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Background Regdanvimab is the only monoclonal antibody available in Korea that targets the receptor-binding domain of SARS-CoV-2. Although the efficacy of regdanvimab against the original and beta variant viruses was demonstrated, it remains uncertain whether it has therapeutic effect on delta variant in the real world. Methods We retrospectively evaluated the characteristics and clinical outcome of patients hospitalized for COVID-19 and treated with regdanvimab in two university-affiliated hospitals between September and December 2021, during the delta variant-predominant period in Korea. Results A total of 374 mild to moderate COVID-19 patients treated with regdanvimab were included in this study. The median age was 65 (interquartile range, IQR 17-92) and 178 (47.6%) patients were male. A total of 322 (86.1%) patients had median 2 (IQR 1-3) risk factors for disease progression. The most common underlying disease was cardiovascular disease (198, 52.9%), followed by diabetes mellitus (95, 25.4%), cancer (40, 10.7%), chronic lung disease (34, 9.1%), immunosuppression (1 7, 4.5%), and chronic kidney disease (12, 3.2%). There were 43 (11.5%) patients with a body mass index ≥ 30. The median time to regdanvimab treatment from symptom onset was 4 (IQR 2-6) days. 226 (60.4%) patients were fully vaccinated, and 109 (29.1%) were not vaccinated at all. 185 (49.5%) patients had pneumonia. Most (342/374, 91.4%) patients improved without any other treatment for COVID-19 and were discharged. Only 32 (8.6%) patients required other therapeutic agents such as remdesivir, corticosteroids or oxygen therapy after regdanvimab administration. The time from regdanvimab infusion to addition of other therapeutic agents was median 5 days (IQR 3-6.5). When comparing the characteristics of 32 patients who needed other treatment with those who improved only with regdanvimab treatment, there was a significant difference in the presence of pneumonia (27/32, 84.4% vs. 158/342, 46.2%, P< 0.001) and there was no significant difference in vaccination status (15/32, 46.9% vs. 211/342 61.7% P=0.101). Conclusion This study shows the potential clinical benefits of regdanvimab in mild to moderate COVID-19 patients in the real world during the delta variant predominant period in Korea. Disclosures All Authors: No reported disclosures.

Data on the longevity of humoral and cell-mediated immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with coronavirus disease 2019 (COVID-19) are limited. We evaluated the detailed kinetics of antibody and T-cell responses at the acute, convalescent, and post-convalescent phases in COVID-19 patients with a wide range of severity. We enrolled patients with COVID-19 prospectively from four hospitals and one community treatment center between February 2020 and January 2021. symptom severity was classified as mild, moderate, or severe/critical. Patient blood samples were collected at 1 week (acute), 1 month (convalescent), and 2 months after symptom onset (post-convalescent). Human SARS-CoV-2 IgG and IgM antibodies were measured using in-house-developed ELISA. The SARS-CoV-2-specific T-cell responses against overlapping peptides of spike proteins and nucleoprotein were measured by interferon-γ enzyme-linked immunospot assays. Twenty-five COVID-19 patients were analyzed (mild, n = 5; moderate, n = 9; severe/critical, n = 11). IgM and IgG antibody responses peaked at 1 month after symptom onset and decreased at 2 months. IgG response levels were significantly greater in the severe/critical group compared with other groups. Interferon-γ-producing T-cell responses increased between 1 week and 1 month after symptom onset, and had a trend toward decreasing at 2 months, but did not show significant differences according to severity. Our data indicate that SARS-CoV-2-specific antibody responses were greater in those with severe symptoms and waned after reaching a peak around 1 month after symptom onset. However, SARS-CoV-2-specific T-cell responses were not significantly different according to symptom severity, and decreased slowly during the post-convalescent phase.

Regdanvimab is the only monoclonal antibody available in Korea that targets severe acute respiratory syndrome coronavirus 2. We retrospectively evaluated the clinical characteristics of 374 adults hospitalized with coronavirus disease 2019 (COVID-19) who were treated with regdanvimab from September through December 2021. In total, 322 (86.1%) patients exhibited risk factors for disease progression. Most patients (91.4%) improved without additional treatment. No patient died or was transferred to intensive care. This study shows that regdanvimab prevented disease progression in high-risk patients with mild to moderate COVID-19 infections during Delta variant predominance.

The severity of COVID-19 ranges from mild to critical diseases. However, limited data have been published on the detailed kinetics of viral load and host immune response throughout the disease course depending on disease severity. In this study, we comprehensively analyzed viral load, antibody responses to SARS-CoV-2, and cytokines/chemokines during the disease course, and identified the factors related to severity. Nasopharyngeal (NP) and plasma specimens were obtained from 31 patients with COVID-19 during hospitalization. Viral RNA in NP specimens was quantified by reverse transcription–PCR. Anti–SARS-CoV-2 antibodies and cytokines/chemokines in plasma specimens were analyzed by ELISA and cytometric bead array. The viral load in patients with COVID-19 peaked at the early stage of the disease and continuously decreased. Severe and critical cases showed higher viral load and prolonged viral shedding than asymptomatic and mild cases. Whereas plasma IgG was gradually increased and maintained during hospitalization, plasma IgM peaked at 3 weeks after symptom onset and dissipated. The antibody response in severe and critical cases was slightly delayed but stronger than those in others. High levels of interferon (IFN)-α, IFN-γ–induced protein-10, monokine induced by IFN-γ, and interleukin-6 at 5–10 days from symptom onset were associated with the severity of COVID-19. Our data indicate that high viral load in the respiratory tract and excessive production of cytokines and chemokines between 1 and 2 weeks from the symptom onset were significantly associated with the severity of COVID-19.

As another wave of COVID-19 outbreak has approached in July 2020, a larger scale COVID-19 pediatric Asian cohort summarizing the clinical observations is warranted. Children confirmed with COVID-19 infection from the Republic of Korea, the Hong Kong Special Administrative Region (HKSAR) and Wuhan, China, during their first waves of local outbreaks were included. Their clinical characteristics and the temporal sequences of the first waves of local paediatric outbreaks were compared. Four hundred and twenty three children with COVID-19 were analyzed. Wuhan had the earliest peak, followed by Korea and HKSAR. Compared with Korea and Wuhan, patients in HKSAR were significantly older (mean age: 12.9 vs. 10.8 vs. 6.6 years, p

Background CT manifestations of SARS-CoV-2 may differ among variants. Purpose To compare the chest CT findings of SARS-CoV-2 between the Delta and Omicron variants. Materials and Methods This retrospective study collected consecutive baseline chest CT images of hospitalized patients with SARS-CoV-2 from a secondary referral hospital when the Delta and Omicron variants were predominant. Two radiologists categorized CT images according to the RSNA classification system for COVID-19 and visually graded pneumonia extent. Pneumonia, pleural effusion, and intrapulmonary vessels were segmented and quantified on CT images using a priori-developed neural networks, followed by reader confirmation. Multivariable logistic and linear regression analyses were performed to examine the associations between the variants and CT category, distribution, severity, and peripheral vascularity. Results In total, 88 patients with the Delta variant (mean age, 67 years ± 15 [SD]; 46 men) and 88 patients with the Omicron variant (mean age, 62 years ± 19; 51 men) were included. Omicron was associated with less frequent, typical peripheral bilateral ground-glass opacity (32% [28 of 88] vs 57% [50 of 88]

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

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., Graphical Abstract

Importance There is limited information describing the full spectrum of coronavirus disease 2019 (COVID-19) and the duration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA detection in children. Objective To analyze the full clinical course and the duration of SARS-CoV-2 RNA detectability in children confirmed with COVID-19 in the Republic of Korea, where rigorous public health interventions have been implemented. Design, Setting, and Participants This case series of children with COVID-19 was conducted in 20 hospitals and 2 nonhospital isolation facilities across the country from February 18, 2020, to March 31, 2020. Children younger than 19 years who had COVID-19 were included. Exposures Confirmed COVID-19, detected via SARS-CoV-2 RNA in a combined nasopharyngeal and oropharyngeal swab or sputum by real-time reverse transcription–polymerase chain reaction. Main Outcomes and Measures Clinical manifestations during the observation period, including the time and duration of symptom occurrence. The duration of SARS-CoV-2 RNA detection was also analyzed. Results A total of 91 children with COVID-19 were included (median [range] age, 11 [0-18] years; 53 boys [58%]). Twenty children (22%) were asymptomatic during the entire observation period. Among 71 symptomatic cases, 47 children (66%) had unrecognized symptoms before diagnosis, 18 (25%) developed symptoms after diagnosis, and only 6 (9%) were diagnosed at the time of symptom onset. Twenty-two children (24%) had lower respiratory tract infections. The mean (SD) duration of the presence of SARS-CoV-2 RNA in upper respiratory samples was 17.6 (6.7) days. Virus RNA was detected for a mean (SD) of 14.1 (7.7) days in asymptomatic individuals. There was no difference in the duration of virus RNA detection between children with upper respiratory tract infections and lower respiratory tract infections (mean [SD], 18.7 [5.8] days vs 19.9 [5.6] days;P = .54). Fourteen children (15%) were treated with lopinavir-ritonavir and/or hydroxychloroquine. All recovered, without any fatal cases. Conclusions and Relevance In this case series study, inapparent infections in children may have been associated with silent COVID-19 transmission in the community. Heightened surveillance using laboratory screening will allow detection in children with unrecognized SARS-CoV-2 infection.

Background There is limited information describing the presenting characteristics and dynamic clinical changes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection diagnosed in the early phase of illness. This study is a case series of patients with coronavirus disease 2019 (COVID-19) admitted to 11 hospitals in Korea. Methods Patients with confirmed SARS-CoV-2 infection by positive polymerase chain reaction (PCR) testing of respiratory specimens by active surveillance that were finally discharged between February 20 and April 30, 2020 were included. Patients were classified into mild and non-mild groups on initial admission according to oxygen demand and Sequential Organ Failure Assessment score, and the mild group was followed up and subgrouped into non-aggravation and aggravation groups. Results A total of 161 patients with SARS-CoV2 infection were enrolled. Among the mild group of 136 patients, 11.7% of patients experienced clinical aggravation during hospitalization, but there was no initial clinical parameter on admission predicting their aggravation. Fever (odds ratio [OR], 4.56), thrombocytopenia (OR, 12.87), fever (OR, 27.22) and lactate dehydrogenase (LDH) > 300 U/L (OR, 18.35), and CRP > 1 mg/dL (OR, 11.31) significantly indicated aggravation in the 1st, 2nd, 3rd, and 4th 5-day periods, respectively. PCR positivity lasted for a median of 22 days and 32 days after the onset of illness in the non-aggravation and aggravation groups, respectively. Conclusion Old age was associated with early severe presentation. Clinical aggravation among asymptomatic or mild patients could not be predicted initially but was heralded by fever and several laboratory markers during the clinical course., Graphical Abstract

We evaluated the clinical characteristics, cytokine/chemokine concentrations, viral shedding and antibody kinetics in 30 patients with Middle East respiratory syndrome (MERS), including 6 non-survivors admitted to 3 MERS-designated hospitals. Old age, low albumin, altered mentality and high pneumonia severity index score at admission were risk factors for mortality. In addition, severe signs of inflammation at initial presentation (at hospital days 1-4), such as high inducible protein-10 (p=0.0013), monocyte chemoattractant protein-1 (p=0.0007) and interleukin 6 (p=0.0007) concentrations, and poor viral control (high viral load at hospital days 5–10, p

Background Vertebral osteomyelitis (VO) is a rare but serious condition, and a potentially significant cause of morbidity. Methicillin-susceptible Staphylococcus aureus (MSSA) is the most common microorganism in native VO. Long-term administration of parenteral and oral antibiotics with good bioavailability and bone penetration is required for therapy. Use of oral β-lactams against staphylococcal bone and joint infections in adults is not generally recommended, but some experts recommend oral switching with β-lactams. This study aimed to describe the current status of antibiotic therapy and treatment outcomes of oral switching with β-lactams in patients with MSSA VO, and to assess risk factors for treatment failure. Materials and Methods This retrospective study included adult patients with MSSA VO treated at nine university hospitals in Korea between 2005 and 2014. Treatment failure was defined as infection-related death, microbiological relapse, neurologic deficits, or unplanned surgical procedures. Clinical characteristics and antibiotic therapy in the treatment success and treatment failure groups were compared. Risk factors for treatment failure were identified using the Cox proportional hazards model. Results A total of 100 patients with MSSA VO were included. All patients were treated, initially or during antibiotic therapy, with one or more parenteral antibiotics. Sixty-nine patients received one or more oral antibiotics. Antibiotic regimens were diverse and durations of parenteral and oral therapy differed, depending on the patient and the hospital. Forty-two patients were treated with parenteral and/or oral β-lactams for a total duration of more than 2 weeks. Compared with patients receiving parenteral β-lactams only, no significant difference in success rates was observed in patients who received oral β-lactams for a relatively long period. Sixteen patients had treatment failure. Old age (adjusted hazard ratio [HR] 5.600, 95% confidence interval [CI] 1.402 – 22.372, P = 0.015) and failure to improve C-reactive protein levels at follow-up (adjusted HR 3.388, 95% CI 1.168 – 9.829, P = 0.025) were independent risk factors for treatment failure. Conclusion In the study hospitals, diverse combinations of antibiotics and differing durations of parenteral and oral therapy were used. Based on the findings of this study, we think that switching to oral β-lactams may be safe in certain adult patients with MSSA VO. Since limited data are available on the efficacy of oral antibiotics for treatment of staphylococcal VO in adults, further evaluation of the role of oral switch therapy with β-lactams is needed.

Background Scrub typhus, severe fever with thrombocytopenia syndrome (SFTS) and human granulocytic anaplasmosis (HGA) are important arthropod-borne infectious diseases in Korea and share a common point that they are transmitted by arthropod bites mostly during outdoor activities and there are considerable overlaps of epidemiologic and clinical features at presentation. We investigated the co-infection of these infections. Methods The study subjects were patients with laboratory-confirmed scrub typhus who were enrolled retrospectively in 2006. SFTS virus (SFTSV) infection was confirmed by a reverse transcriptase polymerase chain reaction (PCR) to amplify partial L segment of SFTSV for molecular diagnosis. HGA was confirmed by a nested PCR to amplify 16S rRNA gene of Anaplasma phagocytophilum. Direct sequencing of the positive PCR products was performed. Clinical features of co-infected subjects were described. Results One-hundred sixty-seven patients with scrub typhus were included in the analysis. Co-infection of A. phagocytophilum was identified in 4.2% of scrub typhus patients (7/167). The route of co-infection was uncertain. The co-infected patients had not different clinical manifestations compared to the patients with scrub typhus only. All the study subjects were negative for SFTSV. Conclusion We found retrospective molecular evidence of the co-infection of scrub typhus and HGA in Korea. HGA may be more prevalent than expected and need to be considered as an important differential diagnosis of febrile patients in Korea., Graphical Abstract

Given the mode of transmission of Middle East respiratory syndrome (MERS), healthcare workers (HCWs) in contact with MERS patients are expected to be at risk of MERS infections. We evaluated the prevalence of MERS coronavirus (CoV) immunoglobulin (Ig) G in HCWs exposed to MERS patients and calculated the incidence of MERS-affected cases in HCWs. We enrolled HCWs from hospitals where confirmed MERS patients had visited. Serum was collected 4 to 6 weeks after the last contact with a confirmed MERS patient. We performed an enzyme-linked immunosorbent assay (ELISA) to screen for the presence of MERS-CoV IgG and an indirect immunofluorescence test (IIFT) to confirm MERS-CoV IgG. We used a questionnaire to collect information regarding the exposure. We calculated the incidence of MERS-affected cases by dividing the sum of PCR-confirmed and serology-confirmed cases by the number of exposed HCWs in participating hospitals. In total, 1169 HCWs in 31 hospitals had contact with 114 MERS patients, and among the HCWs, 15 were PCR-confirmed MERS cases in study hospitals. Serologic analysis was performed for 737 participants. ELISA was positive in five participants and borderline for seven. IIFT was positive for two (0.3%) of these 12 participants. Among the participants who did not use appropriate personal protective equipment (PPE), seropositivity was 0.7% (2/294) compared to 0% (0/443) in cases with appropriate PPE use. The incidence of MERS infection in HCWs was 1.5% (17/1169). The seroprevalence of MERS-CoV IgG among HCWs was higher among participants who did not use appropriate PPE.

We performed a point seroprevalence survey of measles among healthcare workers (HCWs) at two Korean teaching hospitals in 2019. A total of 2,830 HCWs underwent an antibody test. The overall seropositivity of measles was 93.1%. The seroprevalence of measles was lowest in HCWs aged 20 - 24 years (81.2%), followed by those aged 25 - 29 years (90.1%). The rates of anti-measles IgG positivity were significantly different between the two hospitals (97.0% vs. 89.4%, P

Objectives To identify characteristics associated with particular groups of uropathogens in catheter-associated urinary tract infection (CA–UTI) and to develop clinical prediction rules for identifying these groups. Methods Demographic, clinical and microbiological data were analysed from patients with CA–UTI. Infections were categorized into enteric Gram-negative rods, nonfermenters, Gram-positive cocci and fungal. Variables were analysed using univariate and multiple logistic regression analyses, and were used to develop clinical prediction rules. Results A total of 492 patients were included in the study. Candida species were the most common uropathogens (30.7%), followed by enterococci (17.3%), Escherichia coli (12.0%), Pseudomonas spp. (10.8%), Klebsiella spp. (7.9%) and staphylococci (6.5%). Clinical prediction rules for the bacterial uropathogenic groups showed poor-to-fair discriminatory power, with sensitivities of 90%. However, clinical prediction rules showed good discriminatory power for fungal infections, with a sensitivity of 67.3% and a specificity of 78.1%. Conclusions Clinical prediction rules developed for identifying specific groups of bacterial uropathogens in patients with CA–UTI had a low sensitivity, whereas those for fungal infections showed good discriminatory power. Further studies to develop more refined and sensitive tools for predicting specific bacterial uropathogens in CA–UTI are warranted.

Summary Background High rates of antimicrobial resistance in Escherichia coli isolated from patients with urinary tract infections have been reported worldwide. The aim of this study was to identify risk factors for resistance to ciprofloxacin (CIP) and cefotaxime (CTX) in E. coli isolated from patients with acute pyelonephritis (APN). Methods We prospectively identified women over 18 y of age who visited the emergency department of one of 10 hospitals with APN and whose urine culture grew E. coli . The study was conducted from April 16 to June 10, 2012. Results Of the 229 patients identified, 173 (75.5%) had community-associated (CA) infections and 56 (24.5%) had healthcare-associated (HCA) infections. Sixty-seven isolates (29.3%) were resistant to CIP, 45 (19.7%) to CTX, and 29 (12.7%) to both CIP and CTX. Multivariate analyses revealed that hematologic disease, chronic kidney disease, a bed-ridden state, indwelling urinary catheter, antibiotic treatment in the preceding 3 months, and isolation of CIP-resistant E. coli in the urine within the preceding 3 months, were significantly associated with resistance to both CIP and CTX. Conclusions Chronic conditions and healthcare-associated factors were related to resistance to both fluoroquinolones and third-generation cephalosporins in women with APN. Continued and vigilant surveillance is necessary to monitor the dissemination of antimicrobial resistance in uropathogens.

Background Vertebral osteomyelitis (VO) is a rare but serious condition, and a potentially significant cause of morbidity. Methicillin-susceptible Staphylococcus aureus (MSSA) is the most common microorganism in native VO. Long-term administration of parenteral and oral antibiotics with good bioavailability and bone penetration is required for therapy. Use of oral β-lactams against staphylococcal bone and joint infections in adults is not generally recommended, but some experts recommend oral switching with β-lactams. This study aimed to describe the current status of antibiotic therapy and treatment outcomes of oral switching with β-lactams in patients with MSSA VO, and to assess risk factors for treatment failure. Materials and methods This retrospective study included adult patients with MSSA VO treated at nine university hospitals in Korea between 2005 and 2014. Treatment failure was defined as infection-related death, microbiological relapse, neurologic deficits, or unplanned surgical procedures. Clinical characteristics and antibiotic therapy in the treatment success and treatment failure groups were compared. Risk factors for treatment failure were identified using the Cox proportional hazards model. Results A total of 100 patients with MSSA VO were included. All patients were treated, initially or during antibiotic therapy, with one or more parenteral antibiotics. Sixty-nine patients received one or more oral antibiotics. Antibiotic regimens were diverse and durations of parenteral and oral therapy differed, depending on the patient and the hospital. Forty-two patients were treated with parenteral and/or oral β-lactams for a total duration of more than 2 weeks. Compared with patients receiving parenteral β-lactams only, no significant difference in success rates was observed in patients who received oral β-lactams for a relatively long period. Sixteen patients had treatment failure. Old age (adjusted hazard ratio [HR] 5.600, 95% confidence interval [CI] 1.402 - 22.372, P = 0.015) and failure to improve C-reactive protein levels at follow-up (adjusted HR 3.388, 95% CI 1.168 - 9.829, P = 0.025) were independent risk factors for treatment failure. Conclusion In the study hospitals, diverse combinations of antibiotics and differing durations of parenteral and oral therapy were used. Based on the findings of this study, we think that switching to oral β-lactams may be safe in certain adult patients with MSSA VO. Since limited data are available on the efficacy of oral antibiotics for treatment of staphylococcal VO in adults, further evaluation of the role of oral switch therapy with β-lactams is needed.

Bone and joint infections, especially implant-associated infections, are difficult to cure. Long-term antibiotic therapy, combined with appropriate surgery and the removal of prostheses, is required. The most common causative organisms in bone and joint infections are staphylococci. Oral agents are often used after an initial course of parenteral antibiotic treatment. However, it is unclear which oral regimens are most effective in staphylococcal bone and joint infections. We review various oral antibiotic regimens and discuss which regimens are effective for this indication.

Acinetobacter baumannii is an important cause of postneurosurgical meningitis. The emergence of carbapenem-resistant strains in this setting has caused a therapeutic challenge. We investigated the clinical implications of postneurosurgical meningitis caused by carbapenem-resistant A. baumannii. In this study, we retrospectively reviewed the medical records of patients more than 16 years of age with A. baumannii meningitis that developed after a neurosurgical procedure at five university-affiliated hospitals between January 2005 and May 2011. Of 40 cases identified, 22 (55.0 %) were caused by carbapenem-resistant strains. Of those evaluable 36 patients with A. baumannii meningitis, 14 (38.9 %) died of meningitis. Meningitis-related mortality was significantly related to carbapenem resistance (59.1 % versus 7.1 %; P = 0.002). In patients with meningitis caused by carbapenem-resistant A. baumannii, colistimethate-containing regimens (4/13 versus 7/9; P = 0.040), intrathecal or intraventricular (IT/IVR) administration of antibiotics (2/13 versus 8/9; P = 0.001), and combined intravenous and IT/IVR therapy (2/13 versus 6/9; P = 0.026) were significantly associated with cure. This study shows that use of colistimethate and combined systemic and local administration of antibiotics should be considered for the treatment of meningitis caused by carbapenem-resistant A. baumannii.

Background Acute pyelonephritis (APN) is one of the most common bacterial infections. Because health care–associated (HCA) infections in the community setting have similar characteristics to hospital-acquired infections, HCA infections should be distinguished from community-acquired (CA) infections. However, the impact of HCA-APN on treatment outcomes has not been clearly defined. This study aimed to analyze the impact of HCA-APN on the appropriateness of empiric antibiotic therapy and outcomes in community-onset APN. Methods We prospectively identified women older than 18years who were hospitalized with APN via the emergency department and whose urine culture grew bacteria at 10 acute care hospitals in South Korea. Results Of the 388 APN episodes that were included, 99 (25.5%) were HCA-APN and 289 (74.5%) were CA-APN. Compared with patients with CA-APN, patients with HCA-APN had comorbid conditions and septic shock more frequently. Health care–associated APN was caused by resistant uropathogens more often. Patients with HCA-APN had poorer outcomes (ie, early/final clinical and microbiologic failures); however, this was not statistically significant. Patients with HCA-APN had significantly longer hospital stays than did patients with CA-APN. In the multivariable logistic regression analysis for inappropriate empiric therapy, HCA-APN (odds ratio, 1.96; 95% confidence interval, 1.07-3.57; P =.03) and being bed-ridden (odds ratio, 3.04; 95% confidence interval, 1.31-7.07; P =.01) were significant. Conclusions Health care–associated APN was associated with inappropriate empiric antibiotic therapy, which might lead to worse outcomes. These HCA factors should be considered when prescribing empiric antibiotic therapy in patients with community-onset APN.

Spinal implant infection is a rare but significant complication of spinal fusion surgery, and the most common pathogen is Staphylococcus aureus. It is difficult to treat due to this pathogen's biofilm-forming ability and antibiotic resistance. We evaluated the therapeutic outcome of treatments for S aureus spinal implant infections. We retrospectively reviewed all patients with S aureus spinal implant infections at 11 tertiary-care hospitals over a 9-year period. Parameters predictive of treatment failure and recurrence were analyzed by Cox regression. Of the 102 patients with infections, 76 (75%) were caused by methicillin-resistant S aureus (MRSA) and 51 (50%) were late-onset infections. In all, 83 (81%) patients were managed by debridement, antibiotics, and implant retention (DAIR) and 19 (19%) had their implants removed. The median duration of all antibiotic therapies was 52 days. During a median follow-up period of 32 months, treatment failure occurred in 37 (36%) cases. The median time to treatment failure was 113 days, being

This study was performed to determine the nationwide antigenic diversity of Orientia tsutsugamushi in South Korea. Sequence analysis was performed around variable domains I and II of a 56-kDa protein-encoding gene. We used eschar to overcome the disadvantages of conventional serotyping. The serological passive hemagglutination assay (PHA) was assessed based on the genotyping results. We analyzed 153 isolates from scrub typhus patients in major endemic areas and found that Boryong was the major strain (68.6%). New strains were also identified: Taguchi (19.6%), Kanda/Kawasaki (9.2%), and UAP7 (1.3%). PHA yielded significantly fewer positive results among Kawasaki strains (P < 0.001), which are not included in the PHA antigen panel. In South Korea, Boryong was still the predominant strain, but the sequence analysis identified new changes in minor strains (30.1%). This antigenic drift had a negative effect on the PHA results. Periodic surveillance of the contemporary strains using sequence analysis is needed.

Urinary tract infections (UTIs) are infectious diseases that commonly occur in communities. Although several international guidelines for the management of UTIs have been available, clinical characteristics, etiology and antimicrobial susceptibility patterns may differ from country to country. This work represents an update of the 2011 Korean guideline for UTIs. The current guideline was developed by the update and adaptation method. This clinical practice guideline provides recommendations for the diagnosis and management of UTIs, including asymptomatic bacteriuria, acute uncomplicated cystitis, acute uncomplicated pyelonephritis, complicated pyelonephritis related to urinary tract obstruction, and acute bacterial prostatitis. This guideline targets community-acquired UTIs occurring among adult patients. Healthcare-associated UTIs, catheter-associated UTIs, and infections in immunocompromised patients were not included in this guideline.

There have been reports in Korea of imported malaria cases of four Plasmodium species, but there has been no report of imported Plasmodium ovale malaria confirmed by molecular biological methods. We report an imported case of that was confirmed by Wright-Giemsa-stained peripheral blood smear and nested polymerase chain reaction targeting the small subunit ribosomal RNA gene. The amplified DNA was sequenced and compared with other registered P. ovale isolates. The isolate in this study was a member of the classic type group. The patient was a 44-yr-old male who had worked as a woodcutter in Cote d'Ivoire in tropical West Africa. He was treated with hydroxychloroquine and primaquine and discharged following improvement. In conclusion, P. ovale should be considered as an etiology in the imported malaria in Korea, because the number of travelers to P. ovale endemic regions has recently increased.

Hantaviruses cause two forms of human disease: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome. Hantavirus infection can occur in pregnant women and it can have an influence on the maternal and fetal outcomes, although this is a rare finding even in endemic areas. We describe here a recent case of HFRS complicating pregnancy.

We report a case of cat scratch disease caused by Bartonella henselae in Korea. A 25-yr-old woman developed left cervical lymphadenopathy with history of contact with a dog. The cervical lymphadenopathy persisted for 1 month and resolved gradually and spontaneously. Serologic test was not done during the acute stage of the disease. Immunofluorescent antibody test performed during the convalescent stage was positive for B. henselae. To confirm B. henselae infection, polymerase chain reaction (PCR) analysis using aspirates of cervical lymph node was performed and the presence of B. henselae DNA was demonstrated. This is the first reported case of cat scratch disease in Korea confirmed by PCR for B. henselae DNA .

This study was conducted to evaluate the appropriateness of the use of targeted antibiotics, and to analyze compliance and the short-term impact of targeted antibiotic advisory consultations, as implemented in our hospital in October 2002. Targeted antibiotics included glycopeptides, carbapenems, antipseudomonal cephalosporins, and aminoglycosides. A total of 339 prescriptions were reviewed from October 2002 through March 2003. Antimicrobial utilization density (AUD), which was the defined daily dose divided by 1000 patient days, was compared quarterly. Overall, 85.6% of the prescriptions were inappropriate, with 73.7% being inappropriate for therapeutic use and 100% inappropriate for prophylactic use. The overall compliance rate of attending physicians with the antibiotic advisory consultations was 46.5%. Compliance was higher in medical services than in surgical services (64.2% vs 43.1%; P = 0.005) and for therapeutic use than for prophylactic use (54.7% vs 36.5%; P = 0.001). The use of all parenteral antibiotics in the hospital decreased, from 770.8 AUD during the first quarter in 2002 to 626.8 AUD during the second quarter in 2003 (P < 0.01). In conclusion, inappropriate antibiotic use for treatment and prophylaxis is common in our hospital. A targeted antibiotic advisory consultation may be an alternative means of ensuring more appropriate antibiotic use. However, more efficient antibiotic control measures should be developed and implemented, and prospective and continuous monitoring of antibiotic use is required.

Two hundred and forty-nine patients with monomicrobial bacteraemia due to third-generation cephalosporin (TGC)-resistant Citrobacter freundii (42), E. aerogenes (23), E. cloacae (143), and Serratia marcescens (41) were analyzed for antibiotic therapy used and outcome. For isolates with resistance to any of the TGCs, all beta-lactams, except imipenem, were considered ineffective. Of 152 patients given appropriate treatment, the mortality rates were 10.9% for 128 patients given monotherapy and 25.0% for 24 patients given combination therapy (P=0.09). Of patients given monotherapy, there were no significant differences in mortality between imipenem, aminoglycoside, and ciprofloxacin treatment groups (P=0.57). Only shock was associated with mortality in multivariate analysis. In conclusion, for patients with TGC-resistant Gram-negative bacteraemia, no significant difference in outcome was observed between single antibiotic therapy groups or monotherapy and combination therapy groups.

Objective:To identify antibiotic resistance trends and risk factors for resistance ofSerratiaspecies to third-generation cephalosporins.Design:Retrospective survey of medical records.Setting:A 2,200-bed, tertiary-care hospital.Patients:One hundred twenty-two patients withSerratiabacteremia between January 1991 and June 2001.Methods:Infectious disease physicians collected data from medical records regarding patient demographics, underlying disease or condition, portal of entry, microorganism, antibiogram, complications, antibiotics received, and outcome.Results:Among 122Serratiaisolates, 117 (95.9%) wereSerratiamarcescens and 110 (90.2%) were of nosocomial origin. During the study period, the 122 isolates showed a high rate of resistance to third-generation cephalosporins (45.9%) and extended-spectrum penicillins (56.6%). The resistance rate to ciprofloxacin was 32.0%. The resistance rate to third-generation cephalosporins increased from 31.7% for 1991 to 1995 to 54.9% for 1996 to 1998 and 50.0% for 1999 to 2001. In the multivariate analysis, prior use of a second-generation cephalosporin (adjusted odds ratio [OR], 5.90; 95% confidence interval [CI95], 1.41 to 24.6;P= .015) or a third-generation cephalosporin (OR, 3.26; CI95, 1.20 to 8.87;P= .020) was a strong independent risk factor for resistance to third-generation cephalosporins. The overall case-fatality rate was 25.4% (Serratiabacteremia-related case-fatality rate, 13.1%).Conclusion:Prior use of a second- or third-generation cephalosporin was the most important risk factor for bacteremia withSerratiaresistant to third-generation cephalosporins, suggesting the need for antibiotic control. The potential role of patient-to-patient spread could not be fully evaluated in this retrospective study.

From 1991 to 2000, 125 sporadic cases of Klebsiella oxytoca bacteremia were analyzed retrospectively to review clinical features and to identify the risk factors associated with resistance to extended-spectrum cephalosporins and fatal outcome. Bacteremia was acquired nosocomially in 52% of the patients. Almost all patients (97%) had an underlying disease, with biliary and pancreatic disease occurring most frequently (55%). The biliary tract was the most common site of infection (44%). Resistance to extended-spectrum cephalosporins was identified in 22 of the 125 (18%) Klebsiella oxytoca blood isolates and resistance to ciprofloxacin in 9 (7%). Only previous antibiotic therapy was strongly associated with resistance to extended-spectrum cephalosporins in patients with Klebsiella oxytoca bacteremia ( P=0.009). The mortality rate was 24% and was higher in patients infected with isolates resistant to extended-spectrum cephalosporins (41% vs. 20%; P=0.04). In multivariate analysis, fatal outcome was independently associated with septic shock, deteriorated mental status, polymicrobial bacteremia, and solid tumor. Surgical therapy had a protective effect (OR, 0.06; 95% CI, 0.005-0.7; P=0.03). In conclusion, Klebsiella oxytoca bacteremia was most commonly associated with biliary tract infection. Previous antibiotic therapy was strongly associated with resistance to extended-spectrum cephalosporins in patients with Klebsiella oxytoca bacteremia.

A retrospective analysis was performed to measure the incidence of pneumococcal bacteremia and to identify risk factors for penicillin resistance and prognostic factors for outcome in adults. A total of 151 cases of pneumococcal bacteremia were identified from 149 adults during the period 1996-2000. The overall rate of penicillin resistance was 49%, ranging from 54.2% in 1996 to 48.5% in 2000 (P=0.93). Rates of resistance to ceftriaxone, clindamycin, erythromycin, and trimethoprim-sulfamethoxazole were 21.6%, 51%, 62%, and 44.7%, respectively. Multidrug resistance was documented in 47.7% of the cases. Penicillin resistance was significantly associated with solid tumor, biliary drainage catheter, and previous beta-lactam therapy in the univariate analysis. However, the associations were not as significant as independent risk factors in the multivariate analysis. Mortality was 23.8% and did not change significantly during the study period (P=0.06). Mortality rates in cases caused by penicillin-susceptible Streptococcus pneumoniae and penicillin-resistant Streptococcus pneumoniae were 23% and 24.7%, respectively (P=0.81). Mortality was not significantly influenced by penicillin resistance, even high-level resistance (24.4% vs. 20%; P=0.64). Multivariate analysis revealed that antineoplastic chemotherapy, respiratory failure, and acute renal failure were independent prognostic factors for mortality. In conclusion, the rate of penicillin resistance among pneumococcal blood isolates was high in the late 1990s, but penicillin resistance, and even high-level penicillin resistance, was not significantly associated with increased mortality in adults with pneumococcal bacteremia.

Background: Resistance of Streptococcus pneumoniae to penicillin is now widespread and rapidly increasing all over the world. This has led to the critical need for alternative antimicrobial therapy. Methods: To assess the activities of antimicrobial combinations, including cefotaxime, ceftriaxone, vancomycin and meropenem, time-kill studies were conducted against five strains of penicillin- and cephalosporin-resistant S. pneumoniae at clinically achievable antimicrobial concentrations in cerebrospinal fluid. Results: Combinations of an extended-spectrum cephalosporin with vancomycin were not synergistic. Meropenem had a comparable bactericidal activity to those combinations, and its killing activity was not affected by the addition of cefotaxime, ceftriaxone or vancomycin. Conclusions: It is suggested that meropenem could be an effective alternative for the treatment of penicillin- and cephalosporin-resistant pneumococcal meningitis. However, more clinical data are required before it can be recommended as an effective antimicrobial agent for such cases.

BACKGROUND:Antibiotics are often administered to terminally ill patients until death, and antibiotic use contributes to the emergence of multidrug-resistant organisms (MDROs). We investigated antibiotic use and the isolation of MDROs among patients who died in general medical wards. METHODS:All adult patients who died in the general internal medicine wards at four acute care hospitals between January and June 2013 were enrolled. For comparison with these deceased patients, the same number of surviving, discharged patients was selected from the same divisions of internal medicine subspecialties during the same period. RESULTS:During the study period, 303 deceased patients were enrolled; among them, 265 (87.5%) had do-not-resuscitate (DNR) orders in their medical records. Antibiotic use was more common in patients who died than in those who survived (87.5% vs. 65.7%, P

Background From May to July 2015, the Republic of Korea experienced the largest outbreak of Middle East respiratory syndrome (MERS) outside the Arabian Peninsula. A total of 186 patients, including 36 deaths, had been diagnosed with MERS-coronavirus (MERS-CoV) infection as of September 30th, 2015. Materials and Methods We obtained information of patients who were confirmed to have MERS-CoV infection. MERS-CoV infection was diagnosed using real-time reverse-transcriptase polymerase chain reaction assay. Results The median age of the patients was 55 years (range, 16 to 86). A total of 55.4% of the patients had one or more coexisting medical conditions. The most common symptom was fever (95.2%). At admission, leukopenia (42.6%), thrombocytopenia (46.6%), and elevation of aspartate aminotransferase (42.7%) were observed. Pneumonia was detected in 68.3% of patients at admission and developed in 80.8% during the disease course. Antiviral agents were used for 74.7% of patients. Mechanical ventilation, extracorporeal membrane oxygenation, and convalescent serum were employed for 24.5%, 7.1%, and 3.8% of patients, respectively. Older age, presence of coexisting medical conditions including diabetes or chronic lung disease, presence of dyspnea, hypotension, and leukocytosis at admission, and the use of mechanical ventilation were revealed to be independent predictors of death. Conclusion The clinical features of MERS-CoV infection in the Republic of Korea were similar to those of previous outbreaks in the Middle East. However, the overall mortality rate (20.4%) was lower than that in previous reports. Enhanced surveillance and active management of patients during the outbreak may have resulted in improved outcomes.

We prospectively evaluated severity predictors in terms of host, microorganism, and treatment factors in 153 eschar-positive scrub typhus patients. Severity was assessed with the Acute Physiology and Chronic Health Evaluation (APACHE) II score (< 10 versus ≥ 10) and predefined criteria of severe complications. Genotypes of Orientia tsutsugamushi were determined. Independent risk factors for severity (APACHE II score ≥ 10) were old age, diabetes mellitus, serum osteopontin > 100 ng/mL, and a group of underlying diseases (congestive heart failure, cerebrovascular disease, chronic liver disease, bronchial asthma, and chronic obstructive lung diseases). Anemia (≤ 10 g/dL) and C-reactive protein > 10 mg/dL were indicators of current severity. Neither the delay in antibiotics administration nor strain types (Boryong, Taguchi, or Kanda/Kawasaki) contributed to the severity. The risk factors for severe complications were similar. Serum osteopontin > 100 ng/mL had a negative predictive value of 96% for severe complications. This marker can be used to rule out severe disease status.

The purpose of this study was to establish a prediction rule for severe illness in adult patients hospitalized with pandemic influenza A (H1N1) 2009. At the time of initial presentation, the baseline characteristics of those with severe illness (i.e., admission to intensive care unit, mechanical ventilation, or death) were compared to those of patients with non-severe illnesses. A total of 709 adults hospitalized with pandemic influenza A (H1N1) 2009 were included: 75 severe and 634 non-severe cases. The multivariate analysis demonstrated that altered mental status, hypoxia (PaO(2)/FiO(2) ≤ 250), bilateral lung infiltration, and old age (≥ 65 yr) were independent risk factors for severe cases (all P0.001). The area under the ROC curve (0.834 [95% CI, 0.778-0.890]) of the number of risk factors were not significantly different with that of APACHE II score (0.840 [95% CI, 0.790-0.891]) (P = 0.496). The presence of ≥ 2 risk factors had a higher sensitivity, specificity, positive predictive value and negative predictive value than an APACHE II score of ≥ 13. As a prediction rule, the presence of ≥ 2 these risk factors is a powerful and easy-to-use predictor of the severity in adult patients hospitalized with pandemic influenza A (H1N1) 2009.