Sung-Ching Pan

Compliance of Health Care Workers with Hand Hygiene Practices: Independent Advantages of Overt and Covert Observers

Background Evaluation and feedback of hand hygiene (HH) compliance are important elements of the WHO multimodal strategy for hospital infection control. Overt observation is recommended, but it may be confounded by Hawthorne effect. Covert observation offers the opportunity to decrease observer bias. In this study we conducted a one year hospital-wide HH promotion program that included medical students (MS) as covert observers. Methods HH compliance for the five WHO indications was determined by trained and validated observers. The overt observers consisted of eleven infection control nurses (ICNs) and two unit HH ambassadors (UAs) in each of 83 wards. The covert observers consisted of nine MS during their rotating clinical clerkships. Feedback was provided to department heads and staff each quarter. Results Of the 23,333 HH observations 76.0% were by MS, 5.3% by ICNs and 18.7% by UAs. The annual compliance rates were MS 44.1%, ICNs 74.4% and UAs 94.1%; P<0.001. The MS found significantly lower annual compliance rates for 4/5 HH indications compared to ICNs and UAs; P<0.05. The ICNs reported significantly improvement from the first to the fourth quarter; P<0.001. This was associated with feedback from the MS of very poor compliance by nurses during the first quarter. Conclusions Based on these findings we recommend a two-pronged approach to HH programs. The role of ICNs and UAs is to educate, serve as role models, establish, sustain good HH practices and provide direct feedback. The role of the covert observers is to measure compliance and provide independent feedback.

restoration of Cellular Immunity Against Tuberculosis in Patients Coinfected With Hiv-1 and Tuberculosis With Effective Antiretroviral Therapy: Assessment by Determination of Cd69 Expression on T Cells After Tuberculin Stimulation

&NA;Whether immunity against opportunistic pathogens can be fully restored by control of HIV‐1 replication remains open to question. This longitudinal study was conducted to measure anti‐tuberculosis (TB) cellular immunity in 13 HIV‐1/TB‐coinfected patients effectively treated by highly active antiretroviral therapy (HAART) in a period of 12 months. In this study, anti‐TB cellular immunity was assessed by determining the frequencies of CD 69 expression on CD4+ and CD8+ T cells in response to purified protein derivative (PPD) stimulation (abbreviated as %CD4+CD69 to PPD and %CD8+CD69 to PPD). Here, we show that %CD4+CD69 to PPD correlated with the results of tuberculin skin tests and interferon‐&ggr; (IFN‐&ggr;) production from PPD‐stimulated CD4+ T cells, and %CD8+CD69 to PPD also correlated with CD8+T cell‐mediated PPD‐specific cytolysis. In overall analysis for these 13 patients, both %CD4+CD69 to PPD and %CD8+CD69 to PPD increased significantly during the 12 months (p = .003 and p < .001, respectively). However, we found %CD4+CD69 to PPD or %CD8+CD69 to PPD failed to increase substantially in some patients (i.e., immunologic nonresponders). A significantly higher proportion of patients whose baseline CD4+ count was <50 cells/mm3 were considered to be CD4+ nonresponders compared with those whose baseline CD4+ count was >50 cells/mm3. Furthermore, baseline CD4+ cell count in nonresponders is significantly lower than that in responders, although the effectiveness of HAART did not differ between them. Our results indicate that PPD‐specific frequencies of CD69 expression may be used as surrogate markers of anti‐TB cellular immunity. By this method, we show that full reconstitution of anti‐TB cellular immunity in HIV‐1/TB coinfected patients may not necessarily be achieved by “successful” HAART and may be influenced by the baseline immune status when HAART is started. These data suggest that the decision to discontinue secondary prophylaxis for opportunistic infections should be cautiously made, even when the CD4+ cell count has significantly increased.

Trends in the Susceptibility of Clinically Important Resistant Bacteria to Tigecycline: Results from the Tigecycline In Vitro Surveillance in Taiwan Study, 2006 to 2010

ABSTRACT The Tigecycline In Vitro Surveillance in Taiwan (TIST) study, a nationwide, prospective surveillance during 2006 to 2010, collected a total of 7,793 clinical isolates, including methicillin-resistant Staphylococcus aureus (MRSA) (n = 1,834), penicillin-resistant Streptococcus pneumoniae (PRSP) (n = 423), vancomycin-resistant enterococci (VRE) (n = 219), extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (n = 1,141), ESBL-producing Klebsiella pneumoniae (n = 1,330), Acinetobacter baumannii (n = 1,645), and Stenotrophomonas maltophilia (n = 903), from different specimens from 20 different hospitals in Taiwan. MICs of tigecycline were determined following the criteria of the U.S. Food and Drug Administration (FDA) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST-2011). Among drug-resistant Gram-positive pathogens, all of the PRSP isolates were susceptible to tigecycline (MIC90, 0.03 μg/ml), and only one MRSA isolate (MIC90, 0.5 μg/ml) and three VRE isolates (MIC90, 0.125 μg/ml) were nonsusceptible to tigecycline. Among the Gram-negative bacteria, the tigecycline susceptibility rates were 99.65% for ESBL-producing E. coli (MIC90, 0.5 μg/ml) and 96.32% for ESBL-producing K. pneumoniae (MIC90, 2 μg/ml) when interpreted by FDA criteria but were 98.7% and 85.8%, respectively, when interpreted by EUCAST-2011 criteria. The susceptibility rate for A. baumannii (MIC90, 4 μg/ml) decreased from 80.9% in 2006 to 55.3% in 2009 but increased to 73.4% in 2010. A bimodal MIC distribution was found among carbapenem-susceptible A. baumannii isolates, and a unimodal MIC distribution was found among carbapenem-nonsusceptible A. baumannii isolates. In Taiwan, tigecycline continues to have excellent in vitro activity against several major clinically important drug-resistant bacteria, with the exception of A. baumannii.

Association between Cytomegalovirus-Specific Reactivity of T cell Subsets and Development of Cytomegalovirus Retinitis in Patients with Acquired Immunodeficiency Syndrome

The association between cytomegalovirus (CMV)-specific reactivity of T cell subsets and development of CMV retinitis (CMV-R) was prospectively studied in 50 CMV-seropositive AIDS patients. The frequency of CMV-specific CD69 expression on CD8 T cells was similar in patients with and patients without CMV-R (median, 1.0% vs. 1.2%; P=.14). However, the frequency of CMV-specific CD69 expression on CD4 T cells was significantly lower in patients with CMV-R than in those without CMV-R (median, 0.4% vs. 2.25%; P<.001). CMV-specific CD4 T cell reactivity in patients who developed CMV-R shortly after starting highly active antiretroviral therapy (HAART) remained low, although the CD4 cell counts increased markedly. Therefore, development of CMV-R is associated with a poor CMV-specific reactivity of CD4 T cells but not with poor reactivity of CD8 T cells. Development of CMV-R after initiation of HAART is associated with a poor reconstitution of CMV-specific immune response, rather than with immune rebound.

Risk of developing severe sepsis after acute kidney injury: a population-based cohort study

IntroductionSepsis has been a factor of acute kidney injury (AKI); however, little is known about dialysis-requiring AKI and the risk of severe sepsis after survival to discharge.MethodsWe conducted a population-based cohort study based on the Taiwan National Health Insurance Research Database from 1999 to 2009. We identified patients with AKI requiring dialysis during hospitalization and survived for at least 90 days after discharge, and matched them with those without AKI according to age, sex, and concurrent diabetes. The primary outcome was severe sepsis, defined as sepsis with a diagnosis of acute organ dysfunction. Individuals who recovered enough to survive without acute dialysis were further analyzed.ResultsWe identified 2983 individuals (mean age, 62 years; median follow-up, 3.96 years) with dialysis-requiring AKI and 11,932 matched controls. The incidence rate of severe sepsis was 6.84 and 2.32 per 100 person-years among individuals with dialysis-requiring AKI and without AKI in the index hospitalization, respectively. Dialysis-requiring AKI patients had a higher risk of developing de novo severe sepsis than the non-AKI group. In subgroup analysis, even individuals with recovery from dialysis-requiring AKI were at high risk of developing severe sepsis.ConclusionsAKI is an independent risk factor for severe sepsis. Even patients who recovered from AKI had a high risk of long-term severe sepsis.

Incidence of and Risk Factors for Infection or Colonization of Vancomycin-Resistant Enterococci in Patients in the Intensive Care Unit

The prevalence of vancomycin-resistant enterococci (VRE) colonization or infection in the hospital setting has increased globally. Many previous studies had analysed the risk factors for acquiring VRE, based on cross-sectional studies or prevalent cases. However, the actual incidence of and risk factors for VRE remain unclear. The present study was conducted in order to clarify the incidence of and risk factors for VRE in the intensive care unit (ICU). From 1st April 2008 to 31st March 2009, all patients admitted to a surgical ICU (SICU) were put on active surveillance for VRE. The surveillance cultures, obtained by rectal swab, were taken on admission, weekly while staying in the SICU, and on discharge from the SICU. A total of 871 patients were screened. Among them, 34 were found to carry VRE before their admission to the SICU, and 47 acquired VRE during their stay in the SICU, five of whom developed VRE infections. The incidence of newly acquired VRE during ICU stay was 21.9 per 1000 patient-days (95% confidence interval [CI], 16.4–29.1). Using multivariate analysis by logistic regression, we found that the length of ICU stay was an independent risk factor for new acquisition of VRE. In contrast, patients with prior exposure to first-generation cephalosporin were significantly less likely to acquire VRE. Strategies to reduce the duration of ICU stay and prudent usage of broad-spectrum antibiotics are the keys to controlling VRE transmission.

Differential impact of late-stage HIV-1 infection on in vitro and in vivo maturation of myeloid dendritic cells.

The functional and phenotypic maturation of myeloid dendritic cells (DCs), circulating and monocyte-derived, from subjects at different stages of HIV-1 infection was evaluated. The results showed that the capacity of circulating DCs was significantly impaired in subjects with CD4+ T cell counts of <200/microL, correlated with the potential of CD40 ligand expression on CD4+ T cells (R = 0.84; P = 0.002), and improved with successful antiretroviral therapy. However, the function and phenotype of monocyte-derived DCs generated by in vitro culture from subjects at any stage of HIV-1 infection were similar to those in uninfected healthy subjects. Our findings suggest that although the potential of myeloid DC precursors to achieve full maturation is preserved in subjects with late-stage HIV-1 infection, in vivo maturation of myeloid DCs was impaired in these subjects, which may be due to decreased potential of CD40 ligand expression on CD4+ T cells. That myeloid DCs fail to achieve full maturation in vivo in late-stage HIV-1 infection may contribute to the failure to induce effective cellular immunity against HIV-1 and opportunistic pathogens.

Age distribution for T cell reactivity to vaccinia virus in a healthy population.

The potential for bioterrorism involving smallpox has led to a debate about the durability of protective immunity against smallpox from vaccination. By assessing the T cell reactivity to vaccinia virus in a healthy population, we show that subjects who were vaccinated within the past 3 decades and who have a visible vaccination scar had remarkable T cell reactivity. However, person who were vaccinated within the past 3 decades but who do not have a scar and those who were vaccinated >4 decades ago had responses as low as those in unvaccinated subjects. Thus, we estimate that the significant T cell memory response to vaccinia virus from successful vaccination may persist for only 20-30 years. Furthermore, we found the vaccinia-specific cellular immunity could be easily assessed by determination of the frequencies of vaccinia-specific CD69 expression on T cell subsets. These data may help in the development of public health strategies to counter bioterrorism threats associated with smallpox.

Effect of diabetes on tuberculosis control in 13 countries with high tuberculosis: a modelling study

BACKGROUND Diabetes increases the risk of tuberculosis incidence and the risk of adverse treatment outcomes in patients with tuberculosis. Because prevalence of diabetes is increasing in low-income and middle-income countries where the burden of tuberculosis is high, prevention of diabetes carries the potential to improve tuberculosis control worldwide. METHODS We used dynamic tuberculosis transmission models to analyse the potential effect of diabetes on tuberculosis epidemiology in 13 countries with high tuberculosis burden. We used data for previous diabetes prevalence in each country and constructed scenarios to represent the potential ranges of future diabetes prevalence. The country-specific model was calibrated to the estimated trend of tuberculosis incidence. We estimated the tuberculosis burden that can be reduced by alternative scenarios of diabetes prevention. FINDINGS If the prevalence of diabetes continues to rise as it has been in the past decade in the 13 countries (base case scenario), by 2035, the cumulative reduction in tuberculosis incidence would be 8·8% (95% credible interval [CrI] 4·0-15·8) and mortality would be 34·0% (30·3-39·6). Lowering the prevalence of diabetes by an absolute level of 6·6-13·8% could accelerate the decline of tuberculosis incidence by an absolute level of 11·5-25·2% and tuberculosis mortality by 8·7-19·4%. Compared with the base case scenario, stopping the rise of diabetes would avoid 6·0 million (95% CrI 5·1-6·9) incident cases and 1·1 million (1·0-1·3) tuberculosis deaths in 13 countries during 20 years. If interventions reduce diabetes incidence by 35% by 2025, 7·8 million (6·7-9·0) tuberculosis cases and 1·5 million (1·3-1·7) tuberculosis deaths could be averted by 2035. INTERPRETATION The diabetes epidemic could substantially affect tuberculosis epidemiology in high burden countries. The communicable disease and non-communicable disease sectors need to move beyond conventional boundaries and link with each other to form a joint response to diabetes and tuberculosis. FUNDING Taiwan National Science Council.

Predictors and prevalence of latent tuberculosis infection in patients receiving long-term hemodialysis and peritoneal dialysis.

Background Tuberculosis is a common infectious disease in long-term dialysis patients. The prevalence of latent tuberculosis infection (LTBI) in this population is unclear, particularly in those receiving peritoneal dialysis (PD). This study investigated the prevalence of LTBI in patients receiving either hemodialysis (HD) or PD to determine predictors of LTBI and indeterminate results of interferon-gamma release assay. Methods Patients receiving long-term (≥3 months) HD or PD from March 2011 to February 2012 in two medical centers were prospectively enrolled. QuantiFERON-Gold in tube (QFT) test was used to determine the status of LTBI after excluding active tuberculosis. The LTBI prevalence was determined in patients receiving different dialysis modes to obtain predictors of LTBI and QFT-indeterminate results. Results Of 427 patients enrolled (124 PD and 303 HD), 91 (21.3%) were QFT-positive, 316 (74.0%) QFT-negative, and 20 (4.7%) QFT-indeterminate. The prevalence of LTBI was similar in the PD and HD groups. Independent predictors of LTBI were old age (OR: 1.034 [1.013–1.056] per year increment), TB history (OR: 6.467 [1.985–21.066]), and current smoker (OR: 2.675 [1.061–6.747]). Factors associated with indeterminate QFT results were HD (OR: 10.535 [1.336–83.093]), dialysis duration (OR: 1.113 [1.015–1.221] per year increment), anemia (OR: 8.760 [1.014–75.651]), and serum albumin level (OR: 0.244 [0.086–0.693] per 1 g/dL increment). Conclusion More than one-fifth of dialysis patients have LTBI. The LTBI prevalence is similar in PD and HD patients but is higher in the elderly, current smokers, and those with prior TB history. Such patients require closer follow-up. Repeated or alternative test may be required for malnutrition patients who received long length of HD.