Comparative analysis of perioperative and long-term outcomes of patients with hepatocellular carcinoma: Nonalcoholic fatty liver disease versus viral hepatitis.

BACKGROUND: Despite the accumulating evidence regarding the oncological differences between nonalcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC) and viral infection-related HCC, the short- and long-term outcomes of surgical resection of NAFLD-related HCC remain unclear. While some reports indicate improved postoperative survival in NAFLD-related HCC, other studies suggest higher postoperative complications in these patients. METHODS: Patients with NAFLD and those with hepatitis viral infection who underwent hepatectomy for HCC at our department were retrospectively analyzed. The clinical, surgical, pathological, and survival outcomes were compared between the two groups. RESULTS: Among the 1047 consecutive patients who underwent hepatectomy for HCC, 57 had NAFLD-related HCC (NAFLD group), and 727 had virus-related HCC (VH group). The body mass index and serum glycated hemoglobin levels were significantly higher in the NAFLD group than in the VH group. There were no significant differences in operative time and bleeding amount. Moreover, the morbidity and the length of postoperative hospital stays were similar across both groups. The pathological results showed that the tumor size was significantly larger in the NAFLD group than in the VH group. No significant differences between the groups in overall or recurrence-free survival were found. In a subgroup analysis with matched tumor diameters, patients in the NAFLD group had a better prognosis after hepatectomy than those in the VH group. CONCLUSION: Surgical outcomes after hepatectomy were comparable between the groups. Subgroup analysis reveals early detection and surgical intervention in NAFLD-HCC may improve prognosis.

Prevalence and Associated Factors of Depression and Anxiety Among Healthcare Workers During the Coronavirus Disease 2019 Pandemic: A Nationwide Study in Korea.

BACKGROUND: A healthcare system's collapse due to a pandemic, such as the coronavirus disease 2019 (COVID-19), can expose healthcare workers (HCWs) to various mental health problems. This study aimed to investigate the impact of the COVID-19 pandemic on the depression and anxiety of HCWs. METHODS: A nationwide questionnaire-based survey was conducted on HCWs who worked in healthcare facilities and public health centers in Korea in December 2020. Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) were used to measure depression and anxiety. To investigate factors associated with depression and anxiety, stepwise multiple logistic regression analysis was performed. RESULTS: A total of 1,425 participating HCWs were included. The mean depression score (PHQ-9) of HCWs before and after COVID-19 increased from 2.37 to 5.39, and the mean anxiety score (GAD-7) increased from 1.41 to 3.41. The proportion of HCWs with moderate to severe depression (PHQ-9 ≥ 10) increased from 3.8% before COVID-19 to 19.5% after COVID-19, whereas that of HCWs with moderate to severe anxiety (GAD-7 ≥ 10) increased from 2.0% to 10.1%. In our study, insomnia, chronic fatigue symptoms and physical symptoms after COVID-19, anxiety score (GAD-7) after COVID-19, living alone, and exhaustion were positively correlated with depression. Furthermore, post-traumatic stress symptoms, stress score (Global Assessment of Recent Stress), depression score (PHQ-9) after COVID-19, and exhaustion were positively correlated with anxiety. CONCLUSION: In Korea, during the COVID-19 pandemic, HCWs commonly suffered from mental health problems, including depression and anxiety. Regularly checking the physical and mental health problems of HCWs during the COVID-19 pandemic is crucial, and social support and strategy are needed to reduce the heavy workload and psychological distress of HCWs.

Workload of Healthcare Workers During the COVID-19 Outbreak in Korea: A Nationwide Survey.

BACKGROUND: As the coronavirus disease 2019 (COVID-19) pandemic is ongoing, heavy workload of healthcare workers (HCWs) is a concern. This study investigated the workload of HCWs responding to the COVID-19 outbreak in South Korea. METHODS: A nationwide cross-sectional survey was conducted from September 16 to October 15, 2020, involving 16 healthcare facilities (4 public medical centers, 12 tertiary-care hospitals) that provide treatment for COVID-19 patients. RESULTS: Public medical centers provided the majority (69.4%) of total hospital beds for COVID-19 patients (n = 611), on the other hand, tertiary care hospitals provided the majority (78.9%) of critical care beds (n = 57). The number of beds per doctor (median [IQR]) in public medical centers was higher than in tertiary care hospitals (20.2 [13.0, 29.4] versus 3.0 [1.3, 6.6], P = 0.006). Infectious Diseases physicians are mostly (80%) involved among attending physicians. The number of nurses per patient (median [interquartile range, IQR]) in tertiary-care hospitals was higher than in public medical centers (4.6 [3.4-5] vs. 1.1 [0.8-2.1], P = 0.089). The median number of nurses per patient for COVID-19 patients was higher than the highest national standard in South Korea (3.8 vs. 2 for critical care). All participating healthcare facilities were also operating screening centers, for which a median of 2 doctors, 5 nurses, and 2 administrating staff were necessary. CONCLUSION: As the severity of COVID-19 patients increases, the number of HCWs required increases. Because the workload of HCWs responding to the COVID-19 outbreak is much greater than other situations, a workforce management plan regarding this perspective is required to prevent burnout of HCWs.

Maternal and Neonatal Outcomes in Pregnant Women With Coronavirus Disease 2019 in Korea.

BACKGROUND: This study aimed to describe the maternal, obstetrical, and neonatal outcomes in pregnant women with coronavirus disease 2019 (COVID-19) and identify the predictors associated with the severity of COVID-19. METHODS: This multicenter observational study included consecutive pregnant women admitted because of COVID-19 confirmed using reverse transcriptase-polymerase chain reaction (RT-PCR) test at 15 hospitals in the Republic of Korea between January 2020 and December 2021. RESULTS: A total of 257 women with COVID-19 and 62 newborns were included in this study. Most of the patients developed this disease during the third trimester. Nine patients (7.4%) developed pregnancy-related complications. All pregnant women received inpatient treatment, of whom 9 (3.5%) required intensive care, but none of them died. The gestational age at COVID-19 diagnosis (odds ratio [OR], 1.096, 95% confidence interval [CI], 1.04-1.15) and parity (OR, 1.703, 95% CI, 1.13-2.57) were identified as significant risk factors of severe diseases. Among women who delivered, 78.5% underwent cesarean section. Preterm birth (38.5%), premature rupture of membranes (7.7%), and miscarriage (4.6%) occurred, but there was no stillbirth or neonatal death. The RT-PCR test of newborns' amniotic fluid and umbilical cord blood samples was negative for severe acute respiratory syndrome coronavirus 2. CONCLUSION: At the time of COVID-19 diagnosis, gestational age and parity of pregnant women were the risk factors of disease severity. Vertical transmission of COVID-19 was not observed, and maternal severity did not significantly affect the neonatal prognosis.

Veno-arterial extracorporeal membrane oxygenation for severe fever with thrombocytopenia syndrome with fulminant myocarditis: a case report.

BACKGROUND: The clinical spectrum of severe fever with thrombocytopenia syndrome (SFTS) is wide, which can range from fever to multiple organ failure. Conservative therapy plays a key role in the treatment of SFTS. However, severe cases of SFTS, such as fulminant myocarditis, may require mechanical hemodynamic support. CASE PRESENTATION: This report presents a case of a 59-year old woman diagnosed with SFTS by reverse-transcription polymerase chain reaction. The patient had no initial symptoms of cardiac involvement and rapidly developed hemodynamic instability 3 days after hospitalization. She suffered from chest pain and had elevated cardiac enzymes. In the absence of atrio-ventricular conduction abnormalities, left ventricular dysfunction, and coronary artery abnormalities by coronary angiography, she was diagnosed with fulminant myocarditis. At that time, her pulse rate nearly dropped to 0 bpm and she developed near complete akinesia of the heart despite vasopressor administration. Veno-arterial extracorporeal membrane oxygenation (ECMO) was initiated with other supportive measures and she fully recovered after 21 days. CONCLUSIONS: This case indicates that SFTS can cause fulminant myocarditis even without evidence of cardiac involvement at presentation. When symptoms and/or signs of acute heart failure develop in patients with SFTS, myocarditis should be suspected and the patient should be promptly evaluated. Additionally, mechanical hemodynamic support like ECMO can be a lifesaving tool in the treatment of fulminant myocarditis.

Case report: nosocomial fungemia caused by Candida diddensiae.

BACKGROUND: Candida diddensiae, a yeast found in olive oil, is considered non-pathogenic to humans. Here, we describe the first case of fungemia caused by C. diddensiae in a hospitalized patient with underlying diseases. CASE PRESENTATION: A 62-year-old woman was admitted because of multiple contusions due to repeated falls and generalized weakness. She presented with chronic leukopenia due to systemic lupus erythematosus, and multiple cranial nerve neuropathies due to a recurring chordoma. She was given a lipid emulsion containing total parenteral nutrition (TPN) starting on the day of admission. Broad-spectrum antibiotics had been administered during her last hospital stay and from day 8 of this hospitalization. However, no central venous catheter was used during this hospital stay. Blood cultures obtained on hospital days 17, 23, and 24 yielded the same yeast, which was identified as C. diddensiae via sequence analyses of the internal transcribed spacer region and D1/D2 regions of the 26S ribosomal DNA of the rRNA gene. In vitro susceptibility testing showed that the minimum inhibitory concentration of fluconazole for all isolates was 8 µg/mL. On day 23, TPN was discontinued and fluconazole therapy was started. Blood cultures obtained on day 26 were negative. The fluconazole therapy was replaced with micafungin on day 26 and the patient exhibited improvements. CONCLUSION: The use of lipid TPN may potentially contribute to the occurrence of nosocomial fungemia by C. diddensiae, an unusual Candida species.

In Vitro Synergy and In Vivo Activity of Tigecycline-Ciprofloxacin Combination Therapy against Vibrio vulnificus Sepsis.

The mortality rate associated with Vibrio vulnificus sepsis remains high. An in vitro time-kill assay revealed synergism between tigecycline and ciprofloxacin. The survival rate was significantly higher in mice treated with tigecycline plus ciprofloxacin than in mice treated with cefotaxime plus minocycline. Thus, combination treatment with tigecycline-ciprofloxacin may be an effective novel antibiotic regimen for V. vulnificus sepsis.

A Prospective Cohort Study of Durations of Staphylococcus aureus Bacteremia According to Different Phenotypes and a New Concept of Persistent Bacteremia.

The purpose of this study was to describe and compare the duration of Staphylococcus aureus bacteremia (SAB) according to methicillin resistance and the primary foci of infection. We also aimed to newly define persistent SAB considering these results. Nonduplicated episodes of SAB in patients aged ≥15 years from 14 hospitals in the Republic of Korea were analyzed between January 2009 and February 2018. The duration of SAB was defined as the number of days from the time of administration of an antibiotic to which the isolate was susceptible after the onset of SAB to the last day of a positive blood culture for S. aureus SAB durations were described and compared based on methicillin resistance and the primary foci of infection. Cases in the top quartile for the duration of bacteremia in the respective clinical context were classified as newly defined persistent SAB, and its association with in-hospital mortality was evaluated. A total of 1,917 cases were analyzed. The duration of SAB was longer in patients with methicillin-resistant SAB (MRSAB; n = 995) than in patients with methicillin-susceptible SAB (MSSAB; n = 922) (median duration, 1 day [interquartile range, 1 to 3 days] for MSSAB and 1 day [interquartile range, 0 to 5 days] for MRSAB; P < 0.001). The duration of bacteremia was longer in patients with endocarditis and bone and joint, endovascular, and surgical site infections and was shorter in patients with skin and soft tissue infections. Newly defined persistent SAB was independently associated with in-hospital mortality (adjusted odds ratio, 1.97; 95% confidence interval, 1.54 to 2.53; P < 0.001). The durations of SAB were dependent on methicillin resistance and the primary foci of infection, and considering these contexts, persistent SAB was significantly associated with in-hospital mortality.

Lack of correlation of virulence gene profiles of Staphylococcus aureus bacteremia isolates with mortality.

PURPOSE: Whole genome sequencing (WGS) analysis of Staphylococcus aureus is increasingly used in clinical practice. Although bioinformatics tools used in WGS analysis readily define the S. aureus virulome, the clinical value of this type of analysis is unclear. Here, virulence genes in S. aureus bacteremia (SAB) isolates were evaluated by WGS, with superantigens (SAgs) further evaluated by conventional PCR and functional assays, and results correlated with mortality. METHODS: 152 SAB isolates collected throughout 2015 at a large Minnesota medical center were studied and associated clinical data analyzed. Virulence genes were identified from previously-reported WGS data (https://doi.org/10.1371/journal.pone.0179003). SAg genes sea, seb, sec, sed, see, seg, seh, sei, sej, and tst were also assessed by individual PCR assays. Mitogenicity of SAgs was assessed using an in vitro proliferation assay with splenocytes from HLA-DR3 transgenic mice. RESULTS: Of the 152 SAB isolates studied, 106 (69%) were methicillin-susceptible S. aureus (MSSA). The number of deaths attributed and not attributed to SAB, and 30-day survivors were 24 (16%), 2 (1%), and 128 (83%), respectively. From WGS data, both MSSA and MRSA had high proportions of adhesion (>80%) and immune-evasion (>70%) genes. There was no difference in virulomes between survivor- and non-survivor-associated isolates. Although over 60% of SAB isolates produced functional SAgs, there were no differences in the distribution or prevalence of SAg genes between survivor- and non-survivor-associated isolates. CONCLUSION: In this study of one year of SAB isolates from a large medical center, the S. aureus virulome, as assessed by WGS, and also for SAgs using individual PCRs and phenotypic characterization, did not impact mortality.

Inoculum effect of methicillin-susceptible Staphylococcus aureus against broad-spectrum beta-lactam antibiotics.

Scarce information concerning the inoculum effect (InE) of methicillin-susceptible Staphylococcus aureus (MSSA) against broad-spectrum ß-lactam antibiotics is available. We investigated the InE of MSSA against ceftriaxone, cefepime, meropenem, ampicillin/sulbactam and piperacillin/tazobactam. The bacteraemic MSSA isolates were collected at ten Korean general hospitals from Sep 2013 to Mar 2015. The InE was defined if MICs of antibiotics at high inoculum (HI, ~5 × 107 CFU/ml) increased beyond the susceptible range compared to those at standard inoculum (SI, ~5 × 105 CFU/ml). All isolates were sequenced for blaZ gene typing. Among 302 MSSA isolates, 254 (84.1%) were positive for blaZ; types A, B, C and D were 13.6%, 26.8%, 43.4% and 0.3%, respectively. Mean HI MICs of all tested antibiotics were significantly increased and increases in HI MIC of piperacillin/tazobactam (HI, 48.14 ± 4.08 vs. SI, 2.04 ± 0.08 mg/L, p < 0.001) and ampicillin/sulbactam (HI, 24.15 ± 1.27 vs. SI, 2.79 ± 0.11 mg/L, p < 0.001) were most prominent. No MSSA isolates exhibited meropenem InE, and few isolates exhibited cefepime (0.3%) and ceftriaxone (2.3%) InE, whereas 43.0% and 65.9% of MSSA isolates exhibited piperacillin/tazobactam and ampicillin/sulbactam InE, respectively. About 93% of type C blaZ versus 45% of non-type C exhibited ampicillin/sulbactam InE (p < 0.001) and 88% of type C blaZ versus 9% of non-type C exhibited piperacillin/tazobactam InE (p < 0.001). A large proportion of MSSA clinical isolates, especially those positive for type C blaZ, showed marked ampicillin/sulbactam InE and piperacillin/tazobactam.

A co-infection case report of Taenia saginata in a patient with subclinical clonorchiasis confirmed by the combination of diagnostic tools.

BACKGROUND: Clonorchiasis is the common parasitic infection in the general population of the Republic of Korea, however, taeniasis is scarcely reported recently. Here, we describe a case of co-infection with the cestode T. saginata in a patient with subclinical clonorchiasis diagnosed by a combination of diagnostic tools in Korea. CASE PRESENTATION: A 56-year-old man visited the hospital having passed proglottids in his stool for the past two months and brought a stool sample with segments to our hospital. He had no abdominal symptoms, such as nausea, vomiting, abdominal pain, diarrhea, or constipation. He used to consume raw beef and fish frequently. We could not find evidence of gravid proglottids which contain fully developed uteri filled with ova or branched uterine structures, within the submitted sample. To identify the tapeworm species, we carried out molecular analyses on the proglottids. The cox1 and ef1a sequences had a 100% match with those of T. saginata and differed from the sequences of the other Taenia species. Upon examination of stool samples fixed by formalin-ether concentration method, no Taenia species ova were observed in 10 slides. Instead, C. sinensis ova were observed, despite the level of IgG specific to C. sinensis being within the normal range. The patient was treated with praziquantel (25 mg/kg, three times a day) for 3 days, and subsequently C. sinensis ova were not found in his stool. CONCLUSION: Our case indicates that a combination of morphological, serological, and molecular diagnostic tools should be used for the accurate diagnosis of subclinical parasitic infections.

Effects of gemfibrozil on sex hormones and reproduction related performances of Oryzias latipes following long-term (155 d) and short-term (21 d) exposure.

Gemfibrozil, a lipid-regulating pharmaceutical, has been widely used for treating dyslipidemia in humans and detected frequently in freshwater environments. Since plasma cholesterol is a precursor of steroid hormones, the use of gemfibrozil may influence the sex hormone balances. However, its endocrine toxicity following long-term exposure is not well understood. The purpose of the present study is to investigate the effects of gemfibrozil on sex hormones and reproductive outcomes in a freshwater fish, following a long-term (155 d) exposure. For this purpose, Japanese medaka embryos (F0) were exposed to a series of gemfibrozil concentrations, i.e., 0, 0.04, 0.4, 3.7, and 40 mg/L for 155 d, and reproductive parameters, sex hormones, and associated gene expressions were assessed. For comparison, a short-term exposure (21 d) was performed separately with adult medaka and measured for sex hormones and related gene expressions. Following the 155 d long-term exposure, the fecundity showed a decreasing pattern. In addition, at 3.7 mg/L gemfibrozil, testosterone (T) level in the female fish was significantly decreased, and the hatchability of F1 fish was significantly decreased. The estrogen receptor (er) or vitellogenin (vtg) genes in gonads and liver were up-regulated. However, plasma cholesterol levels did not show significant changes in both sexes. The observations from the short-term (21 d) exposure were different from those of the long-term exposure. Following the short-term exposure, decreased 17ß-estradiol (E2), and 11-ketotestosterone (11-KT) levels along with decrease plasma cholesterol were observed in the male fish. The hormone disruption following the short-term exposure appears to be associated with the hypocholesterolemic activity of gemfibrozil. Our results show that the mechanisms of gemfibrozil toxicity may depend on the exposure duration. Consequences of long-term exposure to other fibrates in the water environment warrant further investigations.

n-Butyl acrylate-induced antioxidant system alteration through two generations in Oryzias latipes.

n-Butyl acrylate (nBA) is one of acrylate esters which has been applied to diverse industrial fields. For unveiling of xeno-estrogenic effects and oxidative stress induction by nBA under two-generational exposure regimen (17 weeks), the biomarkers relevant to an estrogenic effect and oxidative stress were analyzed. Acute toxicity value of nBA in Oryzias latipes was 7.2 mg/L (96 h-LC50). Over exposure time, the significant transcriptional change of cytochrome P450 19A (CYP19A) and vitellogenin 1/2 (VTG1/2) was not observed (one-way ANOVA, P < 0.05), meaning no estrogenic effect of nBA. Significant reduction of glutathione (GSH) content was observed in F0 male and female fish, while in F1 male, the content was increased (P < 0.05). Catalase (CAT) activity of male fish showed the significant decrease in both F0 and F1 fish, showing multi-generational suppressing effect of nBA on CAT activity. But in case of reactive oxygen species (ROS), expression level and glutathione S-transferase (GST) activity were not modulated in response to nBA. These findings suggest that nBA could affect an antioxidant system alteration through GSH depletion and inhibition of CAT activity which could be transferred to the next generation, whereas xeno-estrogenic effect would be questionable.

Dysfunction of Circulating Natural Killer T Cells in Patients With Scrub Typhus.

Background: Human natural killer T (NKT) cells are known to serve as regulatory and/or effector cells in infectious diseases. However, little is known about the role of NKT cells in Orientia tsutsugamushi infection. Accordingly, the objective of this study was to examine the level and function of NKT cells in patients with scrub typhus. Methods: This study included 62 scrub typhus patients and 62 healthy controls (HCs). NKT cell level and function in peripheral blood samples were measured by flow cytometry. Results: Proliferation of NKT cells and their ability to produce interferon-γ and interleukin-4 (IL-4) were significantly lower in scrub typhus patients compared to those in HCs. However, circulating NKT cell levels were comparable between patients and HCs. Expression levels of CD69, programmed death-1 (PD-1), lymphocyte activation gene-3 (LAG-3), and T-cell immunoglobulin domain and mucin domain-containing molecule-3 (TIM-3) were significantly increased in scrub typhus patients. Elevated expression of CD69, PD-1, LAG-3, and TIM-3, impaired proliferation, and decreased IL-4 production by NKT cells were recovered in the remission phase. Conclusions: This study demonstrates that circulating NKT cells are numerically preserved but functionally impaired in scrub typhus patients. In addition, NKT cell dysfunction is recovered in the remission phase.

Case report: dual primary AIDS-defining cancers in an HIV-infected patient receiving antiretroviral therapy: Burkitt's lymphoma and Kaposi's sarcoma.

BACKGROUND: The incidence of AIDS-defining cancers (ADCs) has decreased markedly in the era of highly active antiretroviral therapy (HAART). The occurrence of two ADCs is rare in people living with HIV or AIDS (PWHA) who are severely immunosuppressed or have incomplete virologic suppression. CASE PRESENTATION: We report a case of dual primary ADCs, especially NHL followed by KS, in a 70-year-old HIV-infected man who was on antiretroviral therapy and had successful virologic suppression. During HAART, he presented with generalized myalgia and abdominal pain. Multiple liver masses were detected and a biopsy revealed Burkitt's lymphoma. After three cycles of anticancer chemotherapy with a favorable response, he was diagnosed with cytomegalovirus retinitis and the anti-cancer chemotherapy was discontinued. Despite successful virologic suppression with HAART, human herpes virus-8 associated Kaposi's sarcoma was diagnosed in his right thigh. He underwent radiation therapy. CONCLUSION: These findings suggest that multiple ADCs can occur in PWHA who are receiving HAART and have successful virologic suppression. Healthcare providers caring for PWHA should maintain vigilance for the development of a broad spectrum of cancers.

Gender affects prognosis of methicillin-resistant Staphylococcus aureus bacteremia differently depending on the severity of underlying disease.

We aimed to elucidate the potential impact of gender on prognosis of Staphylococcus aureus bacteremia (SAB). We analyzed SAB cases prospectively collected over an 8-year period at 11 hospitals in Korea. SAB-related mortality was pre-defined as a death within 30 days from the onset of SAB without other apparent cause of death. The effect of gender on SAB-related mortality was examined in the entire cohort and in subgroups stratified according to methicillin resistance and Charlson's comorbidity-weighted index (CCWI) score. Those factors independently associated to SAB-related mortality were explored. Among 1974 eligible cases, SAB-related mortality rates in male and female were 21.2% (259/1224) and 21.9% (164/750), respectively (P = 0.786). The SAB-related mortality rate was independently higher in male than that in female in CCWI score ≤ 3 methicillin-resistant SAB (MRSAB) group (15.9 vs. 6.2%; aOR 3.65, 95% CI 1.46-9.13; P = 0.006) while the association tended to be inverse when CCWI score rises. Interaction between CCWI score and gender to MRSAB-related mortality was significant in multivariate analysis (aOR 0.85, 95% CI 0.74-0.96; P = 0.011). There was no significant interaction between gender and CCWI in entire SAB or methicillin-susceptible SAB cohorts. Gender may affect clinical outcomes of MRSAB differently depending on the severity of underlying disease.

Case report: detection of the identical virus in a patient presenting with severe fever with thrombocytopenia syndrome encephalopathy and the tick that bit her.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease. Haemophysalis longicornis ticks have been considered the vector of severe fever with thrombocytopenia syndrome virus (SFTSV). However, clear data on the transmission of SFTS from ticks to humans are limited. CASE PRESENTATION: We report an 84-year-old woman who presented with fever and altered mentality, which was confirmed as SFTS with encephalopathy by reverse-transcription polymerase chain reaction in blood and cerebrospinal fluid. The SFTSV was also identified in the tick that bit her, H. longicornis. Phylogenetic analyses indicated that the SFTSV from the patient and the tick was identical. The patient gradually recovered with treatments of corticosteroids and immunoglobulin. CONCLUSION: These findings provide further evidence of SFTS viral transmission from H. longicornis to human.

Activity of Tedizolid in Methicillin-Resistant Staphylococcus epidermidis Experimental Foreign Body-Associated Osteomyelitis.

We developed a rat model of methicillin-resistant Staphylococcus epidermidis (MRSE) foreign body-associated osteomyelitis and used it to compare tedizolid alone and in combination with rifampin against rifampin alone, vancomycin plus rifampin, and vancomycin alone. A clinical strain of MRSE was inoculated into the proximal tibia, and a stainless steel wire with a precolonized MRSE biofilm was implanted. Following a 1-week infection period, 92 rats received either no treatment (n = 17) or 14 days of intraperitoneal tedizolid (n = 15), tedizolid plus rifampin (n = 15), rifampin (n = 15), vancomycin plus rifampin (n = 15), or vancomycin (n = 15). Quantitative bone and wire cultures were performed after treatment completion and also 1 week after infection in a separate group of five rats. The median quantity of staphylococci in bone after the 1-week infection period was 4.89 log10 CFU/g bone (interquartile range, 3.83 to 5.33 log10 CFU/g bone); staphylococci were recovered from all associated wires. A median quantity of staphylococci of 3.70 log10 CFU/g bone was detected in bones of untreated control rats after 3 weeks. Quantities of staphylococci in bones of all treatment groups except the group receiving vancomycin alone (2.78 log10 CFU/g) were significantly lower than those for untreated controls, with no staphylococci being detected in the groups receiving rifampin monotherapy, tedizolid-plus-rifampin combination therapy, and vancomycin-plus-rifampin combination therapy. Quantities of staphylococci on wires from all treatment groups that included rifampin were significantly lower than those for untreated controls. No resistance to rifampin, tedizolid, or vancomycin was detected. Tedizolid combined with rifampin was active in a rat model of MRSE foreign body-associated osteomyelitis.

Impact of Vancomycin MIC on Treatment Outcomes in Invasive Staphylococcus aureus Infections.

There are conflicting data on the association of vancomycin MIC (VAN-MIC) with treatment outcomes in Staphylococcus aureus infections. We investigated the relationship between high VAN-MIC and 30-day mortality and identified the risk factors for mortality in a large cohort of patients with invasive S. aureus (ISA) infections, defined as the isolation of S. aureus from a normally sterile site. Over a 2-year period, 1,027 adult patients with ISA infections were enrolled in 10 hospitals, including 673 (66%) patients with methicillin-resistant S. aureus (MRSA) infections. There were 200 (19.5%) isolates with high VAN-MIC (≥1.5 mg/liter) by Etest and 87 (8.5%) by broth microdilution (BMD). The all-cause 30-day mortality rate was 27.4%. High VAN-MIC by either method was not associated with all-cause 30-day mortality, and this finding was consistent across MIC methodologies and methicillin susceptibilities. We conclude that high VAN-MIC is not associated with increased risk of all-cause 30-day mortality in ISA infections. Our data support the view that VAN-MIC alone is not sufficient evidence to change current clinical practice.

Activity of Tedizolid in Methicillin-Resistant Staphylococcus aureus Experimental Foreign Body-Associated Osteomyelitis.

We compared tedizolid alone and tedizolid with rifampin to rifampin and vancomycin plus rifampin in a rat model of methicillin-resistant Staphylococcus aureus (MRSA) foreign body-associated osteomyelitis. The study strain was a prosthetic joint infection-associated isolate. Steady-state pharmacokinetics for intraperitoneal administration of tedizolid, vancomycin, and rifampin were determined in uninfected rats. MRSA was inoculated into the proximal tibia, and a wire was implanted. Four weeks later, the rats were treated intraperitoneally for 21 days with tedizolid (n = 14), tedizolid plus rifampin (n = 11), rifampin (n = 16), or vancomycin plus rifampin (n = 13). Seventeen rats received no treatment. After treatment, quantitative bone cultures were performed. Blood was obtained for determination of drug trough concentrations in the tedizolid and tedizolid plus rifampin groups. The mean peak plasma concentration and mean area under the concentration-time curve from time zero to 24 h for tedizolid were 12 µg/ml and 60 µg · h/ml, respectively. The bacterial loads in all treatment groups were significantly lower than those in the control group; those in the tedizolid- plus rifampin-treated animals were not significantly different from those in the vancomycin- plus rifampin-treated animals. The range of mean plasma trough concentrations in the tedizolid group was 0.44 to 0.73 µg/ml. Although neither tedizolid nor vancomycin resistance was detected in isolates recovered from bones, rifampin resistance was detected in 10 animals (63%) in the rifampin group, 8 animals (73%) in the tedizolid plus rifampin group, and a single animal (8%) in the vancomycin plus rifampin group. Tedizolid alone or tedizolid combined with rifampin was active in a rat model of MRSA foreign body-associated osteomyelitis. The emergence of rifampin resistance was noted in animals receiving tedizolid plus rifampin.