The Efficacy and Safety of High-dose Daptomycin in the Treatment of Complicated Skin and Soft Tissue Infections in Asians.

OBJECTIVE: To compare the efficacy and safety of standard-dose (SD) daptomycin with those of high-dose (HD) daptomycin in complicated skin and soft tissue infections (cSSTIs) in an Asian population. MATERIALS AND METHODS: Patients from three medical centers diagnosed with cSSTIs were screened in the clinical information system. Patients included in the analysis were divided into two groups: those who received daptomycin at doses ≥ 6 mg/kg (HD group) and those receiving 4 mg/kg (SD group). The demographics and clinical treatment information were analyzed. RESULTS: Overall, 155 patients were recruited, including 108 patients in the SD group and 47 patients in the HD group. The rate of healthcare-associated infections was higher in the HD group (61.70% vs. 37.04%), demonstrating a statistically significant difference (P = 0.005). Compared with the SD group, the HD group had statistically significant early clinical stabilization (72.34% vs 52.78%, P = 0.023). The results of the multivariate analysis indicated that HD daptomycin was an independent effector for early clinical stabilization (HR=0.394, P < 0.001). The rate of drug-related adverse events was equally distributed in the HD and SD groups (36.17% vs. 26.85%, P = 0.243). CONCLUSION: Compared with SD daptomycin, HD daptomycin increased the rate of early clinical stabilization in Asian patients with cSSTIs, whereas the incidence of adverse events did not increase.

The combination of decoy receptor 3 and soluble triggering receptor expressed on myeloid cells-1 for the diagnosis of nosocomial bacterial meningitis.

BACKGROUND: Early diagnosis and appropriate antibiotic treatment can significantly reduce mortality of nosocomial bacterial meningitis. However, it is a challenge for clinicians to make an accurate and rapid diagnosis of bacterial meningitis. This study aimed at determining whether combined biomarkers can provide a useful tool for the diagnosis of bacterial meningitis. METHODS: A retrospective study was carried out. Cerebrospinal fluid (CSF) levels of decoy receptor 3 (DcR3) and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: The patients with bacterial meningitis had significantly elevated levels of the above mentioned biomarkers. The two biomarkers were all risk factors with bacterial meningitis. The biomarkers were constructed into a "bioscore". The discriminative performance of the bioscore was better than that of each biomarker, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.842 (95% confidence intervals (CI) 0.770-0.914; p< 0.001). CONCLUSIONS: Combined measurement of CSF DcR3 and sTREM-1 concentrations improved the prediction of nosocomial bacterial meningitis. The combined strategy is of interest and the validation of that improvement needs further studies.

Herpes simplex virus-1 infection or Simian virus 40-mediated immortalization of corneal cells causes permanent translocation of NLRP3 to the nuclei.

AIM: To investigate into the potential involvement of pyrin containing 3 gene (NLRP3), a member of the nucleotide-binding oligomerization domain-like receptors with cytosolic pattern recognition, in the host defense of corneas against viruses. METHODS: The herpes viral keratitis model was utilized in BALB/c mice with inoculation of herpes simplex virus-1 (HSV-1). Corneal tissues removed during therapy of patients with viral keratitis as well as a Simian vacuolating virus 40 (SV40)-immortalized human corneal epithelial cell line were also examined. Immunohistochemistry was used to detect NLRP3 in these subjects, focusing on their distribution in tissue or cells. Western blot was used to measure the level of NLRP3 and another two related molecules in NLPR3 inflammasome, namely caspase-1 and IL-1ß. RESULTS: The NLRP3 activation induced by HSV-1 infection in corneas was accompanied with redistribution of NLRP3 from the cytoplasm to the nucleus in both murine and human corneal epithelial cells. Furthermore, in the SV40-immortalized human corneal epithelial cells, NLRP3 was exclusively located in the nucleus, and treatment of the cells with high concentration of extracellular potassium (known as an inhibitor of NLRP3 activation) effectively drove NLRP3 back to the cytoplasm as reflected by both immunohistochemistry and Western blot. CONCLUSION: It is proposed that herpes virus infection activates and causes redistribution of NLRP3 to nuclei. Whether this NLRP3 translocation occurs with other viral infections and in other cell types merit further study.

Predictive value of decoy receptor 3 in postoperative nosocomial bacterial meningitis.

Nosocomial bacterial meningitis requires timely treatment, but what is difficult is the prompt and accurate diagnosis of this disease. The aim of this study was to assess the potential role of decoy receptor 3 (DcR3) levels in the differentiation of bacterial meningitis from non-bacterial meningitis. A total of 123 patients were recruited in this study, among them 80 patients being with bacterial meningitis and 43 patients with non-bacterial meningitis. Bacterial meningitis was confirmed by bacterial culture of cerebrospinal fluid (CSF) culture and enzyme-linked immunosorbent assay (ELISA) was used to detect the level of DcR3 in CSF. CSF levels of DcR3 were statistically significant between patients with bacterial meningitis and those with non-bacterial meningitis (p<0.001). A total of 48.75% of patients with bacterial meningitis received antibiotic>24 h before CSF sampling, which was much higher than that of non-bacterial meningitis. CSF leucocyte count yielded the highest diagnostic value, with an area under the receiver operating characteristic curve (ROC) of 0.928, followed by DcR3. At a critical value of 0.201 ng/mL for DcR3, the sensitivity and specificity were 78.75% and 81.40% respectively. DcR3 in CSF may be a valuable predictor for differentiating patients with bacterial meningitis from those with non-bacterial meningitis. Further studies are needed for the validation of this study.