therapy (ART) could reduce serious AIDS and non-AIDS events and deaths but could also increase costs. In January 2016, the Spanish guidelines were updated to recommend ART at any CD4 count. However, the epidemiologic and economic impacts of early ART initiation in Spain remain unclear. METHODS: The Johns Hopkins HIV Economic-Epidemiologic Mathematical Model (JHEEM) was utilized to estimate costs, transmissions, and outcomes in Spain over 20 years. We compared implementation of guidelines for early ART initiation to a counterfactual scenario deferring ART until CD4-counts fall below 350 cells/mm3. We additionally studied the impact of early ART initiation in combination with improvements to HIV screening, care linkage and engagement. RESULTS: Early ART initiation (irrespective of CD4-count) is expected to avert 20,100 [95% Uncertainty Range (UR) 11,100-83,000] new HIV cases over the next two decades compared to delayed ART (28% reduction), at an incremental health system cost of €1.05 billion [€0.66 - €1.63] billion, and an incremental cost-effectiveness ratio (ICER) of €29,700 [€13,700 - €41,200] per QALY gained. Projected ICERs declined further over longer time horizon; e.g., an ICER of €12,691 over 30 years. Furthermore, the impact of early ART initiation was potentiated by improved HIV screening among high-risk individuals, averting an estimated 41,600 [23,200-172,200] HIV infections (a 58% decline) compared to delayed ART. CONCLUSIONS: Recommendations for ART initiation irrespective of CD4-counts are cost-effective and could avert > 30% of new cases in Spain. Improving HIV diagnosis can amplify this impact.

Comparative genomic analysis and characteristics of NCCP15740, the major type of enterotoxigenic Escherichia coli in Korea.

BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) cause infectious diarrhea and diarrheal death. However, the genetic properties of pathogenic strains vary spatially and temporally, making prevention and treatment difficult. In this study, the genomic features of the major type of ETEC in Korea from 2003 to 2011 were examined by whole-genome sequencing of strain NCCP15740, and a comparative genomic analysis was performed with O6 reference strains. RESULTS: The assembled genome size of NCCP15740 was 4,795,873 bp with 50.54% G+C content. Using rapid annotation using subsystem technology analysis, we predicted 4492 ORFs and 17 RNA genes. NCCP15740 was investigated for enterotoxin genes, colonization factor (CF) genes, serotype, multilocus sequence typing (MLST) profiles, and classical and nonclassical virulence factors. NCCP15740 belonged to the O6:H16 serotype and possessed enterotoxin genes encoding heat-stable toxin (STh) and heat-labile toxin (LT); 87.5% of the O6 serotype strains possessed both toxin types. NCCP15740 carried the colonization factors CS2 and CS3, whereas most O6 strains carried CS2-CS3-CS21 (79.2%). NCCP15740 harbored fewer virulence factors (59.4%) than the average observed in other O6 strains (62.0%). Interestingly, NCCP15740 did not harbor any nonclassical virulence genes. CONCLUSIONS: The major type of ETEC in Korea had the same MLST sequence type as that of isolates from the USA obtained in 2011 and 2014, but had different colonization factor types and virulence profiles. These results provide important information for the development of an ETEC vaccine candidate.

Incidence of disseminated Mycobacterium avium-complex infection in HIV patients receiving antiretroviral therapy with use of Mycobacterium avium-complex prophylaxis.

The incidence of disseminated Mycobacterium avium complex (MAC) infection in HIV patients has fallen markedly since the introduction of effective antiretroviral therapy (ART). However, current guidelines still recommend primary prophylaxis. We conducted a retrospective cohort study in a university-affiliated hospital from January 1998 to January 2014. During that period, HIV patients who had at least one CD4 cell count below 50 cells/mm3 and had been treated with ART were enrolled. We compared incidence of disseminated MAC infection in the 12 months after the first CD4 cell count below 50 cells/mm3 between prophylaxis and nonprophylaxis groups. A total of 157 patients were enrolled and the total observation period was 144 patient-years (PY). Thirty-three patients (21%) received primary MAC prophylaxis. The initial CD4 cell count of the prophylaxis group was lower than that of the nonprophylaxis group ( P = 0.024), but the proportion of patients who reached a CD4 cell count >100 cells/mm3 ( P = 0.234) and were virologically suppressed ( P = 0.513) 12 months after ART commencement was not different in the prophylaxis and nonprophylaxis groups. The incidence of MAC did not differ significantly between the groups (3.4/100 PY versus 0.8/100 PY, P = 0.368). Routine MAC prophylaxis may be not required in the era of effective ART.

Stepwise intervention including 1-on-1 counseling is highly effective in increasing influenza vaccination among health care workers.

BACKGROUND: The influenza vaccination rate among health care workers (HCWs) remains suboptimal. We attempted to increase vaccine uptake in HCWs by nonmandatory measures, including 1-on-1 counseling. METHODS: In 2015 we used a stepwise approach including (1) text messaging on the last day of the vaccination period, (2) extending the vaccination period by 3 days, (3) education for the low uptake group, and (4) 1-on-1 counseling for unvaccinated HCWs after the 3 interventions. RESULTS: There were 1,433 HCWs included. By the end of the initial 3 days, the uptake rate was 80.0% (1,146/1,433). During an extension for a further 3 days, 33 additional HCWs received the vaccine. One month after starting the vaccination, 90.1% (1,291/1,433) of the HCWs were vaccinated, but this included only 76.1% (210/276) of the doctors (lowest among HCWs). After 3 educational presentations targeted at the unvaccinated doctors, no additional individuals were vaccinated in the following 2 weeks. After 1-on-1 counseling for unvaccinated HCWs, the overall vaccination rate increased to 94.7% (1,357/1,433) in 2015, higher than in the previous year (82.5%, P < .001). Of the unvaccinated doctors, 63.2% (43/68) were vaccinated, therefore achieving 92.4% (255/276) compliance, higher than the 56.5% in the previous year (152/269, P < .001). CONCLUSIONS: Stepwise intervention including 1-on-1 counseling is effective in increasing influenza vaccination rates among HCWs.