Importance of Reviewing Antibiotic Courses by 48 Hours: Risk Factors for Third-Generation Cephalosporin Resistance Among AmpC Harboring Organisms in Urine and Respiratory Cultures.

BACKGROUND: Citrobacter, Enterobacter, Morganella, and Serratia (AmpC organisms) species can exhibit third-generation cephalosporin (TGC) resistance after TGC exposure. We aimed to assess if institutional TGC utilization correlated with institutional AmpC organism susceptibility and if prior TGC exposure ≤48 hours were associated with TGC resistance in the first culture of a future infection episode caused by an AmpC organism. METHODS: A 5-year retrospective cohort study was performed, including AmpC organisms isolated from pediatric urinary and respiratory tract cultures at an institution with TGC courses reviewed by the antimicrobial stewardship program at 48 hours. Correlations were assessed by Pearson's correlation. Multivariable logistic regression identified factors independently associated with TGC resistance in a subcohort of infection episodes. RESULTS: Among 654 cultures, AmpC organism TGC susceptibility increased from 74% in 2013 to 89.3% in 2017, and this correlated with a 26.1% decrease in TGC utilization (R = -0.906; P = 0.034). Among 275 AmpC organism infections, 21.1% were resistant. Resistance occurred in 13.6%, 17.4%, and 56.5% of infections with no exposure, ≤48 hours, and >48 hours of TGC exposure in the past 30 days, respectively. TGC exposure ≤48 hours was not associated with resistance (odds ratio [OR], 1.26; 95% confidence interval [CI], 0.32-4.94; P = 0.74), whereas, TGC exposure >48 hours was (OR, 8.7; 95% CI, 3.67-20.6; P < 0.001). Infections in 2017 were less likely to be resistant (OR, 0.25; 95% CI, 0.08-0.8; P = 0.019). CONCLUSIONS: Decreased TGC utilization, likely related to antimicrobial stewardship, correlated with increased AmpC organism susceptibility. Limiting TGC exposure to ≤48 hours when possible may reduce AmpC organism resistance in future infections.

Enhancing the Cancer Cell Growth Inhibitory Effects of Table Grape Anthocyanins.

The risk for breast and colon cancer may be lowered in part by high intake of fruits and vegetables. Fruits such as grapes are abundant in bioactive compounds such as anthocyanins. The potential anticancer activity of anthocyanins may be limited by their metabolism in the gut and liver. One metabolic transformation is due to the enzyme catechol-O-methyltransferase (COMT), which methylates polyphenols such as anthocyanins. Entacapone is a clinically used inhibitor of COMT, and has been shown to modulate the methylation of food-derived polyphenols. In this study, we compared the effect of entacapone on the cell viability of colon (Caco-2 and HT-29) and breast (MDA-MB-231) cancer cell lines treated with anthocyanins. Cells were treated with either cyanidin-3-glucoside, delphinidin-3-glucoside, or an anthocyanin-rich grape extract, in the absence or presence of entacapone. Cell viability was assessed using the thiazolyl blue tetrazolium bromide (MTT) assay. Entacapone in combination with the anthocyanins had a greater than additive effect on growth inhibition of the Caco-2 cells. In the MDA-MB-231 cell line, entacapone similarly enhanced the growth inhibitory activity of the anthocyanin extract. Entacapone also had antiproliferative effects when used as a single treatment. Total hydroperoxides was quantified in the cell culture media. Greater concentrations of the treatments resulted in higher levels of total hydroperoxides, indicating that oxidative stress may be an important mechanism for growth inhibition. In conclusion, the antiproliferative activity of fruit-derived anthocyanins was improved in human cancer cell lines by the clinically used drug entacapone. The efficacy and mechanisms of entacapone/anthocyanin combinations should be carefully studied in vivo. PRACTICAL APPLICATION: Chemical components of grapes are good for our health and have been shown to lower risk for certain cancers. Their beneficial health effects could also be enhanced by consuming other molecules that improve their bioavailability.