ABSTRACT
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.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacterial Infections/drug therapy , Bacterial Infections/mortality , Drug Utilization/standards , Mortality , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Hospitals , Humans , Male , Middle Aged , Prospective Studies , Taiwan/epidemiologyABSTRACT
Diabetic nephropathy is a common causative factor of chronic kidney disease (CKD). DPP-4 inhibitor has the ability to improve kidney function and renal microvasculature. In the present study, we investigate the deleterious effects of IS on proximal tubular cells and the protective role of DPP-4 inhibitor. Human kidney 2 (HK-2) cells were exposed to IS in the presence or absence of DPP-4 inhibitor. Effects of DPP-4 inhibitor on viability of HK-2 cells were determined by MTT assay. Reactive oxygen species (ROS) production was examined using fluorescent microscopy. Levels of cleaved caspase-3, transforming growth factor-beta (TGF-ß), α-smooth muscle actin (α-SMA) and NF-kappaB p65 and phosphorylation of AKT and extracellular signal-regulated kinase (ERK) were detected by immunoblotting. Production of ROS and level of cleaved caspase-3 were increased by IS in a dose-dependent manner. The phosphorylation of AKT and ERK p65 were decreased alongside activation of NF-κB. Expression of TGF-ß and α-SMA, were upregulated in IS-treated HK-2 cells. Treatment with DPP-4 inhibitor resulted in a significant increase in cell viability and a decrease of ROS production in IS-treated HK-2 cells. DPP-4 inhibitor restored IS-induced deactivations of AKT and ERK and inhibited activation of NF-κB in IS-treated HK-2 cells. Moreover, DPP-4 inhibitor could also attenuate IS-induced up-regulation of TGF-ß and α-SMA expression. These findings suggest that DPP-4 inhibitor possesses anti-apoptotic activity to ameliorate the IS-induced renal damage, which may be partly attributed to regulating ROS/p38MAPK/ERK and PI3K-AKT pathways as well as downstream NF-κB signaling pathway.
