Tubo-ovarian abscess caused by Clostridioides difficile after eight months of surgery: Case report and review of extraintestinal abdominal abscess cases.

We present a case of tubo-ovarian abscess (TOA) caused by Clostridioides difficile (CD) in a 43-year-old female. Despite lacking a history of sexually transmitted diseases, the patient had undergone paraovarian cystectomy nine months before admission. Transvaginal ultrasonography performed eight months post-surgery revealed left ovarian enlargement, accompanied by subsequent lower abdominal pain and fever exceeding 38 °C. As oral antibiotic treatment was ineffective, the patient was admitted to our hospital. Computed tomography upon admission revealed a massive TOA. Surgical drainage of the abscess was performed, and CD was identified in the culture from the pus. The TOA was treated with a three-month course of metronidazole and oral amoxicillin/clavulanic acid. While CD is commonly associated with colitis, extraintestinal manifestations are exceptionally rare. This case represents the inaugural report of TOA resulting from CD. A literature review on abdominal and pelvic CD abscesses found that patients undergoing surgical drainage had a favorable prognosis. Therefore, surgical intervention plays an important role in the management of CD abscesses.

Staphylococcus haemolyticus attenuates the antibacterial effect of teicoplanin via aggregates and biofilms.

OBJECTIVES: This study aimed to determine the inhibitory and bactericidal effects of teicoplanin (TEC) on TEC-susceptible Staphylococcus haemolyticus isolated from a patient with cancer in whom infection persisted despite TEC therapy. We also focused on the biofilm-forming ability of the isolate in vitro. METHODS: S. haemolyticus clinical isolate (strain 1369A) and its control strain, ATCC 29970 were cultured in Luria-Bertani (LB) broth with TEC. The inhibitory and bactericidal effects of TEC on planktonic, adherent, biofilm-dispersed, and biofilm-embedded cells of these strains were analyzed by using a biofilm formation/viability assay kit. The expression of biofilm-related genes was measured using quantitative real-time polymerase chain reaction (qRT-PCR). Biofilm formation was determined by using scanning electron microscopy (SEM). RESULTS: The clinical isolate of S. haemolyticus had enhanced ability to bacterial growth, adherence, aggregation, and biofilm formation, thus the inhibitory and bactericidal effects of TEC on planktonic, adherent, biofilm-dispersed, and biofilm-embedded cells of the isolate were attenuated. Additionally, TEC induced cell aggregation, biofilm formation, and some biofilm-related gene expression of the isolate. CONCLUSION: The clinical isolate of S. haemolyticus is resistant to TEC treatment due to cell aggregation and biofilm formation.

Changes in health and sleep quality after anti-retroviral treatment modification in Japanese people living with HIV.

BACKGROUND: Anti-retroviral treatment (ART) modification for treatment simplification is performed in virologically controlled people living with Human Immunodeficiency Virus (PLWH). However, studies on the impact of these stable treatment modifications on health-related quality of life (HRQoL) measured using patient-reported outcomes (PROs) in clinical practice are scarce; this was the focus of this study. METHODS: PLWH who visited Teikyo University Hospital between October 2019 and March 2021, and whose ART was changed to a newly recommended single-tablet regimen for treatment simplification, were included in the study. HRQoL and sleep quality were evaluated using the Short-Form (SF) 8 and Pittsburgh Sleep Quality Index (PSQI) global score, respectively, at two time points: before and after treatment modification. Comorbidities, duration of Human Immunodeficiency Virus diagnosis, ART initiation, ART regimens, and blood test data before and after treatment were assessed. The SF-8 was used to calculate the physical component summary (PCS) and mental component summary (MCS) scores. RESULTS: Forty-nine patients (all male) were included into the study. There was no change in the PCS score before and after ART modification. The MCS score significantly improved from 48.50 ± 6.56 to 50.76 ± 4.37 (p = 0.0159). Thirteen patients' ARTs were changed to dolutegravir/lamivudine. Their HRQoL and sleep quality changes were further analyzed. Their MCS and PSQI scores had improved significantly. Thirty patients' ARTs were changed to bictegravir/tenofovir alafenamide/emtricitabine; however, there were no significant changes in their HRQoL or PSQI score. CONCLUSION: ART modification for treatment simplification based on PROs may improve the HRQoL of PLWH.

Urine neutrophil gelatinase-associated lipocalin as a biomarker of adult pyelonephritis.

BACKGROUND: Pyelonephritis is a common infection at any age. Urine neutrophil gelatinase-associated lipocalin (NGAL), a novel biomarker of acute renal failure, is related to pyelonephritis in pediatric patients, although the significance of this urine biomarker in adult patients are not clear. We investigated the relationship between urine NGAL of pyelonephritis and non-pyelonephritis. PATIENTS AND METHODS: We prospectively enrolled adult patients who were hospitalized due to pyelonephritis or non-pyelonephritis. Pyelonephritis was diagnosed in patients with fever and bacteriuria, with no any other infection focuses. Non-pyelonephritis was diagnosed in patients who had fever and another infection focus without bacteriuria. Urine samples were collected on days 0, 3 and 7. Urine NGAL levels were measured by ELISA. RESULTS: There were 35 patients in the pyelonephritis group and 19 patients in the non-pyelonephritis group. Urine NGAL level were significantly higher in the pyelonephritis group than the non-pyelonephritis group on day 0 (median 302 ng/mL vs 25 ng/mL, p = 0.006). The area under the receiver operating characteristic curve of NGAL was 0.78 (p = 0.006). Urine NGAL level had a specificity of 66.7% and sensitivity of 87.0% at the cut-off level of 250 ng/mL for diagnosing pyelonephritis. CONCLUSIONS: Urine NGAL level at the diagnosis of infection are elevated in adult patients with pyelonephritis, but not in those with non-pyelonephritis. Urine NGAL might be a supportive biomarker for the diagnosis of pyelonephritis.

First case of necrotizing fasciitis and bacteremia caused by Bifidobacteriumbreve.

We report the first case of necrotizing fasciitis and bacteremia caused by Bifidobacterium breve. Some Bifidobacterium breve strains are known as probiotic bacterium. However, it causes bacteremia in infants and immunocompromised patients. Our patient developed necrotizing fasciitis which was thought to have been infected from chronic diabetic foot ulcers. Bifidobacterium breve was isolated from the patient's blood and soft tissue sample. The patient underwent amputation and intravenous antibiotics administration.

Changing trends in lipid profile and biomarkers of renal function and bone metabolism before and after switching from tenofovir disoproxil fumarate to tenofovir alafenamide: a prospective observational study.

BACKGROUND: Antiretrovirals, including tenofovir, can suppress human immunodeficiency virus (HIV) infection but cannot completely eradicate it. Patients with HIV infection are administered antiretroviral drugs over a long term; thus, managing consequent adverse drug reactions, such as renal dysfunction and bone mineral loss, is important. Currently, highly sensitive biomarkers that can detect adverse drug reactions early have not been well studied. METHODS: This single-center, prospective, observational study explored changes in the biomarkers of renal function, bone metabolism, and lipid profile before and after switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) in patients with HIV infection. RESULTS: All 31 enrolled patients had been treated with antiretrovirals for more than 5 years. The rate of proteinuria decreased significantly after starting TAF-containing antiretroviral regimen. The urinary liver-type fatty acid binding protein (L-FABP)/creatinine ratio was significantly decreased at 3 and 6 months after switching to TAF compared with that before switching to TAF (- 0.5 µg/g Cr at 3 months, and - 0.8 µg/g Cr at 6 months; p < 005 for both at 3 and 6 months). The urinary N-terminal telopeptide (NTx)/creatinine ratio decreased over the study period, and the ratios were significantly different between 3 and 6 months (- 11 nmol/mmol Cr at 3 months, - 15.2 nmol/mmol Cr at 6 months; p = 0.0069 at 3 months, p < 0.0001 at 6 months). Low density lipoprotein-cholesterol level significantly increased at 3 (+ 26 mg/dL) and 6 months (+ 13 mg/dL) compared with that at the baseline (p < 0.0001). CONCLUSIONS: Switching from TDF to TAF decreased the levels of renal and bone biomarkers, such as urinary L-FABP and NTx, but increased low density lipoprotein-cholesterol levels. Future studies should evaluate if these biomarkers, such as urinary L-FABP and NTx, truly detect serious adverse drug reactions early.

Severe cellulitis caused by Achromobacter xylosoxidans after allogeneic hematopoietic stem cell transplantation.

Achromobacter xylosoxidans (A. xylosoxidans) is an aerobic gram-negative bacillus and often isolated from aquatic environments. It is supposed to cause infections in patients with malignancy or immunodeficiency. It causes various healthcare-associated infections, but cellulitis is rare. Herein, we report the first case of sever cellulitis by A. xylosoxidans after allogeneic hematopoietic stem cell transplantation (HSCT). A 49-year-old man underwent allogeneic HSCT from 8/8 HLA-matched unrelated donor with myeloablative conditioning for relapsed acute myeloid leukemia. He developed skin chronic graft versus host disease 11 months after HSCT. During the prolonged treatment with prednisolone and cyclosporine, he developed cellulitis on his left leg and admitted to our hospital. Blood and exudate culture revealed A. xylosoxidans. Although empirical therapy with cefepime was ineffective, his symptoms were dramatically improved after administration of meropenem. To our knowledge, this is the first case of A. xylosoxidans cellulitis after allogeneic HSCT. A. xylosoxidans should be considered as a possible cause of cellulitis in post-allogeneic HSCT patients on prolonged immunosuppressive therapy.

A rare case of a prostatic abscess, bacteremia and chronic granulomatous disease associated with Klebsiella pneumoniae.

Chronic granulomatous disease (CGD) is a primary immunodeficiency disease characterized by severe recurrent infections such as pneumonia, liver and skin infections. However, prostatic abscesses are rare as only two cases have been reported thus far. We present the case of a 41-year-old patient with CGD who was admitted to the hospital with fever and subsequently, Klebsiella pneumoniae was identified on blood culture. Abdominal computed tomography revealed a prostatic abscess. He improved with intravenous antibiotics and drainage of the abscess. After he was taken off the intravenous antibiotics and started on an oral agent, he was discharged from the hospital. We confirmed a reduction in the prostatic abscess size and continued the antibiotic therapy for 52 days. A prostatic abscess is an uncommon disease being diagnosed at a median age of 49 years. Sometimes it is discovered in patients with fever of unknown origin and might be considered as an infection site of CGD patients.

Bacterial peritonitis in a patient with malignant ascites caused by pancreatic carcinoma: Case report and review of literature.

Bacterial peritonitis, an infection of the ascitic fluid, can be classified etiologically as spontaneous or secondary bacterial peritonitis. The former is mainly caused by portal hypertension and its subsequent effects, whereas the latter is caused by the direct dissemination of bacteria into the peritoneal cavity. Previous reports have described some distinguishing features of these two entities. Here, we report the first known case of bacterial peritonitis with Aeromonas hydrophilia and Escherichia coli in a patient with malignant ascites associated with pancreatic carcinoma who exhibited features of both spontaneous and secondary peritonitis. Our report suggests that clinicians should also consider bacterial peritonitis in patients with malignant ascites who present with ostensibly cancer-related symptoms.

Bilateral Candida endophthalmitis accompanying Candida lusitaniae bloodstream infection: A case report.

Candida lusitaniae is an uncommon cause of candidiasis in humans. Ocular manifestations of C. lusitaniae infection have not been reported. C. lusitaniae is either intrinsically resistant to amphotericin B or can acquire such resistance. We describe a case of bilateral endophthalmitis due to C. lusitaniae bloodstream infection in a liver transplant patient with rectal cancer. The patient suffered fungemia and endophthalmitis and was treated with liposomal amphotericin B. The isolate was identified as C. lusitaniae by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, the system based on biochemical tests, and sequencing of the internal transcribed spacer region. The minimal inhibitory concentrations were 0.06 µg/mL for amphotericin B and 2.0 µg/mL for fluconazole. Repeat blood cultures were negative and the endophthalmitis improved following treatment with liposomal amphotericin B. However, the treatment was changed to fluconazole due to nephrotoxicity. No recurrence occurred after completion of treatment.

Catheter-related bloodstream infection caused by Kodamaea ohmeri: A case report and literature review.

Kodamaea ohmeri is a rare yeast pathogen that has recently emerged as an important cause of fungemia in immunocompromised patients. However, appropriate therapy for this infection remains unclear. We report a case of catheter-related blood stream infection caused by K. ohmeri in a 58-year-old patient who improved after removal of the central venous catheter and administration of micafungin. Considering the antibiotic susceptibility of this pathogen and reviewing literature, echinocandins may be the first choice for an empiric therapy for this pathogen.

A pathologically proven case of adult-onset HIV-related lymphocytic interstitial pneumonia with acute exacerbation treated with steroid and antiretroviral therapy.

Lymphocytic interstitial pneumonia (LIP) is a rare opportunistic illness in human immunodeficiency virus (HIV)-infected adults, although it is relatively common among HIV-infected children. Most adult cases have been reported in African and Afro-Caribbean patients and few cases have been reported from Asia. Acute exacerbation of HIV-related LIP has not been well described. Here we report a pathologically proven case of acute exacerbation of adult-onset HIV-related LIP. The patient was an African immigrant living in Japan who presented with chronic dyspnea and diffuse bilateral pulmonary infiltrates. His clinical, radiological, and pathological findings were consistent with those of LIP. After a diagnostic surgical lung biopsy, his hypoxemia and pulmonary infiltrates exacerbated rapidly over a few days, although his condition had not progressed during the previous year. LIP may be an important differential diagnosis among adult patients in Asian countries, especially patients of non-Asian ethnicity.

Disseminated Nontuberculous Mycobacterium Infection During Treatment of Multiple Myeloma: A Case Report and Review of the Literature.

Multiple myeloma (MM) is a plasma B-cell malignancy characterized by immune dysfunction, with infection representing a major complication. Bacteria, including Streptococcus pneumoniae, are common pathogens in patients with MM, but reports on infections with nontuberculous mycobacteria (NTM) have been limited. We herein report a case of disseminated NTM infection in a patient with MM undergoing treatment with immunomodulatory drugs. At the diagnosis, the patient showed lymphocytopenia and was treated with clarithromycin, rifampicin, and ethambutol; however, culture positivity persisted, and the patient died. The possibility of NTM infection should be considered in cases of unexplained deterioration of the MM patient's general condition.

Low visceral fat volume and hypoalbuminemia as prognostic markers in hospitalized patients with coronavirus disease 2019 during the omicron variant epidemic.

BACKGROUND & AIMS: The rate of severe cases of coronavirus disease 2019 (COVID-19) has decreased since the Omicron variant became epidemic. Visceral fat volume was a risk factor for COVID-19 severity with prior prevalent variants, but whether visceral fat volume remains a risk factor for the Omicron variant is unclear. We investigated the associations of clinical factors including visceral fat volume with severity and mortality among hospitalized patients with COVID-19 during the Omicron variant epidemic. METHODS: This was a single-center retrospective cohort study conducted at the Teikyo University Hospital in Japan. We included hospitalized patients with COVID-19 during the Omicron variant epidemic who underwent computed tomography of the abdomen. Clinical data were obtained from the medical records and visceral fat area (VFA) was measured using a 3-dimensional image analysis system volume analyzer. Severity was determined by the presence or absence of oxygen supplementation. RESULTS: Among the 226 patients, 66 patients showed moderate severity and 29 patients were non-survivors. Hypoalbuminemia was associated with severity (odds ratio [OR] 3.93, 95 % confidence interval [CI] 1.91-8.07; p = 0.0002), and hypoalbuminemia (OR 8.38, 95%CI 2.37-29.58; p = 0.0010) and low VFA (OR 3.40, 95%CI 1.15-10.06; p = 0.027) were associated with mortality. Decision tree analysis showed that mortality rate in the hypoalbuminemia and low-VFA group (37.3 %) was significantly higher than in other groups (p ≤ 0.01). CONCLUSIONS: Low visceral fat volume and hypoalbuminemia were associated with mortality in hospitalized patients with COVID-19 during the Omicron variant epidemic. Classification by VFA and serum albumin may allow simple prediction of mortality risk among hospitalized patients with COVID-19.

High D-glucose levels induce ACE2 expression via GLUT1 in human airway epithelial cell line Calu-3.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the host cell by binding to angiotensin-converting enzyme 2 (ACE2) receptors. ACE2 is expressed on human airway epithelial cells. Increased ACE2 expression may be associated with potentially high risk of COVID-19. However, the factors responsible for the regulation of ACE2 expression in human airway epithelial cells are unknown. Furthermore, hyperglycemia is a risk factor for poor disease prognosis. RESULTS: In this study, we investigated the effects of D-glucose on ACE2 mRNA and protein expressions in Calu-3 bronchial submucosal cells. The cells were cultured in minimal essential medium containing different D-glucose concentrations. After 48 and 72 h of high D-glucose (1000 mg/dL) treatment, ACE2 mRNA expressions were significantly increased. ACE2 protein expressions were significantly increased after 24 h of high D-glucose treatment. ACE2 mRNA expression was enhanced by a D-glucose concentration of 550 mg/dL or more after 72 h of treatment. In addition, we investigated the role of glucose transporters (GLUTs) in Calu-3 cells. ACE2 mRNA and protein expressions were suppressed by the GLUT1 inhibitor BAY-876 in high D-glucose-treated Calu-3 cells. GLUT-1 siRNA was also used and ACE2 mRNA expressions were suppressed in high D-glucose-treated Calu-3 cells with GLUT-1 knockdown. CONCLUSIONS: This is the first report indicating that high D-glucose levels induced ACE2 expression via GLUT1 in bronchial submucosal cells in vitro. As hyperglycemia can be treated appropriately, these findings could help reduce the risk of worsening of coronavirus disease 2019.

Association Between the Levels of Serum Free Testosterone and Lifestylerelated Diseases in People Living with HIV.

BACKGROUND: Recently, male hypogonadism was reported to be prevalent in people living with HIV (PLWH), even in cases diagnosed based on the serum free testosterone level (fTST). However, studies on the management of PLWH showing the relationship between male hypogonadism and lifestyle-associated diseases, are sparse. OBJECTIVE: This study evaluated the relationship between serum fTST levels and lifestyle-related diseases in virologically stable PLWH. METHODS: This study was a retrospective cohort single-center study. The study included HIVinfected men on antiretroviral therapy, with available data on serum fTST levels at Teikyo University Hospital between June 2020 and September 2020. Clinical information was collected at the time of fTST measurement. A simple regression analysis was used to identify continuous variables significantly associated with serum fTST levels. Student's t-test and Mann-Whitney U test were also used to identify non-continuous variables that were significantly correlated with serum fTST levels. RESULTS: Sixty male patients were evaluated. The median age was 47 (40-62) years. Low serum fTST levels were significantly associated with old age, low hemoglobin and total cholesterol levels, and high hemoglobin A1c levels. Non-use of INSTI and comorbid hypertension were also significantly associated with low serum fTST levels. CONCLUSION: Hypertension and the serum hemoglobin A1c level as a standard parameter for diabetes was significantly associated with low serum fTST levels in Japanese male PLWH. This study suggested that sex-hormone replacement therapy could be a preferred option for PLWH with low serum fTST levels to manage their long-term complications.

Relationship of sleep disorders with long-term complications and health-related quality of life in people with well-controlled human immunodeficiency virus.

ABSTRACT: Although sleep disorders are common in patients with human immunodeficiency virus (HIV) infection, they have not been adequately evaluated under currently advanced treatments, mainly with integrase strand transfer inhibitors. However, the relationship of sleep disorders with long-term complications and quality of life (QOL) status in patients infected with HIV is still poorly understood. Such associations are important in the management of outpatients with HIV. Hence, this study aimed to evaluate these associations.This cross-sectional observational study assessed the QOL changes of patients with HIV before and after the treatment regimen change. Male patients with well-controlled HIV who attended our hospital and changed HIV medications for reasons other than treatment failure between October 2019 and September 2021 were included. At the time of regimen change, sleep disorder status was assessed according to the Pittsburgh sleep quality index (PSQI), and health-related QOL (HRQOL) was assessed using the medical outcomes study 8-item short form health survey. In addition, we collected information on age, blood tests, and long-term comorbid conditions present during the evaluation. The HIV treatment regimen was also reviewed.Out of 45 male Japanese patients with HIV that were included in this study, 24 (53.3%) and 21 (46.7%) were classified into the sleep disorder group and nonsleep disorder group, respectively, according to their PSQI scores. The sleep disorder group had a significantly lower HRQOL mental component summary (P = .0222) than the nonsleep disorder group. The prevalence rates of hypertension, dyslipidemia, and diabetes mellitus were not significantly different between the 2 groups. In addition, a significant correlation was observed between PSQI scores and the HRQOL status (mental component summary, P = .0450; physical component summary, P = .0350).Sleep disorders remain common in patients with well-controlled HIV infection receiving current treatment. Sleep disorder is significantly associated with a low HRQOL in these patients. Hence, sleep status evaluation is necessary to improve HIV management.

Prospective audit and feedback implementation by a multidisciplinary antimicrobial stewardship team shortens the time to de-escalation of anti-MRSA agents.

Prospective audit and feedback (PAF) is considered an effective procedure for appropriate antibiotic use. However, its effect on the time to de-escalation is unclear. We aimed to evaluate the effect of daily PAF implementation, focusing on the time to de-escalation of anti-methicillin-resistant Staphylococcus aureus (MRSA) agents as an outcome measure. To this end, a single-center, retrospective, quasi-experimental study including patients treated with intravenous anti-MRSA agents during pre-PAF (April 1, 2014 to March 31, 2015) and post-PAF (April 1, 2015 to March 31, 2016) periods was conducted. The time to de-escalation was estimated using the Kaplan-Meier method, and Cox proportional hazard analysis was performed to assess the effect of daily PAF implementation on the time to de-escalation. Interrupted time series analysis was used to evaluate the relationship between daily PAF implementation and anti-MRSA agent utilization data converted to defined daily dose (DDD) and days of therapy (DOT) per 1,000 patient days. The median time to de-escalation was significantly shorter in the post-PAF period than in the pre-PAF period (6 days vs. 7 days, P < 0.001). According to multivariate analysis, PAF implementation was independently associated with a shorter time to de-escalation (hazard ratio [HR], 1.18; 95% confidence interval [CI], 1.02 to 1.35). There were no significant differences in hospital mortality, 30-day mortality, and length of stay between the two periods. Interrupted time series analysis showed significant reductions in the trends of DDD (trend change, -0.65; 95% CI, -1.20 to -0.11) and DOT (trend change, -0.74; 95% CI, -1.33 to -0.15) between the pre-PAF and post-PAF periods. Daily PAF implementation for patients treated with intravenous anti-MRSA agents led to a shorter time to de-escalation and lower consumption of anti-MRSA agents without worsening the clinically important outcomes.

A Cold-Blooded Tiptoer: Nonresolving Cellulitis in an Immunocompromised Patient.

Mycobacterium haemophilum is a nontuberculous mycobacteria (NTM) with a predilection for skin and soft tissue infection (SSTI) in the immunocompromised host. We report a case of disseminated M haemophilum infection initially presenting as a nonresolving subacute cellulitis of bilateral lower extremities. Genetic sequencing was used for final identification, while a commercially available polymerase chain reaction test returned a false-positive result for Mycobacterium intracellulare. Consequently, we highlight the importance of M haemophilum as a major differential diagnosis of SSTI in the immunocompromised host and the need for careful interpretation of rapid diagnostic tests.

The Clinical Effect of Seasonal Flu Vaccination on Health-Related Quality of Life.

PURPOSE: This study aimed to determine the clinical effect of seasonal flu vaccination in adult outpatients based on the effect on health-related quality of life (HRQOL). PATIENTS AND METHODS: We reviewed the clinical data of adult flu outpatients with mild symptoms who presented to the outpatient clinic of Teikyo University Hospital, Tokyo, Japan, from 2018 to 2020 winter season and were enrolled in the prospective observational study of the clinical efficacy of anti-flu agents (UMIN000034896). We evaluated influenza vaccination status, clinical symptoms, and the status of HRQOL as measured by Short Form-8® (SF-8®) at first visit. The SF-8® survey generated two-component summaries; a physical component summary and a mental component summary. RESULTS: The data of 79 patients were evaluated in this study. Of the 79 patients, 37 were vaccinated for influenza at least three weeks before contracting seasonal influenza. Not every patient needed to be hospitalized for treatment. There were no significant differences in clinical backgrounds between vaccinated patients and non-vaccinated patients. Univariate analysis showed influenza vaccination was significantly associated with higher scores on the physical component summary of HRQOL (p=0.0011). CONCLUSION: Influenza vaccinations would be clinically valuable for adult outpatients with seasonal flu and mild symptoms, because they can significantly inhibit the decrease of HRQOL due to influenza infection.