Treatment responses to integrase strand-transfer inhibitor-containing antiretroviral regimens in combination with short-course rifapentine-based regimens for latent tuberculosis infection among people with HIV.

BACKGROUND: Real-world experience with combinations of short-course rifapentine-based regimens and integrase strand-transfer inhibitor (InSTI)-containing antiretroviral therapy (ART) in management of latent tuberculous infection (LTBI) is limited among people with HIV (PWH). METHODS: From August 2019 to October 2022, PWH receiving 3 months of weekly rifapentine plus isoniazid (3HP) or 1 month of daily rifapentine plus isoniazid (1HP) in combination with ART were included. The primary outcome was virologic response within 12 months after LTBI treatment, and the secondary outcomes included treatment completion rate and safety of LTBI regimens. RESULTS: During the study period, 479 PWH (94.6% male; median age, 43 years) were included: 142 received 1HP and bictegravir (BIC)-containing regimens (1HP/BIC group), 46 1HP and dolutegravir (DTG)-containing regimens (1HP/DTG group), 38 3HP and BIC-containing regimens (3HP/BIC group), 214 3HP and DTG-containing regimens (3HP/DTG group), 17 1HP and other ART regimens (1HP/others group), and 22 3HP/other ART regimens (3HP/others group). In the intention-to-treat analysis, the proportions of PWH maintaining plasma HIV-1 RNA <200 copies/mL within 12 months after LTBI treatment completion were 96.5% (1HP/BIC), 100% (1HP/DTG), 100% (3HP/BIC), 95.8% (3HP/DTG), 100% (1HP/others), and 100% (3HP/others). The overall completion rates were >80% for all treatment groups, whereas >50% of the included PWH experienced any adverse event. LTBI regimens and ART combinations were not associated with virologic response and completion rate. CONCLUSION: Combinations of short-course rifapentine-based regimens and InSTI-containing ART maintained viral suppression for most PWH within 12 months of LTBI treatment completion with low rates of grade 3 or higher adverse events.

Impact of comorbidities on the serological response to COVID-19 vaccination in a Taiwanese cohort.

BACKGROUND/AIMS: Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the best policies to control COVID-19 pandemic. The serological response to COVID-19 vaccination in Taiwanese patients with different comorbidities is elusive. METHODS: Uninfected subjects who received 3 doses of mRNA vaccines (BNT162b2 [Pfizer-BioNTech, BNT] and mRNA-1273 [Moderna]), viral vector-based vaccines (ChAdOx1-S (AZD1222, AZ) or protein subunit vaccines (Medigen COVID-19 vaccine) were prospectively enrolled. The SARS-CoV-2-IgG spike antibody level was determined within three months after the 3rd dose of vaccination. The Charlson Comorbidity Index (CCI) was applied to determine the association between vaccine titers and underlying comorbidities. RESULTS: A total of 824 subjects were enrolled in the current study. The proportions of CCI scores of 0-1, 2-3 and > 4 were 52.8% (n = 435), 31.3% (n = 258) and 15.9% (n = 131), respectively. The most commonly used vaccination combination was AZ-AZ-Moderna (39.2%), followed by Moderna-Moderna-Moderna (27.8%). The mean vaccination titer was 3.11 log BAU/mL after a median of 48 days after the 3rd dose. Factors associated with potentially effective neutralization capacity (IgG level ≥ 4160 AU/mL) included age ≥ 60 years (odds ratio [OR]/95% confidence interval [CI]: 0.50/0.34-0.72, P < 0.001), female sex (OR/CI: 1.85/1.30-2.63, P = 0.001), Moderna-Moderna-based vaccination (compared to AZ-AZ-based vaccination, OR/CI: 6.49/3.90-10.83, P < 0.001), BNT-BNT-based vaccination (compared to AZ-AZ-based vaccination, OR/CI: 7.91/1.82-34.3, P = 0.006) and a CCI score ≥ 4 (OR/CI: 0.53/0.34-0.82, P = 0.004). There was a decreasing trend in antibody titers with increasing CCI scores (trend P < 0.001). Linear regression analysis revealed that higher CCI scores (ß: - 0.083; 95% CI: - 0.094-0.011, P = 0.014) independently correlated with low IgG spike antibody levels. CONCLUSIONS: Subjects with more comorbidities had a poor serological response to 3 doses of COVID-19 vaccination.

Short time to positivity of blood culture predicts mortality and septic shock in bacteremic patients: a systematic review and meta-analysis.

BACKGROUND: The value of time to positivity (TTP) on diagnosis for catheter-related bloodstream infection and distinguishment on bacteria group and infection source has been investigated. However, the relationship between TTP and patient outcome requires verification, and we performed a systematic review and meta-analysis. METHODS: We searched PubMed, EMBASE, CINAHL, Cochrane Library, Web of Science for publications associated with the topic. We included studies that researched the TTP on predicting patient mortality and septic shock. Quality assessment is performed with Critical Appraisal Skills Programme (CASP). The analysis is performed using Review Manager Version 5.0.24. on articles available for data extraction on the exact population of each outcome group. The existence of publication bias was assessed by funnel plots. Statistical heterogeneity was evaluated using the Cochran Q and [Formula: see text] statistics. The outcome is reported as an odds ratio. PROSPERO registration: CRD42021272286. RESULTS: Twenty-four eligible studies were included in our study. Twenty-four in the mortality group and six in the septic shock group. Mortality is significantly associated with the short time to positivity group with an odds ratio of 2.98 (95% CI: 2.25-3.96, p-value < 0.001). The odds ratio for developing septic shock in the short TTP group is 4.06 (95% CI: 2.41-6.84, p-value < 0.001). Subgroup analysis revealed short TTP as a significant predictor of mortality and septic shock in Gram's positive and Gram's negative related bloodstream infections. TTP is not associated with mortality among patients with candidaemia. CONCLUSIONS: Short time to positivity is a reliable marker for patient outcome in certain bacterial species. Studies concerning confounding factors such as the delay in bottle loading and other confounding factors are needed to enhance external validity.

Structural insights into Nirmatrelvir (PF-07321332)-3C-like SARS-CoV-2 protease complexation: a ligand Gaussian accelerated molecular dynamics study.

Coronavirus 3C-like protease (3CLpro) is found in SARS-CoV-2 virus, which causes COVID-19. 3CLpro controls virus replication and is a major target for target-based antiviral discovery. As reported by Pfizer, Nirmatrelvir (PF-07321332) is a competitive protein inhibitor and a clinical candidate for orally delivered medication. However, the binding mechanisms between Nirmatrelvir and 3CLpro complex structures remain unknown. This study incorporated ligand Gaussian accelerated molecular dynamics, the one-dimensional and two-dimensional potential of mean force, normal molecular dynamics, and Kramers' rate theory to determine the binding and dissociation rate constants (koff and kon) associated with the binding of the 3CLpro protein to the Nirmatrelvir inhibitor. The proposed approach addresses the challenges in designing small-molecule antiviral drugs.

Impact of Age on Outcome of Rifapentine-Based Weekly Therapy for Latent Tuberculosis Infection.

BACKGROUND: Weekly rifapentine and isoniazid (3HP) is gaining popularity for latent tuberculosis infection treatment because of its short course and high completion rate. Prior to widespread use, comprehensive 3HP treatment assessment covering an all-age population is essential. METHODS: Participants receiving ≥1 3HP dose from September 2014 to December 2019 were stratified into elderly (≥65 years), middle-aged (>35 & <65 years), and younger (≤35 years) age groups. This study investigated the impact of age on treatment outcome, particularly systemic drug reactions (SDRs) and 3HP discontinuation. RESULTS: Overall, 134 of 579 (23.1%) participants were elderly. The completion rate was 83.1% overall and was highest and lowest in the younger group (94.5%) and elderly (73.9%) group, respectively. However, the 3HP discontinuation rate was not significantly different among the 3 groups in multivariate logistic regression analysis. In total, 362 (62.5%) participants experienced 1 or more adverse drug reactions (ADRs), of which 38 (10.5%) and 98 (27.1%) required temporary and permanent treatment interruption, respectively. The SDR risk was 11.2% in overall and 17.1% in the middle-aged group, 3.04-fold higher than that in the elderly group (P = .025). This finding was consistently observed in different clinical settings. Hypertensive events accompanied with flu-like symptoms occurred in 11.2% of elderly participants, and accounted for 50% of grade ≥3 ADRs. CONCLUSIONS: With proper medical support and programmatic follow-up, the 3HP completion rate is >70% even in elderly participants. In middle-aged and elderly individuals, 3HP should be employed with caution because of risk of SDRs and hypertensive events, respectively. Summary: Under programmatic medical support, widespread use of weekly rifapentine and isoniazid (3HP) for latent tuberculosis treatment is possible for its high completion rate. 3HP should be employed with caution for risk of systemic drug reactions and hypertensive events in middle-aged and elderly individuals, respectively.

Clinical Impact of the Revised 2019 CLSI Levofloxacin Breakpoints in Patients with Enterobacterales Bacteremia.

The Clinical and Laboratory Standards Institute (CLSI) revised the fluoroquinolone MIC breakpoints for Enterobacterales in 2019, based on pharmacokinetic/pharmacodynamic analyses. However, clinical evidence supporting these breakpoint revisions is limited. A retrospective study was conducted at 3 hospitals in Taiwan between January 2017 and March 2019. Patients treated with levofloxacin for bacteremia caused by members of the Enterobacterales with high MICs (1 or 2 µg/ml; levofloxacin susceptible by pre-2019 CLSI breakpoints) were compared with those with low-MIC bacteremia (≤0.5 µg/ml; levofloxacin susceptible by 2019 CLSI breakpoints) to assess therapeutic effectiveness by multivariable logistic regression. The primary outcome was 30-day mortality, and the secondary outcome was the emergence of levofloxacin-resistant isolates within 90 days after levofloxacin initiation. A total of 308 patients were eligible for the study. Kaplan-Meier analysis showed that patients infected with high-MIC isolates (n = 63) had a significantly lower survival rate than those infected with low-MIC isolates (n = 245) (P = 0.001). Multivariable logistic regression revealed that high levofloxacin MIC was a predictor of 30-day mortality (odds ratio [OR], 6.05; 95% confidence interval [CI], 1.51 to 24.18; P = 0.011). We consistently found similar results in a propensity score-matched cohort (OR, 5.38; 95% CI, 1.06 to 27.39; P = 0.043). The emergence of levofloxacin-resistant isolates was more common in the high-MIC group than the low-MIC group (25.0% versus 7.5%; P = 0.065). An estimated area under the concentration-time curve/MIC ratio of ≥87 was significantly associated with better survival (P = 0.002). In conclusion, patients infected with isolates with levofloxacin MICs within the pre-2019 CLSI susceptible range of 1 or 2 µg/ml exhibited higher mortality than those infected with isolates with MICs of ≤0.5 µg/ml.

First case report of Anaerobiospirillum succiniciproducens bacteremia in an HIV-infected patient in Taiwan - Molecular identification from a positive blood culture bottle.

Anaerobiospirillum succiniciproducens is a gram-negative, spiral-shaped anaerobe, that is a rare but potentially lethal cause of bacteremia in humans, particularly in immunocompromised hosts. We reported a 69-year-old HIV-infected male presenting with dysphagia, odynophagia and fulminant pneumonia who died. In addition, in a literature review, we summarized the characteristics of 19 adult patients with A. succiniciproducens bacteremia, which were confirmed by matrix-assisted laser desorption ionization-time of flight mass spectrometry or molecular methods. Among those, the presentation of gastrointestinal conditions was the only independent risk factor for mortality. Clinicians should be aware of this pathogen, especially when a culture is negative but a Gram stain reveals gram-negative spiral-shaped bacteria.

Effect of 9,12-Octadecadiynoic Acid on Neurobehavioral Development in Caenorhabditis elegans.

Human breast milk lipids have major beneficial effects: they promote infant early brain development, growth and health. To identify the relationship between human breast milk lipids and infant neurodevelopment, multivariate analyses that combined lipidomics and psychological Bayley-III scales evaluation were utilized. We identified that 9,12-octadecadiynoic acid has a significantly positive correlation with infant adaptive behavioral development, which is a crucial neurodevelopment to manage risk from environmental stress. To further clarify the biological function of 9,12-octadecadiynoic acid in regulating neurodevelopment, Caenorhabditis elegans (C. elegans) was used as a model to investigate the effect of 9,12-octadecadiynoic acid on neurobehavioral development. Supplementation with 9,12-octadecadiynoic acid from the L1 to L4 stage in larvae affected locomotive behaviors and foraging ability that were not socially interactive, implying that 9,12-octadecadiynoic acid is involved in regulating the serotonergic neuronal ability. We found that supplementary 0.1 µM 9,12-octadecadiynoic acid accelerated the locomotive ability and foraging ability via increasing the expression of serotonin transporter mod-1. Antioxidant defense genes, sod-1, sod-3 and cyp-35A2 are involved in 9,12-octadecadiynoic acid-induced motor neuronal activity. Nevertheless, supplementary 9,12-octadecadiynoic acid at concentrations above 1 µM significantly attenuated locomotive behaviors, foraging ability, serotonin synthesis, serotonin-related gene expressions and stress-related gene expression, resulting in the decreased longevity of worms in the experiment. In conclusion, our study demonstrates the biological function of 9,12-octadecadiynoic acid in governing adaptive behavioral development.

Early Seroreversion After 2 Doses of Hepatitis A Vaccination in Human Immunodeficiency Virus-Positive Patients: Incidence and Associated Factors.

Serological responses (Seroresponse) and durability of hepatitis A virus (HAV) vaccination are reduced among human immunodeficiency virus (HIV)-positive patients. Incidence of and associated factors with early seroreversion (loss of seroresponse) among HIV-positive patients who have achieved seroresponses after two doses of HAV vaccination remain unclear. In this multicenter study, we followed HIV-positive adults who had mounted seroresponses after completing two doses of HAV vaccination during a recent outbreak of acute hepatitis A between 2015 and 2017, a 1:4 case-control study was conducted to identify factors associated with seroreversion. Case patients were those with seroreversion, and controls were those with similar follow-up durations who were able to maintain seroresponses. During the study period, 49 of the 1,256 patients (3.9%) seroreverted after a median follow-up of 611 days. In a case-control study, seroreversion was more likely to occur in patients with a higher weight (adjusted odds ratio [aOR], 1.703; 95% confidence interval [CI], 1.292-2.323, per 10-kg increment) and HIV viremia at the time of vaccination (aOR, 2.922; 95% CI, 1.067-7.924), whereas positive seroresponse at 6 months of HAV vaccination and higher CD4 lymphocyte counts at vaccination were inversely associated with early seroreversion with an aOR of 0.059 (95% CI, 0.020-0.154) and 0.837 (95% CI, 0.704-0.979, per 100-cell/mm3 increment), respectively, in multivariable analyses. Conclusion: During an outbreak setting, early seroreversion following two-dose HAV vaccination occurred in 3.9% of HIV-positive patients. Lower and delayed seroresponses to HAV vaccination, a higher weight, and HIV viremia and lower CD4 lymphocyte counts at the time of HAV vaccination were associated with early seroreversion. Regular monitoring of seroresponse and booster vaccination might be warranted, especially in HIV-positive adults with predictors of early seroreversion.

Less Severe but Prolonged Course of Acute Hepatitis A in Human Immunodeficiency Virus (HIV)-Infected Patients Compared With HIV-Uninfected Patients During an Outbreak: A Multicenter Observational Study.

Background: This multicenter retrospective cohort study aimed to compare the clinical presentations and evolution of acute hepatitis A (AHA) between human immunodeficiency virus (HIV)-infected patients and HIV-uninfected counterparts during the AHA outbreak. Methods: Clinical and laboratory data were collected from the medical records of the patients with AHA at the 14 hospitals around Taiwan between May 2015 and May 2017. Results: A total of 297 adult patients with AHA were included during the study period. Their mean age was 31.4 years (range, 19.0-76.1 years); 93.4% were men and 58.6% were men who have sex with men. Of 265 patients with known HIV serostatus, 166 (62.6%) were HIV infected. Compared with HIV-uninfected patients, HIV-infected patients had a lower peak alanine aminotransferase (ALT) level (median, 1312 vs 2014 IU/L, P = .003), less coagulopathy (6.0% vs 16.2%, P = .007), and less hepatomegaly or splenomegaly on imaging studies, but a higher rate of delayed resolution of hepatitis (38.8% vs 21.3%, P = .009). HIV-infected patients with plasma RNA load <1000 copies/mL while receiving combination antiretroviral therapy (cART) had a higher peak ALT level (median, 1420 vs 978 IU/L, P = .006) and less delay in resolution of hepatitis (30.6% vs 48.8%, P = .047) than patients without cART or with plasma RNA load ≥1000 copies/mL. Conclusions: During an AHA outbreak, HIV-infected patients had a lower severity, but delayed resolution, of AHA than HIV-uninfected patients. Better viral suppression by cART alleviated the impact of HIV infection on the disease course of AHA in HIV-infected patients.

Mirabegron is alternative to antimuscarinic agents for overactive bladder without higher risk in hypertension: a systematic review and meta-analysis.

PURPOSE: Mirabegron, a ß3-adrenoceptor agonist, was approved for overactive bladder (OAB), but worsened hypertension was a potential risk based on its mechanism of action. Besides, head to head comparisons were limited between mirabegron and antimuscarinic agents, the prior first-line pharmacotherapy of OAB. In this regard, we performed a systematic review and meta-analysis to compare their efficacy as well as safety, especially in blood pressure changes. MATERIALS AND METHODS: Literature search was conducted in PubMed, Medline and seven randomized clinical trial (RCT) register databases of WHO, EU, USA, Taiwan, China, Japan and Cochrane. Completed RCTs for OAB with mirabegron and antimuscarinics were identified and the last comprehensive search was run in August 2017. Cochrane risk of bias tool was used to assess the potential bias, and RevMan5 software was performed for meta-analysis. RESULTS: Seven eligible RCTs (four for mirabegron vs. tolterodine and three for mirabegron vs. solifenacin) were included and demonstrated similar efficacy in micturitions, incontinence, and nocturia between mirabegron and antimuscarinics. In hypertension issue, no statistical differences were showed in risk ratio (RR) of hypertension events, change of blood pressure from baseline and change of blood pressure from placebo for all participants. On the other hand, RR of dry mouth was significantly lower in mirabegron users. CONCLUSIONS: Mirabegron was not inferior effective in improving OAB symptoms compared with antimuscarinic agents. In addition, mirabegron presented lower incidence of dry mouth and not higher risk for hypertension. Therefore, mirabegron has potential to be an alternative therapeutic option for OAB control.

Metformin is associated with a lower risk of active tuberculosis in patients with type 2 diabetes.

BACKGROUND AND OBJECTIVE: Metformin is an oral anti-diabetic therapy (ADT) to manage type 2 diabetes mellitus (T2DM), and has been reported to have potential anti-tuberculosis (TB) effects. This study investigates the risk of active TB among persons with T2DM who were treated with various ADT and insulin therapies. METHODS: We conducted a nationwide population-based cohort study using the Taiwan Longitudinal Health Insurance Database, including 49 028 T2DM patients who were metformin users (n = 44 002) or non-users (n = 5026). A total of 5026 propensity score-matched pairs of metformin users and non-users with T2DM were evaluated from 1998 to 2010. The data were analysed using Cox proportional hazard models. RESULTS: Patients with T2DM had a significantly higher rate of incident TB than did the control subjects (adjusted hazard ratio: 2.01; 95% confidence interval (95% CI): 1.80-2.25). After adjusting for comorbidities, diabetes complications, ADT type and statin use, metformin use was an independent factor for predicting a reduced risk of active TB (adjusted relative risk (aRR): 0.24; 95% CI: 0.18-0.32). The association between metformin use and active TB risk was also consistent in most subgroup analyses, except for patients with metabolic disorders (aRR: 0.46; 95% CI: 0.11-1.87). This protective effect of metformin was dose-dependent but diminished gradually in the elderly population. CONCLUSION: Among all types of ADT and insulin therapies, metformin is the only agent with a decreased risk of active TB in the T2DM population. However, this effect was diminished in the elderly population and was not observed in patients with metabolic disorders.

Incidence rates of tuberculosis in chronic hepatitis C infected patients with or without interferon based therapy: a population-based cohort study in Taiwan.

BACKGROUND: It is debated whether interferon-based therapy (IBT) would affect the incidence of active tuberculosis (TB) among hepatitis C virus (HCV) infected patients. Although some case reports have demonstrated a possible association, the results are currently inconclusive. Therefore, we conducted a nation-wide population study to investigate the incidence of active TB in HCV infected patients receiving IBT in Taiwan. METHODS: This 9-year cohort study was based on the Longitudinal Health Insurance Database 2000 (LHID 2000) consisting of 1,000,000 beneficiaries randomly selected from all Taiwan National Health Insurance enrollees in 2000 ( >23.7 million). This insurance program covers all citizens in Taiwan. We conducted a retrospective cohort study that identified subjects with HCV infection. IBTs were defined as regimens that included interferon α, peginterferon α2a and peginterferon α2b for at least 2 months. Among them, 621 subjects received IBT, and 2,460 age- and gender-matched subjects were enrolled for analysis. The Cox proportional hazards models were used to estimate the hazard ratio (HR) for active TB, and associated confidence intervals (CIs), comparing IBT cohort and untreated cohort. The endpoint in this study was whether an enrolled subject had a new diagnosis of active TB. RESULTS: During the 9-year enrollment period, the treated and untreated cohorts were followed for a mean (± SD) duration of 6.97 ± 0.02 years and 8.21 ± 0.01 years, respectively. The cumulative incidence rate of active TB during this study period was 0.150 and 0.151 per 100 person-years in the IBT treated and untreated cohorts, respectively. There was no significant difference in the incidence of active TB in either cohort during a 1-year follow-up (Adjusted Hazard Ratio (AHR): 2.81, 95% Confidence Interval (95% CI): 0.61-12.98) or the long-term follow-up (AHR: 1.02, 95% CI: 0.28-3.78). The Cox proportional hazards model demonstrated that IBT was not a risk factor for active TB . The only risk factor for active TB was the occurrence of hepatic encephalopathy. CONCLUSION: Our results showed that IBT is associated with increased hazard of active TB in HCV infected patients in 1-year follow-up; however, the effect sizes were not statistically significant.

Ruxolitinib associated psoas muscle tuberculosis abscess in a primary myelofibrosis woman: A case report and literature review.

RATIONALE: Primary myelofibrosis is a subtype of myeloproliferative neoplasm that leads to bone marrow fibrosis. Historically, the only curative option for primary myelofibrosis was allogeneic hematopoietic stem cell transplant. Ruxolitinib, a Janus kinase inhibitor, is now used for the treatment of primary myelofibrosis and polycythemia vera. It effectively improves symptoms related to splenomegaly and anemia. However, its association with the development of opportunistic infections has been observed in clinical studies and practical application. PATIENT CONCERNS: A 64-year-old female with primary myelofibrosis and chronic hepatitis B infection who received ruxolitinib treatment. She was admitted for spiking fever and altered consciousness. DIAGNOSIS: Tuberculosis meningitis was suspected but cerebrospinal fluid can't identify any pathogens. An abdominal computed tomography scan revealed a left psoas abscess and an enlarged spleen. A computed tomography-guided pus drainage procedure was performed, showing a strong positive acid-fast stain and a positive Mycobacterium tuberculosis polymerase chain reaction result. INTERVENTIONS: antituberculosis medications were administered. The patient developed a psoas muscle abscess caused by tuberculosis and multiple dermatomes of herpes zoster during antituberculosis treatment. OUTCOMES: The patient was ultimately discharged after 6 weeks of treatment without apparent neurological sequelae. LESSONS: This case underscores the importance of clinicians evaluating latent infections and ensuring full vaccination prior to initiating ruxolitinib-related treatment for primary myelofibrosis.

Trends and the associated factors of optimal immunological response and virological response in late anti-retroviral therapy initiation HIV cases in Taiwan from 2009 to 2020.

BACKGROUND: Late cART initiation (CD4 count ≤200 cells/µL or AIDS-defining opportunistic illnesses [AOIs] at cART initiation) impedes CD4 count recovery and virologic suppression after cART initiation. However, studies to evaluate trends of and modifiable factors for optimal immunological response (IR) and virological response (VR) in people living with HIV (PLWH) with late cART initiation with the current HIV treatment strategies are limited. METHODS: We retrospectively identified 475 PLWH with late cART initiation in 2009-2020. Patients were grouped based on the presence of IR (CD4 count ≥200 cells/µL) or VR (plasma viral load [PVL] ≤ 50 copies/mL) within 18 months after cART initiation (403 [84.8%] IR(+) and 72 [15.2%] IR(-); 422 [88.8%] VR(+) and 53 [11.2%] VR(-)). We used Joinpoint regression to identify IR (+) and VR(+) proportion changes. RESULTS: From 2009 to 2020, the proportion of IR(+) patients remained unchanged (75% to 90%, P = 0.102), whereas that of VR(+) patients increased significantly (75% to 95%, P = 0.007). No join point was identified for either IR(+) or VR(+), and the annual percentage change was 0.56% (nonsignificant) and 1.35% (significant) for IR(+) and VR(+), respectively. Compared to IR(-) patients, IR(+) patients were more likely to have a higher pre-cART PVL, to start with a first-line INSTI-based regimen, or to start cART within 14 days of HIV diagnosis but were less likely to have chronic kidney disease, composite AOIs, or a lower pre-cART CD4 count. Compared to VR(-) patients, VR(+) patients were more likely to start a single-tablet regimen but were less likely to have a higher pre-cART PVL. CONCLUSIONS: Our study identified several modifiable factors for optimal IR (rapid cART initiation and INSTI-based regimen initiation) and for optimal VR (STR initiation) among late initiators, which may guide early treatment modifications to reduce their AIDS-defining event incidence and mortality.

The impact of the fluconazole trailing effect on the persistence of Candida albicans bloodstream infection when treated with fluconazole.

OBJECTIVES: The trailing effect of Candida species is a phenomenon characterized by reduced but persistent growth at antifungal concentrations above the MIC. We assessed the impact of trailing growth on the persistence of Candida albicans candidemia in patients receiving fluconazole (FLC) therapy. METHODS: We retrospectively investigated candidemia isolates at three hospitals in southern Taiwan between 2013 and 2020. Patients treated with FLC for FLC-susceptible C. albicans candidemia were enrolled. The degree of trailing was determined as the average growth above the MIC divided by the measured growth at the lowest drug concentration using the EUCAST method and classified into four categories: residual (0.1-5%), slight (6-10%), moderate (11-15%), and heavy trailers (>15%). RESULTS: Among isolates from 190 patients, the proportions of heavy trailers at 24 hours, 48 hours, and 72 hours were 63.7% (121/190), 63.2% (120/190), and 74.7% (142/190), respectively. Persistent candidemia was observed in 17 (8.9 %) patients. The proportion of persistent C. albicans candidemia in heavy trailing isolates at 48 hours was higher than in isolates without heavy trailing (13.3% [16/120] vs. 1.4% [1/70], p = 0.007). A multivariate analysis showed that immunosuppression (OR = 7.92; 95% CI: 2.38-26.39, p = 0.001), hospitalization days after the index date of C. albicans identification (OR = 1.03; 95% CI: 1.01-1.05, p = 0.011), and heavy trailing isolates at 48 hours (OR = 10.04; 95% CI: 1.27-79.88, p = 0.029) were independent factors for persistent candidemia. DISCUSSION: The current study revealed that heavy trailing in C. albicans isolates is associated with persistent candidemia in patients receiving FLC treatment.

The impact of inappropriate antibiotics on bacteremia patients in a community hospital in Taiwan: an emphasis on the impact of referral information for cases from a hospital affiliated nursing home.

BACKGROUND: Evidence for the impact of inappropriate antimicrobial therapy on bacteremia is mainly from studies in medical centers. We investigated the impact of inappropriate antimicrobial therapy on bacteremia in a community hospital. In particular, patients from the hospital's affiliated nursing home were sent to the hospital with adequate referral information. METHODS: We performed a retrospective study to collect data of patients with bacteremia in a community hospital in Taiwan from 2005 to 2007. RESULTS: A total of 222 patients with blood stream infection were diagnosed, of whom 104 patients (46.8%) died. The rate of initial inappropriate antibiotic prescriptions was high (59%). Multivariate analysis revealed that patients with initial inappropriate antibiotics, patients with ventilator support and patients requiring ICU care were the independent predictors for inhospital mortality. Patients referred from the hospital-affiliated nursing home and patients with normal WBC counts had better survival outcome. More than 80% cases infected with methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecalis received initial inappropriate antimicrobial therapy. With the longer delay to administer appropriate antibiotic, a trend of higher mortality rates was observed. CONCLUSIONS: Bacteremia patients from a hospital-affiliated nursing home had a better prognosis, which may have been due to the adequate referral information. Clinicians should be aware of the commonly ignored drug resistant pathogens, and efforts should be made to avoid delaying the administration of appropriate antibiotic therapy.

Impact of Plastic-Wrap Properties and Cleaning Intervals on the Disinfection of Elevator Buttons.

Fomite transmission is a possible route by which different pathogens spread within facilities. In hospital settings, elevator buttons are widely observed to be covered with various types of plastic wraps; however, limited information is available concerning the impact of different plastic materials on cleaning. Our study aimed to identify which plastic material is suitable for the coverage of elevator buttons and the optimal intervals for their cleaning. We tested six plastic covers, including polyethylene (PE), polymethylpentene (PMP), polyvinyl chloride (PVD), and polyvinylidene chloride (PVDC) plastic wraps; a thermoplastic polyurethane (TPU) keyboard cover; and a polyethylene terephthalate-ethylene vinyl acetate (PET-EVA) laminating film, which are plastic films. The bioburden on the elevator buttons at different time intervals was measured using an adenosine triphosphate (ATP) bioluminescence assay. Our results show that wraps made of PVDC had superior durability compared with those of PMP, PVC, and PVDC, in addition to the lowest detectable ATP levels among the six tested materials. Regarding different button locations, the highest ATP values were found in door-close buttons followed by door-open, and first-floor buttons after one- and three-hour intervals (p = 0.024 and p < 0.001, respectively). After routine disinfection, the ATP levels of buttons rapidly increased after touching and became more prominent after three hours (p < 0.05). Our results indicate that PVDC plastic wraps have adequate durability and the lowest residual bioburden when applied as covers for elevator buttons. Door-close and -open buttons were the most frequently touched sites, requiring more accurate and precise disinfection; therefore, cleaning intervals of no longer than three hours may be warranted.

Dolutegravir-induced growth and lifespan effects in Caenorhabditis elegans.

BACKGROUND: Integrase strand transfer inhibitor (INSTIs)-based combination antiretroviral treatment in people living with HIV (PLWH) has been reportedly correlated with several adverse effects, such as weight gain, fetal defects or psychiatric disorders. METHODS: To comprehensively understand the adverse effect of INSTIs, our study utilized Caenorhabditis Elegans (C. elegans) as a model to investigate how dolutegravir (DTG) affected its life cycle, growth, reproduction and lifespan. RESULTS: Our results indicated that DTG enhanced body growth at the early stage of treatment, but no change was detected for long-term treatment. The treatment also influenced the reproductive system, decreased egg-hatching but had no effect on egg-laying. Besides, DTG resulted in lifespan reduction, which is dependent on increased levels of reactive oxidative species (ROS) accumulation. Treatment with N-acetyl-cysteine (NAC) in worms restrained intracellular ROS accumulation and improved DTG-induced lifespan reduction. CONCLUSIONS: Our study demonstrates for the first time the effect of DTG treatment on life cycle. DTG-induced adverse effects are potentially associated with intracellular ROS accumulation. Quenching ROS accumulation might provide a novel strategy for dealing with the adverse effects of INSTIs.

Effect of omega-6 linoleic acid on neurobehavioral development in Caenorhabditis elegans.

Linoleic acid (LA, omega-6), an essential polyunsaturated fatty acid, is supplied by vegetable oils such as corn, sunflower and soybean. Supplementary LA in infants and children is required for normal growth and brain development, but has also been reported to induce brain inflammation and neurodegenerative diseases. This controversial role of LA development requires further investigation. Our study utilized Caenorhabditis elegans (C. elegans) as a model to clarify the role of LA in regulating neurobehavioral development. A mere supplementary quantity of LA in C. elegans larval stage affected the worm's locomotive ability, intracellular ROS accumulation and lifespan. We found that more serotonergic neurons were activated by supplementing LA above 10 µM thereby promoting locomotive ability with upregulation of serotonin-related genes. Supplementation with LA above 10 µM also inhibited the expression of mtl-1, mtl-2 and ctl-3 to accelerate oxidative stress and attenuate lifespan in nematodes; however, enhancement of stress-related genes such as sod-1, sod-3, mtl-1, mtl-2 and cyp-35A2 by supplementary LA under 1 µM decreased oxidative stress and increased the worm's lifespan. In conclusion, our study reveals that supplementary LA possesses both pros and cons in worm physiology and provides new suggestions for LA intake administration in childhood.