ABSTRACT
Currently, assays for rapid therapeutic drug monitoring (TDM) of ß-lactam antibiotics in blood, which might be of benefit in optimizing doses for treatment of critically ill patients, remain challenging. Previously, we developed an assay for determining the penicillin-class antibiotics in blood using a thermometric penicillinase biosensor. The assay eliminates sample pretreatment, which makes it possible to perform semicontinuous penicillin determinations in blood. However, penicillinase has a narrow substrate specificity, which makes it unsuitable for detecting other classes of ß-lactam antibiotics, such as cephalosporins and carbapenems. In order to assay these classes of clinically useful antibiotics, a novel biosensor was developed using New Delhi metallo-ß-lactamase-1 (NDM-1) as the biological recognition layer. NDM-1 has a broad specificity range and is capable of hydrolyzing all classes of ß-lactam antibiotics in high efficacy with the exception of monobactams. In this study, we demonstrated that the NDM-1 biosensor was able to quantify multiple classes of ß-lactam antibiotics in blood plasma at concentrations ranging from 6.25 mg/L or 12.5 mg/L to 200 mg/L, which covered the therapeutic concentration windows of the tested antibiotics used to treat critically ill patients. The detection of ceftazidime and meropenem was not affected by the presence of the ß-lactamase inhibitors avibactam and vaborbactam, respectively. Furthermore, both free and protein-bound ß-lactams present in the antibiotic-spiked plasma samples were detected by the NDM-1 biosensor. These results indicated that the NDM-1 biosensor is a promising technique for rapid TDM of total ß-lactam antibiotics present in the blood of critically ill patients.
ABSTRACT
BACKGROUND: This study aimed to test the feasibility and titration methods used to achieve specific blood pressure (BP) control targets in hypertensive patients of rural China. METHODS: A randomized, controlled, open-label trial was conducted in Rongcheng, China. We enrolled 105 hypertensive participants aged over 60 years, and who had no history of stroke or cardiovascular disease. The patients were randomly assigned to one of three systolic-BP target groups: standard: 140 to < 150 mmHg; moderately intensive: 130 to < 140 mmHg; and intensive: < 130 mmHg. The patients were followed for 6 months. DISCUSSION: The optimal target for systolic blood pressure (SBP) lowering is still uncertain worldwide and such information is critically needed, especially in China. However, in China the rates of awareness, treatment and control are only 46.9%, 40.7%, and 15.3%, respectively. It is challenging to achieve BP control in the real world and it is very important to develop population-specific BP-control protocols that fully consider the population's characteristics, such as age, sex, socio-economic status, compliance with medication, education level, and lifestyle. This randomized trial showed the feasibility and safety of the titration protocol to achieve desirable SBP targets (< 150, < 140, and < 130 mmHg) in a sample of rural, Chinese hypertensive patients. The three BP target groups had similar baseline characteristics. After 6 months of treatment, the mean SBP measured at an office visit was 137.2 mmHg, 131.1 mmHg, and 124.2 mmHg, respectively, in the three groups. Home BP and central aortic BP measurements were also obtained. At 6 months, home BP measurements (2 h after drug administration) showed a mean SBP of 130.9 mmHg in the standard group, 124.9 mmHg in the moderately intensive group, and 119.7 mmHg in the intensive group. No serious adverse events were recorded over the 6-month study period. Rates of adverse events, including dry cough, palpitations, and arthralgia, were low and showed no significant differences between the three groups. This trial provided real-world experience and laid the foundation for a future, large-scale, BP target study. TRIAL REGISTRATION: Feasibility Study of the Intensive Systolic Blood Pressure Control; ClinicalTrials.gov, ID: NCT02817503. Registered retrospectively on 29 June 2016.
Subject(s)
Antihypertensive Agents/therapeutic use , Blood Pressure/drug effects , Hypertension/drug therapy , Blood Pressure Determination , China , Clinical Trials, Phase IV as Topic , Humans , Hypertension/diagnosis , Hypertension/physiopathology , Pilot Projects , Practice Guidelines as Topic , Randomized Controlled Trials as Topic , Rural Health , Treatment OutcomeABSTRACT
OBJECTIVE: To clarify the taxonomic status of Anopheles yatsushiroensis in Rongcheng City of Shandong Province. METHODS: By the end of August 2009, Anopheles yatsushiroensis were collected in the western suburbs of Wangjia Village of Rongcheng City, and raised for the next generation of various types of adult mosquitoes. Through morphological identification of filial generation various types, mosquito feet of 1-2 mosquitoes of various types were taken for complete DNA extraction, and complete sequence analysis of rDNA-ITS2 alignment was made by PCR. Multiple sequnence comparison was carried out with those previously documented by DNAstar7.1, including An. yatsushiroensis in Shandong Province (YSD, AY306128), An. yatsushiroensis in Sichuan Province (YSC, AY170925), An. yatsushiroensis in Liaoning Province (YLN, AY170923) and An. yatsushiroensis from South Korea (YK, AF146749). RESULTS: 56 An. yatsushiroensis with blood meal were collected in Rongcheng City, of which 7 successfully laid eggs, and received 354 adult mosquitoes of filiar generation, including 240 An. yatsushiroensis (Y type), 8 An. pullus (P type) and 106 hybrid type (H). The rDNA-ITS2 sequence alignment homology between single-parent female offspring of adult mosquitoes and various types of An. yatsushiroensis segments (JN865249, JN865246, JN865247, JN865248) was 98.7-100%, and the rDNA-ITS2 sequence alignment homology to those from Sichuan (YSC), Liaoning (YLN) and Korea (YK) was 98.5%-99.3%, 98.7%-99.6% and 98.7 to 100%, respectively, while to the original An. yatsushiroensis from Rongcheng (YSD), it was only 67.1%-68.5%. CONCLUSION: There are Y, P and H types of An. yatsushiroensis in Rongcheng City, Shandong Province, but the rDNA-ITS2 sequence is close to An. pullus. The local distribution of An. pullus is deduced.
