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Background Metronidazole is a widely used antibiotic to treat anaerobic and protozoal infections. However, neurologic adverse events associated with metronidazole have been reported in case series and case reports. Previous publications implicated that long-term usage and cumulative dose are risk factors for this adverse event. Still, little is known about the risk factor of the metronidazole-associated neurologic adverse events. Therefore, we conducted a retrospective study to investigate the risk factors for the metronidazole-associated neurologic adverse events through a matched case-control study. Methods This retrospective study enrolled patients prescribed metronidazole from January 2006 to July 2021 at Severance Hospital, a tertiary hospital in South Korea. Case patients were defined as those who developed central nervous system (CNS) adverse events or peripheral nervous system (PNS) adverse events during the study period with causality assessment. In a 1 to 3 ratio, case patients were compared to a control group of the patients without neurologic adverse events, matched on age and cumulative dose of metronidazole. Results 92838 patients were prescribed metronidazole during the study period. Among them, 52 patients showed metronidazole-associated neurologic adverse events (39 patients with CNS, 27 patients with PNS adverse events, and 14 patients with both). The proportion of chronic kidney disease (CKD), solid organ transplantation, liver cirrhosis (LC), intravenous (IV) administration of metronidazole, and concomitant use of a proton pump inhibitor was significantly higher in the case group. The body weight, hemoglobin, and serum albumin levels were lower, and Sequential Organ Failure Assessment scores were higher in the case group. Multivariate conditional logistic regression analysis demonstrated LC, CKD, IV administration, and lower body weight as risk factors for metronidazole-associated neurologic adverse events. Conclusion In this case-control study, LC, CKD, IV administration, and lower body weight were associated with the metronidazole-associated neurologic adverse events. Prolonged metronidazole treatment in patients with the risk factors requires careful examination for these adverse events. Disclosures All Authors: No reported disclosures.

Background Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system (CNS) caused by reactivation of JC virus, almost in patients with immunosuppressive conditions. PML is a fatal infection with a reported 3-month mortality rate of 30–50% and a 2-month mortality rate of up to 90% in the non-human immunodeficiency virus (HIV) population. Despite high mortality, studies on PML are still lacking due to its low prevalence and incidence. Therefore, this study aimed to figure out long-term prognosis of PML and prognostic factors for mortality through a long observation period. Methods We retrospectively reviewed 68 PML patients with admitted to two tertiary hospitals in South Korea from 1999 to 2021. A total of 47 PML patients were finally enrolled after exclusion. The primary endpoint was long-term overall mortality. For survival analysis, Kaplan-Meier curve and Cox proportional hazards model were used. Each patient was followed up until death or until the end of the study period, whichever came first. Results The median follow-up duration was 20 (interquartile range [IQR], 3–79) months. The median age was 46 years, 27 (57.4%) were diagnosed with HIV, 19 (40.4%) were using immunosuppressive drugs. The median last follow-up modified Rankin Scale (mRS) was higher in non-HIV PML patients group (5 [IQR, 4–6] vs 4 [IQR, 2–5], p=0.020). The median survival duration was 184 (IQR 74–1,566) days in the non-HIV group and 1,564 (IQR 254–3,444) days in the HIV group. The overall mortality rate of PML patients was significantly higher in non-HIV group (80.0% vs 40.7%, p=0.007), also confirmed by the Kaplan-Meier curve and log-rank test (p=0.007). Initial mRS (HR 1.685, 95% CI: 1.028–2.762, p=0.038), HIV patients with highly active antiretroviral therapy (HAART) (HR 0.374, 95% CI: 0.172–0.815, p=0.013) had a significant effect on overall mortality. Conclusion With the widespread adoption of HAART, the survival duration of HIV patients with PML has been extended, but the mortality rate is still high. Also, the prognosis for PML in non-HIV patients is still frustrated. Initial mRS is a significant risk factor for long-term overall mortality in PML patients. Early detection of PML and early initiation of HAART in HIV patients may improve the patient's prognosis. Disclosures All Authors: No reported disclosures.

Background Invasive aspergillosis (IA) is a great threat to the severely immunocompromised and patients with coronavirus disease (COVID-19). However, diagnosis of IA is often difficult due to need for invasive biopsy and low sensitivity of other diagnostic tests. Next-generation sequencing (NGS) of plasma cell free DNA (cfDNA) can be a novel non-invasive diagnostic modality. We evaluated the clinical accuracy and utility of microbial cfDNA NGS for the diagnosis of IA in patients with hematologic malignancy (HM) and COVID-19. Methods A single-center prospective study of plasma microbial cfDNA NGS was conducted in a tertiary-care hospital in South Korea. We enrolled adult patients with HM and COVID-19, who suspected IA and performed conventional diagnostic tests for IA. The results of NGS were compared with the diagnosis of IA through conventional methods. IA cases were diagnosed according to EORTC/MSG definitions in patients with HM, and modified AspICU criteria in patients with COVID-19. (Figure 1). Figure 1.Flow chart for the participant selection method used in this study Results Between March 2021 and January 2022, a total of 33 participants (22 [64.7%] male, median age 66.0 [50.5, 72.0]) were enrolled;19 participants with HM and 15 with COVID-19 were analyzed (Figure1 and Table1). In participants with HM, aspergillus cfDNA was detected in 100% of both proven (1/1) and probable (12/12) IA cases, and 33.3% of both possible (1/3) and no IA (1/3) cases. In participants with COVID-19, 46.2% of probable IA (6/13) showed positive aspergillus cfDNA. Detection rate of aspergillus cfDNA was significantly higher in proven/probable IA cases in participants with HM compared to participants with COVID-19. (100% vs 46.2%, p=0.005) (Figure 2). As shown in Table 2, among proven/probable IA cases, participants with positive aspergillus cfDNA showed significantly higher rate of having uncontrolled hematologic disease, receiving stem cell transplantation and recent chemotherapy. In three participants with HM, non-aspergillus strains confirmed by cfDNA NGS were in accordance with pathogens identified through conventional culture methods. Table 1.Baseline characteristics of participants suspected of invaisve aspergillosis performing microbial cell free DNA NGSFigure 2.cfDNA detection rate in participants with suspected fungal infection according to the EORTC/MSG or modified AspICU diagnostic criteria Conclusion Detection of aspergillus cfDNA showed high concordance in the results of conventional diagnostic methods in proven/probable IA of patients with HM and could be a helpful non-invasive approach to IA diagnosis in those populations. Disclosures All Authors: No reported disclosures.

Background During the novel coronavirus SARS-CoV-2 pandemic, a considerable number of pneumothorax and pneumomediastinum associated with COVID-19 have been reported, and the incidence was higher in critically ill patients. Despite using a protective ventilation strategy, barotrauma still occurs in COVID-19 patients with invasive mechanical ventilation. This study aims to identify the risk factors and clinical characteristics of pneumothorax and pneumomediastinum in COVID-19 by a matched case-control study. Methods This retrospective study enrolled adult patients diagnosed with a COVID-19, admitted to a critical care unit in South Korea from 2020 March 1st to 2022 January 31st. COVID-19 patients with pneumothorax and pneumomediastinum were compared, in a 1 to 2 ratio, to a control group of COVID-19 patients without pneumothorax and pneumomediastinum, matched on age, gender, and worst National Institute of Allergy and Infectious Diseases ordinal scale (NIAID-OS). Conditional logistic regression analysis was performed to assess the risk factors for pneumothorax and pneumomediastinum in COVID-19. Results A total of 427 patients with COVID-19 were admitted during the study period. Of these patients, 24 patients were diagnosed as pneumothorax or pneumomediastinum. When comparing the characteristics of both groups, body mass index (BMI) was significantly lower in the case group (22.8 kg/m2 and 24.7 kg/m2; P = 0.048). BMI was statistically significant risk factor for barotrauma in univariate conditional logistic regression analysis (Odds ratio (OR), 0.85; Confidence interval (CI), 0.72-0.996; P = 0.044) but not in multivariate analysis. For the patients with invasive mechanical ventilation, the period from symptom onset to intubation was longer in the case-patients (13 and 9.5 days; P = 0.032). Univariate conditional logistic regression analysis showed the statistical significance of the period from symptom onset to intubation (OR, 1.14; CI, 1.006-1.293; P = 0.041). Conclusion In this case-control study with age, gender, severity matching, lower BMI was associated with the pneumothorax in COVID-19, and delayed application of invasive mechanical ventilation might contribute to this complication. Disclosures All Authors: No reported disclosures.

Background Infective endocarditis is not a prevalent disease but has a high mortality rate. Especially left-sided infective endocarditis (LSIE) shows a higher mortality rate than right-sided infective endocarditis. Surgical treatment is occasionally considered for LSIE, but not much data is available on the long-term prognostic factors for LSIE after surgical treatment. This study investigated the risk factors for long-term mortality in LSIE patients who underwent surgical treatment. Methods This retrospective study enrolled adult patients with LSIE admitted to Severance Hospital in South Korea and underwent surgical treatment from November 2005 to August 2017. The primary outcome was overall all-cause mortality. Multivariate Cox regression analyses were performed to assess the risk factors for long-term mortality of LSIE with surgical treatment. Results 239 cases with LSIE who underwent surgery were enrolled in this study. The median follow-up period was 6.2 years, and there were 34 deaths (14.2%) during the period. The mortality group showed older age (61.0 [53.0-72.0] vs 51.0 [39.0-61.0] years, P = 0.001), more chronic kidney disease (17.6% vs 3.9%, P = 0.007), more chronic liver disease (CLD) (14.7% vs 3.4%, P = 0.017), more cerebral embolisms (58.8% vs 26.8%, P < 0.001), less isolated mitral valve involvement (29.4% vs 52.7%, P = 0.020), and higher Sequential Organ Failure Assessment score (2.0 [1.0-4.0] vs 1.0 [1.0-2.0], P = 0.014). The survivor and mortality groups showed no statistical difference in the time to surgery. Multivariate Cox analyses demonstrated cerebral embolism (Hazard ratio (HR): 3.62, 95% Confidence Interval (CI): 1.79-7.31, P < 0.001), CLD (HR: 4.24, CI: 1.53-11.76, P = 0.005), and age (HR: 1.03, CI: 1.00-1.06, per 1 year, P = 0.021) as risk factors for overall mortality. Kaplan-Meier survival curve showed significant difference between the patients with and without cerebral embolism (P < 0.001, log-rank). Figure 1.Kaplan-Meier survival curve for overall mortality Conclusion Cerebral embolism, CLD, and older age were associated with the long-term mortality in LSIE patients who underwent surgery. Preventive strategies for cerebral embolism are essential for the improvement in LSIE treatment. Disclosures All Authors: No reported disclosures.

Background COVID-19 increase the risk of invasive pulmonary aspergillosis. However, the risk factors and fungal origin of COVID-19 associated pulmonary aspergillosis (CAPA) is not fully defined yet. We aim to identify the risk factors for CAPA in severe COVID-19 and evaluate association between fungal contamination within the air of negative pressure rooms and diagnosis of CAPAs. Methods We performed a retrospective case-control study to identify risk factors for CAPA with 420 severe COVID-19 patients from March 2020 to January 2022 who admitted to a tertiary care hospital in South Korea. CAPA was defined with modified AspICU criteria. Control, matched by admission date and severity of COVID-19 at admission, was selected for each case. Air sampling and fungal culture was done on Jan 2022 with a microbial air sampler (MAS-100NT) at 11 spaces in the COVID-19 designated isolation ward including 9 negative pressure isolation rooms (IRs). A cross-sectional comparison between rooms with and without airborne fungal contamination was performed. Results A total of 420 COVID-19 patients were hospitalized during the study period, and 51 patients were diagnosed with CAPA (prevalence 12.14%, incidence 6.26 per 1000 patient•day). Multivariate analysis showed that older age (odds ratio [OR] 1.051, 95% confidence intervals [CI] 1.006-1.009, p=0.025), mechanical ventilator use (OR 2.692, 95% CI 1.049-6.911, p=0.04), and lymphopenia (OR 4.353, 95% CI 1.727-10.975, p=0.02) were independent risk factors for CAPA. (Table 1, 2) Aspergillus spp. was identified within the air from 7 out of 11 spaces including 6 IRs and 1 doctors’ room. (Figure 1). All 6 IRs with positive aspergillus culture were being occupied by patients at least 8 days. Among 6 patients, 3 had already been diagnosed with CAPA whereas the other 3 were not diagnosed with CAPA through the observation period. Among 4 patients in isolation rooms without airborne aspergillus contamination, one patient had been diagnosed as CAPA before air sampling. (Table 3). Conclusion Association between CAPA and airborne aspergillus contamination within the negative pressure room could not be demonstrated in this study. Rather than environmental factors, patient factors such as older age, ventilator care, and lymphopenia were found to be associated with CAPA diagnosis. Disclosures All Authors: No reported disclosures.

Background Infective endocarditis (IE) remains a major medical problem with high morbidity and mortality. Appropriate antibiotic treatment in patients with IE lowers the risk of embolism, recurrence, and long-term mortality. However, there are concerns about renal toxicity and an increase in the incidence of resistant strains due to long-term use of antibiotics. In this study, we compare the difference in overall mortality according to the duration of postoperative antibiotics therapy in patients with IE for each group. Methods From 2005 to 2017, we retrospectively reviewed 416 patients with IE at a 2400-bed tertiary hospital in South Korea. A total of 239 IE patients who underwent valve surgery and appropriate antibiotics duration were enrolled. The primary endpoint was long-term overall mortality. The secondary endpoints were reoperation rate, recurrence rate, and postoperative complications, such as new-onset heart failure, paravalvular and embolic complications. Results The median follow-up duration was 71 (interquartile range, 46–109) months. The duration of postoperative antibiotic therapy was less than 2 weeks in 67 patients (28.0%) and more than 2 weeks in 127 patients (72.0%). The median age was 53 years. The overall mortality was 13.0% (31/239). There were no statistical differences in overall mortality (13.4% vs. 12.8%, p=0.894), reoperation (6.0% vs. 4.1%, p=0.507), and recurrence (7.5% vs. 2.9%, p=0.148) between patients with postoperative antibiotic therapy for ≥2 weeks and less than 2 weeks. The duration of postoperative antibiotic therapy based on 2 weeks in the Kaplan-Meier curve was not associated with overall mortality (log-rank test, p=0.971). Conclusion In conclusion, there was no statistically significant difference in the overall mortality, recurrence, and reoperation rate according to the duration of postoperative antibiotic therapy. When surgery and recommended total antibiotics duration are properly performed according to guidelines, the effect of duration of postoperative antibiotic therapy on overall mortality, recurrence rate, and reoperation rate is reduced to a statistically insignificant extent. Disclosures All Authors: No reported disclosures.

Background The superinfection of multidrug-resistant bacteria is an important complication in critically ill COVID-19 patients. An outbreak of carbapenem-resistant Acinetobacter baumannii (CRAB) occurred in an isolation ward for COVID-19. We performed an outbreak investigation, and successfully controlled the outbreak with the enhanced environmental cleaning and additional gowning and gloving. Methods This study analyzed all COVID-19 patients with CRAB in any specimen, who admitted to an isolation ward for COVID-19 of a tertiary hospital in South Korea from October to November 2021. Results During the outbreak period, a total of 23 patients with COVID-19 and CRAB were identified (Figure 1). Index case was 85-year old female patient who was referred from a long-term care facility. The mean age of cases was 72.9 and 14 (60.9%) patients were male. In most patients (91.3%), CRAB were identified in sputum culture, two were identified in blood culture at initial, and four patients were identified in sputum and blood culture at the same time. Most of the patients were applying high flow nasal cannula (26.1%) or mechanical ventilation (60.9%)(Table1). As shown in figure2, CRAB outbreak occurred mainly in the wards around the index case, and in particular, environmental culture was carried out in the area marked with a rectangle. CRAB was cultured on the floor, air inlet, air outlet, and window frame of the ward except for wards 3305 and 3319. Phenotypic antimicrobial resistance patterns of CRAB isolates from patients and environment were identical, and additional whole genome sequencing analyses are ongoing to find the clonality of isolates. We applied the infection control measures with the enhanced environmental cleaning using sodium hypochlorite(NaClO) 1000ppm and phenolic compounds more than twice a day, enhanced hand hygiene, and additional gowning and gloving over personal protective equipment (PPE) mandatory for COVID-19 on 29th October. No additional CRAB cases occurred since 2nd November 2021 for two weeks. Figure 1.Daily number of cases with carbapenem-resistant Acinetobacter baumannii during outbreak periodFigure 2.Floor plan of isolation ward with Acinetobacter baumannii outbreak Conclusion Even when PPEs and precautions for COVID-19 are applied to isolation wards for COVID-19, it is helpful for preventing transmission of multidrug-resistant bacteria to apply additional contact precautions and environmental cleaning. Disclosures All Authors: No reported disclosures.

Background Roseomonas species are slow-growing Gram-negative cocobacillus, and were first reported in 1993. Roseomonas have been isolated from environmental sources and can cause bacteremia in humans, especially in immunocompromised patients. Since these species were difficult to isolate and infections with these species are not common, there are only a few studies on their characteristics. Therefore, we aim to expand our knowledge of clinical features, antimicrobial susceptibility patterns, and treatment outcomes for Roseomonas human infections. Methods From January 2006 to March 2022, patients with Roseomonas isolated from blood and other aseptic sources were extracted from three tertiary hospitals in South Korea. Underlying conditions, clinical manifestations, antimicrobial susceptibility patterns, and outcomes were reviewed through the medical records. Results During the study period, a total of 39 patients (46.2% were male) with Roseomonas infections were included. The median age was 50 (interquartile range, 33.5-62.5) years old, and seven patients (17.9%) were under age 18. Of the 39 patients, 13 patients (33.3%) had malignancies, five patients (12.8%) had neutropenia with an absolute neutrophil count of fewer than 1000 cells/mm3. Blood isolates were the most common (26 cases), followed by catheter blood (3 cases), and soft tissue (3 cases). Twenty-one cases (53.8%) were cultured after 48 hours of incubation, and co-infection with other bacteria was identified in nine cases (23.1%). Twenty-eight patients (71.8%) were symptomatic, with fever (30.8%) being the most common symptom. Amikacin showed a high susceptible rate (95.7%) to isolated Roseomonas. Tigecycline also showed high susceptible rates (92.9% , respectively). The susceptible rate of levofloxacin was 85.0%. On the other hand, the susceptible rate of piperacillin-tazobactam (5.9%) and meropenem (47.6%) were below 50%. There were two cases (5.1%) of in-hospital mortality. Conclusion Although not common, Roseomonas species can cause bacteremia and even death, especially in immunocompromised individuals. Since Roseomonas are challenging to isolate and generally show resistance to antibiotics commonly used for Gram-negative bacterial infections, careful attention is warranted in selecting antibiotics. Disclosures All Authors: No reported disclosures.