Effects of Omicron Infection and Changes in Serum Antibody Response to Wild-Type, Delta, and Omicron After a Booster Dose With BNT163b2 Vaccine in Korean Healthcare Workers

Background@#Although the primary vaccine coverage rate for coronavirus disease 2019 (COVID-19) in South Korea has exceeded 80%, the coronavirus continues to spread, with reports of a rapid decline in vaccine effectiveness. South Korea is administering booster shots despite concerns about the effectiveness of the existing vaccine. @*Methods@#Neutralizing antibody inhibition scores were evaluated in two cohorts after the booster dose. For the first cohort, neutralizing activity against the wild-type, delta, and omicron variants after the booster dose was evaluated. For the second cohort, we assessed the difference in neutralizing activity between the omicron infected and uninfected groups after booster vaccination. We also compared the effectiveness and adverse events (AEs) between homologous and heterologous booster doses for BNT162b2 or ChAdOx1 vaccines. @*Results@#A total of 105 healthcare workers (HCWs) that were additionally vaccinated with BNT162b2 at Soonchunhyang University Bucheon Hospital were enrolled in this study.Significantly higher surrogate virus neutralization test (sVNT) inhibition (%) was observed for the wild-type and delta variants compared to sVNT (%) for the omicron after the booster dose (97%, 98% vs. 75%; P < 0.001). No significant difference in the neutralizing antibody inhibition score was found between variants in the BNT/BNT/BNT group (n = 48) and the ChA/ChA/BNT group (n = 57). Total AEs were not significantly different between the ChA/ ChA/BNT group (85.96%) and the BNT/BNT group (95.83%; P = 0.11). In the second cohort with 58 HCWs, markedly higher sVNT inhibition to omicron was observed in the omicroninfected group (95.13%) compared to the uninfected group (mean of 48.44%; P < 0.001) after four months of the booster dose. In 41 HCWs (39.0%) infected with the omicron variant, no difference in immunogenicity, AEs, or effectiveness between homogeneous and heterogeneous boosters was observed. @*Conclusion@#Booster vaccination with BNT162b2 was significantly less effective for the neutralizing antibody responses to omicron variant compared to the wild-type or delta variant in healthy population. Humoral immunogenicity was sustained significantly high after 4 months of booster vaccine in the infected population after booster vaccination.Further studies are needed to understand the characteristics of immunogenicity in these populations.

Machine-Learning-Based Approach to Differential Diagnosis in Tuberculous and Viral Meningitis

Background@#Tuberculous meningitis (TBM) is the most severe form of tuberculosis, but differentiating between the diagnosis of TBM and viral meningitis (VM) is difficult. Thus, we have developed machine-learning modules for differentiating TBM from VM.Material and Methods: For the training data, confirmed or probable TBM and confirmed VM cases were retrospectively collected from five teaching hospitals in Korea between January 2000 - July 2018. Various machine-learning algorithms were used for training. The machinelearning algorithms were tested by the leave-one-out cross-validation. Four residents and two infectious disease specialists were tested using the summarized medical information. @*Results@#The training study comprised data from 60 patients with confirmed or probable TBM and 143 patients with confirmed VM. Older age, longer symptom duration before the visit, lower serum sodium, lower cerebrospinal fluid (CSF) glucose, higher CSF protein, and CSF adenosine deaminase were found in the TBM patients. Among the various machinelearning algorithms, the area under the curve (AUC) of the receiver operating characteristics of artificial neural network (ANN) with ImperativeImputer for matrix completion (0.85; 95% confidence interval 0.79 - 0.89) was found to be the highest. The AUC of the ANN model was statistically higher than those of all the residents (range 0.67 - 0.72, P <0.001) and an infectious disease specialist (AUC 0.76; P = 0.03). @*Conclusion@#The machine-learning techniques may play a role in differentiating between TBM and VM. Specifically, the ANN model seems to have better diagnostic performance than the non-expert clinician.

Machine-Learning-Based Approach to Differential Diagnosis in Tuberculous and Viral Meningitis

Background@#Tuberculous meningitis (TBM) is the most severe form of tuberculosis, but differentiating between the diagnosis of TBM and viral meningitis (VM) is difficult. Thus, we have developed machine-learning modules for differentiating TBM from VM.Material and Methods: For the training data, confirmed or probable TBM and confirmed VM cases were retrospectively collected from five teaching hospitals in Korea between January 2000 - July 2018. Various machine-learning algorithms were used for training. The machinelearning algorithms were tested by the leave-one-out cross-validation. Four residents and two infectious disease specialists were tested using the summarized medical information. @*Results@#The training study comprised data from 60 patients with confirmed or probable TBM and 143 patients with confirmed VM. Older age, longer symptom duration before the visit, lower serum sodium, lower cerebrospinal fluid (CSF) glucose, higher CSF protein, and CSF adenosine deaminase were found in the TBM patients. Among the various machinelearning algorithms, the area under the curve (AUC) of the receiver operating characteristics of artificial neural network (ANN) with ImperativeImputer for matrix completion (0.85; 95% confidence interval 0.79 - 0.89) was found to be the highest. The AUC of the ANN model was statistically higher than those of all the residents (range 0.67 - 0.72, P <0.001) and an infectious disease specialist (AUC 0.76; P = 0.03). @*Conclusion@#The machine-learning techniques may play a role in differentiating between TBM and VM. Specifically, the ANN model seems to have better diagnostic performance than the non-expert clinician.

Infectious Diseases Physician Workforce in Korea

This study aimed to evaluate the infectious disease (ID) physician workforce in Korea. We investigated the acquisition of ID physicians from 1992 to 2019 with their current working place in the Health Care System. We defined ID physicians working at general or tertiarycare hospitals as active ID physicians. A total 275 physicians acquired ID as a sub-specialty.Among the 275, 242 were active ID physicians. The density of active ID physicians was 0.47 per 100,000 population. Of all the 17 administrative districts, 11 (64.7%) fell short of 0.47, and 131 medical institutions employed the service of ID physicians. The median number of beds per adult ID physician was 372 (interquartile range, 280–507). It is essential to secure human resources to respond to emerging infectious diseases and perform the inherent work of ID physicians.

Infectious Diseases Physician Workforce in Korea

This study aimed to evaluate the infectious disease (ID) physician workforce in Korea. We investigated the acquisition of ID physicians from 1992 to 2019 with their current working place in the Health Care System. We defined ID physicians working at general or tertiarycare hospitals as active ID physicians. A total 275 physicians acquired ID as a sub-specialty.Among the 275, 242 were active ID physicians. The density of active ID physicians was 0.47 per 100,000 population. Of all the 17 administrative districts, 11 (64.7%) fell short of 0.47, and 131 medical institutions employed the service of ID physicians. The median number of beds per adult ID physician was 372 (interquartile range, 280–507). It is essential to secure human resources to respond to emerging infectious diseases and perform the inherent work of ID physicians.

Early Intravenous Colistin Therapy as a Favorable Prognostic Factor for 28-day Mortality in Patients with CRAB Bacteremia: a Multicenter Propensity Score-Matching Analysis

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) infection is associated with high mortality. One of the strategies to reduce the mortality in patients with CRAB infections is to use intravenous colistin early but the effect of this strategy has not been proven. Therefore, we investigated the association of early colistin therapy with 28-day mortality in patients with CRAB bacteremia. METHODS: This retrospective multicenter propensity score-matching analysis was conducted in the Korea by reviewing the medical records of adult patients with CRAB bacteremia between January 2012 and March 2015. Early colistin therapy was defined as intravenous colistin administration for > 48 hours within five days after the blood culture collection. To identify the risk factors associated with the 28-day mortality in CRAB bacteremia, the clinical variables of the surviving patients were compared to those of the deceased patients. RESULTS: Of 303 enrolled patients, seventy-six (25.1%) patients received early colistin therapy. The 28-day mortality was 61.4% (186/303). Fatal or rapidly-fatal McCabe classifications, intensive care unit admission, Sequential Organ Failure Assessment scores ≥ 8, vasopressor use, and acute kidney injury were statistically independent poor prognostic factors. Catheter-related infection and early colistin therapy (adjusted odds ratio [aOR], 0.45; 95% confidence interval [CI], 0.21–0.94) were independent favorable prognostic factors associated with 28-day mortality in patients with CRAB bacteremia. Early colistin therapy was still significantly associated with lower 28-day mortality in the propensity score-matching analysis (aOR, 0.31; 95% CI, 0.11–0.88). CONCLUSION: This study suggests that early colistin therapy might help reduce the mortality of patients with CRAB bacteremia.

Antibiotic Treatment of Vertebral Osteomyelitis caused by Methicillin-Susceptible Staphylococcus aureus: A Focus on the Use of Oral β-lactams

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.

Outcome in Patients with Fever of Unknown Origin whose ¹⁸Fluoro-Deoxyglucose Positron Emission Tomography/Computerized Tomography Finding is Non-Diagnostic

Prognosis has not been known for patients with fever of unknown origin (FUO) whose ¹⁸fluoro-deoxyglucose (¹⁸F-FDG) positron emission tomography/computerized tomography (PET/CT) finding is non-diagnostic. A total of eight patients with FUO that underwent ¹⁸F-FDG PET/CT were retrospectively identified January 2016 - June 2017 in a tertiary hospital in Korea. Of these, two patients were diagnosed with microscopic polyangitis and Kikuchi's disease and one patient was transferred to another hospital. Of five patients whose diagnoses were not confirmed, four patients received non-steroidal anti-inflammatory drug and/or low dose steroid and symptoms disappeared. Our study suggests that outcome of patients with FUO whose ¹⁸F-FDG PET/CT finding is non-diagnostic would be favorable.

Low Lymphocyte Proportion in Bronchoalveolar Lavage Fluid as a Risk Factor Associated with the Change from Trimethoprim/sulfamethoxazole used as First-Line Treatment for Pneumocystis jirovecii Pneumonia

BACKGROUND: Trimethoprim/sufamethoxazole (TMP/SMX) is the recommended treatment for Pneumocystis jirovecii pneumonia (PCP). However, the efficacy and the safety of alternative salvage treatments are less guarauteed especially when patient experiences treatment failure and/or an adverse drug reactions (ADR). The purpose of this study is to recognize potential risk factors imitating successful treatment with TMP/SMX among PCP patients. MATERIALS AND METHODS: Ninety one adult patients diagnosed with PCP were included after searching electronical medical records from January 2013 through July 2015 at Asan Medical Center Seoul, Korea. We compared clinical characteristics and laboratory findings including bronchoalveolar lavage (BAL) fluid analysis in patients who experienced TMP/SMX treatment failure or ADR (the case group) versus those who did not (the control group). RESULTS: Among the enrolled PCP patients, 39 (42.9%) required salvage treatment owing to either treatment failure (28, 28.6%) and/or ADR (17, 18.7%). The BAL lymphocyte percentage (25% [IQR, 8–40%] vs. 47% [IQR, 15–62%]; P = 0.005) was lower in the case group. Diabetes mellitus (adjusted odds ratio [aOR] 4.98, 95% confidence interval [95% CI] 1.20–18.58), glomerular filtration rate ≤50 mL/min (aOR 4.48, 95% CI 1.08–18.66), and BAL lymphocyte percentage ≤45% (aOR 9.25, 95% CI 2.47–34.58) were independently associated with the case group in multivariate analysis. CONCLUSION: This study suggests that BAL lymphocyte count may play some role during PCP treatment. Further studies should be followed to reveal what the role of BAL lymphocyte is in the PCP treatment.

Outcome in Patients with Fever of Unknown Origin whose ¹⁸Fluoro-Deoxyglucose Positron Emission Tomography/Computerized Tomography Finding is Non-Diagnostic

Prognosis has not been known for patients with fever of unknown origin (FUO) whose ¹⁸fluoro-deoxyglucose (¹⁸F-FDG) positron emission tomography/computerized tomography (PET/CT) finding is non-diagnostic. A total of eight patients with FUO that underwent ¹⁸F-FDG PET/CT were retrospectively identified January 2016 - June 2017 in a tertiary hospital in Korea. Of these, two patients were diagnosed with microscopic polyangitis and Kikuchi's disease and one patient was transferred to another hospital. Of five patients whose diagnoses were not confirmed, four patients received non-steroidal anti-inflammatory drug and/or low dose steroid and symptoms disappeared. Our study suggests that outcome of patients with FUO whose ¹⁸F-FDG PET/CT finding is non-diagnostic would be favorable.

Low Lymphocyte Proportion in Bronchoalveolar Lavage Fluid as a Risk Factor Associated with the Change from Trimethoprim/sulfamethoxazole used as First-Line Treatment for Pneumocystis jirovecii Pneumonia

BACKGROUND: Trimethoprim/sufamethoxazole (TMP/SMX) is the recommended treatment for Pneumocystis jirovecii pneumonia (PCP). However, the efficacy and the safety of alternative salvage treatments are less guarauteed especially when patient experiences treatment failure and/or an adverse drug reactions (ADR). The purpose of this study is to recognize potential risk factors imitating successful treatment with TMP/SMX among PCP patients. MATERIALS AND METHODS: Ninety one adult patients diagnosed with PCP were included after searching electronical medical records from January 2013 through July 2015 at Asan Medical Center Seoul, Korea. We compared clinical characteristics and laboratory findings including bronchoalveolar lavage (BAL) fluid analysis in patients who experienced TMP/SMX treatment failure or ADR (the case group) versus those who did not (the control group). RESULTS: Among the enrolled PCP patients, 39 (42.9%) required salvage treatment owing to either treatment failure (28, 28.6%) and/or ADR (17, 18.7%). The BAL lymphocyte percentage (25% [IQR, 8–40%] vs. 47% [IQR, 15–62%]; P = 0.005) was lower in the case group. Diabetes mellitus (adjusted odds ratio [aOR] 4.98, 95% confidence interval [95% CI] 1.20–18.58), glomerular filtration rate ≤50 mL/min (aOR 4.48, 95% CI 1.08–18.66), and BAL lymphocyte percentage ≤45% (aOR 9.25, 95% CI 2.47–34.58) were independently associated with the case group in multivariate analysis. CONCLUSION: This study suggests that BAL lymphocyte count may play some role during PCP treatment. Further studies should be followed to reveal what the role of BAL lymphocyte is in the PCP treatment.

Antimicrobial therapy for methicillin-resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of healthcare-associated infections. Recently, community-associated MRSA has emerged, manifesting as skin and soft tissue infections in patients without any prior healthcare contact. Vancomycin, a glycopeptide in clinical use for more than 50 years, still remains an acceptable treatment option. However, significant concerns have been raised regarding the decreasing susceptibility of S. aureus to this agent. The growing awareness of the limitations of vancomycin has served as an impetus for development of newer agents. There has been an increase in the number of agents available to treat MRSA infections. Linezolid, daptomycin, telavancin, and ceftaroline have received regulatory approval in the last decade for the treatment of MRSA. Although these drugs do have certain differentiating attributes and may offer some advantages over vancomycin, they also have significant limitations.

Hospital-based Influenza Morbidity and Mortality (HIMM) Surveillance for A/H7N9 Influenza Virus Infection in Returning Travelers

Since 2013, the Hospital-based Influenza Morbidity and Mortality (HIMM) surveillance system began a H7N9 influenza surveillance scheme for returning travelers in addition to pre-existing emergency room (ER)-based influenza-like illness (ILI) surveillance and severe acute respiratory infection (SARI) surveillance. Although limited to eastern China, avian A/H7N9 influenza virus is considered to have the highest pandemic potential among currently circulating influenza viruses. During the study period between October 1st, 2013 and April 30th, 2016, 11 cases presented with ILI within seven days of travel return. These patients visited China, Hong Kong, or neighboring Southeast Asian countries, but none of them visited a livestock market. Seasonal influenza virus (54.5%, 6 among 11) was the most common cause of ILI among returning travelers, and avian A/H7N9 influenza virus was not detected during the study period.

Antimicrobial therapy for methicillin-resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of healthcare-associated infections. Recently, community-associated MRSA has emerged, manifesting as skin and soft tissue infections in patients without any prior healthcare contact. Vancomycin, a glycopeptide in clinical use for more than 50 years, still remains an acceptable treatment option. However, significant concerns have been raised regarding the decreasing susceptibility of S. aureus to this agent. The growing awareness of the limitations of vancomycin has served as an impetus for development of newer agents. There has been an increase in the number of agents available to treat MRSA infections. Linezolid, daptomycin, telavancin, and ceftaroline have received regulatory approval in the last decade for the treatment of MRSA. Although these drugs do have certain differentiating attributes and may offer some advantages over vancomycin, they also have significant limitations.

Community-Associated Methicillin-Resistant Staphylococcus aureus in Nosocomial Infections

No abstract available.

Is the Initial Size of Tuberculous Lymphadenopathy associated with Lymph Node Enlargement during Treatment?

There are little data on the changes in lymph node (LN) size during the treatment of tuberculous lymphadenopathy (TB LAP). This study aimed to provide data on LN changes during treatment. Between March 2014 and December 2015, 20 patients who were diagnosed with cervical TB LAP were enrolled. LN enlargement within two months (50%, 4/8 vs. 8.3%, 1/12; P = 0.04) was more frequently observed in patients with initial LN size ≥ 7.5 cm². Enlarged LNs were excised in three patients owing to pain and fistula formation. Initial LN size may be associated with LN enlargement during treatment.

Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia

Methicillin-resistant Staphylococcus aureus (MRSA) is a significant cause of health care-associated infections. Vancomycin remains an acceptable treatment option. There has been a welcome increase in the number of agents available for the treatment of MRSA infection. These drugs have certain differentiating attributes and may offer some advantages over vancomycin, but they also have significant limitations. These agents provide some alternative when no other options are available.

Severe Influenza Treatment Guideline / 대한내과학회지

No abstract available.

Oral Antimicrobial Therapy: Efficacy and Safety for Methicillin-Resistant Staphylococcus aureus Infections and Its Impact on the Length of Hospital Stay

BACKGROUND: Carefully switching from intravenous to oral antibiotic therapy has shown to reduce treatment costs and lengths of hospital stay as well as increase safety and comfort in patients with infections. The aim of this study was to compare the clinical efficacy and safety between the patients treated with glycopeptides (case group), and the patients given oral antibiotics, as the initial or step-down therapy (control group), in the treatment of patients with methicillin-resistant Staphylococcus aureus (MRSA) infection. MATERIALS AND METHODS: A multicenter observational study was retrospectively performed in 7 teaching hospitals in Korea from January to December 2012. The study included adult patients (> or = 18 years) with infection caused by MRSA isolates, susceptible to clindamycin, erythromycin, and ciprofloxacin. The primary end point was treatment outcome, including all-cause mortality and switching of antibiotics. Drug-related adverse events and the lengths of hospital stay were also compared between the two treatment groups. RESULTS: During the study period, 107 patients (43 cases and 64 controls) with MRSA infections were enrolled from the participating hospitals. The most common sites of MRSA infection were skin and soft tissue (n = 28) and bone and joint (n = 26). The median Charlson comorbidity index (P = 0. 560), the frequency of severe sepsis (P = 0.682) or thrombocytopenia (P = 1.000), and median level of serum C-reactive protein (P = 0.157) at the onset of MRSA infections were not significantly different between the case and control groups. The oral antibiotics most frequently prescribed in the case group, were fluoroquinolones (n = 29) and clindamycin (n = 8). The median duration of antibiotic treatment (P = 0.090) and the occurrence of drug-related adverse events (P = 0.460) did not reach statistically significant difference between the two groups, whereas the total length of hospital stay after the onset of MRSA infection was significantly shorter in the case group than the control group [median (interquartile range), 23 days (8-41) vs. 32 days (15-54), P = 0.017]. In multivariate analyses, the type of antibiotic used was not an independent risk factor for treatment failure. The statistically significant factors associated with treatment failure included underlying hepatic diseases, prior receipt of antibiotics, and foreign body retention. CONCLUSIONS: This study indicates that oral antibiotic therapy with active agents against MRSA isolates can be considered as the initial or step-down therapy for the treatment of MRSA infections and also reduce the length of hospital stay.

Guideline on the prevention and control of seasonal influenza in healthcare setting

No abstract available.