Neurological and Psychiatric Manifestations of Post-COVID-19 Conditions.

BACKGROUND: We aimed to investigate the factors associated with neurological manifestations of post-coronavirus disease 2019 (COVID-19) conditions. METHODS: We retrospectively collected data from 440 patients who visited our post-COVID-19 clinic more than 4 weeks after severe acute respiratory syndrome coronavirus 2 infection. We analyzed the prevalence of different neurological symptoms (brain fog, memory impairment, headache, and dizziness) and assessed the associated factors. RESULTS: Brain fog was the most common symptom, observed in 170 patients (38.6%), followed by headaches (n = 137, 31.1%), dizziness (n = 128, 29%), and memory impairment (n = 104, 23.6%). Brain fog was associated with hyposmia or hypogeusia (odds ratio [OR], 2.54; P < 0.001), Fatigue Severity Scale (FSS) (OR, 1.06; P < 0.001), and Hospital Anxiety and Depression Scale-Anxiety (OR, 1.09; P = 0.037). Memory impairment was associated with sleep problems (OR, 2.83; P < 0.001), FSS (OR, 1.05; P < 0.001), and age (OR, 1.02; P = 0.015). Headache was associated with sleep problems (OR, 2.28; P = 0.001), sex (OR, 1.68; P = 0.042), and FSS (OR, 1.04; P < 0.001). Dizziness was associated with sleep problems (OR, 2.88; P < 0.001), and FSS (OR, 1.04; P < 0.001). The incidence of brain fog (P < 0.001), memory impairment (P < 0.001), dizziness (P = 0.007), and headache (P = 0.045) accompanied by hyposmia and hypogeusia was higher in patients with the aforementioned symptoms than in those without. CONCLUSION: This study suggests that there is a relationship between neurological symptoms and other clinical factors, such as fatigue, depression, anxiety, hyposmia, and hypogeusia.

Persistent Symptoms After Acute COVID-19 Infection in Omicron Era.

BACKGROUND: We aim to compare the clinical characteristics and subjectively reported symptoms of the acute coronavirus disease (COVID) phase and those of the post-acute COVID phase to examine varying factors that affect the number of persistent symptoms and their categories. METHODS: We categorized 1,122 patients who visited the post coronavirus disease 2019 (COVID-19) clinic into two groups: "acute group" (< 4 weeks following diagnosis of COVID-19) and "post-acute group" (> 4 weeks following diagnosis of COVID-19). We statistically compared clinical characteristics between the two groups and determined which factors are associated with the number of persistent symptoms and their categories. RESULTS: The persistent symptoms of post COVID-19 conditions were classified into three categories as follows: Category A (the prevalence of symptoms is higher in the acute-visit group than in the post-acute-visit group), Category B (the prevalence of symptoms is not different between the two groups) and Category C (the prevalence of symptoms is higher in the post-acute-visit group than in the acute-visit group). Category A mainly included respiratory symptoms. Category B had generalized weakness, weight loss, cardiologic symptoms, hypogeusia, hyposmia, anxiety, and various gastrointestinal symptoms. Category C included fatigue, decreased attention, depression, blurred vision, hair loss, and sexual dysfunction. Anxiety, depression, fatigue and age were also associated with the number of symptoms and their categories, and anxiety is the most correlated factor (P < 0.001) among them. CONCLUSION: The persistent symptoms of post COVID-19 condition involve multi-organ and continue for four weeks or greater. Therefore, long-term observation and multidisciplinary interventions are essential for patients with post COVID-19 conditions.

SARS-CoV-2 Antibody Response to the BNT162b2 mRNA Vaccine in Persons with Past Natural Infection.

There are still no agreed guidelines on the vaccination of coronavirus disease 2019 (COVID-19) for previously infected patients. Here, we present two seropositive healthcare workers (HCWs) working in an isolation ward who recovered from COVID-19 in April 2020 and got vaccinated with BNT162b2 vaccine in March 2021. We have assessed the clinical course, vaccine-related adverse events, and antibody response after natural infection and after first and second dose vaccination. One of the two HCWs was asymptomatic during quarantine, but the other had mild upper respiratory infection symptoms 1 day before admission, and the symptoms continued for 9 days. There was no pneumonic infiltration in chest X-ray in both patients, and no COVID-19 specific treatment was administered. Total immunoglobulin antibody and neutralizing antibody to anti-spike protein receptor-binding domain of severe acute respiratory syndrome coronavirus 2 were confirmed to be present in both HCWs in blood tests performed at 2 weeks and 4 weeks after discharge. Antibody response to mRNA vaccination showed marked elevation after the first vaccination, which was 30-40 times higher than that of antibody titer after natural infection in each patient (83.2 U/mL vs. > 2,500 U/mL in patient 1; 61.6 U/mL vs. > 2,500 U/mL in patient 2). Signal inhibition rate of neutralizing antibodies was also increased to over 97%. Due to this increased effect, there was little difference in antibody levels after the first and second dose. Both patients 1 and 2 suffered more from adverse vaccine reactions after the second vaccination than from COVID-19 symptoms.

Comparison of Antibody Response Elicited by ChAdOx1 and BNT162b2 COVID-19 Vaccine.

BACKGROUND: ChAdOx1 and BNT162b2 vaccines are currently commonly used against coronavirus disease 2019 worldwide. Our study was designed to determine the serostatus and relative levels of anti-S and neutralizing antibodies in patients who were administered either ChAdOx1 or BNT162b2 vaccine. In addition, we investigated whether the antibody response to each vaccine differed according to sex and age. METHODS: Healthcare workers (HCWs) at a general hospital who were vaccinated with two doses of either ChAdOx1 or BNT162b2 were invited to participate in this prospective cohort study. Blood samples of HCWs vaccinated with both ChAdOx1 doses over a period of 12 weeks were collected at weeks 4 and 8 post first vaccination and 2 weeks post second vaccination. Blood samples of HCWs vaccinated with BNT162b2 were collected in the third week after the first dose, and the second dose was then administered on the same day; two weeks post second dose (5 weeks after the first dose), blood samples were collected to assess the antibody response. The titers of anti-S antibodies against the severe acute respiratory syndrome coronavirus 2 spike (S) protein receptor-binding domain and the neutralizing antibodies in the collected blood were evaluated. RESULTS: Of the 309 HCWs enrolled in the study, 205 received ChAdOx1 and 104 received BNT162b2. Blood samples from participants receiving either the ChAdOx1 or BNT162b2 vaccine exhibited substantial anti-S and neutralizing antibody seropositivity subsequent to the second dose. All participants (100%) from both vaccine groups were seropositive for anti-S antibody, while 98% (201/205) of ChAdOx1-vaccinated individuals and 100% (104/104) of BNT162b2-vaccinated individuals were seropositive for neutralizing antibodies. The median levels of anti-S and neutralizing antibodies were significantly higher in the BNT162b2-vaccinated group than the ChAdOx1-vaccinated group; in particular, anti-S antibody titers of 1,020 (interquartile range, 571.0-1,631.0) U/mL vs. 2,360 (1,243-2,500) U/mL, P < 0.05, were recorded for the ChAdOx1 and BNT162b2 groups, respectively, and neutralizing antibody titers of 85.0 (65.9-92.1%) vs. 95.8 (94.4-96.6%), P < 0.05, were recorded for the ChAdOx1 and BNT162b2 groups, respectively. In the ChAdOx1 vaccine group, the neutralizing antibody level was significantly higher in women than in men (85.7 [70.3-92.5%] vs. 77.7 [59.2-91.0%], P < 0.05); however, the neutralizing antibody titer in the BNT162b2 vaccine group did not vary between the two sexes (95.9 [95.2-96.6%] vs. 95.2 [93.5-96.3%], P = 0.200). Analysis of the correlation of antibody profiles with age revealed that the levels of anti-S antibodies and signal inhibition rate (SIR) of neutralizing antibodies decreased significantly with age. CONCLUSION: Both the ChAdOx1- and BNT162b2-vaccinated groups showed high seropositivity for anti-S and neutralizing antibodies. The SIR of neutralizing antibodies in the ChAdOx1 vaccine group was higher in women than in men. Enhanced antibody responses were observed in participants vaccinated with BNT162b2 compared to those vaccinated with the ChAdOx1 vaccine.

Case of the Index Patient Who Caused Tertiary Transmission of COVID-19 Infection in Korea: the Application of Lopinavir/Ritonavir for the Treatment of COVID-19 Infected Pneumonia Monitored by Quantitative RT-PCR.

Since mid-December of 2019, coronavirus disease 2019 (COVID-19) infection has been spreading from Wuhan, China. The confirmed COVID-19 patients in South Korea are those who came from or visited China. As secondary transmissions have occurred and the speed of transmission is accelerating, there are rising concerns about community infections. The 54-year old male is the third patient diagnosed with COVID-19 infection in Korea. He is a worker for a clothing business and had mild respiratory symptoms and intermittent fever in the beginning of hospitalization, and pneumonia symptoms on chest computerized tomography scan on day 6 of admission. This patient caused one case of secondary transmission and three cases of tertiary transmission. Hereby, we report the clinical findings of the index patient who was the first to cause tertiary transmission outside China. Interestingly, after lopinavir/ritonavir (Kaletra, AbbVie) was administered, ß-coronavirus viral loads significantly decreased and no or little coronavirus titers were observed.

Molecular Epidemiology of Human Adenovirus-Associated Febrile Respiratory Illness in Soldiers, South Korea1.

During January 2013-April 2014, we subjected nasopharyngeal specimens collected from patients with acute febrile respiratory illness in a military hospital to PCR testing to detect 12 respiratory viruses and sequence a partial hexon gene for human adenovirus (HAdV) molecular typing. We analyzed the epidemiologic characteristics of HAdV infections and compared clinical characteristics of HAdV types. Among the 305 patients with acute febrile respiratory illness, we detected respiratory viruses in 139 (45.6%) patients; HAdV was the most prevalent virus (69 cases). Of the 40 adenoviruses identified based on type, HAdV-55 (29 cases) was the most prevalent, followed by HAdV-4 (9 cases). HAdV-55 was common in patients with pneumonia (odds ratio 2.17; 95% CI 0.48-9.86) and hospitalized patients (odds ratio 5.21; 95% CI 1.06-25.50). In soldiers with HAdV infection in Korea, HAdV-55 was the most prevalent type and might be associated with severe clinical outcomes.

Vaccination policy in Korean armed forces: current status and future challenge.

Infectious diseases have historically resulted in suspended or cancelled military operations. Vaccination for disease prevention is a critical component of the military's force readiness doctrine. Until recently, Korea had not recognized the importance of vaccinating military personnel. However, a 2011 meningococcal disease outbreak at an army recruit training center led to dramatic changes in the paradigm of traditional medical practice in the Korean armed forces. A new vaccination policy was formed by a 2012 Military Healthcare Service Act. Since then, Neisseria meningitidis, hepatitis A, and measles-mumps-rubella vaccines have been routinely administered to all new recruits early in basic training to ensure protection against these diseases. All active-duty soldiers also receive seasonal influenza vaccination annually. Despite quantitative improvements in vaccination policies, several instances of major infectious diseases and adverse vaccine reactions have threatened soldier health. In the future, vaccination policies in the Korean armed forces should be based on epidemiologic data and military medical research for vaccine use and safety management.

Acute lower respiratory tract infections in soldiers, South Korea, April 2011-March 2012.

During April 2011-March 2012, we retrospectively reviewed medical records for South Korea soldiers to assess the etiology and epidemiology of acute viral lower respiratory tract infections. Adenovirus was the most commonly identified virus (63.2%) and the most common cause of pneumonia (79.3%) and hospitalization (76.6%); 3 soldiers died of adenovirus-related illness.

Incidence and risk factors of tuberculosis in patients with human immunodeficiency virus infection.

Korea is a low prevalence country for human immunodeficiency virus (HIV) infection and has an intermediate tuberculosis (TB) burden. We previously reported that the incidence of TB in HIV-infected patients was 9.6 cases per 100 person-years (P-Y) between 1988 and 1997. The aims of the present study were to measure any change in incidence from the previous study, and to identify risk factors for TB in HIV-infected patients. We reviewed all medical records of HIV-infected patients who were followed-up in one tertiary hospital between 1998 and 2010. Over the total observation period of 5858.33 P-Y, TB developed in 70 patients (1.19 cases per 100 P-Y; 95% confidence interval [CI], 0.91-1.47 cases per 100 P-Y). Based on Poisson regression, one risk factor associated with TB was an initial CD4+ cell count below 200 cells/µL (relative risk, 2.34; 95% CI, 1.47-3.73). Mean CD4+ cell counts of pulmonary, extrapulmonary, and both pulmonary and extrapulmonary TB were 179.8 cells/µL, 138.3 cells/µL, and 114.2 cells/µL, respectively (P = 0.55). In conclusion, the incidence of TB in HIV-infected patients has decreased since the previous study. An initial CD4+ cell count below 200 cells/µL is an independent risk factor for development of TB in HIV-infected patients.

Rapidly Declining SARS-CoV-2 Antibody Titers within 4 Months after BNT162b2 Vaccination.

The efficacy and safety of the BNT162b2 vaccine are known, but antibodies are expected to decrease over time after vaccination. We collected blood samples from 104 fully vaccinated health care workers at 3 and 5 weeks after first vaccination and 4 months after second vaccination. Antibody titers and neutralizing antibodies were measured. In our study, both antibody titers and neutralizing antibodies increased significantly at 5 weeks after first vaccination but decreased rapidly at 4 months after second vaccination. Additionally, the results showed a significant decrease regardless of gender or age. Further studies are needed to help determine the interval of SARS-CoV-2 vaccinations.

Reactogenicity after the first and second doses of BNT162b2 mRNA coronavirus disease vaccine: a single-center study.

PURPOSE: This study was conducted to determine differences in adverse events associated with the first and second doses of the BNT162b2 coronavirus disease 2019 vaccine based on the age and sex of recipients. MATERIALS AND METHODS: An online survey on the post-vaccination adverse events of healthcare workers was conducted from March 2021 to April 2021. The differences in the types of adverse events, including severity, onset time, and duration of symptoms, and how the adverse events were dealt with by the patient were analyzed based on the age and sex. The profiles of adverse events were compared after the first and second vaccination doses. RESULTS: Among the 131 participants who participated in the online survey out of 208 vaccine recipients, 43 and 80 recipients of the BNT162b2 vaccine experienced adverse events after the first and second dose, respectively. No sex-related differences were observed in the profiles of adverse events in vaccinated recipients. The overall frequency of adverse events did not differ based on age after the first dose. After the second dose, the frequency of adverse events, including both local and systemic reactions was significantly higher in the younger age group than in the older age group. CONCLUSION: The BNT162b2 vaccine resulted in a higher frequency of adverse events after the second dose than after the first dose especially in the younger age group; however, no sex-related differences associated with these adverse events were observed.

Genetic factors influencing severe atazanavir-associated hyperbilirubinemia in a population with low UDP-glucuronosyltransferase 1A1*28 allele frequency.

BACKGROUND: High prevalence of severe atazanavir-associated hyperbilirubinemia in Asians with low prevalence of the UDP-glucuronosyltransferase (UGT)1A1*28 polymorphism suggests the importance of genetic factors other than UGT1A1*28 for atazanavir-associated hyperbilirubinemia in these populations. METHODS: Serum bilirubin levels were measured in 129 Korean human immunodeficiency virus-infected patients 3 months after initiation of atazanavir (400 mg per day) with good adherence to medication. The multidrug resistance gene 1 (MDR1) C3435T and G2677T/A variations and UGT1A1*6 and *28 were examined by direct sequencing of DNA from peripheral whole blood samples. The associations between genetic polymorphisms and severe (grade 3-4) hyperbilirubinemia were evaluated using multivariate logistic regression analysis including demographic and clinical variables. RESULTS: The median patient age was 39 years (interquartile range, 34-51 years), and 91% were men. At baseline, the median CD4 cell count was 261 cells/microL (interquartile range, 181-405 cells/microL). Severe hyperbilirubinemia was detected in 27 patients (21%). The independent risk factors for severe hyperbilirubinemia were low baseline CD4 cell count (adjusted odds ratio per 10 cells/microL increase, 0.97; 95% confidence interval, 0.94-0.99), UGT1A1*28 (adjusted odds ratio, 4.15; 95% confidence interval, 1.46-11.84), and MDR1 G2677T/A (adjusted odds ratio, 9.65; 95% confidence interval, 1.09-85.61). Of 19 patients with wild-type alleles for both MDR1 2677 and UGT1A1*28, none developed severe hyperbilirubinemia. CONCLUSION: The MDR1 G2677T/A variation and UGT1A1*28 are independent risk factors for severe atazanavir-associated hyperbilirubinemia in Korean human immunodeficiency virus-infected patients.

Clinical features, risk factors and outcomes of bacteremia due to enterococci with high-level gentamicin resistance: comparison with bacteremia due to enterococci without high-level gentamicin resistance.

High-level gentamicin resistance (HLGR) in enterococci has increased since the 1980s, but the clinical significance of the resistance and its impact on outcome have not been established. One hundred and thirty-six patients with bacteremia caused by enterococci with HLGR (HLGR group) were compared with 79 patients with bacteremia caused by enterococci without HLGR (non-HLGR group). Hematologic malignancy, neutropenia, Enterococcus faecium infection, nosocomial infection and monomicrobial bacteremia were more common in the HLGR group than the non-HLGR group, and APACHE II scores were also higher (P<0.05, in each case). Neutropenia, monomicrobial infection, stay in intensive care at culture, and use of 3rd generation cephalosporin, were independent risk factors for acquisition of HLGR enterococcal bacteremia. Fourteen-day and 30-day mortalities were higher in the HLGR group than the non-HLGR group in univariate analysis (37% vs. 15%, P=0.001; 50% vs. 22%, P<0.001). However, HLGR was not an independent risk factor for mortality due to enterococcal bacteremia in multivariate analysis. Therefore, HLGR enterococcal bacteremia is associated with more severe comorbid conditions and higher mortality than non-HLGR enterococcal bacteremia but the HLGR itself does not contribute significantly to mortality.

Spectrum of intracranial parenchymal lesions in patients with human immunodeficiency virus infection in the Republic of Korea.

The incidence of specific intracranial parenchymal lesions of HIV-infected patients varies considerably between countries. In the Republic of Korea, the number of HIV-infected patients is increasing, but little is known regarding the spectrum of intracranial parenchymal lesions in these patients. The aim of the present study was to obtain this information. To identify HIV patients with intracranial parenchymal lesions, the electronic database of radiological reports for 1,167 HIV-infected patients, seen from 1999 to 2008 at the Seoul National University Hospital, were reviewed. Neuroradiologic studies were performed on 165 of these patients, and intracranial parenchymal lesions were detected in 40 (3.4%) of them. Thirty-seven were male, and median age was 41 yr (range, 26-61). At the time of the diagnosis of intracranial parenchymal lesions, median CD4(+) lymphocyte count was 40 cells/microL (range 5-560) and in 33 (82.5%) patients, it was less than 200 cells/microL. Progressive multifocal leukoencephalopathy (12 patients) is the most frequent intracranial parenchymal lesions, followed by intracranial tuberculoma (7 patients), primary central nervous system lymphoma (7 patients), intracranial cryptococcoma (4 patients), Toxoplasma encephalitis (4 patients), and disseminated non-tuberculous mycobacterial infection (3 patients).

Should HLA-B*5701 screening be performed in every ethnic group before starting abacavir?

Human leukocyte antigen allele (HLA)-B*5701 is associated with abacavir hypersensitivity. However, the carriage rate of HLA-B*5701 has rarely been studied in Asians. In 534 Korean patients with human immunodeficiency virus infection, HLA-B*5701 status was determined by polymerase chain reaction with HLA-B*5701-specific primers. No patients had the HLA-B*5701 allele (95% confidence interval, 0%-0.7%). This explains the paucity of immunologically confirmed cases of abacavir hypersensitivity in Koreans.

Salvage treatment for persistent methicillin-resistant Staphylococcus aureus bacteremia: efficacy of linezolid with or without carbapenem.

BACKGROUND: Persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with high mortality rates, but no treatment strategy has yet been established. We performed this study to evaluate the efficacy of linezolid with or without carbapenem in salvage treatment for persistent MRSA bacteremia. METHODS: All adult patients with persistent MRSA bacteremia for 7 days from January 2006 through March 2008 who were treated at Seoul National University Hospital were studied. The results of linezolid salvage therapy with or without carbapenem were compared with those of salvage therapy with vancomycin plus aminoglycosides or rifampicin. RESULTS: Thirty-five patients with persistent MRSA bacteremia were studied. The early microbiological response (ie, negative results for follow-up blood culture within 72 hours) was significantly higher in the linezolid-based salvage therapy group than the comparison group (75% vs 17%; P =.006). Adding aminoglycosides or rifampicin to vancomycin was not successful in treating any of the patients, whereas linezolid-based therapy gave an 88% salvage success rate P =.001). The S. aureus-related mortality rate was lower for patients treated with a linezolid salvage regimen than for patients continually treated with a vancomycin-based regimen (13% vs 53%; P =.030). CONCLUSIONS: Linezolid-based salvage therapy effectively eradicated S. aureus from the blood for patients with persistent MRSA bacteremia. The salvage success rate was higher for linezolid therapy than for vancomycin-based combination therapy.

Clinical outcomes of spontaneous bacterial peritonitis due to extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella species: a retrospective matched case-control study.

BACKGROUND: Clinical outcomes of spontaneous bacterial peritonitis (SBP) due to extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella species (ESBL-EK) have not been adequately investigated. METHODS: We conducted a retrospective matched case-control study to evaluate the outcomes of SBP due to ESBL-EK compared with those due to non-ESBL-EK. Cases were defined as patients with liver cirrhosis and SBP due to ESBL-EK isolated from ascites. Control patients with liver cirrhosis and SBP due to non-ESBL-EK were matched in a 3:1 ratio to cases according to the following five variables: age (+/- 5 years); gender; species of infecting organism; Child-Pugh score (+/- 2); Acute Physiological and Chronic Health Evaluation II score (+/- 2). 'Effective initial therapy' was defined as less than 72 hours elapsing between the time of obtaining a sample for culture and the start of treatment with an antimicrobial agent to which the EK was susceptible. Cephalosporin use for ESBL-EK was considered 'ineffective', irrespective of the minimum inhibitory concentration. ESBL production was determined according to the Clinical and Laboratory Standards Institute guidelines on stored isolates. RESULTS: Of 1026 episodes of SBP in 958 patients from Jan 2000 through Dec 2006, 368 (35.9%) episodes in 346 patients were caused by SBP due to EK, isolated from ascites. Of these 346 patients, twenty-six (7.5%) patients with SBP due to ESBL-EK were compared with 78 matched controls. Treatment failure, evaluated at 72 hours after initial antimicrobial therapy, was greater among the cases (15/26, 58% vs. 10/78, 13%, P = .006); 30-day mortality rate was also higher than in the controls (12/26, 46% vs. 11/78, 15%, P = .001). When the case were classified according to the effectiveness of the initial therapy, 'ineffective initial therapy' was associated with higher 30-day mortality rate (11/18, 61% vs. 1/8, 13%, P = .036). CONCLUSION: SBP due to ESBL-EK had poorer outcomes than SBP due to non-ESBL-EK. Ineffective initial therapy seems to be responsible for the higher rate of treatment failure and mortality in SBP due to ESBL-EK.

Prevalence of primary antiretroviral resistance: trends in Korea.

Primary drug resistance is an emerging problem in HIV infections. We have investigated the current prevalence of primary resistance in Korea and compared it with previous data. Drug-naive HIV patients attending the outpatient clinic of Seoul National University Hospital between April and August 2006 were enrolled. A medical interview and a genotypic resistance test were performed for each patient. The International AIDS Society-USA Panel consensus statement issued in 2006 was used to define resistance mutations. Eighty-one drug-naive HIV patients were enrolled. Two (2.5%) were infected with primary drug-resistant virus: M41L and K103N, respectively. In our previous study, conducted between 1998 and 2002, three (6%) of 50 subjects harbored resistant viruses. Thus the frequency of primary resistance was lower in the present sample than in the earlier one, though the difference is not statistically significant (p = 0.37). In view of our findings, routine antiretroviral resistance tests for drug-naive HIV patients are not obligatory in Korea.

Effect of tumor necrosis factor-alpha on intracellular Staphylococcus aureus in vascular endothelial cells.

Although tumor necrosis factor-alpha (TNF-alpha) is an important host factor against intracellular bacteria, little is known about the effect of TNF-alpha on the persistence of intracellular Staphylococcus aureus in vascular endothelial cells. It was investigated whether recombinant human TNF-alpha influences the survival of intracellular S. aureus (ATCC 29213) in human umbilical vein endothelial cells (HUVEC) under a condition with an antistaphylococcal agent, and its mechanism. The HUVECs were incubated with TNF-alpha, oxacillin, or both in 24-well plates for up to 48 h following internalization of S. aureus (10(6) CFU well(-1)) into HUVECs for 1 h. TNF-alpha (1 ng mL(-1)) significantly reduced the number of intracellular S. aureus in HUVECs, and TNF-alpha plus oxacillin eliminated more intracellular S. aureus in HUVEC than oxacillin alone. The LDH viability assay and quantification of apoptosis using photometric enzyme-immunoassay showed that TNF-alpha preferentially induced cell death and apoptosis of HUVECs infected with S. aureus compared with noninfected HUVECs. These results indicate that TNF-alpha helps antistaphylococcal antibiotics to eliminate intracellular S. aureus in vascular endothelial cells, partly because TNF-alpha preferentially induces apoptosis of endothelial cells infected by S. aureus.