Prospective antimicrobial audit and feedback did not decrease case fatality: Experiences from a hospital in northern Taiwan.

INTRODUCTION: Although a prospective antimicrobial audit and feedback is an effective strategy in an antibiotic stewardship program, previous researchers have not adequately demonstrated a successful impact on patient outcomes. In this study, the causes of fatalities associated with a prospective antimicrobial audit and feedback were analyzed. METHODOLOGY: Between June and September 2014, applications for 16 target parenteral formulas (including ceftriaxone, ceftazidime, cefepime, piperacillin/tazobactam, vancomycin, teicoplanin, ertapenem, imipenem/cilastatin, meropenem, levofloxacin, moxifloxacin, ciprofloxacin, tigecycline, linezolid, daptomycin, and amikacin), which were not approved by infectious diseases (ID) specialists, were followed up until patients were either discharged or passed away. RESULTS: Of the 292 cases studied, 193 (66%) were male, with a mean age (standard deviation) of 65.5 (19.3) years. There were five reasons for rejection, including dosage adjustments (37%), no evidence of bacterial infection (28.8%), modifications according to antimicrobial susceptibility (18.8%), target pathogens not being covered (7.2%), and redundant therapy (4.1%). Multiple logistic regression analysis demonstrated that an age greater than 75 years (odds ratio [OR]: 2.58; 95% confidence interval [CI]: 1.32-5.50; p = 0.005) was associated with significant mortality, while urinary tract (OR: 0.26; 95% CI: 0.09-0.70; p = 0.013) and soft tissue/bone infections (OR: 0.18; 95% CI: 0.05-0.61; p = 0.006) were associated with survival. Adjustments according to ID physicians' recommendations were not statistically significant (OR: 0.53; 95% CI: 0.27-1.06; p = 0.074). CONCLUSIONS: Antimicrobial adjustments according to ID physicians' recommendations showed only marginally preventative effects against fatalities.

Chrysin restores PDGF-induced inhibition on protein tyrosine phosphatase and reduces PDGF signaling in cultured VSMCs.

Previous studies have shown that an increased intake of dietary flavonoids is associated with a decreased risk of cardiovascular diseases (CVDs). PDGF is a major mitogen for vascular smooth muscle cell (VSMC) and participates in the pathogenesis of many CVDs. The study investigated whether the flavone chrysin affected PDGF functions in VSMCs and neointma formation in rat artery. We found that chrysin concentration-dependently inhibited PDGF-induced proliferation and chemotaxis and reduced PDGF signaling in VSMCs. Chrysin attenuated H(2)O(2) signaling and PDGF-induced reactive oxygen species production and NADPH oxidase activation but did not interfere with PDGF binding to VSMCs. The further analyses revealed that chrysin relieved PDGF-induced inhibition on activity of protein tyrosine phosphatase (PTP) and reduced PDGF-induced oxidation of PTP cysteinyl active site. Moreover, it inhibited PDGF receptor autophosphorylation induced by low-dose vanadate (an inhibitor for PTP). The effect of chrysin, but not of the flavonoid (-)-epigallocatechin-3-gallate and antioxidant N-acetylcysteine, on PDGF signaling and PTP activity was reversed by depletion of intracellular glutathione (GSH), suggesting an involvement of chrysin on GSH/glutaredoxin system for PTP reactivation. Finally, to demonstrate the effectiveness of chrysin in vivo, we showed that oral administration of chrysin before and after angioplasty could reduce neointima formation in balloon-injured carotid artery in rats. In conclusion, we provide here evidence that chrysin can regulate intracellular PTP activity during PDGF signaling, inhibits PDGF-induced VSMC proliferation and chemotaxis, and reduces arterial intima hyperplasia in vivo.