Trends, clinical characteristics, antimicrobial susceptibility patterns, and outcomes of Campylobacter bacteraemia: a multicentre retrospective study.

PURPOSE: We aimed to explore the clinical characteristics of Campylobacter bacteraemia and identify the trends, risk factors for mortality, and antimicrobial susceptibility patterns from clinical samples. METHODS: This retrospective cohort study included patients confirmed to have Campylobacter bacteraemia from seven hospitals between January 2010 and June 2021. Data on demographics and underlying history, clinical manifestation, and antimicrobial susceptibility patterns were collected and analyzed. Annual cases of Campylobacter enteritis were extracted from a public database. RESULTS: A total of 108 patients were included, and five species were isolated. Campylobacter jejuni accounted for 54 (50.0%) cases and 17 (16%) patients had no symptoms other than fever. In-hospital mortality occurred in 14 (13.0%) patients. C. jejuni bacteraemia was associated with lower mortality compared to non-C. jejuni bacteraemia. Underlying cancer and septic shock were the significant factors associated with in-hospital mortality. Quinolone resistance was high (59%), whereas only 4% of isolates exhibited macrolide resistance. There has been a significant increase in the number of Campylobacter enteritis cases, which was strongly correlated with the number of Campylobacter bacteraemia cases (Pearson's coefficient: 0.953; p < 0.0001). CONCLUSION: The notably increasing incidence of Campylobacter bacteraemia and antibiotic resistance patterns can challenge the treatment, necessitating collective efforts of national surveillance and networks by many departments.

Association between CYP2D6 phenotype and recurrence of Plasmodium vivax infection in south Korean patients.

BACKGROUND: Primaquine is activated by CYP2D6 in the hepatocytes. In Korea, primaquine is the only hypnozoitocidal agent used for patients with vivax malaria. Thus, patients with poor CYP2D6 activity could have an increased risk of primaquine failure and subsequent relapse. The study sought to identify the association between CYP2D6 phenotype and recurrence of malaria in Korean patients. METHODS: A total of 102 patients with vivax malaria were prospectively enrolled from eight institutions in Korea. An additional 38 blood samples from patients with recurred vivax malaria were provided by the Korea Disease Control and Prevention Agency. Malaria recurrence was defined as more than one episode of vivax malaria in the same or consecutive years. CYP2D6 star alleles, phenotypes, and activity scores were examined. RESULTS: Genotyping for CYP2D6 was successful in 101 of the prospectively enrolled patients and 38 samples from the Korea Disease Control and Prevention Agency, of which 91 were included in the no-recurrence group and 48 were included in the recurrence group. Reduced CYP2D6 activity (intermediate metabolizer) phenotype was more common in the recurrence group than in the no-recurrence group (OR, 2.33 (95% CI, 1.14-4.77); p = 0.02). Patients with lower CYP2D6 activity had a higher probability of recurrence (p = 0.029). CONCLUSION: This study suggests that CYP2D6 polymorphism may affect primaquine efficacy and thus Plasmodium vivax recurrence in Korea.

Four Times of Relapse of Plasmodium vivax Malaria Despite Primaquine Treatment in a Patient with Impaired Cytochrome P450 2D6 Function.

Plasmodium vivax exhibits dormant liver-stage parasites, called hypnozoites, which can cause relapse of malaria. The only drug currently used for eliminating hypnozoites is primaquine. The antimalarial properties of primaquine are dependent on the production of oxidized metabolites by the cytochrome P450 isoenzyme 2D6 (CYP2D6). Reduced primaquine metabolism may be related to P. vivax relapses. We describe a case of 4 episodes of recurrence of vivax malaria in a patient with decreased CYP2D6 function. The patient was 52-year-old male with body weight of 52 kg. He received total gastrectomy and splenectomy 7 months before the first episode and was under chemotherapy for the gastric cancer. The first episode occurred in March 2019 and each episode had intervals of 34, 41, and 97 days, respectively. At the first and second episodes, primaquine was administered as 15 mg for 14 days. The primaquine dose was increased with 30 mg for 14 days at the third and fourth episodes. Seven gene sequences of P. vivax were analyzed and revealed totally identical for all the 4 samples. The CYP2D6 genotype was analyzed and intermediate metabolizer phenotype with decreased function was identified.

Effects of early corticosteroid use in patients with severe coronavirus disease 2019.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with acute respiratory distress syndrome, and corticosteroids have been considered as possible therapeutic agents for this disease. However, there is limited literature on the appropriate timing of corticosteroid administration to obtain the best possible patient outcomes. METHODS: This was a retrospective cohort study including patients with severe COVID-19 who received corticosteroid treatment from March 2 to June 30, 2020 in seven tertiary hospitals in South Korea. We analyzed the patient demographics, characteristics, and clinical outcomes according to the timing of steroid use. Twenty-two patients with severe COVID-19 were enrolled, and they were all treated with corticosteroids. RESULTS: Of the 22 patients who received corticosteroids, 12 patients (55%) were treated within 10 days from diagnosis. There was no significant difference in the baseline characteristics. The initial PaO2/FiO2 ratio was 168.75. The overall case fatality rate was 25%. The mean time from diagnosis to steroid use was 4.08 days and the treatment duration was 14 days in the early use group, while those in the late use group were 12.80 days and 18.50 days, respectively. The PaO2/FiO2 ratio, C-reactive protein level, and cycle threshold value improved over time in both groups. In the early use group, the time from onset of symptoms to discharge (32.4 days vs. 60.0 days, P = 0.030), time from diagnosis to discharge (27.8 days vs. 57.4 days, P = 0.024), and hospital stay (26.0 days vs. 53.9 days, P = 0.033) were shortened. CONCLUSIONS: Among patients with severe COVID-19, early use of corticosteroids showed favorable clinical outcomes which were related to a reduction in the length of hospital stay.

Clinical and Virologic Effectiveness of Remdesivir Treatment for Severe Coronavirus Disease 2019 (COVID-19) in Korea: a Nationwide Multicenter Retrospective Cohort Study.

BACKGROUND: Remdesivir is widely used for the treatment of coronavirus disease 2019 (COVID-19), but controversies regarding its efficacy still remain. METHODS: A retrospective cohort study was conducted to evaluate the effect of remdesivir on clinical and virologic outcomes of severe COVID-19 patients from June to July 2020. Primary clinical endpoints included clinical recovery, additional mechanical ventilator (MV) support, and duration of oxygen or MV support. Viral load reduction by hospital day (HD) 15 was evaluated by calculating changes in cycle threshold (Ct) values. RESULTS: A total of 86 severe COVID-19 patients were evaluated including 48 remdesivir-treated patients. Baseline characteristics were not significantly different between the two groups. Remdesivir was administered an average of 7.42 days from symptom onset. The proportions of clinical recovery of the remdesivir and supportive care group at HD 14 (56.3% and 39.5%) and HD 28 (87.5% and 78.9%) were not statistically different. The proportion of patients requiring MV support by HD 28 was significantly lower in the remdesivir group than in the supportive care group (22.9% vs. 44.7%, P = 0.032), and MV duration was significantly shorter in the remdesivir group (average, 1.97 vs. 5.37 days; P = 0.017). Analysis of upper respiratory tract specimens demonstrated that increases of Ct value from HD 1-5 to 11-15 were significantly greater in the remdesivir group than the supportive care group (average, 10.19 vs. 5.36; P = 0.007), and the slope of the Ct value increase was also significantly steeper in the remdesivir group (average, 5.10 vs. 2.68; P = 0.007). CONCLUSION: The remdesivir group showed clinical and virologic benefit in terms of MV requirement and viral load reduction, supporting remdesivir treatment for severe COVID-19.

A Simple Scoring System Using the Red Blood Cell Distribution Width, Delta Neutrophil Index, and Platelet Count to Predict Mortality in Patients With Severe Sepsis and Septic Shock.

PURPOSE: The purpose of our study was to investigate whether a simple scoring system based on the red blood cell distribution width (RDW), delta neutrophil index (DNI), and platelet count was associated with the prognosis of patients with sepsis, and whether this scoring system was more useful than each individual parameter. MATERIALS AND METHODS: We conducted a retrospective cohort study involving adult patients who received intensive therapy due to severe sepsis and septic shock from January 2010 to December 2015 at a tertiary teaching hospital in South Korea. RESULTS: A total of 730 patients were included in this study. Each patient was rated on a scale of 0 to 3 according to the new scoring system using the platelet count, RDW, and DNI. Point values were assigned based on the following definitions: RDW > 14.5%, DNI > 5.0%, and platelet count < 150 000/mm3. The 28-day mortality rate was 12.6% (92/730). The nonsurvivors had higher scores than the survivors (2.05 ± 0.80 vs 1.06 ± 0.87, P < .001). In the multivariate Cox proportional hazard analysis, the scoring system was an independent predictor of the 28-day mortality. The scoring system was well calibrated (P = .81 for the goodness-of-fit test) and discriminated (area under the receiver operating characteristic curve = 0.785). CONCLUSION: Our new scoring system using the RDW, DNI, and platelet count was useful for predicting the mortality in patients with severe sepsis and septic shock.

Pregnancy Rates and Outcomes of HIV-Infected Women in Korea.

BACKGROUND: Antepartum, intrapartum, and postpartum preventive measures with antiretroviral drugs, appropriate delivery methods, and discouraging breastfeeding significantly decrease the risk of mother-to-child transmission of human immunodeficiency virus (HIV) infection. Herein, we investigated the pregnancy outcomes in HIV-infected Korean women. METHODS: We retrospectively reviewed medical records of childbearing-age HIV-infected women between January 2005 and June 2017 at four tertiary care hospitals in Korea. RESULTS: Among a total of 95 HIV infected women of child-bearing age with 587.61 years of follow-up duration, 15 HIV-infected women experienced 21 pregnancies and delivered 16 infants. The pregnancy rate was 3.57 per 100 patient-years. Among the 21 pregnancies, five ended with an induced abortion, and 16 with childbirth including two preterm deliveries at 24 and 35 weeks of gestation, respectively. The two preterm infants had low birth weight and one of them died 10 days after delivery due to respiratory failure. Among the 14 full-term infants, one infant was small for gestational age. There were no HIV-infected infants. CONCLUSION: The pregnancy rate of HIV-infected women in Korea is lower than that of the general population. Although several adverse pregnancy outcomes were observed, mother-to-child transmission of HIV infection was successfully prevented with effective preventive measures.

Pooled nucleic acid testing to identify antiretroviral treatment failure during HIV infection in Seoul, South Korea.

BACKGROUND: There have been various efforts to identify less costly but still accurate methods for monitoring the response to HIV treatment. We evaluated a pooling method to determine if this could improve screening efficiency and reduce costs while maintaining accuracy in Seoul, South Korea. METHODS: We conducted the first prospective study of pooled nucleic acid testing (NAT) using a 5 minipool + algorithm strategy versus individual viral load testing for patients receiving antiretroviral therapy (ART) between November 2011 and August 2012 at an urban hospital in Seoul, South Korea. The viral load assay used has a lower level of detection of 20 HIV RNA copies/ml, and the cost per assay is US$ 136. The 5 minipool +algorithm strategy was applied and 43 pooled samples were evaluated. The relative efficiency and accuracy of the pooled NAT were compared with those of individual testing. RESULTS: Using the individual viral load assay, 15 of 215 (7%) plasma samples had more than 200 HIV RNA copies/ml. The pooled NAT using the 5 minipool + algorithm strategy was applied to 43 pooled samples; 111 tests were needed to test all samples when virologic failure was defined at HIV RNA ≥ 200 copies/ml. Therefore, 104 tests were saved over individual testing, with a relative efficiency of 0.48. When evaluating costs, a total of US$ 14,144 was saved for 215 individual samples during 10 months. The negative predictive value was 99.5% for all samples with HIV RNA ≥ 200 copies/ml. CONCLUSIONS: The pooled NAT with 5 minipool + algorithm strategy seems to be a very promising approach to effectively monitor patients receiving ART and to save resources.

Risk factors and microbiological features of recurrent Escherichia coli bloodstream infections.

Understanding the risk factors and microbiological features in recurrent Escherichia coli BSI is helpful for clinicians. Data of patients with E. coil BSI from 2017 to 2018 were collected. Antimicrobial resistance rates of E. coli were determined. We also identified the ST131 and ESBL genotype to evaluate the molecular epidemiology of E. coli. Whole genome sequencing was conducted on the available ESBL-producing E. coli samples. Of 808 patients with E. coli BSI, 57 (6.31%) experienced recurrence; 29 developed at 4-30 days after initial BSI (early onset recurrence) and 28 at 31-270 days after initial BSI (late onset recurrence). One hundred forty-nine patients with single episode, whose samples were available for determining the molecular epidemiology, were selected for comparison. Vascular catheterization (adjusted odds ratio [aOR], 4.588; 95% confidence interval [CI], 1.049-20.068), ESBL phenotype (aOR, 2.037; 95% CI, 1.037-3.999) and SOFA score ≥9 (aOR, 3.210; 95% CI, 1.359-7.581) were independent risk factors for recurrence. The proportion of ST131 and ESBL genotype was highest in early onset recurrent BSI (41.4% and 41.4%, respectively), from which E. coil had the highest resistance rates to most antimicrobial agents. Whole genome sequencing on 27 of ESBL-producing E. coli (11 from single episode, 11 from early onset recurrence, and 5 from late onset recurrence) demonstrated that various virulence factors, resistant genes, and plasmid types existed in isolates from all types of BSI. Risk factors contributing to the recurrence and microbiological features of E. coli causing recurrent BSI may be helpful for management planning in the clinical setting.

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

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

A Case of African Tick-Bite Fever in a Returning Traveler from Southern Africa.

African tick-bite fever (ATBF), caused by Rickettsia africae, is the second most frequent cause of fever after malaria in travelers returning from Southern Africa. As the Korean outbound travelers are increasing every year, tick-borne rickettsial diseases as a cause of febrile illness are likely to increase. We describe a febrile Korean returning traveler who showed two eschars after visiting the rural field in Manzini, Swaziland. We performed nested polymerase chain reaction using the eschar and diagnosed the patient with ATBF. He was treated with oral doxycycline for 7 days, and recovered without any complications. We believe that the present case is the first ATBF case diagnosed in a Korean traveler.

Risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections: a nationwide population-based study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has rapidly turned into a public health emergency worldwide; however, the risk factors for infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been well-described. We aimed to identify the clinical risk factors for SARS-CoV-2 infections in Korea, where social distancing and face masks have been strongly recommended. METHODS: The data of individuals who underwent the reverse transcription polymerase chain reaction test for SARS-CoV-2 between January 3 and May 31, 2020 were retrieved from the Health Insurance Review and Assessment Service dataset. We used multivariable logistic regression models to identify the risk factors for SARS-CoV-2 infections in the population. RESULTS: We retrieved the results of 219,729 SARS-CoV-2 tests, of which 7,333 were positive results. In the multivariable analysis, female sex was associated with a higher risk of testing positive for SARS-CoV-2 [odds ratio (OR) =1.30, 95% confidence interval (CI): 1.24-1.37, P<0.0001]. Additionally, populations living in areas that had large outbreaks of COVID-19 were at an increased risk of testing positive for SARS-CoV-2 (OR =6.87, 95% CI: 6.55-7.21, P<0.0001). The odds of a positive test were greater for the Medical Aid beneficiaries (OR =1.99, 95% CI: 1.82-2.18, P<0.0001) than for the National Health Insurance beneficiaries. Individuals with diabetes mellitus (DM) were more likely to test positive (OR =1.15, 95% CI: 1.07-1.24, P=0.0002). CONCLUSIONS: Women, individuals living in areas with large outbreaks of COVID-19, Medical Aid beneficiaries, and individuals with DM might have greater risks of contracting SARS-CoV-2 infections despite practicing social distancing and using face masks.

Modelling the impact of rapid diagnostic tests on Plasmodium vivax malaria in South Korea: a cost-benefit analysis.

BACKGROUND: Rapid diagnostic tests (RDTs) are widely used for diagnosing Plasmodium vivax malaria, especially in resource-limited countries. However, the impact of RDTs on P. vivax malaria incidence and national medical costs has not been evaluated. We assessed the impact of RDT implementation on P. vivax malaria incidence and overall medical expenditures in South Korea and performed a cost-benefit analysis from the payer's perspective. METHODS: We developed a dynamic compartmental model for P. vivax malaria transmission in South Korea using delay differential equations. Long latency and seasonality were incorporated into the model, which was calibrated to civilian malaria incidences during 2014-2018. We then estimated averted malaria cases and total medical costs from two diagnostic scenarios: microscopy only and both microscopy and RDTs. Medical costs were extracted based on data from a hospital in an at-risk area for P. vivax malaria and were validated using Health Insurance Review and Assessment Service data. We conducted a cost-benefit analysis of RDTs using the incremental benefit:cost ratio (IBCR) considering only medical costs and performed a probabilistic sensitivity analysis to reflect the uncertainties of model parameters, costs and benefits. RESULTS: The results showed that 55.3% of new P. vivax malaria cases were averted, and $696 214 in medical costs was saved over 10 years after RDT introduction. The estimated IBCR was 2.5, indicating that RDT implementation was beneficial, compared with microscopy alone. The IBCR was sensitive to the diagnosis time reduction, infectious period and short latency period, and provided beneficial results in a benefit over $10.6 or RDT cost under $39.7. CONCLUSIONS: The model simulation suggested that RDTs could significantly reduce P. vivax malaria incidence and medical costs. Moreover, cost-benefit analysis demonstrated that the introduction of RDTs was beneficial over microscopy alone. These results support the need for widespread adoption of RDTs.

Longitudinal study of meningococcal carriage rates in university entrants living in a dormitory in South Korea.

University students, especially those living in dormitories, are known to have a high risk of invasive meningococcal disease. We performed a longitudinal study to investigate the change in Neisseria meningitidis carriage rates and identify the risk factors for carriage acquisition in university students in South Korea. We recruited university entrants who were admitted to a student dormitory. Pharyngeal swabs were taken from participants at baseline, 1 month, and 3 months, and the subjects completed a questionnaire. Culture and real-time polymerase chain reaction (PCR) for species-specific ctrA and sodC genes were performed. The cultured isolates or PCR-positive samples were further evaluated for epidemiologic characterization using serogrouping, PorA typing, FetA typing, and multilocus sequence typing (MLST). At the first visit, we enrolled 332 participants who were predominantly male (64.2%) with a median age of 19 years. Meningococcal carriage rates increased from 2.7% (95% confidence interval [CI] 0.9-4.4%) at baseline to 6.3% (95% CI 3.4-9.0%) at 1 month and 11.8% (95% CI 7.8-15.6%) at 3 months. Nongroupable isolates accounted for 50.0% of all isolates, with serogroup B being the next most prevalent (24.1%). In the study population, male sex (OR 2.613, 95% CI 1.145-5.961, p = 0.022) and frequent pub or club visits (OR 3.701, 95% CI 1.536-8.919, p = 0.004) were significantly associated with meningococcal carriage. Based on serotype and MLST analyses, six carriers transmitted meningococci to other study participants. N. meningitidis carriage rates among new university entrants who lived in a dormitory significantly increased within the first 3 months of dormitory stay, probably owing to the transmission of identical genotype among students. Based on the risk of meningococcal disease, meningococcal vaccination should be considered for students before dormitory admission.

Cost-effectiveness analysis of pre-exposure prophylaxis for the prevention of HIV in men who have sex with men in South Korea: a mathematical modelling study.

In February 2018, the Ministry of Food and Drug Safety in Korea approved tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) co-formulate for use in pre-exposure prophylaxis (PrEP) for the prevention of human immunodeficiency virus (HIV) infection. This study aimed to estimate the cost-effectiveness of PrEP in men who have sex with men (MSM), a major risk group emerging in Korea. A dynamic compartmental model was developed for HIV transmission and progression in MSM aged 15-64 years. With a combined model including economic analysis, we estimated averted HIV infections, changes in HIV prevalence, discounted costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). PrEP was evaluated in both the general MSM and high-risk MSM populations and was assumed to reduce infection risk by 80%. Implementing PrEP in all MSM would avert 75.2% HIV infections and facilitate a gain of 37,372 QALYs at a cost of $274,822 per QALY gained over 20 years relative to the status quo. Initiating PrEP in high-risk MSM with an average of eight partners per year (around 20% of MSM) would improve the cost-effectiveness, averting 78.0% HIV infections and add 29,242 QALYs at a cost of $51,597 per QALY gained, which is within the willingness-to-pay threshold for Korea of $56,000/QALY gained. This result was highly sensitive to annual PrEP costs, quality-of-life for people who are on PrEP, and initial HIV prevalence. Initiating PrEP in a larger proportion of MSM in Korea would prevent more HIV infections, but at an increasing cost per QALY gained. Focusing PrEP on higher risk MSM and any reduction in PrEP cost would improve cost-effectiveness.

Absence of neutralizing activity in serum 1 year after successful treatment with antivirals and recovery from MERS in South Korea.

We evaluated the neutralizing activity in serum from three patients >1 year after recovery from Middle East respiratory syndrome (MERS) associated with mild pneumonia treated with antivirals during the MERS outbreak in South Korea at 2015. The neutralizing activity in serum was measured by pseudovirus inhibition assays. Three-fold diluted serum of subjects showed only 9.7%, 10.3%, and 2.2% reductions in relative light units. So, significant neutralizing activity was not demonstrated in any sera of three patients with mild pneumonia >1 year after being successfully treated with antiviral agents and recovering from MERS coronavirus infection.

Integrase Strand Transfer Inhibitor Resistance Mutations in Antiretroviral Therapy-Naive and Treatment-Experienced HIV Patients in South Korea.

Updated guidelines for the treatment of antiretroviral therapy (ART)-negative patients with HIV recommend integrase strand transfer inhibitor (INSTI)-based regimens. HIV patients are tested for resistance to antiretrovirals, and the reported prevalence of transmitted INSTI resistance remains rare worldwide. However, no data related to INSTI resistance in Korean HIV patients have been reported. We aimed to determine the prevalence of INSTI resistance-related mutations in South Korea. We subjected both ART-naive (n = 58) and ART-experienced Korean HIV patients (n = 41) to genotypic resistance analysis and determined a prevalence of INSTI major resistance mutations of 3.4% (n = 2) among ART-naive patients and 22.0% (n = 9) among ART-experienced patients. In the former group, both major INSTI resistance cases involved the nonpolymorphic E92Q mutation in the integrase strand. Our findings suggest that INSTI resistance testing should be included in the standard resistance screening protocols for Korean HIV patients.

Changes in the utilization patterns of antifungal agents, medical cost and clinical outcomes of candidemia from the health-care benefit expansion to include newer antifungal agents.

OBJECTIVES: In 2014, South Korea expanded its national health insurance coverage to include newer antifungal agents, such as echinocandins. This study aimed to investigate the effects of policy change on the prescription patterns of antifungals, medical costs and clinical outcomes of candidemia. METHODS: This retrospective cohort enrolled hospitalized patients with candidemia at three tertiary care hospitals in South Korea from January 2012 to December 2015. The utilization of antifungal agents, medical costs, length of hospital stay (LOS), and mortality before and after the health-care benefit expansion were compared, and the factors associated with all-cause 28-day mortality during the study period were analyzed. RESULTS: A total of 769 candidemia cases were identified. The incidence of candidemia did not significantly vary during the study period (P = 0.253). The proportion of echinocandins, as the initial antifungal agent, and medical costs associated with candidemia significantly increased since the change in insurance coverage (P < 0.001). There was no significant difference in LOS and mortality associated with candidemia before and after the health-care benefit expansion (P = 0.696 and 0.931, respectively). Multivariate logistic regression analysis showed that initial treatment with caspofungin was associated with decreased mortality (adjusted odds ratio: 0.784; 95% confidence interval: 0.681-0.902; reference: fluconazole). CONCLUSIONS: Although the utilization of newer antifungal agents and medical cost for candidemia has significantly increased since the health-care benefit expansion, there has been no change in the outcome of candidemia. However, the further increased use of newer antifungals may improve the outcome of candidemia in this country.

An Outbreak of KPC-Producing Klebsiella pneumoniae Linked with an Index Case of Community-Acquired KPC-Producing Isolate: Epidemiological Investigation and Whole Genome Sequencing Analysis.

Aims: A hospital outbreak of Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (KPN) linked with an index case of community-acquired infection occurred in an urban tertiary care hospital in Seoul, South Korea. Therefore, we performed an outbreak investigation and whole genome sequencing (WGS) analysis to trace the outbreak and investigate the molecular characteristics of the isolates. Results: From October 2014 to January 2015, we identified a cluster of three patients in the neurosurgery ward with sputum cultures positive for carbapenem-resistant KPN. An epidemiological investigation, including pulsed-field gel electrophoresis analysis was performed to trace the origins of this outbreak. The index patient's infection was community acquired. Active surveillance cultures using perirectal swabbing from exposed patients, identified one additional patient with KPC-producing KPN colonization. WGS analyses using PacBio RSII instruments were performed for four linked isolates. WGS revealed a genetic linkage of the four isolates belonging to the same sequence type (ST307). All KPN isolates harbored conjugative resistance plasmids, which has blaKPC-2 carbapenemase genes contained within the Tn4401 "a" isoform and other resistance genes. However, WGS showed only three isolates among four KPC-producing KPN were originated from a common origin. Conclusions: This report demonstrates the challenge that KPC-2-producing KPN with the conjugative resistance plasmid may spread not only in hospitals but also in community, and WGS can help to accurately characterize the outbreak.

In vivo efficacy of combination of colistin with fosfomycin or minocycline in a mouse model of multidrug-resistant Acinetobacter baumannii pneumonia.

Unfortunately, the options for treating multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) infections are extremely limited. Recently, fosfomycin and minocycline were newly introduced as a treatment option for MDR A. baumannii infection. Therefore, we investigated the efficacy of the combination of colistin with fosfomycin and minocycline, respectively, as therapeutic options in MDR A. baumannii pneumonia. We examined a carbapenem-resistant A. baumannii isolated from clinical specimens at Severance Hospital, Seoul, Korea. The effect of colistin with fosfomycin, and colistin with minocycline on the bacterial counts in lung tissue was investigated in a mouse model of pneumonia caused by MDR A. baumannii. In vivo, colistin with fosfomycin or minocycline significantly (p < 0.05) reduced the bacterial load in the lungs compared with the controls at 24 and 48 h. In the combination groups, the bacterial loads differed significantly (p < 0.05) from that with the more active antimicrobial alone. Moreover, the combination regimens of colistin with fosfomycin and colistin with minocycline showed bactericidal and synergistic effects compared with the more active antimicrobial alone at 24 and 48 h. This study demonstrated the synergistic effects of combination regimens of colistin with fosfomycin and minocycline, respectively, as therapeutic options in pneumonia caused by MDR A. baumannii.