Increasing trend of fluconazole-non-susceptible Cryptococcus neoformans in patients with invasive cryptococcosis: a 12-year longitudinal study.

BACKGROUND: This study aimed to investigate the rate of fluconazole-non-susceptible Cryptococcus neoformans in Southern Taiwan for the period 2001-2012 and analyze the risk factors for acquiring it among patients with invasive cryptococcosis. METHODS: All enrolled strains were isolated from blood or cerebrospinal fluid samples of the included patients. If a patient had multiple positive results for C. neoformans, only the first instance was enrolled. Susceptibility testing was performed using the Clinical and Laboratory Standards Institutes M27-A3 broth micro-dilution method. The MIC interpretative criteria for susceptibility to fluconazole were ≤ 8 µg/ml. A total of 89 patients were included. Patients (n = 59) infected by fluconazole-susceptible strains were compared with those (n = 30) infected by non-susceptible strains. The patients' demographic and clinical characteristics were analyzed. RESULTS: The rate of fluconazole-non-susceptible C. neoformans in the study period significantly increased over time (p < 0.001). The C. neoformans isolated in 2011-2012 (odds ratio: 10.68; 95 % confidence interval: 2.87-39.74; p < 0.001) was an independent predictive factor for the acquisition of fluconazole-non-susceptible C. neoformans. CONCLUSIONS: The rate of fluconazole-non-susceptible C. neoformans has significantly increased recently. Continuous and large-scale anti-fungal susceptibility tests for C. neoformans are warranted to confirm this trend.

Use of simple clinical and laboratory predictors to differentiate influenza from dengue and other febrile illnesses in the emergency room.

BACKGROUND: Clinical differentiation of influenza from dengue and other febrile illnesses (OFI) is difficult, and available rapid diagnostic tests have limited sensitivity. METHODS: We conducted a retrospective study to compare clinical and laboratory findings between (i) influenza and dengue and (ii) influenza and OFI. RESULTS: Of 849 enrolled patients, the mean time between illness onset and hospital presentation was 1.7, 3.7, and 3 days for influenza, dengue, and OFI, respectively. Among pediatric patients (≤18 years) (445 influenza, 24 dengue, and 130 OFI), we identified absence of rashes, no leukopenia, and no marked thrombocytopenia (platelet counts <100 × 10(9) cells/L) as predictors to distinguish influenza from dengue, whereas rhinorrhea, malaise, sore throat, and mild thrombocytopenia (platelet counts 100-149 × 10(9)/L) were predictors that differentiated influenza from OFI. Among adults (>18 years) (81 influenza, 124 dengue, and 45 OFI), no leukopenia and no marked thrombocytopenia distinguished influenza from dengue, while rhinorrhea and malaise differentiated influenza from OFI. A diagnostic algorithm developed to distinguish influenza from dengue using rash, leukopenia, and marked thrombocytopenia showed >90% sensitivity to identify influenza in pediatric patients. CONCLUSIONS: This study identified simple clinical and laboratory parameters that can assist clinicians to distinguish influenza from dengue and OFI. These findings may help clinicians diagnose influenza and facilitate appropriate management of affected patients, particularly in resource-poor settings.

Correlation of anti-fungal susceptibility with clinical outcomes in patients with cryptococcal meningitis.

BACKGROUND: This study aimed to investigate the correlation of minimum inhibiting concentrations (MICs), obtained by broth micro-dilution, and clinical response in patients with cryptococcal meningitis. METHODS: Using retrospective analyses covering the period 2001-2010, factors affecting clinical therapeutic cure in patients with cryptococcal meningitis 10 weeks after the start of anti-fungal therapy were identified. Specific emphasis was placed on the role of anti-fungal susceptibility. RESULTS: Of 46 patients with cryptococcal meningitis identified, 21 were cured after 10 weeks of treatment. Overall, 12 strains (26.1%) were resistant to fluconazole (>8 µg/ml) and 8 (17.4%) had an MIC >1 µg/ml for amphotericin B. Twenty-three patients received combination amphotericin B and fluconazole as their initial antifungal therapy, 17 were given amphotericin B only, five received fluconazole only, and one received a combination of amphotericin B and flucytosine. After 2 weeks, all patients received fluconazole (400-600 mg daily for 8 weeks at least, then 200 mg daily thereafter). The presence of isolates resistant to fluconazole (MIC >8 µg/ml; 4.8% vs. 44%, p < 0.01) were statistically significant among patients who were cured. Anti-fungal susceptibility, reflected by fluconazole MIC >8 µg/ml, was an independent predictor of therapeutic cure at 10-week evaluation (OR = 15.7; 95% CI: 1.8-135.9; p = 0.01), but higher MIC of amphotericin B (>1 µg/ml) was not. CONCLUSIONS: The MICs of fluconazole, determined by the CLSI method, may be a potential predictor of therapeutic cure in patients with cryptococcal meningitis.

Clinical characteristics and risk factors for fatality in patients with bloodstream infections caused by glucose non-fermenting gram-negative Bacilli.

BACKGROUND/PURPOSE: Glucose non-fermenting Gram-negative bacilli (GNF-GNB) bloodstream infections (BSIs) are often hospital-acquired and are important causes of morbidity and mortality. Our objectives were to evaluate the epidemiology and clinical characteristics of GNF-GNB BSIs, and to identify risk factors for fatality. METHODS: We retrospectively reviewed cases of GNF-GNB BSIs in adult patient (≥ 18 years of age) hospitalized between January and December 2005. RESULTS: A total 221 GNF-GNB bacteremic episodes (200 hospital-acquired and 21 community-acquired) in 215 patients (123 men and 92 women; mean age, 63.38±16.10 years) were included in our study. Of these, 52.5% were elderly (age > 65). Malignancy (43.0%), diabetes mellitus (22.6%) and steroid use (22.6%) were the major underlying diseases/conditions. Central venous catheter (CVC) placement had been carried out in 57.5% of patients. The 28-day mortality was significantly higher in those patients with: liver cirrhosis, steroid use, pneumonia as the primary source of infection, intensive care unit-acquired infections, septic shock, and a high Pitt bacteremia score (≥ 4 points). Liver cirrhosis [odds ratio (OR)=6.4; 95% confidence interval (CI)=1.7-23.9; p < 0.01)], hematologic malignancy (OR=3.9; 95% CI=1.1-14.1; p=0.04), pneumonia (OR=4.0; 95% CI=1.4 - 11.0; p< 0.01), septic shock (OR=13.0; 95% CI=4.6-36.6; p< 0.01), and intensive care unit-acquired infections (OR=2.9; 95% CI=1.1-8.0; p= 0.04) were all independent risk factors for fatality. CONCLUSION: Our data suggested that CVC placement and steroid use predispose to GNF-GNB bacteremia. Early removal of CVC and avoidance of steroids may minimize the chances of acquiring this infection, which is of particular importance for patients at high risk of mortality once they are infected with GNF-GNB.