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.

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.

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.

Early enteral nutrition in patients with out-of-hospital cardiac arrest under target temperature management was associated with a lower 7-day bacteremia rate: A post-hoc analysis of a retrospective cohort study.

INTRODUCTION: Early enteral nutrition (EN) is a nutritional strategy for reducing the incidence of in-hospital infections. However, the benefits of early EN, under targeted temperature management (TTM) in patients with out-of-hospital cardiac arrest (OHCA), remain unclear. We aimed to evaluate the effect of early EN on the infective complications of OHCA patients who underwent TTM. METHODS: We retrospectively searched the clinical databases of two adult emergency tertiary referral hospitals in southern Taiwan and identified patients admitted for OHCA who underwent TTM between 2017 and 2022. The 85 enrolled patients were divided into two groups based on timing: early EN (EN within 48 h of admission) and delayed EN (EN > 48 h after admission). Clinical outcomes of 7-day infective complications between the two groups were analyzed. RESULTS: Early EN was provided to 57 (67 %) of 85 patients and delayed EN was provided to the remaining 28 (33 %) patients. No significant differences in baseline patient characteristics were observed between the two groups. In addition, no differences in clinical outcomes were observed, except that the early EN group had a lower 7-day bacteremia rate (5.3 % vs. 26.9 %, p = 0.013). Gram-negative bacteria were the major pathogen among the 7-day infective complications. CONCLUSION: In OHCA patients treated with TTM, early EN was associated with a lower 7-day bacteremia rate. Furthermore, the application of early EN in this population was well tolerated without significant adverse events.

Differences in characteristics, aetiologies, isolated pathogens, and the efficacy of antibiotics in adult patients with preseptal cellulitis and orbital cellulitis between 2000-2009 and 2010-2019.

BACKGROUND/AIMS: To understand whether the epidemiology, aetiologies, common pathogens and the antibiotic efficacy against the identified bacteria of periorbital cellulitis in adults have changed recently (2010-2019) compared with the past decade (2000-2009). METHODS: Adult patients (n=224) diagnosed with preseptal cellulitis and orbital cellulitis admitted to Kaohsiung Veterans General Hospital during 2000-2019 were retrospectively reviewed. Demographic and clinical characteristics, isolated pathogens and antibiotic susceptibility tests against the commonly cultured bacteria were analysed. RESULTS: Preseptal cellulitis showed a tendency of female predominance. Patients in their 60s showed an incidence peak; more cases were observed during winter. The most common predisposing factor was dacryocystitis (15.5%-30.5%), followed by hordeolum (15.5%-24.8%). Aetiology of sinusitis (p=0.001) decreased and that of conjunctivitis (p=0.007) increased significantly with time. Culture results of nasopharyngeal swabs and local abscess showed higher positivity rate than conjunctival swab. The most common isolates were methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus, coagulase-negative staphylococci and Pseudomonas aeruginosa. Antibiotics including fluoroquinolones and vancomycin were effective; in contrast, ampicillin/sulbactam and oxacillin showed decreasing efficacy against gram-positive bacteria. For antibiotic treatment against P. aeruginosa, fluoroquinolones, ceftazidime, piperacillin and imipenem were ideal choices. CONCLUSION: In isolated pathogens, the increasing trend of methicillin-resistant S. aureus detection was compatible with reducing oxacillin efficacy against periorbital infection. In our study, the report of antibiotic efficacy against the most common identified bacteria offered empirical choices for hospitalised patients with periorbital infection before obtaining culture results.

Antibiotic Choices for Pediatric Periorbital Cellulitis-A 20-Year Retrospective Study from Taiwan.

The delayed treatment of pediatric periorbital cellulitis may have severe consequences. In addition, the antibiotic efficacy against causative bacteria may change over time, and it is important to understand the appropriate antibiotic options for effective treatment in pediatric patients. We compared the changes in cultured bacteria and drug susceptibility tests between two decades, 2010-2019 and 2000-2009, to establish antibiotics for empirical use. The patient characteristics, etiologies, culture sites, and isolated bacteria, and the antibiotic susceptibility tests of the admitted pediatric patients (n = 207) diagnosed with preseptal and orbital cellulitis during 2000 to 2019, were recorded. Insect/animal bites (p = 0.084) showed an increasing trend, and sinusitis (p = 0.016) showed a significant decrease in the past decades. The most common bacteria were Staphylococcus aureus, and methicillin-resistant S. aureus (MRSA) infections increased in recent decades (p = 0.01). Moreover, we found that vancomycin was ideal for MRSA infections. The decreasing efficacy of oxacillin correlates with the increasing proportion of MRSA in pediatric periorbital cellulitis. Our study thus offers antibiotic choices against the most common isolates that can be administered before culture results are available.

Non-nosocomial healthcare-associated infective endocarditis in Taiwan: an underrecognized disease with poor outcome.

BACKGROUND: Non-nosocomial healthcare-associated infective endocarditis (NNHCA-IE) is a new category of IE of increasing importance. This study described the clinical and microbiological characteristics and outcome of NNHCA-IE in Taiwan. METHODS: A retrospective study was conducted of all patients with IE admitted to the Kaohsiung Veterans General Hospital in Kaohsiung, Taiwan over a five-year period from July 2004 to July 2009. The clinical and microbiological features of NNHCA-IE were compared to those of community-acquired and nosocomial IE. Predictors for in-hospital death were determined. RESULTS: Two-hundred episodes of confirmed IE occurred during the study period. These included 148 (74%) community-acquired, 30 (15%) non-nosocomial healthcare-associated, and 22 (11%) nosocomial healthcare-associated IE. Staphylococcus aureus was the most frequent pathogen. Patients with NNHCA-IE compared to community-acquired IE, were older (median age, 67 vs. 44, years, p < 0.001), had more MRSA (43.3% vs. 9.5%, p < 0.001), more comorbidity conditions (median Charlson comorbidity index [interquartile range], 4[2-6] vs. 0[0-1], p < 0.001), a higher in-hospital mortality (50.0% vs. 17.6%, p < 0.001) and were less frequently recognized by clinicians on admission (16.7% vs. 47.7%, p = 0.002). The overall in-hospital mortality rate for all patients with IE was 25%. Shock was the strongest risk factor for in-hospital death (odds ratio 7.8, 95% confidence interval 2.4-25.2, p < 0.001). CONCLUSIONS: NNHCA-IE is underrecognized and carries a high mortality rate. Early recognition is crucial to provide optimal management and improve outcome.

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.

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.

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.

Highly active antiretroviral therapy-related hepatotoxicity in human immunodeficiency virus and hepatitis C virus co-infected patients with advanced liver fibrosis in Taiwan.

BACKGROUND: The prevalence of patients co-infected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is higher in Taiwan than in Western countries. This study aimed to analyze the frequency and risk factors for highly active antiretroviral therapy (HAART)-related liver toxicity in patients co-infected with HIV and HCV with advanced liver fibrosis in Taiwan. METHODS: This retrospective cohort study included 228 HAART-experienced and HAART-naïve patients who were co-infected with HIV and HCV from January 2013 to December 2013 in Taiwan. Transaminase elevation (TE) was defined by grades. Fibrosis 4 score and aspartate-to-platelet ratio index were used to evaluate liver fibrosis. Cox proportional hazard regression model was used to analyze the risk factors for time to TE events. RESULTS: A total of 228 patients were included. Only two episodes (1.28%) of high-grade TE were observed. The overall prevalence rate of TE was 16%, and the incidence was 1.38 cases/100 patient-months. Two predictive factors of TE were the initiation of HAART during the study period and CD4 cell count less than 350 cells/mm(3). Subgroup analysis showed that HAART improved liver fibrosis status in patients who had advanced liver fibrosis at baseline (p = 0.033). CONCLUSION: The frequency of HAART-related TE in HIV and HCV co-infected patients in Taiwan was much lower than that observed in previous studies. Pre-existing advanced liver fibrosis had no influence on the frequency of TE. The use of HAART showed benefits on liver fibrosis progression in patients with underlying advanced liver fibrosis.

Prevalence of latent tuberculosis infection in persons with and without human immunodeficiency virus infection using two interferon-gamma release assays and tuberculin skin test in a low human immunodeficiency virus prevalence, intermediate tuberculosis-burden country.

BACKGROUND: The risk of tuberculosis (TB) is higher in human immunodeficiency virus (HIV)-infected patients and intravenous drug users (IDUs). We determined the prevalence and risk factors of latent TB infection (LTBI) in individuals with or without HIV infection, including IDUs, in a country with a low HIV prevalence, an intermediate TB burden, and a high Bacillus Calmette-Guérin (BCG) vaccine coverage using two interferon-gamma release assays (IGRAs) and the tuberculin skin test (TST). METHODS: For this prospective, cross-sectional study, HIV-infected and -uninfected patients from a regional hospital and medical center in Taiwan were enrolled. Results of the two IGRAs [QuantiFERON-TB Gold (QFT-G) and QuantiFERON-TB Gold In-Tube (QFT-GIT)] and the TST were compared. Risk factors for positivity were analyzed. RESULTS: We recruited 233 patients [198 (85%) men; mean age, 39.4 years]. Most patients (74%) were BCG vaccinated. The prevalence of LTBI was estimated to be 22.8% by TST, 15.9% by QFT-G, and 20.6% by QFT-GIT. HIV-infected individuals had fewer positive QFT-GIT [7.0% vs. 28.6%, p < 0.001, adjusted odds ratio (aOR) = 0.28, p = 0.05] and TST results, and more indeterminate QFT-G responses (9.3% vs. 0.7%, p = 0.002). Concordance between IGRAs and TST was very poor in HIV-infected patients (κ < 0.05). Independent risk factors for IGRA positivity were increasing age (QFT-G: aOR = 1.98, p = 0.03; QFT-GIT: aOR = 2.00, p = 0.01) and IDUs (aOR = 4.33, p = 0.05 by QFT-G). CONCLUSION: HIV-infected persons had a significantly lower response to both IGRAs and TST. High discordance was found between the two generations of IGRAs and between IGRAs and TST. Increasing age, a known risk factor for LTBI, was significantly associated with IGRAs, but not with TST.

Prevalence and associated factors for HIV-1 transmitted drug resistance in voluntary clients for counseling and testing in Southern Taiwan.

BACKGROUND: According to the World Health Organization, HIV-transmitted drug resistance (TDR) is increasing. We analyzed voluntary counseling test data from a hospital in Southern Taiwan to investigate the TDR pattern in Southern Taiwan, the potential relationship between sexual behavior and HIV transmission, and HIV drug-resistant strain transmission. METHODS: Genotypic resistance assays were performed on treatment-naïve HIV patients recruited from voluntary counseling testing (VCT) in Southern Taiwan from 2007 to 2011. Drug resistance-associated mutations were interpreted with Stanford University HIV Drug Resistance Database HIVdb program. Socio-demographics and sexual activity were recorded from the VCT questionnaire. Logistic regression analysis was used to analyze the risk factors for TDR, and a phylogenetic tree was constructed to elucidate the pattern of HIV drug-resistant strains. RESULTS: Among the 161 treatment-naïve HIV-infected patients, most were men who reported having sex with men. The overall TDR rate was 10.6%. Patients with a history of sexually transmitted diseases had a 7.8-fold higher risk of becoming infected with genotypic resistant strains. CONCLUSION: In Southern Taiwan, the HIV TDR rate was 10.6% among those receiving VCT. Our findings suggest that sexual behavior may play an important role in HIV drug-resistant strain transmission.

Rapid onset of rhabdomyolysis after switching to a raltegravir-based antiretroviral regimen.

Raltegravir is the first integrase inhibitor antiretroviral agent that has been demonstrated to have antiviral efficacy and safety. However, the US Food and Drug Administration has recommended use with caution in patients with risk factors for rhabdomyolysis, based on four case reports of rhabdomyolysis in patients with identifiable risk factors. We present a 32-year-old Asian man with human immunodeficiency virus (HIV), but without other underlying diseases, who developed rapid-onset, raltegravir-associated rhabdomyolysis and hyperlactatemia. Our patient lacked predisposing factors for rhabdomyolysis, and the rapid onset time of 4 days was the shortest reported. Therefore, clinicians should exercise caution when using raltegravir and closely monitor all patients for the symptoms of muscle pain and weakness. This case has been reported to the National Adverse Drug Reactions Reporting System of the Department of Health in Taiwan.

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.

Higher rate of hepatitis events in patients with human immunodeficiency virus, hepatitis B, and hepatitis D genotype II infection: a cohort study in a medical center in southern Taiwan.

BACKGROUND: The epidemiology and impact of hepatitis δ virus (HDV) on hepatic outcomes and virological and immunological responses to highly active antiretroviral therapy (HAART) in human immunodeficiency virus (HIV) patients coinfected with hepatitis B virus (HBV) in northern Taiwan have been reported. However, the epidemiology and impact of HDV infection in HIV-HBV coinfection patients in southern Taiwan remains uncertain. METHODS: In this cohort study, a total of 64 HIV patients coinfected with HBV were identified between January 1, 2009 and May 30, 2012. The seroprevalence of anti-HDV antibodies, HDV genotyping, clinical manifestations and hepatic outcomes were compared between the patients with and without HDV coinfection, and laboratory examinations and hepatic outcomes were recorded. RESULTS: Among the 64 HIV patients coinfected with HBV, seven were seropositive for HDV (10.9%). There were no statistically significant differences in risk factors for acquiring HIV infection. During a median observation period of 27.8 months, the adjusted hazard ratio of HDV and HBV genotype (type B vs. non-type B) on hepatitis flare-ups were 62.132 (p = 0.04) and 0.028 (p = 0.01), respectively. All seven patients had genotype II and were HDV viremic. The phylogenetic tree analysis and clinical history evaluation did not identify any clusters of HDV infection. CONCLUSION: HDV infection resulted in higher rate of hepatitis flare-ups, but it did not have a statistical significance on HIV progression and immunological response to HAART. Whether higher rate of HDV viremia has worse impact on the hepatic outcomes requires further investigation.

Prevalence of latent tuberculosis infection in BCG-vaccinated healthcare workers by using an interferon-gamma release assay and the tuberculin skin test in an intermediate tuberculosis burden country.

BACKGROUND: The risk of healthcare workers (HCWs) acquiring tuberculosis (TB) infection is high. We determined the prevalence of latent TB infection (LTBI) in HCWs with a high Bacille Calmette-Guérin (BCG) vaccine coverage in an intermediate TB burden country by using an interferon-gamma release assay [QuantiFERON-TB Gold (QFT-G)] and by using the tuberculin skin test (TST). Risk factors associated with a positive test were determined. METHODS: This prospective cross-sectional study enrolled HCWs from a medical center in Taiwan. Participants were grouped into workers without exposure (Group 1) and workers who self-reported a history of TB exposure (Group 2). All participants completed a questionnaire to collect demographic information and risk factors for acquiring TB. The QFT-G test and the TST were administered and risk factors for a positive test were analyzed. RESULTS: We recruited 193 HCWs [149 (77.2%) female workers] with a mean age of 35.6 years. All were BCG-vaccinated. The prevalence of LTBI was 88.8% (based on the TST) and 14.5% (based on the QFT-G test). There was no difference between HCWs with and without known exposure to TB. Agreement between the tests was poor (i.e., the kappa value was less than 0.05). Multivariable logistic regression showed that only the QFT-G test was associated with age (35 years or greater) (adjusted OR, 2.53; p = 0.03). CONCLUSION: By using the QFT-G test or TST, this study found a similar prevalence of LTBI in HCWs with and without known exposure to TB. This suggests that in intermediate TB burden countries exposure to TB may occur within the hospital and within the community. Compared to the TST, the QFT-G test was correlated better with age, which is a known risk factor for latent TB infection.

A Clinical Algorithm to Identify HIV Patients at High Risk for Incident Active Tuberculosis: A Prospective 5-Year Cohort Study.

BACKGROUND: Predicting the risk of tuberculosis (TB) in people living with HIV (PLHIV) using a single test is currently not possible. We aimed to develop and validate a clinical algorithm, using baseline CD4 cell counts, HIV viral load (pVL), and interferon-gamma release assay (IGRA), to identify PLHIV who are at high risk for incident active TB in low-to-moderate TB burden settings where highly active antiretroviral therapy (HAART) is routinely provided. MATERIALS AND METHODS: A prospective, 5-year, cohort study of adult PLHIV was conducted from 2006 to 2012 in two hospitals in Taiwan. HAART was initiated based on contemporary guidelines (CD4 count < = 350/µL). Cox regression was used to identify the predictors of active TB and to construct the algorithm. The validation cohorts included 1455 HIV-infected individuals from previous published studies. Area under the receiver operating characteristic (ROC) curve was calculated. RESULTS: Seventeen of 772 participants developed active TB during a median follow-up period of 5.21 years. Baseline CD4 < 350/µL or pVL ≥ 100,000/mL was a predictor of active TB (adjusted HR 4.87, 95% CI 1.49-15.90, P = 0.009). A positive baseline IGRA predicted TB in patients with baseline CD4 ≥ 350/µL and pVL < 100,000/mL (adjusted HR 6.09, 95% CI 1.52-24.40, P = 0.01). Compared with an IGRA-alone strategy, the algorithm improved the sensitivity from 37.5% to 76.5%, the negative predictive value from 98.5% to 99.2%. Compared with an untargeted strategy, the algorithm spared 468 (60.6%) from unnecessary TB preventive treatment. Area under the ROC curve was 0.692 (95% CI: 0.587-0.798) for the study cohort and 0.792 (95% CI: 0.776-0.808) and 0.766 in the 2 validation cohorts. CONCLUSIONS: A validated algorithm incorporating the baseline CD4 cell count, HIV viral load, and IGRA status can be used to guide targeted TB preventive treatment in PLHIV in low-to-moderate TB burden settings where HAART is routinely provided to all PLHIV. The implementation of this algorithm will avoid unnecessary exposure of low-risk patients to drug toxicity and simultaneously, reduce the burden of universal treatment on the healthcare system.

Elevated cerebrospinal fluid nitrite level in human immunodeficiency virus-infected patients with neurosyphilis.

BACKGROUND/PURPOSE: Human immunodeficiency virus (HIV) and syphilis coinfection is a common phenomenon. A percentage of neurosyphilis cases is asymptomatic in HIV-infected patients. The diagnosis of neurosyphilis is more difficult because of the alteration of cerebrospinal fluid (CSF) presentation by the HIV itself. The CSF levels of the degradation products of nitric oxide (NO; e.g., nitrate and nitrite) are reportedly elevated in animals and patients with bacterial meningitis. We hypothesized that an elevated CSF nitrite concentration may be present in patients coinfected with HIV and neurosyphilis. METHODS: This cohort study was conducted from January 2007 to June 2008. Forty patients were enrolled and included seven patients in the control group and 33 HIV-infected patients with or without syphilis. Nitrite levels in the serum and the CSF were measured by using the Griess assay. RESULTS: The CSF nitrite levels were significantly higher in HIV-infected patients with neurosyphilis, compared to the control group or patients with HIV infection only or patients with HIV and syphilis coinfection (p = 0.026). The CSF nitrite levels were correlated with the CSF white blood cell counts (Spearman correlation test, r(2) = 0.324; p < 0.001). There was no significant difference between different groups in serum nitrite levels. CONCLUSION: Marked elevation of CSF nitrite level was observed in HIV-infected patients with neurosyphilis.