The varicella-zoster virus ORF16 protein promotes both the nuclear transport and the protein abundance of the viral DNA polymerase subunit ORF28.

Although all herpesviruses utilize a highly conserved replication machinery to amplify their viral genomes, different members may have unique strategies to modulate the assembly of their replication components. Herein, we characterize the subcellular localization of seven essential replication proteins of varicella-zoster virus (VZV) and show that several viral replication enzymes such as the DNA polymerase subunit ORF28, when expressed alone, are localized in the cytoplasm. The nuclear import of ORF28 can be mediated by the viral DNA polymerase processivity factor ORF16. Besides, ORF16 could markedly enhance the protein abundance of ORF28. Noteworthily, an ORF16 mutant that is defective in nuclear transport still retained the ability to enhance ORF28 abundance. The low abundance of ORF28 in transfected cells was due to its rapid degradation mediated by the ubiquitin-proteasome system. We additionally reveal that radicicol, an inhibitor of the chaperone Hsp90, could disrupt the interaction between ORF16 and ORF28, thereby affecting the nuclear entry and protein abundance of ORF28. Collectively, our findings imply that the cytoplasmic retention and rapid degradation of ORF28 may be a key regulatory mechanism for VZV to prevent untimely viral DNA replication, and suggest that Hsp90 is required for the interaction between ORF16 and ORF28.

Alanine aminotransferase to aspartate aminotransferase ratio and hepatitis B virus on metabolic syndrome: a community-based study.

Background: The serum aminotransferase elevation in metabolic syndrome (MetS) reflected hepatosteatosis, but there is a conflict with the coexistence of viral hepatitis, especially for the hepatitis B virus (HBV). Thus, this study aimed to investigate the relationship between the alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ratio, MetS, and HBV infection in a rural Taiwanese population. Methods: We conducted a cross-sectional analysis in southern Taiwan between March and December 2019. Multivariable logistic regression analyses adjusted for demographics, education, dietary behaviors, irregular exercise, substance use, and viral markers were performed to investigate the association between the ALT/AST ratio and MetS. Results: Altogether, 2,416 participants (891 men and 1,525 women; mean age, 64.1 ± 14.9 years) were enrolled. Of the participants, 22.7% (n = 519) were seropositive for viral hepatitis. In the multivariable analysis, age [odds ratio (OR) 1.02, 95% CI 1.01-1.03, p < 0.001], ALT/AST ratio >1 (OR 2.63, 95% CI 2.15-3.21, p < 0.001), education (OR 0.96, 95% CI 0.94-0.98, p < 0.001), and HBV seropositivity (OR 0.70, 95% CI 0.52-0.95, p = 0.021) were associated with the risk of MetS. The area under the curve of the ALT/AST ratio was 0.62 (95% CI 0.60-0.64, p < 0.001), and the cutoff value was >0.852 for the Youden index. Conclusion: An ALT/AST ratio >1 could be a simple index for MetS prediction during community checkups. In contrast to age and betel nut chewing, HBV seropositivity and higher education might be inversely associated with MetS. Aggressive health promotion for MetS prevention has emerged as essential in participants without HBV and with lower education levels. Further large-scale, longitudinal studies are needed to unlink these correlations.

Changes in interferon-γ release assay readout after COVID-19 vaccination: A prospective cohort study.

OBJECTIVES: Interferon-γ release assays (IGRAs) are widely used in public health practice to diagnose latent tuberculosis. During the COVID-19 pandemic and rollout of COVID-19 vaccination, it has remained unclear whether COVID-19 vaccines interfere with IGRA readouts. METHODS: We prospectively recruited healthcare workers during their annual occupational health examinations in 2021. Baseline IGRA readouts were compared with follow-up data after the participants had received two doses of COVID-19 vaccination. RESULTS: A total of 134 baseline IGRA-negative cases (92 with ChAdOx1 vaccine, 27 with mRNA-1273 vaccine, and 15 with heterologous vaccination) and seven baseline IGRA-positive cases were analyzed. Among the baseline IGRA-negative cases, there were decreased interferon-γ concentrations over the Nil (P = 0.005) and increased Mitogen-Nil (P < 0.001) values after vaccination. For TB2-Nil value, a similar trend (P = 0.057) of increase was observed. Compared with the 0.35 IU/ml threshold, the baseline and follow-up readout differences were less than |± 0.10| IU/ml over the TB1-Nil and TB2-Nil values in >90% baseline IGRA-negative cases. No significant readout difference was observed among baseline IGRA-positive cases. CONCLUSION: COVID-19 vaccination did not change IGRA interpretation in most cases. Cases showing conversion/borderline IGRA readouts should be given special consideration.

Bacteremia detection from complete blood count and differential leukocyte count with machine learning: complementary and competitive with C-reactive protein and procalcitonin tests.

BACKGROUND: Biomarkers, such as leukocyte count, C-reactive protein (CRP), and procalcitonin (PCT), have been commonly used to predict the occurrence of life-threatening bacteremia and provide prognostic information, given the need for prompt intervention. However, such diagnosis methods require much time and money. Therefore, we propose a method with a high prediction capability using machine learning (ML) models based on complete blood count (CBC) and differential leukocyte count (DC) and compare its performance with traditional CRP or PCT biomarker methods and those of models incorporating CRP or PCT biomarkers. METHODS: We collected 366,586 daily blood culture (BC) results, of which 350,775 (93.2%), 308,803 (82.1%), and 23,912 (6.4%) cases were issued CBC/DC (CBC/DC group), CRP with CBC/DC (CRP&CBC/DC group), and PCT with CBC/DC (PCT&CBC/DC group), respectively. For the ML methods, conventional logistic regression and random forest models were selected, trained, applied, and validated for each group. Fivefold validation and prediction capability were also evaluated and reported. RESULTS: Overall, the ML methods, such as the random forest model, demonstrated promising performances. When trained with CBC/DC data, it achieved an area under the ROC curve (AUC) of 0.802, which is superior to the prediction conventionally made with CRP/PCT levels (0.699/0.731). Upon evaluating the performance enhanced by incorporating CRP or PCT biomarkers, it reported no substantial AUC increase with the addition of either CRP or PCT to CBC/DC data, which suggests the predicting power and applicability of using only CBC/DC data. Moreover, it showed competitive prognostic capability compared to the PCT test with similar all-cause in-hospital mortality (45.10% vs. 47.40%) and overall median survival time (27 vs. 25 days). CONCLUSIONS: The ML models using only CBC/DC data yielded more accurate bacteremia predictions compared to those by methods using CRP and PCT data and reached similar prognostic performance as by PCT data. Thus, such models are potentially complementary and competitive with traditional CRP and PCT biomarkers for conducting and guiding antibiotic usage.

Nutrition Assessment and Adverse Outcomes in Hospitalized Patients with Tuberculosis.

BACKGROUND: Malnutrition in patients with tuberculosis (TB) is associated with poor outcomes. This study assessed the validity of the patient-generated subjective global assessment (PG-SGA) in adult TB patients and examined the association of the PG-SGA score with adverse outcomes. METHODS: This is a retrospective chart review study compared with the well-nourished and malnourished TB patients. The nutritional status was determined using the PG-SGA for adult patients (n = 128). Clinical outcomes included liver injury and mortality. Adverse outcomes included hepatitis during anti-tuberculosis therapy. RESULTS: By comparing nutritional status using global assessment, well-nourished patients had a significantly higher body weight index (p = 0.002), a lower PG-SGA score (p < 0.001), and lower diabetic rate (p = 0.029). Malnourishment was a risk factor (p = 0.022) for liver injury and fatal outcomes (p < 0.001). A higher PG-SGA score was a risk factor for liver injury (p = 0.002) and an independent risk factor for fatal outcomes (p = 0.031). ROC analysis for outcome prediction showed that a PG-SGA score of 5.5 points yielded the most appropriate sensitivity (61.5%) and specificity (64.7%). CONCLUSION: Both global assessment and the total PG-SGA score were related to tuberculosis outcome and liver injury during anti-TB treatment.

Interventions for bacterial folliculitis and boils (furuncles and carbuncles).

BACKGROUND: Bacterial folliculitis and boils are globally prevalent bacterial infections involving inflammation of the hair follicle and the perifollicular tissue. Some folliculitis may resolve spontaneously, but others may progress to boils without treatment. Boils, also known as furuncles, involve adjacent tissue and may progress to cellulitis or lymphadenitis. A systematic review of the best evidence on the available treatments was needed. OBJECTIVES: To assess the effects of interventions (such as topical antibiotics, topical antiseptic agents, systemic antibiotics, phototherapy, and incision and drainage) for people with bacterial folliculitis and boils. SEARCH METHODS: We searched the following databases up to June 2020: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, and Embase. We also searched five trials registers up to June 2020. We checked the reference lists of included studies and relevant reviews for further relevant trials.  SELECTION CRITERIA: We included randomised controlled trials (RCTs) that assessed systemic antibiotics; topical antibiotics; topical antiseptics, such as topical benzoyl peroxide; phototherapy; and surgical interventions in participants with bacterial folliculitis or boils. Eligible comparators were active intervention, placebo, or no treatment. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Our primary outcomes were 'clinical cure' and 'severe adverse events leading to withdrawal of treatment'; secondary outcomes were 'quality of life', 'recurrence of folliculitis or boil following completion of treatment', and 'minor adverse events not leading to withdrawal of treatment'. We used GRADE to assess the certainty of the evidence. MAIN RESULTS: We included 18 RCTs (1300 participants). The studies included more males (332) than females (221), although not all studies reported these data. Seventeen trials were conducted in hospitals, and one was conducted in clinics. The participants included both children and adults (0 to 99 years). The studies did not describe severity in detail; of the 232 participants with folliculitis, 36% were chronic. At least 61% of participants had furuncles or boils, of which at least 47% were incised. Duration of oral and topical treatments ranged from 3 days to 6 weeks, with duration of follow-up ranging from 3 days to 6 months. The study sites included Asia, Europe, and America. Only three trials reported funding, with two funded by industry. Ten studies were at high risk of 'performance bias', five at high risk of 'reporting bias', and three at high risk of 'detection bias'. We did not identify any RCTs comparing topical antibiotics against topical antiseptics, topical antibiotics against systemic antibiotics, or phototherapy against sham light. Eleven trials compared different oral antibiotics. We are uncertain as to whether cefadroxil compared to flucloxacillin (17/21 versus 18/20, risk ratio (RR) 0.90, 95% confidence interval (CI) 0.70 to 1.16; 41 participants; 1 study; 10 days of treatment) or azithromycin compared to cefaclor (8/15 versus 10/16, RR 1.01, 95% CI 0.72 to 1.40; 31 participants; 2 studies; 7 days of treatment) differed in clinical cure (both very low-certainty evidence). There may be little to no difference in clinical cure rate between cefdinir and cefalexin after 17 to 24 days (25/32 versus 32/42, RR 1.00, 95% CI 0.73 to 1.38; 74 participants; 1 study; low-certainty evidence), and there probably is little to no difference in clinical cure rate between cefditoren pivoxil and cefaclor after 7 days (24/46 versus 21/47, RR 1.17, 95% CI 0.77 to 1.78; 93 participants; 1 study; moderate-certainty evidence). For risk of severe adverse events leading to treatment withdrawal, there may be little to no difference between cefdinir versus cefalexin after 17 to 24 days (1/191 versus 1/200, RR 1.05, 95% CI 0.07 to 16.62; 391 participants; 1 study; low-certainty evidence). There may be an increased risk with cefadroxil compared with flucloxacillin after 10 days (6/327 versus 2/324, RR 2.97, 95% CI 0.60 to 14.62; 651 participants; 1 study; low-certainty evidence) and cefditoren pivoxil compared with cefaclor after 7 days (2/77 versus 0/73, RR 4.74, 95% CI 0.23 to 97.17; 150 participants; 1 study; low-certainty evidence). However, for these three comparisons the 95% CI is very wide and includes the possibility of both increased and reduced risk of events. We are uncertain whether azithromycin affects the risk of severe adverse events leading to withdrawal of treatment compared to cefaclor (274 participants; 2 studies; very low-certainty evidence) as no events occurred in either group after seven days. For risk of minor adverse events, there is probably little to no difference between the following comparisons: cefadroxil versus flucloxacillin after 10 days (91/327 versus 116/324, RR 0.78, 95% CI 0.62 to 0.98; 651 participants; 1 study; moderate-certainty evidence) or cefditoren pivoxil versus cefaclor after 7 days (8/77 versus 5/73, RR 1.52, 95% CI 0.52 to 4.42; 150 participants; 1 study; moderate-certainty evidence). We are uncertain of the effect of azithromycin versus cefaclor after seven days due to very low-certainty evidence (7/148 versus 4/126, RR 1.26, 95% CI 0.38 to 4.17; 274 participants; 2 studies). The study comparing cefdinir versus cefalexin did not report data for total minor adverse events, but both groups experienced diarrhoea, nausea, and vaginal mycosis during 17 to 24 days of treatment. Additional adverse events reported in the other included studies were vomiting, rashes, and gastrointestinal symptoms such as stomach ache, with some events leading to study withdrawal. Three included studies assessed recurrence following completion of treatment, none of which evaluated our key comparisons, and no studies assessed quality of life. AUTHORS' CONCLUSIONS: We found no RCTs regarding the efficacy and safety of topical antibiotics versus antiseptics, topical versus systemic antibiotics, or phototherapy versus sham light for treating bacterial folliculitis or boils. Comparative trials have not identified important differences in efficacy or safety outcomes between different oral antibiotics for treating bacterial folliculitis or boils. Most of the included studies assessed participants with skin and soft tissue infection which included many disease types, whilst others focused specifically on folliculitis or boils. Antibiotic sensitivity data for causative organisms were often not reported. Future trials should incorporate culture and sensitivity information and consider comparing topical antibiotic with antiseptic, and topical versus systemic antibiotics or phototherapy.

Gulllain-Barre Syndrome After Trivalent Influenza Vaccination in Adults.

Lines of evidence suggest trivalent influenza vaccination may be associated with Guillain-Barre syndrome (GBS), an immune-mediated acute inflammatory neuropathy. On the other hand, this vaccination protects against influenza infection, which has been demonstrated as a trigger of GBS. To clarify the net effect of trivalent influenza vaccines on GBS, we conducted a retrospective nationwide nested case-control study using the database of the Taiwan National Health Insurance program. We identified 182 hospitalized patients with GBS aged ≥50 years from 2007 to 2015 as the cases, and 910 hospitalized patients, matched by gender, age, date of hospitalization, comorbidities, and medications, as the control subjects. Nearby and remote exposures of vaccination were defined as subjects who had received trivalent influenza vaccine 42 (nearby exposure) and 90 days (remote exposure) before the date of hospitalization, respectively. We found 7 (3.85%) GBS patients and 26 (2.86%) matched control subjects who demonstrated nearby exposures of influenza vaccine (odds ratio: 1.46, 95% confidence interval: 0.56-3.78). Seventeen (9.34%) GBS patients were exposed to influenza vaccines remotely, while the number of remote exposure of influenza vaccines in matched control subjects was 72 (7.91%, odds ratio: 1.26, 95% confidence interval: 0.67-2.38). These results do not support an association between trivalent influenza vaccine and GBS among the patients aged ≥50 years.

Association between hepatitis C virus infection and osteoporotic fracture risk among postmenopausal women: a cross-sectional investigation in Taiwan.

PURPOSE: Early low bone mass is a risk factor for osteoporotic fractures associated with multiple factors, including menopause and chronic liver diseases. Hepatitis C virus (HCV) also plays a major role in chronic liver disease and has many extrahepatic consequences, such as decreased bone mineral density (BMD). This study aimed to examine the hypothesis that HCV seropositivity is independently associated with menopausal BMD loss. METHODS: This community-based, cross-sectional study was based in two rural townships in Yunlin County, Taiwan. A total of 636 menopausal women aged 45-80 years who underwent annual health checks were included. Viral markers of HCV, dual-energy X-ray absorptiometry and fracture risk assessment tool (FRAX) scores were measured. Logistic regression analysis was performed to assess the association between various predictors and the presence of low BMD. RESULTS: The participants (median age: 65 years) had a HCV seropositivity rate of 32.2%. BMD was significantly lower in the HCV-seropositive participants in different anatomic locations than in the seronegative individuals (lumbar spine: -1.5 vs -1.1; total hip: -0.9 vs -0.6; femoral neck: -1.2 vs -1.0; p<0.05). HCV-seropositive subjects had higher rates of major osteoporotic fractures (11.3%±7.6%vs 9.0±6.8%; p<0.001) and hip fractures (3.4%±4.7%vs 2.3±4.9%; p=0.006) and a higher risk of lower BMD (osteopenia and osteoporosis) based on a multivariable regression analysis (adjusted OR: 1.8; 95% CI 1.16 to 2.81; p=0.009). CONCLUSIONS: HCV infection may be an independent risk factor for menopausal BMD loss and fractures predicted by FRAX.

Tigecycline-based versus sulbactam-based treatment for pneumonia involving multidrug-resistant Acinetobacter calcoaceticus-Acinetobacter baumannii complex.

BACKGROUND: The treatment options for pneumonia involving multidrug-resistant Acinetobacter calcoaceticus-Acinetobacter baumannii (MDR Acb) complex are limited, and the optimal treatment has not been established. METHODS: To compare the efficacy of tigecycline-based with sulbactam (or ampicillin/sulbactam)-based therapy for pneumonia involving MDR Acb complex, we conducted a retrospective study comparing 84 tigecycline-treated adult patients during the period August 2007 to March 2010 with 84 sulbactam or ampicillin/sulbactam-treated adult patients during the period September 2004 to July 2007. Both groups had the matched Acute Physiology and Chronic Health Evaluation (APACHE) II score and received treatment for at least 7 days. RESULTS: The mean APACHE II score was 20.1 for both groups. More patients in sulbactam group had ventilator use (89.3 % versus 69.0 %), bilateral pneumonia (79.8 % versus 60.7 %) and combination therapy (84.5 % versus 53.6 %), particularly with carbapenems (71.4 % versus 6.0 %), while more patients in tigecycline group had delayed treatment (41.7 % versus 26.2 %) (P <0.05). At the end of treatment, more patients in sulbactam group had airway MDR Acb complex eradication (63.5 % versus 33.3 %, P <0.05). The clinical resolution rate was 66.7 % for both groups. The mortality rate during treatment was 17.9 % in sulbactam group, and 25.0 % in tigecycline group (P = 0.259). The multivariate analysis showed that bilateral pneumonia was the only independent predictor for mortality during treatment (adjusted odds ratio, 2.717; 95 % confidence interval, 1.015 to 7.272). CONCLUSIONS: Patients treated with either tigecycline-based or sulbactam-based therapy had a similar clinical outcome, but tigecycline group had a lower microbiological eradiation rate.

Clinical manifestations, course, and outcome of patients with neutralizing anti-interferon-γ autoantibodies and disseminated nontuberculous mycobacterial infections.

Neutralizing anti-interferon-γ autoantibody (nAIGA)-associated immunodeficiency is an emerging medical issue worldwide. In the present study, we describe and discuss the clinical features and outcomes of patients with nAIGAs and disseminated infections by nontuberculous mycobacteria (dNTM).We thoroughly reviewed the medical records of all patients. Microorganisms and nAIGAs were identified using previously described methods with modifications. All data were calculated and analyzed using SPSS software.Among 46 adult patients with dNTM infections, we identified 45 cases (97.8%) with nAIGAs. The average patient age was 58.6 years, and there was no sex predominance. Cervical lymphadenitis (81.8%) was the most common clinical manifestation. Endocrine disorder was the leading comorbidity (7 cases). Malignancies were found in 4 patients, and all of the malignancies originated from the T-cell/macrophage lineage. More than half of the identifiable isolates were slow-growing NTMs. Twenty-eight (62.2%) and 18 (40.0%) patients had a history of zoster and salmonellosis, respectively. A high proportion of patients with recurrent episodes of NTM infection or a history of zoster and dNTM infection had initial nAIGA titers ≥10 dilution (P < 0.05). Twenty-seven patients (60.0%) required long-term antimycobacterial therapy and had at least 1 episode of recurrent NTM disease. No mortality was related to dNTM infection.In Taiwan, nAIGAs are a recently recognized mechanism of dNTM infection. Long term of antibiotic treatment and adherence to medical advice are necessary to improve the clinical outcome of patients with nAIGAs.

Sexual Dimorphic Metabolic Alterations in Hepatitis C Virus-infected Patients: A Community-Based Study in a Hepatitis B/Hepatitis C Virus Hyperendemic Area.

The impact of sex on metabolic alterations in individuals with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection remains elusive.A community-based study was performed to assess sex, age, body mass index, the lipid profile, blood pressure, glucose, alanine aminotransferase, HBV surface antigen (HBsAg), and HCV antibody levels, smoking and alcohol drinking habits, and cardiometabolic diseases, including diabetes, hypertension, cardiovascular events, and renal diseases. The HCV-RNA level and genotype were further assessed in HCV antibody-positive subjects, and the hepatitis B e antigen and HBV-DNA levels were further examined in HBsAg-positive subjects.Among the 10,959 adults enrolled, 1949 (17.8%) and 1536 (14.0%) were HBV and HCV-infected, respectively. Univariate and multivariate analyses showed that the lipid profile and hypertension were independently associated with HCV infection (95% confidence intervals of odds ratios [OR 95% CI]: total cholesterol [TC] = 0.508-0.677; triglycerides = 0.496-0.728; hypertension = 0.669-0.937), but not with HBV infection. Consistently, HCV, but not HBV infection, was negatively associated with the TC and triglyceride levels (OR 95% CI for TC: 0.450-0.601; triglycerides: 0.443-0.671). Generalized linear models revealed that HCV infection, sex, and age interactively affected the lipid profile (OR 95% CI TC = 1.189-1.385; triglycerides = 1.172-5.289). Age-stratification analysis showed that the lipid levels were lower in both the HCV-positive females aged ≥49 years (TC, P < 0.001; triglycerides, P = 0.001) and males of all ages (TC, P < 0.001; triglycerides, P < 0.001) compared with their sex and age-matched HCV-negative counterparts. HCV infection was associated with a higher body mass index (≥49 years, ß = 0.405, P = 0.002) and increased rates of cardiovascular events (<49 years, OR 95% CI 1.23-9.566), diabetes (≥49 years, OR 95% CI 1.114-1.932), and renal diseases (≥49 years, OR 95% CI 1.23-9.55), and with a lower rate of hypertension (≥49 years, OR 95% CI 0.616-0.964) in the females, but not in the males, as determined by multivariate analyses.Only HCV infection was associated with metabolic alterations in this HBV/HCV-hyperendemic area. Females aged ≥49 years and males of all ages exhibited HCV-associated hypolipidemia. HCV-associated cardiometabolic diseases were evident only in the females. Sex dimorphism in HCV-associated metabolic complications warrants personalized follow-up of HCV-positive patients.

Impact of Apolipoprotein B on Hepatosteatosis in a Population Infected with Hepatitis C Virus: A Cross-Sectional Observational Study.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is an established risk factor for diabetes, cardiovascular disease, antiviral treatment resistance, and progression of chronic hepatitis C virus (HCV) infection to fibrosis. Apolipoprotein-B 100 (ApoB-100) is a dyslipidemia marker and steatosis predictor. We assess the correlation between ApoB-100 and hepatosteatosis. METHODS: This cross-sectional study enrolled 1,218 HCV-seropositive participants from a 2012-2013 health checkup in Taiwan. NAFLD was detected using ultrasound. All anthropometric and laboratory studies that included ApoB-100 were evaluated whether or not ApoB-100 predicts NAFLD. Logistic regression was also used to examine the association between ApoB-100 and NAFLD. RESULTS: Participants were 47.16 ± 16.08 years old (mean age). The overall prevalence of NAFLD was 35.8% (n = 436; 32.8% men, 38.1% women). Participants with ApoB-100 ≥ 8 had a significantly higher incidence of NAFLD (39.4 vs. 29.4%; 95% CI 0.044-0.156; p < 0.001). After confounding factors had been adjusted for, ApoB-100 was significantly associated with NAFLD (OR 5.45; 95% CI 1.64-18.06; p = 0.006) and high-grade hepatosteatosis (OR 7.73; 95% CI 1.74-34.35; p = 0.007). CONCLUSION: ApoB-100 is strongly associated with NAFLD in people with non-genotype 3 HCV; greater ApoB-100 content is significantly correlated with higher-grade hepatosteatosis.

The clinical outcomes of oldest old patients with tuberculosis treated by regimens containing rifampicin, isoniazid, and pyrazinamide.

OBJECTIVES: To investigate the clinical characteristics, adverse drug reactions, and outcomes of the oldest old patients (aged ≥80 years) with tuberculosis (TB) treated with rifampicin, isoniazid, and pyrazinamide (RIP)-containing regimens. DESIGN: A retrospective chart review study. SETTING: A 1,200-bed tertiary teaching hospital in southwest Taiwan. PARTICIPANTS: We conducted a retrospective observational study between January 1, 2005 and December 31, 2011. Seven hundred adult patients (aged ≥18 years) with TB treated with RIP-containing anti-TB regimens were reviewed, including 161 oldest old patients. OUTCOME MEASURES: Clinical outcomes included clinical responsiveness and microbiological eradication. Adverse outcomes included drug-induced hepatitis, and other symptoms included gastrointestinal upset (eg, abdominal pain, vomiting, diarrhea, or dyspepsia), skin rash, joint pain, and hyperuricemia. RESULTS: Compared with the non-oldest old adult patients, the oldest old patients more frequently had hepatitis (P=0.014), gastrointestinal upset (P=0.029), and unfavorable outcomes (P<0.001). In a multivariate analysis, hepatitis during treatment (adjusted odds ratio: 3.482, 95% confidence interval: 1.537-7.885; P<0.003) and oldest old age (adjusted odds ratio: 5.161, 95% confidence interval: 2.294-11.613; P<0.010) were independent risk factors for unfavorable outcomes. In the oldest old patients with hepatitis, rifampicin use was more common in the favorable outcome group than in the unfavorable outcome group (100% vs 37.5%; P=0.001). CONCLUSION: The oldest old age and hepatitis during RIP treatment were associated with unfavorable outcomes. For the oldest old patients with TB having hepatitis during treatment, rifampicin rechallenge and use might benefit the treatment outcome.

Serum aminotransferase ratio is independently correlated with hepatosteatosis in patients with HCV: a cross-sectional observational study.

OBJECTIVES: The incidence of non-alcoholic fatty liver disease (NAFLD) is significant in hepatitis C virus (HCV) carriers due to multiple mechanisms, and this worsens the progression of chronic liver diseases, such as cirrhosis and hepatocellular carcinoma, and death. The purpose of this study was to examine whether the alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratio correlates with the status of hepatosteatosis. DESIGN: A cross-sectional observational study. SETTING: Community-based annual examination in northern Taiwan. PARTICIPANTS: A total of 1354 participants (age 20 years or over) were enrolled after excluding participants with HCV seronegative, laboratory or questionnaires loss, moderate alcohol consumption, liver cirrhosis, tumours and postlobectomy. OUTCOME MEASURES: Fatty liver was diagnosed according to echogenic findings. NAFLD included grades 1-3 fatty liver and high-degree NAFLD defined grades 2-3 fatty liver. RESULTS: 580 males and 774 females with a mean age of 47.2 (SD=16.1) years were cross-sectionally studied. The participants with NAFLD have significantly higher levels of ALT/AST ratio, fasting glucose, triglyceride and systolic/diastolic blood pressure than non-NAFLD participants. The association between NAFLD and ALT/AST was significant even when adjusting for the metabolic syndrome (aOR 1.90; 95% CI 1.37 to 2.65; p<0.001). In patients with a high degree of NAFLD, the ALT/AST ratio was still a significant predictor for hepatosteatosis (aOR 2.44; 95% CI 1.58 to 3.77; p<0.001). CONCLUSIONS: The ALT/AST ratio could be a strong risk of hepatosteatosis in patients with chronic HCV infection.

Sulbactam treatment for pneumonia involving multidrug-resistant Acinetobacter calcoaceticus-Acinetobacter baumannii complex.

BACKGROUND: Multidrug-resistant (MDR) Acinetobacter calcoaceticus-Acinetobacter baumannii (Acb) complex has become an important cause of nosocomial pneumonia. Sulbactam is a ß-lactamase inhibitor with antimicrobial activity against MDR Acb complex. METHODS: To investigate outcomes of pneumonia involving MDR Acb complex treated with sulbactam or ampicillin/sulbactam for at least 7 days, we conducted a retrospective study of 173 adult patients over a 34 month period. RESULTS: Of 173 patients, 138 (79.8%) received combination therapy, mainly with carbapenems (119/138, 86.2%). The clinical response rate was 67.6% and the 30 day mortality rate was 31.2%. The independent predictors of clinical failure were malignancy, bilateral pneumonia and shorter duration of treatment. In patients with sulbactam-susceptible strains, there was no difference in clinical and microbiological outcome between combination therapy and monotherapy. Compared to the sulbactam-susceptible group, the sulbactam-resistant group had a lower rate of airway eradication, a longer duration of treatment and a higher rate of combination therapy with predominantly carbapenems (p < 0.05). There was no significant difference between the two groups in clinical resolution and 30 day mortality rates. CONCLUSIONS: Sulbactam could be a treatment option for pneumonia involving MDR Acb complex, and combination therapy with carbapenems could be considered for sulbactam-resistant cases.

Peritonitis as presentation of aorto-caval fistula with Salmonella choleraesuis-associated abdominal aortic aneurysm.

BACKGROUND: The majority of aorto-caval fistulae occur spontaneously, either as a result of rupture of an existing atherosclerotic abdominal aortic aneurysm into the vena cava or secondary to iatrogenic injuries during peripheral angiography or surgery. Aorto-caval fistula from an infected aortic aneurysm is a rare scenario, but potentially lethal. METHODS: Case report and review of the literature. CASE REPORT: A 63-year-old female with diabetes mellitus and liver cirrhosis was admitted for intractable abdominal pain with rebound tenderness. A computed tomography scan demonstrated an abdominal aortic aneurysm and ill-defined peri-aortic fluid with air density and evidence of a fistula between the aorta and the inferior vena cava. Salmonella cholerasuis had been isolated from a blood culture at a previous admission. Urgent endovascular exclusion of the aorto-caval fistula was carried out, and the infra-renal abdominal aneurysm was repaired using a Cook Zenith TX2 aortic stent graft. She received parenteral ceftriaxone for four weeks. CONCLUSIONS: This case shows acceptable short-term results after endovascular repair of a Salmonella-infected aorto-caval fistula.

The clinical implication and prognostic predictors of tigecycline treatment for pneumonia involving multidrug-resistant Acinetobacter baumannii.

OBJECTIVES: To investigate the clinical implication and prognostic predictors of tigecycline treatment for pneumonia involving multidrug-resistant Acinetobacter baumannii (MDRAB). METHODS: A retrospective observational study over a 32-month period for adult patients receiving tigecycline treatment at least 7 days for pneumonia involving MDRAB. RESULTS: We reviewed 112 patients with 116 episodes of tigecycline-treated pneumonia involving MDRAB. The mean age was 70.8 years. The mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 21.7. Seventy episodes (60.3%) had clinical resolution. The episodes with monomicrobial MDRAB pneumonia had a significantly lower clinical resolution rate than polymicrobial pneumonia (14/31, 45.2% vs. 56/85, 65.9%; p = 0.044). The independent predictors for failure of clinical resolution were female gender, malignancy, bilateral pneumonia, monomicrobial pneumonia, and higher APHCHE II scores. Forty-two episodes (36.2%) had the 30-day mortality, and the only independent predictor was deterioration of pneumonia on chest radiographs. CONCLUSIONS: A high disease severity, bilateral pneumonia, and monomicrobial MDRAB pneumonia predicted failure of clinical resolution, and deterioration of pneumonia predicted mortality. MDRAB in monomicrobial pneumonia was the most certain to be causal. The clinical resolution rate from such pneumonia might reflect the ultimate efficacy of tigecycline in treating MDRAB pneumonia and the overall efficacy might be overestimated.

Clinical significance of and outcomes for Bacteroides fragilis bacteremia.

BACKGROUND AND PURPOSE: Bacteroides fragilis is a virulent anaerobic pathogen, resulting in considerable mortality. This study was conducted to investigate the clinical characteristics, significance of polymicrobial bacteremia, and treatment outcomes of B. fragilis bacteremia. METHODS: This retrospective analysis enrolled 199 adult patients with B. fragilis bacteremia, who were admitted to hospital between January 2004 and May 2007. Chi-squared and Fisher's exact tests were used for comparison. A p value of <0.05 was considered statistically significant. RESULTS: 142 patients with B. fragilis bacteremia (71.4%) had at least 1 underlying disease. Malignancy was the commonest comorbidity (n = 62; 31.2%). Intra-abdominal infection accounted for 49.3% of the infection sources. Seventy seven patients (38.7%) had polymicrobial bacteremia and Escherichia coli was the most common concurrent isolate (n = 24). There was no significant difference in septic shock incidence and clinical outcome between the monomicrobial and polymicrobial groups. The overall 30-day crude mortality rate was 30.7%. Inappropriate early antimicrobial therapy did not affect outcome, but a higher mortality rate was noted for patients who never received appropriate antimicrobial therapy (55.2% vs 26.5%; p = 0.002). Independent risk factors for mortality were age 65 years and older (p = 0.010), malignancy (p = 0.001), shock (p < 0.001), thrombocytopenia (p = 0.026), and lack of surgical intervention (p = 0.035). CONCLUSIONS: B. fragilis bacteremia causes a high mortality rate, especially for elderly people and patients with cancer. Clinicians should be alert to the infectious focus, and appropriate surgical intervention may be necessary to improve outcomes.

Characteristics and factors influencing treatment outcome of renal and perinephric abscess--a 5-year experience at a tertiary teaching hospital in Taiwan.

BACKGROUND AND PURPOSE: Diagnosis of renal or perinephric abscess is still a challenge for physicians. This study investigated the effect of location and size of abscess and the time of diagnosis on treatment outcomes. METHODS: This retrospective analysis enrolled 159 adult patients with renal, perinephric or mixed-type (renal plus perinephric) abscess hospitalized between June 2001 and June 2006. The outcomes of these patients were classified into "poor" and "success" in order to elucidate associated risk factors. 106 patients had clear information of the timing of diagnosis and were categorized into "early" and "delayed" diagnosis groups, depending on whether the diagnosis was made within or after 5 days of admission. RESULTS: Compared with the early diagnosis group (n = 78), the delayed diagnosis group (n = 28) were older (59.9 +/- 15.9 vs 50.9 +/- 14.9 years, p=0.005) and had less costovertebral angle knocking pain (85.7% vs 51.3%, p=0.021), a higher rate of renal insufficiency (57.1% vs 15.4%, p<0.001) and hospital stay over 22 days (71.4% vs 24.4%, p<0.001). There was no significant difference between these two groups in clinical outcomes. Compared with renal abscess, both perinephric and mixed-type abscess had higher rates of larger abscess (>5 cm in diameter) [84.1% vs 25.6%, p<0.001; and 55.6% vs 25.6%, p=0.012, respectively] and lower rates of Escherichia coli infection (24.4% vs 59.4%, p<0.001; and 26.7% vs 59.4%, p=0.021, respectively). Among all culture-positive patients, the proportion of Klebsiella pneumoniae was 25.6%. Perinephric abscess had higher rates of percutaneous (56.3% vs 31.5%; p=0.005) and surgical drainage (29.2% vs 7.6%; p=0.001) than renal abscess. In multivariate analysis, age > or =65 years (p=0.006; odds ratio [OR], 7.008; 95% confidence interval [CI], 1.75-28.141), thrombocytopenia (p=0.002; OR [95% CI], 10.434 [2.344-46.444]), and abscess without drainage (p=0.001; OR [95% CI], 9.984 [2.640-37.758]) were independent factors for poor outcome (mortality or nephrectomy). CONCLUSION: Old age, renal insufficiency and lack of costovertebral angle knocking pain may contribute to delayed diagnosis of renal or perinephric abscess, and prolonged hospital stay. The location and size of abscess did not affect clinical outcome in this study, which might be due to adequate abscess drainage. K. pneumoniae is not uncommon in renal or perinephric abscess in Taiwan.