Optimal exposure targets for vancomycin in the treatment of neonatal coagulase-negative Staphylococcus infection: A retrospective study based on electronic medical records.

BACKGROUND: The currently advocated ratio of area under the curve (AUC) over 24 h to minimum inhibitory concentration (AUC/MIC) > 400 and AUC < 600 mg h/L as the therapeutic drug monitoring (TDM) target of vancomycin is based on data from multiple observational studies in adult patients with methicillin-resistant Staphylococcus aureus (MRSA) infection. It may not be applicable to newborns with coagulase-negative Staphylococcus (CoNS) infection. We conducted a retrospective study to identify the optimal exposure targets for vancomycin in the treatment of neonatal CoNS infection. METHODS: Based on the inclusion and exclusion criteria, serum vancomycin concentration, demographics, clinical data, and related laboratory data of newborns who received vancomycin intravenous infusion from June 1, 2016 to February 1, 2021 were collected retrospectively. The AUC was calculated using the maximum a posteriori Bayesian (MAPB) method. The vancomycin exposure threshold of AUC/MIC for efficacy and AUC for toxicity (acute kidney injury, AKI) were determined based on receiver operating characteristic (ROC) curve analysis. The correlation between vancomycin exposure and both clinical effect and nephrotoxicity was analyzed using logistic multivariate regression. RESULTS: In total, 153 patients and 245 vancomycin concentrations (160 trough and 85 peak concentrations) were included. The ROC curve analysis showed that the exposure thresholds of AUC/MIC for clinical efficacy and AUC for nephrotoxicity were 281 and 602 mg h/L, respectively. The multivariate regression analysis showed that AUC/MIC > 280 was a predictor of efficacy (OR: 13.960, 95% CI: 1.891-103.078, P < 0.05) and AUC > 600 mg h/L was associated with AKI (OR: 9.008, 95% CI: 2.706-29.983, P < 0.05). The vancomycin AUC/MIC threshold for treating neonatal CoNS infection with vancomycin is lower than the currently advocated AUC/MIC >400. CONCLUSION: The optimal exposure targets for vancomycin in neonatal CoNS infection were AUC/MIC > 280 and AUC < 600 mg h/L.

Screening of Drug Metabolizing Enzymes for the Ginsenoside Compound K In Vitro: An Efficient Anti-Cancer Substance Originating from Panax Ginseng.

Ginsenoside compound K (CK), a rare ginsenoside originating from Panax Ginseng, has been found to possess unique pharmacological activities specifically as anti-cancers. However, the role of cytochrome P450s (CYPs) in the metabolism of CK is unclear. In this study, we screened the CYPs for the metabolism of CK in vitro using human liver microsomes (HLMs) or human recombinant CYPs. The results showed that CK inhibited the enzyme activities of CYP2C9 and CYP3A4 in the HLMs. The Km and Vmax values of CK were 84.20±21.92 µM and 0.28±0.04 nmol/mg protein/min, respectively, for the HLMs; 34.63±10.48 µM and 0.45±0.05 nmol/nmol P450/min, respectively, for CYP2C9; and 27.03±5.04 µM and 0.68±0.04 nmol/nmol P450/min, respectively, for CYP3A4. The IC50 values were 16.00 µM and 9.83 µM, and Ki values were 14.92 µM and 11.42µM for CYP2C9 and CYP3A4, respectively. Other human CYP isoforms, including CYP1A2, CYP2A6, CYP2D6, CYP2E1, and CYP2C19, showed minimal or no effect on CK metabolism. The results suggested that CK was a substrate and also inhibitors for both CYP2C9 and CYP3A4. Patients using CK in combination with therapeutic drugs that are substrates of CYP2C9 and CYP3A4 for different reasons should be careful, although the inhibiting potency of CK is much poorer than that of enzyme-specific inhibitors.

[Study on extraction of active ingredients from Andrographis paniculatal using the orthogonal experiment with supercritical carbon dioxide].

This paper studied the extraction technology of active ingredients from Andrographis paniculatal using the orthogonal experiment with supercritical CO2. The active ingredients of this extract had higher purity and more stable quality than those came from conventional extract technology. And the target ingredients, dehydrated andrographolidume and andrographolidume, had higher content. Furthermore this method had shorter technology process and saved a great deal of solvent than conventional ethanol extraction, which was exactly suitable for industrialization manufacture. The optimization condition was: extractor pressure 25 MPa, extractor temperature 46 degrees C, separator I pressure 6 MPa, separator I temperature 65 degrees C, separator II pressure 6 MPa, separator II temperature 45 degrees C, CO2 rate of flow 40 kg/h.