Prediction of incidence of neurological disorders in HIV-infected persons in Taiwan: a nested case-control study.

BACKGROUND: Neurological disorders are still prevalent in HIV-infected people. We aimed to determine the prevalence of neurological disorders and identify their risk factors in HIV-infected persons in Taiwan. METHODS: We identified 30,101 HIV-infected people between 2002 and 2016 from the National Health Insurance Research Database in Taiwan, and analyzed the incidence of neurological disorders. We applied a retrospective, nested case-control study design. The individuals with (case group) and without (control group) a neurological disorder were then matched by age, sex and time. Factors associated with neurological disorders were analyzed using a conditional logistic regression model, and a nomogram was generated to estimate the risk of developing a neurological disorder. RESULTS: The incidence of neurological disorders was 13.67 per 1000 person-years. The incidence remained stable during the observation period despite the use of early treatment and more tolerable modern anti-retroviral therapy. The conditional logistic regression model identified nine clinical factors and comorbidities that were associated with neurological disorders, namely age, substance use, traumatic brain injury, psychiatric illness, HIV-associated opportunistic infections, frequency of emergency department visits, cART adherence, urbanization, and monthly income. These factors were used to establish the nomogram. CONCLUSION: Neurological disorders are still prevalent in HIV-infected people in Taiwan. To efficiently identify those at risk, we established a nomogram with nine risk factors. This nomogram could prompt clinicians to initiate further evaluations and management of neurological disorders in this population.

The first imported case of monkeypox in Taiwan.

he first imported case of monkeypox in Taiwan was diagnosed in an Asian man with HIV-1 infection and asymptomatic COVID-19, returning from Germany. Atypical presentations included asynchronous skin lesions, anogenital lesions and prominent inguinal lymphadenopathy. Whole genomic sequence alignment indicate that the Taiwan strain clustered together with human monkeypox virus West African clade B.1, currently circulating in Europe. Prompt diagnosis and infection control measures are crucial to mitigate the spread of monkeypox.

Effect of Anti-CD4 Antibody UB-421 on HIV-1 Rebound after Treatment Interruption.

BACKGROUND: Administration of a single broadly neutralizing human immunodeficiency virus (HIV)-specific antibody to HIV-infected persons leads to the development of antibody-resistant virus in the absence of antiretroviral therapy (ART). It is possible that monotherapy with UB-421, an antibody that blocks the virus-binding site on human CD4+ T cells, could induce sustained virologic suppression without induction of resistance in HIV-infected persons after analytic treatment interruption. METHODS: We conducted a nonrandomized, open-label, phase 2 clinical study evaluating the safety, pharmacokinetics, and antiviral activity of UB-421 monotherapy in HIV-infected persons undergoing analytic treatment interruption. All the participants had undetectable plasma viremia (<20 copies of HIV RNA per milliliter) at the screening visit. After discontinuation of ART, participants received eight intravenous infusions of UB-421, at a dose of either 10 mg per kilogram of body weight every week (Cohort 1) or 25 mg per kilogram every 2 weeks (Cohort 2). The primary outcome was the time to viral rebound (≥400 copies per milliliter). RESULTS: A total of 29 participants were enrolled, 14 in Cohort 1 and 15 in Cohort 2. Administration of UB-421 maintained virologic suppression (<20 copies per milliliter) in all the participants (94.5% of measurements at study visits 2 through 9) during analytic treatment interruption, with intermittent viral blips (range, 21 to 142 copies per milliliter) observed in 8 participants (28%). No study participants had plasma viral rebound to more than 400 copies per milliliter. CD4+ T-cell counts remained stable throughout the duration of the study. Rash, mostly of grade 1, was a common and transient adverse event; one participant discontinued the study drug owing to a rash. A decrease in the population of CD4+ regulatory T cells was observed during UB-421 monotherapy. CONCLUSIONS: UB-421 maintained virologic suppression (during the 8 to 16 weeks of study) in participants in the absence of ART. One participant discontinued therapy owing to a rash. (Funded by United Biomedical and others; ClinicalTrials.gov number, NCT02369146.).

Durability of single tablet regimen for patients with HIV infection in Southern Taiwan: data from a real-world setting.

BACKGROUND: A single-tablet regimen (STR) has been associated with better drug adherence. However, the durability of different STRs was unknown in the real-world settings. Our aim was to investigate the durability of different initial STR regimens in antiretroviral-naive patients starting STR in southern Taiwan. METHOD: This was a retrospective study of antiretroviral-naive patients that initiated first-line antiretroviral regimens with STRs between May 2016 and December 2017. The primary endpoint was time to virological failure. Secondary endpoints were STR discontinuation due to toxicity/intolerance. Durability was defined as time from the initiation until discontinuation/modification. Kaplan- Meier curves were plotted assessing time to virological suppression, treatment failure and discontinuation for the three STRs and Cox proportional hazards model was used to analyze the factors associated with time to viral suppression, treatment failure or discontinuation. RESULTS: Two hundred and twenty-three patients were included: The median follow-up duration (IQR) was 73.9 (48-101.6) weeks, 25 patients (11%) experienced virological failure; the 48 weeks probability of treatment failure was 22.9% (16/70) for Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate (EFV/FTC/TDF), 24.1% (13/54) for Emtricitabine/Rilpivirine/Tenofovir Disoproxil Fumarate (FTC/RPV/TDF) and 24.2% (24/99) for Abacavir/Dolutegravir/Lamivudine (ABC/DTG/3TC) (p=0.16). Fifty-six patients (25%) discontinued their STRs owing to toxicity/intolerance. When compared to EFV/FTC/TDF, treatment with FTC/RPV/TDF (aHR 8.39, CI 1.98-35.58, p = 0.004) and ABC/DTG/3TC (aHR 8.40, CI 2.39-29.54, p=0.001) were more likely to have treatment failure. The predictors for treatment failure included age ≦ 30 years old (aHR 3.73, CI 1.25-11.17, p = 0.018), switch between different STR (aHR 2.3, CI 1.18-4.50, p = 0.001) and free of active syphilis infection (aHR 0.24, CI 0.08-0.73, p = 0.012). The risk factor for treatment discontinuation included younger age ≦ 30 years old (aHR 3.82, CI 1.21-12.37, p = 0.023), treatment with EFV/FTC/TDF (aHR 8.65, CI 2.64-28.39, p < 0.001) and free of active syphilis infection (aHR 0.16, CI 0.04-0.62, p = 0.006). CONCLUSION: Younger age was associated with treatment failure and drug discontinuation. Active syphilis infection s/p treatment was associated with free from treatment failure and discontinuation. This probably driven by the more frequently sexual health education and counseling when patients had syphilis infection. Treatment with ABC/DTG/3TC was associated with higher risk of treatment failure. The STR durability was dependent on the drug toxicity/intolerance, age and syphilis infection.

Dexamethasone downregulates the expressions of MMP-9 and oxidative stress in mice with eosinophilic meningitis caused by Angiostrongylus cantonensis infection.

Steroids have been shown to be beneficial in patients and mice with eosinophilic meningitis caused by Angiostrongylus cantonensis infection; however, the mechanism for this beneficial effect is unknown. We speculated that the effect of steroids in eosinophilic meningitis caused by A. cantonensis infection may be mediated by the downregulation of matrix metallopeptidase-9 (MMP-9) and oxidative stress pathways via glucocorticoid receptors (GRs). We found blood-brain barrier (BBB) dysfunction in mice with eosinophilic meningitis 2-3 weeks after infection as evidenced by increased extravasation of Evans blue and cerebrospinal fluid (CSF) albumin levels. The administration of dexamethasone significantly decreased the amount of Evans blue and CSF albumin. The effect of dexamethasone was mediated by GRs and heat shock protein 70, resulting in subsequent decreases in the expressions of nuclear factor kappa B (NF-κB), c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) in the CSF and brain parenchymal after 2 weeks of steroid administration. Steroid treatment also decreased CSF/brain homogenate MMP-9 concentrations, but had no effect on CSF MMP-2 levels, indicating that MMP-9 rather than MMP-2 played a major role in BBB dysfunction in mice with eosinophilic meningitis. The concentration of 8-hydroxy-2'-deoxyguanosine (8-OHdG) gradually increased after 1-3 weeks of infection, and the administration of dexamethasone significantly downregulated the concentration of oxidized derivative 8-OHdG in CSF. In conclusion, increased 8-OHdG and MMP-9 concentrations were found in mice with eosinophilic meningitis caused by A. cantonensis infection. The effect of dexamethasone was mediated by GRs and significantly decreased not only the levels of 8-OHdG and MMP-9 but also NF-κB, JNK and ERK.

Impact of archived M184V/I mutation on the effectiveness of switch to co-formulated elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide among virally suppressed people living with HIV.

OBJECTIVES: Real-world experience regarding the effectiveness of co-formulated elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide (EVG/C/FTC/TAF) as a switch regimen is sparse among people living with HIV (PLWH) harbouring the M184V/I mutation with or without thymidine analogue-associated mutations (TAMs). METHODS: In this retrospective multicentre study, PLWH who were switched to EVG/C/FTC/TAF after having achieved viral suppression (plasma HIV RNA <200 copies/mL) for 6 months or longer were included. Patients with archived M184V/I mutation (case patients) were matched to controls without M184V/I mutation at a 1:4 ratio. Patients with a history of virological failure or resistance to elvitegravir were excluded. The primary endpoint was virological non-success (plasma HIV RNA ≥50 copies/mL) at Week 48 of switch using a modified FDA snapshot analysis. RESULTS: Overall, 100 case patients with the M184V/I mutation were identified, including 6 (6.0%) with K65R and 13 (13.0%) with at least one TAM, and were matched to 400 controls in terms of gender, age (mean = 40.3 versus 39.7 years) and cumulative exposure duration to tenofovir disoproxil fumarate (median = 146 versus 143 weeks). At Week 48, the rate of virological non-success for the case patients and controls was 5.0% (5/100) and 3.3% (13/400), respectively (difference = 1.7%; 95% CI = -2.9%-6.3%), while the rate of virological success was 88.0% and 89.5% for the case patients and controls, respectively. The presence of the K65R mutation or TAMs was not associated with virological non-response. CONCLUSIONS: Among virally suppressed PLWH, EVG/C/FTC/TAF is effective in maintaining viral suppression at Week 48 despite archived M184V/I mutation with or without TAMs.

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.

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.

Dexamethasone Downregulates Expressions of 14-3-3ß and γ-Isoforms in Mice with Eosinophilic Meningitis Caused by Angiostrongylus cantonensis Infection.

Steroids are commonly used in patients with eosinophilic meningitis caused by A. cantonensis infections. The mechanism steroids act on eosinophilic meningitis remains unclear. In this mouse experiments, expressions of 14-3-3 isoform ß and γ proteins significantly increased in the CSF 2-3 weeks after the infection, but not increasedin the dexamethasone-treated group. Expression of 14-3-3 ß, γ, ε, and θ isoforms increased in brain meninges over the 3-week period after infection and decreased due to dexamethasone treatment. In conclusion, administration of dexamethasone in mice with eosinophilic meningitis decreased expressions of 14-3-3 isoform proteins in the CSF and in brain meninges.

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.

AIDS-related opportunistic illnesses and early initiation of HIV care remain critical in the contemporary HAART era: a retrospective cohort study in Taiwan.

BACKGROUND: No study has reported the epidemiology of AIDS-related opportunistic illnesses (AOIs) in patients with newly diagnosed HIV infection in Taiwan in the past decade. Understanding the current trends in AOI-related morbidity/mortality is essential in improving patient care and optimizing current public health strategies to further reduce AOIs in Taiwan in the era of contemporary highly active antiretroviral therapy (HAART). METHODS: Eligible patients were evaluated at two referral centers between 2010 and 2015. The patients were stratified by date of diagnosis into three periods: 2010-2011, 2012-2013, and 2014-2015. The demographics, HIV stage at presentation according to the United States CDC 2014 case definition, laboratory variables, and the occurrence of AOIs and associated outcomes were compared among the patients. Logistic regression and Cox regression were respectively used to identify variables associated with the occurrence of AOIs within 90 days of HIV enrollment and all-cause mortality. RESULTS: Over a mean observation period of 469 days, 1264 patients with newly diagnosed HIV with a mean age of 29 years and mean CD4 count of 275 cells/µL experienced 394 AOI episodes in 290 events. At presentation, 37.7% of the patients had AIDS; the frequency did not significantly differ across groups. The overall proportion of AOIs within the study period was 21.0%, and no decline across groups was observed. The majority of AOIs (91.7%) developed within 90 days of enrollment. All-cause and AOI-related mortality did not significantly differ across groups. Throughout the three study periods, AOIs remained the main cause of death (47/56, 83.9%), especially within 180 days of enrollment (40/42, 95.2%). A CD4 cell count of < 200 cells/µL at presentation was associated with increased adjusted odds of an AOI within 90 days [adjusted odds ratio, 40.84; 95% confidence intervals (CI), 12.59-132.49] and an elevated adjusted hazard of all-cause mortality (adjusted hazard ratio, 11.03; 95% CI, 1.51-80.64). CONCLUSIONS: Despite efforts toward HIV prevention and management, early HIV care in Taiwan continues to be critically affected by AOI-related morbidity and mortality in the era of contemporary HAART. Additional targeted interventions are required for the earlier diagnosis of patients with HIV.

Efficacy and safety of switching from nevirapine immediate-release twice daily to nevirapine extended-release once daily in virologically suppressed HIV-infected patients: a retrospective cohort study in Taiwan.

BACKGROUND: Whether the non-inferior efficacy and safety results of switching virologically suppressed HIV-1-infected patients from nevirapine immediate-release (NVP-IR) to NVP extended-release (NVP-XR) demonstrated in the TRANxITION study conducted in Europe and North America are also applicable to virologically suppressed HIV-infected Taiwanese patients remains unknown. We evaluated the comparative safety and efficacy of continuing NVP-IR versus switching to NVP-XR in virologically suppressed HIV-infected Taiwanese adults receiving combined antiretroviral therapy (cART) regimens. METHODS: We conducted a retrospective cohort study at Kaohsiung Veterans General Hospital from April 1, 2013, to March 31, 2015. Eighty-four virologically suppressed HIV-infected adults receiving NVP-IR cART were split into two groups: those continuing with NVP-IR (n = 49) and those being switched to NVP-XR (n = 35). Demographic characteristics, clinical variables, and laboratory findings were compared. Therapeutic drug monitoring of steady-state plasma NVP concentrations and genotype analysis of CYP2B6 516 were also performed in 22 participants. The primary endpoint was continued virological suppression at the end of the study. Secondary endpoints were time to loss of virological response and adverse events. RESULTS: During a mean follow-up of 18.4 months, the NVP-XR group demonstrated similar success at maintaining virological response compared with the NVP-IR group (82.9% vs. 85.7%; P = 0.72). Cox regression analysis indicated that there were no significant differences between NVP regimens for time to loss of virological response (hazard ratio: 0.940; P = 0.754). Furthermore, there were no significant differences in adverse events between these two groups. In the 22 participants, there was a non-significantly lower level of steady-state plasma NVP concentrations in the NVP-XR group than in NVP-IR recipients (5145.0 ng/mL vs. 6775.0 ng/mL; P = 0.267). The prevalence of CYP2B6 516 GT was 86.6%, and there was no significant difference in the distribution of CYP2B6 516 between these two groups. CONCLUSIONS: We found that switching from NVP-IR to NVP-XR appeared to have similar safety and efficacy compared with continuing NVP-IR among virologically suppressed, HIV-infected Taiwanese patients. Our finding of higher Ctrough levels in both groups compared with other studies conducted in Caucasian populations and the high prevalence of CYP2B6 516 GT requires further investigation in a larger Taiwanese cohort.

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.

Development of a prediction model for bacteremia in hospitalized adults with cellulitis to aid in the efficient use of blood cultures: a retrospective cohort study.

BACKGROUND: Cellulitis is a common infectious disease. Although blood culture is frequently used in the diagnosis and subsequent treatment of cellulitis, it is a contentious diagnostic test. To help clinicians determine which patients should undergo blood culture for the management of cellulitis, a diagnostic scoring system referred to as the Bacteremia Score of Cellulitis was developed. METHODS: Univariable and multivariable logistic regression analyses were performed as part of a retrospective cohort study of all adults diagnosed with cellulitis in a tertiary teaching hospital in Taiwan in 2013. Patients who underwent blood culture were used to develop a diagnostic prediction model where the main outcome measures were true bacteremia in cellulitis cases. Area under the receiver operating characteristics curve (AUC) was used to demonstrate the predictive power of the model, and bootstrapping was then used to validate the performance. RESULTS: Three hundred fifty one cases with cellulitis who underwent blood culture were enrolled. The overall prevalence of true bacteremia was 33/351 cases (9.4 %). Multivariable logistic regression analysis showed optimal diagnostic discrimination for the combination of age ≥65 years (odds ratio [OR] = 3.9; 95 % confidence interval (CI), 1.5-10.1), involvement of non-lower extremities (OR = 4.0; 95 % CI, 1.5-10.6), liver cirrhosis (OR = 6.8; 95 % CI, 1.8-25.3), and systemic inflammatory response syndrome (SIRS) (OR = 15.2; 95 % CI, 4.8-48.0). These four independent factors were included in the initial formula, and the AUC for this combination of factors was 0.867 (95 % CI, 0.806-0.928). The rounded formula was 1 × (age ≥65 years) + 1.5 × (involvement of non-lower extremities) + 2 × (liver cirrhosis) + 2.5 × (SIRS). The overall prevalence of true bacteremia (9.4 %) in this study could be lowered to 1.0 % (low risk group, score ≤1.5) or raised to 14.7 % (medium risk group, score 2-3.5) and 41.2 % (high risk group, score ≥4.0), depending on different clinical scores. CONCLUSIONS: Determining the risk of bacteremia in patients with cellulitis will allow a more efficient use of blood cultures in the diagnosis and treatment of this condition. External validation of this preliminary scoring system in future trials is needed to optimize the test.

Orbital apex syndrome: an unusual complication of herpes zoster ophthalmicus.

BACKGROUND: Herpes zoster ophthalmicus is defined as herpes zoster involvement of the ophthalmic division of the trigeminal nerve. Ocular involvement occurs in 20-70% of patients with herpes zoster ophthalmicus and may include blepharitis, keratoconjunctivitis, iritis, scleritis, and acute retinal necrosis. Orbital apex syndrome is a rare but severe ocular complication of herpes zoster ophthalmicus. We present here the first reported case of herpes zoster ophthalmicus complicated by orbital apex syndrome in a patient from Taiwan. CASE PRESENTATION: A 78-year-old man initially presented with patchy erythema and herpetiform vesicles on his left forehead and upper eyelid. He subsequently developed left-sided ocular complications including reduced visual acuity, anisocoria, ptosis, and complete ophthalmoplegia. Orbital magnetic resonance imaging (MRI) was performed on day 6 of admission to search for signs of the common causes of orbital apex syndrome such as hemorrhage, neoplasm, and cavernous sinus thrombosis. The MRI showed only orbital myositis and enhancement of the retro-orbital optic nerve sheath. The patient was diagnosed with herpes zoster ophthalmicus complicated by orbital apex syndrome. Although the ocular complications partially resolved after systemic antiviral therapy for 15 days and steroid therapy tapered over 12 weeks, there was residual limitation of abduction and paralysis of the left upper eyelid at follow-up at 180 days after the onset of symptoms. The orbital MRI findings at 180 days showed no significant changes compared with the MRI findings on day 6 of admission. CONCLUSIONS: Primary care physicians should be aware of this rare but potentially sight-threatening complication of herpes zoster ophthalmicus. The appropriate therapy for orbital apex syndrome due to herpes zoster ophthalmicus and the potential outcomes of this condition require further investigation.

Clinical and microbiological characteristics of purulent and non-purulent cellulitis in hospitalized Taiwanese adults in the era of community-associated methicillin-resistant Staphylococcus aureus.

BACKGROUND: The risk factors, microbial etiology, differentiation, and clinical features of purulent and non-purulent cellulitis are not well defined in Taiwan. METHODS: We conducted a retrospective cohort study of hospitalized adults with cellulitis in Taiwan in 2013. The demographic characteristics, underlying diseases, clinical manifestations, laboratory and microbiological findings, treatments, and outcomes were compared for patients with purulent and non-purulent cellulitis. RESULTS: Of the 465 patients, 369 had non-purulent cellulitis and 96 had purulent cellulitis. The non-purulent group was significantly older (p = 0.001) and was more likely to have lower limb involvement (p < 0.001), tinea pedis (p = 0.003), stasis dermatitis (p = 0.025), a higher Charlson comorbidity score (p = 0.03), and recurrence at 6 months post-infection (p = 0.001) than the purulent group. The purulent group was more likely to have a wound (p < 0.001) and a longer hospital stay (p = 0.001) and duration of antimicrobial therapy (p = 0.003) than the non-purulent group. The etiological agent was identified in 35.5 % of the non-purulent cases, with ß-hemolytic streptococci the most frequent cause (70.2 %). The etiological agent was identified in 83.3 % of the purulent cases, with Staphylococcus aureus the predominant pathogen (60 %): 50 % of these were methicillin-resistant S. aureus (MRSA). In multivariable analysis, purulent group (odds ratio (OR), 5.188; 95 % confidence interval (CI), 1.995-13.493; p = 0.001) was a positive predictor of MRSA. The prescribed antimicrobial agents were significantly different between the purulent and non-purulent groups, with penicillin the most frequently used antimicrobial agent in the non-purulent group (35.2 %), and oxacillin the most frequent in the purulent group (39.6 %). The appropriate antimicrobial agent was more frequently prescribed in the non-purulent group than in the purulent group (83.2 % vs. 53.8 %, p < 0.001). CONCLUSIONS: The epidemiology, clinical features, and microbiology of purulent and non-purulent cellulitis were significantly different in hospitalized Taiwanese adults. Purulence was a positive predictor of MRSA as the causal agent of cellulitis. These findings provide added support for the adoption of the IDSA guidelines for empirical antimicrobial therapy of cellulitis in Taiwan.

Emergence of sporadic non-clustered cases of hospital-associated listeriosis among immunocompromised adults in southern Taiwan from 1992 to 2013: effect of precipitating immunosuppressive agents.

BACKGROUND: Sporadic non-clustered hospital-associated listeriosis is an emerging infectious disease in immunocompromised hosts. The current study was designed to determine the impact of long-term and precipitating immunosuppressive agents and underlying diseases on triggering the expression of the disease, and to compare the clinical features and outcome of hospital-associated and community-associated listeriosis. METHODS: We reviewed the medical records of all patients with Listeria monocytogenes isolated from sterile body sites at a large medical center in southern Taiwan during 1992-2013. Non-clustered cases were defined as those unrelated to any other in time or place. Multivariable regression analysis was used to determine factors associated with prognosis. RESULTS: Thirty-five non-clustered cases of listeriosis were identified. Twelve (34.2%) were hospital-associated, and 23 (65.7%) were community-associated. The 60-day mortality was significantly greater in hospital-associated than in community-associated cases (66.7% vs. 17.4%, p = 0.007). Significantly more hospital-associated than community-associated cases were treated with a precipitating immunosuppressive agent within 4 weeks prior to onset of listeriosis (91.7% vs. 4.3%, respectively p < 0.001). The median period from the start of precipitating immunosuppressive treatment to the onset of listeriosis-related symptoms was 12 days (range, 4-27 days) in 11 of the 12 hospital-associated cases. In the multivariable analysis, APACHE II score >21 (p = 0.04) and receipt of precipitating immunosuppressive therapy (p = 0.02) were independent risk factors for 60-day mortality. CONCLUSIONS: Sporadic non-clustered hospital-associated listeriosis needs to be considered in the differential diagnosis of sepsis in immunocompromised patients, particularly in those treated with new or increased doses of immunosuppressive agents.

Concomitant emphysematous prostatic and periurethral abscesses due to Klebsiella pneumoniae: a case report and review of the literature.

Although gas-forming infections of the urinary tract account for a very small percentage of all urinary tract infections, they can lead to mortality if an early diagnosis is not made and aggressive management initiated. Emphysematous urinary tract infections occur mainly in patients with poorly controlled diabetes mellitus or an obstructed urinary tract. Here we present a case of concomitant emphysematous prostatic and periurethral abscesses caused by Klebsiella pneumoniae in a 70-year-old male with poorly controlled diabetes mellitus. Given the high prevalence of patients with diabetes mellitus and the high mortality rate associated with emphysematous prostatic abscesses, clinicians should be aware of this rare but potentially fatal condition.

Increased expression of the kynurenine pathway in mice with eosinophilic meningitis caused by Angiostrongylus cantonensis infection.

Angiostrongylus cantonensis is the major cause of eosinophilic meningitis worldwide. The imbalance of neurotoxic and neuroprotective metabolites in the kynurenine pathway (KP) have been suggested to contribute to the pathogenesis of central nervous system (CNS) infection. We hypothesized that KP may also be involved in parasitic eosinophilic meningitis. BALB/c mice were orally infected with 40 A. cantonensis L3, intraperitoneal dexamethasone at a dose of 500 µg/kg/day was administered from the seventh day of infection until the end of the study. The Evans blue method was used to analyze blood-brain barrier (BBB) dysfunction, and indoleamine 2,3-dioxygenase (IDO) proteins levels was measured by Western blot, immunohistochemistry (IHC), and immunofluorescence. Tryptophan and kynurenine concentrations were analyzed by IHC and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The concentrations of Evans blue, IDO, tryptophan and kynurenine in the different groups of mice were compared using the nonparametric Kruskal-Wallis test. BBB dysfunction was found in mice with eosinophilic meningitis. The administration of dexamethasone significantly decreased the amount of Evans blue. An increased IDO expression was shown in Western blot, IHC and immunofluorescence following 2-3 weeks infection. Increased tryptophan and kynurenine expressions in the brain and cerebrospinal fluid (CSF) were also found in IHC and LC-MS/MS studies. The administration of dexamethasone significantly decreased the amount of IDO, tryptophan and kynurenine. In conclusion, A. cantonensis infection inducing BBB damage, then increased the influx of tryptophan into CSF. The administration of dexamethasone significantly decreased the amount of IDO, tryptophan and kynurenine.

Use of staged molecular analysis to determine causes of unexplained central nervous system infections.

No agent is implicated in most central nervous system (CNS) infections. To investigate cerebrospinal fluid samples from patients with CNS infections of unknown cause in 1 hospital in Taiwan, we used a staged molecular approach, incorporating techniques including multiplex MassTag PCR, 16S rRNA PCR, DNA microarray, and high-throughput pyrosequencing. We determined the infectious agent for 31 (24%) of 131 previously negative samples. Candidate pathogens were identified for 25 (27%) of 94 unexplained meningitis cases and 6 (16%) of 37 unexplained encephalitis cases. Epstein-Barr virus (18 infections) accounted for most of the identified agents in unexplained meningitis cases, followed by Escherichia coli (5), enterovirus (2), human herpesvirus 2 (1), and Mycobacterium tuberculosis. Herpesviruses were identified in samples from patients with unexplained encephalitis cases, including varicella-zoster virus (3 infections), human herpesvirus 1 (2), and cytomegalovirus (1). Our study confirms the power of multiplex MassTag PCR as a rapid diagnostic tool for identifying pathogens causing unexplained CNS infections.