Hesperetin activates CISD2 to attenuate senescence in human keratinocytes from an older person and rejuvenates naturally aged skin in mice.

BACKGROUND: CDGSH iron-sulfur domain-containing protein 2 (CISD2), a pro-longevity gene, mediates healthspan in mammals. CISD2 is down-regulated during aging. Furthermore, a persistently high level of CISD2 promotes longevity and ameliorates an age-related skin phenotype in transgenic mice. Here we translate the genetic evidence into a pharmaceutical application using a potent CISD2 activator, hesperetin, which enhances CISD2 expression in HEK001 human keratinocytes from an older person. We also treated naturally aged mice in order to study the activator's anti-aging efficacy. METHODS: We studied the biological effects of hesperetin on aging skin using, firstly, a cell-based platform, namely a HEK001 human keratinocyte cell line established from an older person. Secondly, we used a mouse model, namely old mice at 21-month old. In the latter case, we investigate the anti-aging efficacy of hesperetin on ultraviolet B (UVB)-induced photoaging and naturally aged skin. Furthermore, to identify the underlying mechanisms and potential biological pathways involved in this process we carried out transcriptomic analysis. Finally, CISD2 knockdown HEK001 keratinocytes and Cisd2 knockout mice were used to study the Cisd2-dependent effects of hesperetin on skin aging. RESULTS: Four findings are pinpointed. Firstly, in human skin, CISD2 is mainly expressed in proliferating keratinocytes from the epidermal basal layer and, furthermore, CISD2 is down-regulated in the sun-exposed epidermis. Secondly, in HEK001 human keratinocytes from an older person, hesperetin enhances mitochondrial function and protects against reactive oxygen species-induced oxidative stress via increased CISD2 expression; this enhancement is CISD2-dependent. Additionally, hesperetin alleviates UVB-induced damage and suppresses matrix metalloproteinase-1 expression, the latter being a major indicator of UVB-induced damage in keratinocytes. Thirdly, transcriptomic analysis revealed that hesperetin modulates a panel of differentially expressed genes that are associated with mitochondrial function, redox homeostasis, keratinocyte function, and inflammation in order to attenuate senescence. Intriguingly, hesperetin activates two known longevity-associated regulators, namely FOXO3a and FOXM1, in order to suppress the senescence-associated secretory phenotype. Finally, in mouse skin, hesperetin enhances CISD2 expression to ameliorate UVB-induced photoaging and this occurs via a mechanism involving CISD2. Most strikingly, late-life treatment with hesperetin started at 21-month old and lasting for 5 months, is able to retard skin aging and rejuvenate naturally aged skin in mice. CONCLUSIONS: Our results reveal that a pharmacological elevation of CISD2 expression at a late-life stage using hesperetin treatment is a feasible approach to effectively mitigating both intrinsic and extrinsic skin aging and that hesperetin could act as a functional food or as a skincare product for fighting skin aging.

Infective Spondylitis with Epidural Abscess Formation Caused by Roseomonas mucosa: A Case Report and Literature Review.

Roseomonas mucosa (R. mucosa) is a pink-pigmented, aerobic, nonfermentative, slow-growing Gram-negative coccus typically isolated from the natural environment, human skin, and hospital environment. This pathogen, in most circumstances, leads to infections in immunocompromised hosts, but it may sometimes invade immunocompetent individuals. Bacteraemia is the most common form of infection caused by R. mucosa. In contrast, only two case reports have described R. mucosa-related epidural abscess formation and infective spondylitis. In this case report, we shared the history and treatment experience of a 76-year-old female who was diagnosed with infective spondylitis and epidural abscess caused by R. mucosa. She received a local transdermal injection into the lower back to relieve her back pain two months before symptom onset, which was considered to be associated with this infection episode. After admission to the hospital, neurosurgeons performed emergent decompression and debridement. She was treated with intravenous ceftriaxone for four weeks, followed by oral ciprofloxacin for another eight weeks. The patient recovered well without any sequelae and had no relapse of infection at least six months after the end of treatment. In addition to the case report, we reviewed the literature for reported cases caused by R. mucosa. Our experience suggests that clinicians should include R. mucosa as one of the possible healthcare-associated pathogens among individuals who have undergone transdermal procedures. We believe that this article will help clinicians better recognize R. mucosa infection.

Predictors of Human Immunodeficiency Virus Pre-Exposure Prophylaxis (PrEP) Uptake in a Sexual Health Clinic With Rapid PrEP Initiation.

Background: Improved pre-exposure prophylaxis (PrEP) uptake is essential for human immunodeficiency virus (HIV) prevention initiatives. Offering PrEP at the time of HIV and sexually transmitted infection (STI) testing can improve uptake. We offered rapid PrEP initiation in a sexual health clinic and assessed predictors of PrEP interest, initiation, linkage, and retention. Methods: Between November 2018 and February 2020, PrEP-eligible individuals who presented to a sexual health clinic were offered a free 30-day supply of PrEP plus linkage to continued PrEP care. Univariable and multivariable analyses of demographic and HIV risk data were conducted to determine predictors of PrEP uptake. Results: Of 1259 adults who were eligible for PrEP (99.7% male, 42.7% White, 36.2% Hispanic), 456 were interested in PrEP, 249 initiated PrEP, 209 were linked, and 67 were retained in care. Predictors of PrEP interest included younger age (P < .01), lower monthly income (P = .01), recreational drug use (P = .02), and a greater number of sexual partners (P < .01). Negative predictors of PrEP initiation included lower monthly income (P = .04), testing positive for chlamydia (P = .04), and exchanging money for sex (P = .01). Negative predictors of linkage included self-identifying as Black (P = .03) and testing positive for an STI (P < .01). Having health insurance positively predicted both linkage (P < .01) and retention (P < .03). Conclusions: A minority of PrEP-eligible HIV and STI testers initiated PrEP when offered, suggesting that easy PrEP access in sexual health clinics alone may not improve uptake. Predictors of uptake included established HIV risk factors and markers of higher socioeconomic status, suggesting that those aware of their risk and with the means to utilize health services engaged best with this model.

Using a Knowledge-Based Clinical Decision Support System to Reduce the Time to Appropriate Antimicrobial Therapy in Hospitalized Patients With Bloodstream Infections: A Single-Center Observational Study.

Background: Inappropriate antimicrobial use is a crucial determinant of mortality in hospitalized patients with bloodstream infections. Current literature reporting on the impact of clinical decision support systems on optimizing antimicrobial prescription and reducing the time to appropriate antimicrobial therapy is limited. Methods: Kaohsiung Veterans General Hospital implemented a hospital-wide, knowledge-based, active-delivery clinical decision support system, named RAPID (Real-time Alert for antimicrobial Prescription from virtual Infectious Diseases experts), to detect whether there was an antimicrobial agent-pathogen mismatch when a blood culture result was positive. Once RAPID determines the current antimicrobials as inappropriate, an alert text message is immediately sent to the clinicians in charge. This study evaluated how RAPID impacted the time to appropriate antimicrobial therapy among patients with bloodstream infections. Results: During the study period, 633 of 11 297 recorded observations (5.6%) were determined as inappropriate antimicrobial prescriptions. The time to appropriate antimicrobial therapy was significantly shortened after the implementation of RAPID (1.65 vs 2.45 hours, P < .001), especially outside working hours (1.24 vs 6.43 hours, P < .001), in the medical wards (1.40 vs 2.14 hours, P < .001), in participants with candidemia (0.74 vs 5.36 hours, P < .001), and for bacteremia due to non-multidrug-resistant organisms (1.66 vs 2.49 hours, P < .001). Conclusions: Using a knowledge-based clinical decision support system to reduce the time to appropriate antimicrobial therapy in a real-world scenario is feasible and effective. Our results support the continued use of RAPID.

The use of statins was associated with reduced COVID-19 mortality: a systematic review and meta-analysis.

BACKGROUND: Statins are widely used to treat people with metabolic and cardiovascular disorders. The effect of statins on coronavirus disease 2019 (COVID-19) is unclear. To investigate the association between statins and COVID-19 outcomes and, if possible, identify the subgroup population that benefits most from statin use. MATERIALS AND METHODS: A systematic review and meta-analysis of published studies that included statin users and described COVID-19 outcomes through 10 November 2020. This study used the generic inverse variance method to perform meta-analyses with random-effects modelling. The main outcomes were evaluation of the need for invasive mechanical ventilator (IMV) support, the need for intensive care unit (ICU) care and death. All outcomes were measured as dichotomous variables. RESULTS: A total of 28 observational studies, covering data from 63,537 individuals with COVID-19, were included. The use of statins was significantly associated with decreased mortality (odds ratio [OR] = 0.71, 95% confidence interval [CI]: 0.55-0.92, I2=72%) and the need for IMV (OR = 0.81, 95% CI: 0.69-0.95, I2=0%) but was not linked to the need for ICU care (OR = 0.91, 95% CI: 0.55-1.51, I2=66%). Subgroup analysis further identified five types of studies in which statin users had even lower odds of death. CONCLUSIONS: The use of statins was significantly associated with a reduced need for IMV and decreased mortality among individuals with COVID-19. Statins may not need to be discontinued because of concern for COVID-19 on admission. Further randomized controlled trial (RCTs) are needed to clarify the causal effect between statin use and severe COVID-19 outcomes.Key messagesParticipants in five types of studies were shown to have even lower odds of death when taking statins.The use of statins was significantly associated with a reduced need for invasive mechanical ventilation and decreased all-cause mortality among individuals with COVID-19. However, statin use did not prevent participants from needing care in the intensive care unit.The results justify performing randomized controlled trials (RCTs) to validate the benefits of statins on COVID-19 outcomes.

Integrase Strand Transfer Inhibitors Play the Main Role in Greater Weight Gain Among Men With Acute and Early HIV Infection.

BACKGROUND: The predictors of weight gain remain unclear in people with acute and early HIV infection (AEH). METHODS: Eligible antiretroviral-naïve men diagnosed with AEH from January 1, 2000, to December 31, 2019, were enrolled in an observational cohort study at the University California, San Diego. The study used multivariable mixed-effect linear regression models to analyze differences in the rate of weight gain over time between participants receiving early vs deferred antiretroviral therapy (ART) treatment, low vs high baseline CD4 count and HIV RNA, and different classes of ART. RESULTS: A total of 463 participants were identified, with mean CD4 cell count of 507 cells/µL and log HIV RNA of 5.0 copies/mL at study entry. There was no difference in the rate of weight gain between participants who did and did not receive ART within 96 weeks of incident HIV infection. Neither a baseline CD4 count of <350 cells/µL nor a baseline HIV RNA of >100 000 copies/mL was a predictor of weight gain. Compared with persons taking non-nucleoside reverse transcriptase inhibitor-based regimens, those who received integrase strand transfer inhibitor (INSTI)-based regimens showed greater weight gain over time. CONCLUSIONS: Neither baseline CD4 count and HIV RNA nor early ART was associated with weight change in the first 96 weeks following incident HIV infection. Use of INSTI-based regimens represented a major driver of weight gain in men who initiated ART with relatively higher CD4 cell counts.

Loading dose and efficacy of continuous or extended infusion of beta-lactams compared with intermittent administration in patients with critical illnesses: A subgroup meta-analysis and meta-regression analysis.

WHAT IS KNOWN AND OBJECTIVE: The role of continuous/extended beta-lactam infusions (CEIs) in improving clinical outcomes among critically ill patients remains controversial. Therefore, we aimed to compare the clinical efficacy of CEI versus intermittent administration (IA) of beta-lactams by performing a systematic review and meta-analysis. METHODS: PubMed, the Cochrane Library and Embase were searched from inception until December 2018 for studies comparing clinical outcomes of CEI versus IA in critically ill patients. The meta-analysis included 18 randomized controlled trials (RCTs) and 13 non-RCTs. RESULTS AND DISCUSSION: For CEI versus IA, the summary relative risk (RR) for overall mortality and clinical cure was 0.82 (95% confidence interval [CI]: 0.72-0.94) and 1.31 (95% CI: 1.15-1.49), respectively. Subgroup and meta-regression analyses of the loading dose revealed a significantly increased clinical cure rate in the loading-dose group (RR: 1.44, 95% CI: 1.22-1.69), which remained significant after adjustments for beta-lactam type, and association between clinical cure and loading dose for clinical cure (RR: 1.47, 95% CI: 1.20-1.80; p = .001). Subgroup analysis of administration type indicated that both groups had low mortality and high clinical cure rates; however, the heterogeneity analysis did not support an association across continuous infusion and extended infusion groups. Subgroup analysis of the Acute Physiology and Chronic Health Evaluation (APACHE) score was conducted; according to APACHE scores ≥ 16, overall mortality and clinical cure significantly differed between CEI and IA. WHAT IS NEW AND CONCLUSION: CEIs with loading-dose treatment may significantly improve the clinical outcomes in critically ill sepsis or septic shock patients.

Identifying predictors for bacterial and fungal coinfection on chest computed tomography in patients with Pneumocystis pneumonia.

BACKGROUND: Pneumocystis pneumonia (PCP) is a common opportunistic infection with high mortality in individuals with decreased immunity. Pulmonary coinfections with PCP are associated with poor prognosis. The study aims to identify radiological predictors for pulmonary coinfections in patients with PCP and risk factors for mortality. METHODS: This is a retrospective, five-year study was conducted in a medical center, enrolling patients diagnosed with PCP, who received a chest computed tomography (CT) scan. The radiological findings and medical records of all participants were reviewed carefully by 2 independent doctors. Univariable and multivariable analysis was performed to identify radiological predictors for pulmonary coinfection and clinical risk factors for poor prognosis. RESULTS: A total of 101 participants were included, of which 39 were HIV-infected and 62 were non-HIV-infected. In multivariable analysis, radiologic predictors on chest CT for coinfection with bacteria pneumonia included lack of ground glass opacity (adjusted odds ratio [aOR], 6.33; 95% confidence interval [CI], 2.03-19.77; p = 0.001) and presence of pleural effusion (aOR, 3.74; 95% CI, 1.27-10.99; p = 0.017). Predictors for fungal pneumonia included diffuse consolidation (adjusted OR, 6.27; 95% CI, 1.72-22.86; p = 0.005) and presence of pleural effusion (adjusted OR, 5.26; 95% CI, 1.44-19.17; p = 0.012). A significantly higher in-hospital mortality was associated with older age, recent corticosteroid exposure, cytomegalovirus coinfection, and acute respiratory failure. CONCLUSION: Early identification of pulmonary coinfections in PCP using radiological features on the CT scans, will enable appropriate treatment which is crucial to improve the prognosis.

Treatment for Mycobacterium abscessus complex-lung disease.

Nontuberculous mycobacterial infections and colonization are becoming more prevalent worldwide. Mycobacterium abscessus complex (MABC) is one of the predominant pathogens capable of a wide spectrum of infections, with 50% of infections involving the lungs. The decision to commence treatment is determined according to the severity of the disease, risk of progressive disease, presence of comorbidities, and goals of treatment. MABC is resistant to standard antituberculous agents and has variable drug susceptibility across different geographical locations, therefore, antibiotic susceptibility testing of all clinically significant isolates is crucial for selecting a treatment strategy. Pulmonary infections due to MABC is difficult to cure using the currently recommended regimens from the American Thoracic Society and British Thoracic Society. Macrolides are the cornerstone of treatment, but the efficacy of macrolide-based chemotherapy may be compromised by resistance. Despite the introduction of new drugs for treatment, treatment outcomes remain unsatisfactory. The combination of surgical resection of limited lung disease regions with a multidrug, macrolide-based therapy offers the optimal chance of achieving clinical cure of the disease. This review focuses on medical treatment of MABC-lung disease and the efficacy of new agents, such as clofazimine, amikacin inhalation therapy, tigecycline and linezolid, for treating MABC-lung disease.

Recommendations and guidelines for the treatment of Clostridioides difficile infection in Taiwan.

Clostridioides difficile infection (CDI) is a major enteric disease associated with antibiotic use and a leading cause of hospital-acquired infections worldwide. This is the first guideline for treatment of CDI in Taiwan, aiming to optimize medical care for patients with CDI. The target audience of this document includes all healthcare personnel who are involved in the medical care of patients with CDI. The 2018 Guidelines Recommendations for Evidence-based Antimicrobial agents use in Taiwan (GREAT) working group was formed, comprising of infectious disease specialists from 13 medical centers in Taiwan, to review the evidence and draft recommendations using the grading of recommendations assessment, development, and evaluation (GRADE) methodology. A nationwide expert panel reviewed the recommendations during a consensus meeting in March 2019. The recommendation is endorsed by the Infectious Diseases Society of Taiwan (IDST). This guideline describes the epidemiology and risk factors of CDI, and provides recommendations for treatment of CDI in both adults and children. Recommendations for treatment of the first episode of CDI, first recurrence, second and subsequent recurrences of CDI, severe CDI, fulminant CDI, and pediatric CDI are provided.

Taiwan guideline on oral pre-exposure prophylaxis for HIV prevention - 2018 update.

Pre-exposure prophylaxis (PrEP) for prevention of human immunodeficiency virus infection is proved to be effective and has been implemented worldwide. This article introduces the guideline development and revised recommendations and guidance on PrEP provision in the updated Taiwan PrEP guideline. The Taiwan PrEP guideline writing group searched randomized controlled trials and guidelines published before October 2017 through Medline/PubMed, Cochrane Database, Embase and ClinicalTrials.gov database. Keywords included pre(-)exposure prophylaxis, PrEP, Truvada, tenofovir, HIV, and AIDS. Each selected article was assessed by two authors using the Grading of Recommendations Assessment, Development and Evaluation. External reviewers were invited to independently evaluate the revised manuscript per the Appraisal of Guidelines for Research and Evaluation II. Before publication, a public consultation was held to reach consensus on the updated guideline among providers, civil society, and Taiwan Centers for Disease Control. Four systematic reviews and 28 original articles were reviewed by Taiwan PrEP writing group. The second version of the Taiwan PrEP guideline was released in March 2018. We recommended daily PrEP use for the following populations: strong recommendation and high quality of evidence for men who have sex with men (MSM) and transgender women (TGW), as well as heterosexual serodiscordant couples; weak recommendation and high quality of evidence for people who inject drugs, while weak recommendation and moderate quality of evidence for at-risk heterosexual men and women. There is high-quality evidence for event-driven PrEP in MSM and likely TGW, and we additionally recognized these key populations could benefit from such dosing regimen.

Trend of HIV transmitted drug resistance before and after implementation of HAART regimen restriction in the treatment of HIV-1 infected patients in southern Taiwan.

BACKGROUND: The use of fixed combination antiretroviral therapy with a low genetic barrier for the treatment of patients infected with human immunodeficiency virus (HIV) may affect the local HIV transmitted drug resistance (TDR) pattern. The present study aimed to investigate changes in the prevalence of HIV TDR following the implementation of a fixed regimen of HIV treatment in Taiwan in 2012. METHODS: TDR was measured in antiretroviral treatment-naïve HIV-1-infected individuals who participated in voluntary counseling and testing between 2007 and 2015 in southern Taiwan. Antiretroviral resistance mutations were interpreted using the HIVdb program from the Stanford University HIV Drug Resistance Database. RESULTS: Sequences were obtained from 377 consecutive individuals between 2007 and 2015. The overall prevalence rates of TDR HIV among the study population from 2007 to 2011 and 2012-2015 were 10.6 and 7.9%, respectively. Among the detected mutations, K103 N and V179D + K103R were more frequently observed after 2012. Four HIV-infected patients with K103 N variants were detected after 2012, and 4 of the 5 patients with V179D + K103R variants were found after 2012. No significant differences were observed in the TDRs among nucleoside reverse transcriptase inhibitors (NRTIs), non-NRTIs (NNRTIs), protease inhibitors, multiple drug resistance, and any drug resistance between period 1 (2007-2011) and period 2 (2012-2015). CONCLUSIONS: A fixed treatment regimen with zidovudine/lamivudine + efavirenz or nevirapine as first-line therapy for treatment-naïve patients infected with HIV did not significantly increase the TDR during the 4-year follow-up period. Due to the increase in NNRTI resistance associated with mutations after 2012, a longer follow-up period and larger sample size are needed in future studies.

Ocular Manifestations of Human Immunodeficiency Virus Infection at a Tertiary Referral Center in Taiwan.

Purpose: To investigate the prevalence and characteristics of ocular manifestations of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) in patients treated at a tertiary referral center in Taiwan during a time of highly active antiretroviral therapy (HAART) Materials and Methods: A retrospective cohort study in Taiwan was performed between January 2006 and July 2016. Ocular examination and systemic information were recorded from the HIV-infected patients. Results: 1242 patients with HIV/AIDS were identified. Ninety patients had ophthalmic records, and HIV-related ocular manifestations were reported in 57 patients. The most prevalent ocular manifestations were cytomegalovirus (CMV) retinitis, ocular syphilis, and HIV microvasculopathy. Mean CD4 count was significantly lower in patients with HIV-related ocular manifestations compared to those without. Conclusion: We found that lower CD4 count, especially <200 cells/µL, was a significant factor for detecting HIV-related ocular manifestations. Comprehensive ophthalmic screening in high-risk group is helpful for early diagnosis and prompt treatment of sight-threatening ocular complications.

Identifying heterogeneity in the Hawthorne effect on hand hygiene observation: a cohort study of overtly and covertly observed results.

BACKGROUND: Observation and feedback are core strategies of hand hygiene (HH) improvement. Direct overt observation is currently the gold standard method. Observation bias, also known as the Hawthorne effect, is a major disadvantage of this method. Our aim was to examine the variation of the Hawthorne effect on HH observation in different healthcare groups and settings. METHODS: A prospective cohort study was performed in a tertiary teaching hospital during a 15-month period. Up to 38 overt observers (82% nurses) and 93 covert observers (81% medical students) participated in HH observation. The HH events observed overtly were matched for occupation, department, observation time, and location with those observed covertly. The data of matched pairs were then analysed to detect possible Hawthorne effects on different variables. RESULTS: A total of 31,522 HH opportunities were observed (4581 overtly, 26,941 covertly). There were 3047 matched pairs after 1:1 matching of overt and covert observations. The overall HH compliance was higher with overt observation than with covert observation (78% vs. 55%, p < 0.001). The Hawthorne effect was nearly three times larger in nurses (30 percentage points) than in physicians (11 percentage points) and was significantly greater in outpatient clinics (41 percentage points) than in intensive care units (11 percentage points). The magnitude of the Hawthorne effect varied among healthcare worker occupations and observation locations (p values both < 0.001) but not among departments, observation times, or HH indications. CONCLUSIONS: Heterogeneity in the Hawthorne effect may influence the interpretation of overt observations and prevent the correct identification of target populations with poor HH compliance. Therefore, directly observed HH compliance may not be an adequate performance indicator for infection control.

HIV-1 integrase strand-transfer inhibitor resistance in southern Taiwan.

The use of antiretroviral therapy has reduced rates of mortality and morbidity in patients with human immunodeficiency virus/acquired immune deficiency syndrome(HIV/AIDS). However, transmission of drug-resistant strains poses a challenge to control the spread of HIV-1. Primary resistance to integrase strand-transfer inhibitors (INSTIs) is rare despite their increased use. The prevalence of transmitted drug resistance (TDR) to INSTIs was 0.9% in northern Taiwan. This study was to analyse the prevalence and risk factors of TDR to INSTIs in southern Taiwan. In this study, we enrolled antiretroviral treatment-naïve HIV-1-infected subjects who underwent voluntary counselling and testing from 2013 to 2016 in southern Taiwan. Genotypic drug resistance, coreceptor tropism (CRT) and INSTI resistance were determined. Logistic regression was used to analyse the risk factors for INSTI polymorphic substitution. Sequences were obtained from 184 consecutive individuals, of whom 96.7% were men who have sex with men and 3.3% were heterosexual. Of the patients, 10% (19/183) had hepatitis B and 33.3% (61/183) had syphilis infection. Subtype B HIV-1 strains were found in 96.1% of the patients. Fifteen patients (8.4%, 15/178) harboured nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors or protease inhibitors resistance. CCR-5 coreceptors were used by 71.4% (130/184) of the patients. None of the patients had INSTI resistance-associated mutations, however 16 patients had INSTI polymorphic substitutions, and they were associated with a higher HIV viral load (p = 0.03, OR 2.4, CI 1.1-5.3) and syphilis infection (p = 0.03, OR 3.7, CI 1.1-12.0). In conclusion, no signature INSTI resistance-associated mutations were detected in our cohort. Continued monitoring of TDR to INSTI is needed due to the increased use of INSTIs.

High rate of HIV-1 drug resistance in treatment failure patients in Taiwan, 2009-2014.

BACKGROUND: Drug resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs) has been associated with loss of viral suppression measured by a rise in HIV-1 RNA levels, a decline in CD4 cell counts, persistence on a failing treatment regimen, and lack of adherence to combination antiretroviral therapy. OBJECTIVES: This study aimed to monitor the prevalence and risk factors associated with drug resistance in Taiwan after failure of first-line therapy. MATERIALS AND METHODS: Data from the Veterans General Hospital Surveillance and Monitor Network for the period 2009-2014 were analyzed. Plasma samples from patients diagnosed with virologic failure and an HIV-1 RNA viral load >1000 copies/mL were analyzed by the ViroSeq™ HIV-1 genotyping system for drug susceptibility. Hazard ratios (HRs) for drug resistance were calculated using a Cox proportional hazard model. RESULTS: From 2009 to 2014, 359 patients were tested for resistance. The median CD4 count and viral load (log) were 214 cells/µL (interquartile range [IQR]: 71-367) and 4.5 (IQR: 3.9-5.0), respectively. Subtype B HIV-1 strains were found in 90% of individuals. The resistance rate to any of the three classes of antiretroviral drugs (NRTI, NNRTI, and PI) was 75.5%. The percentage of NRTI, NNRTI, and PI resistance was 58.6%, 61.4%, and 11.4%, respectively. The risk factors for any class of drug resistance included age ≤35 years (adjusted HR: 2.30, CI: 1.48-3.56; p<0.0001), initial NNRTI-based antiretroviral regimens (adjusted HR: 1.70, CI: 1.10-2.63; p=0.018), and current NNRTI-based antiretroviral regimens when treatment failure occurs (odds ratio: 4.04, CI: 2.47-6.59; p<0.001). There was no association between HIV-1 subtype, viral load, and resistance. CONCLUSION: This study demonstrated a high level of resistance to NRTI and NNRTI in patients with virologic failure to first-line antiretroviral therapy despite routine viral load monitoring. Educating younger men who have sex with men to maintain good adherence is crucial, as PI use is associated with lower possibility of drug resistance.

Evaluation of a matrix-assisted laser desorption ionization-time of flight mass spectrometry assisted, selective broth method to screen for vancomycin-resistant enterococci in patients at high risk.

BACKGROUND: Bile esculin azide with vancomycin (BEAV) medium is a sensitive, but slightly less specific method for vancomycin-resistant enterococci (VRE) screening. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a rapid method for identification of clinical pathogens. This study aimed to assess the performance of a novel combination screening test for VRE, using BEAV broth combined with MALDI-TOF MS. MATERIALS AND METHODS: Clinical specimens were collected from patients at risk of VRE carriage, and tested by the novel combination method, using selective BEAV broth culture method followed by MALDI-TOF MS identification (SBEAVM). The reference method used for comparison was the ChromID VRE agar method. RESULTS: A total of 135 specimens were collected from 78 patients, and 63 specimens tested positive for VRE positive using the ChromID VRE method (positive rate 46.7%). The sensitivity, specificity, positive predictive value, and negative predictive value of SBEAVM method after an incubation period of 28 hours were 93.7%, 90.3%, 89.4%, and 94.2%, respectively. The SBEAVM method when compared to the ChromID VRE method had a shorter turnaround time (29 vs. 48-72 hours) and lower laboratory cost ($2.11 vs. $3.23 per test). CONCLUSIONS: This study demonstrates that SBEAVM is a rapid, inexpensive, and accurate method for use in VRE screening.

A nationwide covert observation study using a novel method for hand hygiene compliance in health care.

BACKGROUND: Evaluation and feedback is a core hand hygiene (HH) improvement strategy. The covert observation method avoids observation bias inherent to the overt method. The aim of the study was to observe HH compliance by a novel covert method in a real-world setting. METHODS: We conducted a 2-year, nationwide, prospective, observational study in teaching hospitals across Taiwan. Medical students and students who may have contact with patients in their careers were recruited as participants. A novel, shorthand notation method for covert observation was used. Observation results were reported through a study website. RESULTS: There were a total of 25,379 HH opportunities covertly observed by 93 observers. Overall HH compliance was 32.0%. Health care workers had the highest HH compliance for indication 4 (42.6%), and the lowest for indication 5 (21.7%). Overall handrubbing percentage was high, reaching 83.6%. The HH compliance increased significantly with an increase in the number of indications within 1 HH opportunity (P < .001). CONCLUSIONS: The overall HH compliance by the covert observation method was low. An innovative shorthand notation method facilitated covert observation, and website reporting was demonstrated to be feasible for large-scale observation.

Synergy of ß-Lactams with Vancomycin against Methicillin-Resistant Staphylococcus aureus: Correlation of Disk Diffusion and Checkerboard Methods.

Modified disk diffusion (MDD) and checkerboard tests were employed to assess the synergy of combinations of vancomycin and ß-lactam antibiotics for 59 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and Mu50 (ATCC 700699). Bacterial inocula equivalent to 0.5 and 2.0 McFarland standard were inoculated on agar plates containing 0, 0.5, 1, and 2 µg/ml of vancomycin. Oxacillin-, cefazolin-, and cefoxitin-impregnated disks were applied to the surface, and the zones of inhibition were measured at 24 h. The CLSI-recommended checkerboard method was used as a reference to detect synergy. The MICs for vancomycin were determined using the Etest method, broth microdilution, and the Vitek 2 automated system. Synergy was observed with the checkerboard method in 51% to 60% of the isolates when vancomycin was combined with any ß-lactam. The fractional inhibitory concentration indices were significantly lower in MRSA isolates with higher vancomycin MIC combinations (P < 0.05). The overall agreement between the MDD and checkerboard methods to detect synergy in MRSA isolates with bacterial inocula equivalent to McFarland standard 0.5 were 33.0% and 62.5% for oxacillin, 45.1% and 52.4% for cefazolin, and 43.1% and 52.4% for cefoxitin when combined with 0.5 and 2 µg/ml of vancomycin, respectively. Based on our study, the simple MDD method is not recommended as a replacement for the checkerboard method to detect synergy. However, it may serve as an initial screening method for the detection of potential synergy when it is not feasible to perform other labor-intensive synergy tests.

Impact of implementation of the World Health Organization multimodal hand hygiene improvement strategy in a teaching hospital in Taiwan.

BACKGROUND: Hand hygiene (HH) is considered to be the most simple, rapid, and economic way to prevent health care-associated infection (HAI). However, poor HH compliance has been repeatedly reported. Our objective was to evaluate the impact of implementing the updated World Health Organization (WHO) multimodal HH guidelines on HH compliance and HAI in a tertiary hospital in Taiwan. METHODS: We conducted a before-and-after interventional study during 2010-2011. A multimodal HH promotion campaign was initiated. Key strategies included providing alcohol-based handrub dispensers at points of care, designing educational programs tailored to the needs of different health care workers, placement of general and individual reminders in the workplace, and establishment of evaluation and feedback for HH compliance and infection rates. RESULTS: Overall HH compliance increased from 62.3% to 73.3% after 1 year of intervention (P < .001). The rate of overall HAI decreased from 3.7% to 3.1% (P < .05), urinary tract infection rate decreased from 1.5% to 1.2% (P < .05), and respiratory tract infection rate decreased from 0.53% to 0.35% (P < .05). This campaign saved an estimated $940,000 and 3,564 admission patient days per year. CONCLUSION: The WHO multimodal HH guidelines are feasible and effective for the promotion of HH compliance and are associated with the reduction of HAIs.