Research design
We performed a single-center, retrospective, case-control, research design study[The First Affiliated Hospital of Bengbu Medical College, the ethics committee of clinical medical research (scientific research project) approval number: 2018KY008, the approval date was August 28, 2018; and on June 23, 2019, the registration number of the China Clinical Trial Registration Center was ChiCTR1900024062.]based on real-world data present in the Hospital Information Management System (HIS). HIS is a database that stores the information recorded during an inpatient’s stay at the hospital. It includes their basic information, daily medication during hospitalization, care, admission, and expenses incurred. According to the Guide to the Monitoring of Chinese Vancomycin Therapeutic Drugs [12], when patient blood concentration was monitored, VAN had to be within the effective concentration range (10-20 μg/mL). The population was divided into the standard group, including patients whose blood concentrations, as measured after the intake of VAN, were within the range of 10-20 μg/mL, and the substandard group, including patients with VAN trough concentrations outside the range of 10-20 μg/mL.
Blood drug concentration monitoring method
The VAN blood concentration was monitored by enzyme amplification immunoassay, using enzyme reagent 1 (vancomycin labeled with bacterial glucose-6-phosphate dehydrogenase [0.21 U/ml], hydroxyethylpiperazine ethylsulfuric acid buffer liquid, calf serum albumin, preservatives, and stabilizers) and reagents 2 (antibody/substrate: murine monoclonal vancomycin antibody [27 μg/mL], calf serum albumin, glucose-6-phosphate [44 mM], nicotinamide adenine dinucleotide [36 mM], preservatives, and stabilizers) were monitored by a fully automated biochemical analyzer (Viva-E: YZB/HOL 1746-2010).
Research object
This study was performed at the First Affiliated Hospital of Bengbu Medical College from January 1, 2017 to December 31, 2018. Inpatients whose VAN blood concentrations were being monitored were selected as subjects. The study protocol was reviewed and approved by the hospital ethics committee. Inclusion criteria were as follows: (1) patients treated with VAN for clinical infections who had their VAN blood concentration monitored; (2) trough concentration of VAN blood concentration and not peak concentration or concentration found immediately after administration; (3) influencing factors of the control group had to be consistent with the influencing factors in the observation group; (4) complete patient data. Exclusion criteria were as follows: (1) vancomycin was not used as the clinical treatment for infection; however, cases treated with norvancomycin were included; (2) patients whose VAN blood concentration was monitored as peak concentration; (3) differing statistical factors between the observation group and control group; (4) invalid clinical data.
Data collection
According to the characteristics of VAN and the actual situation provided in the HIS, the electronic database was designed to collect the following data: (1) demography: age and sex; (2) past history of drug allergy, smoking, and alcohol abuse; (3) vital signs: body temperature (36.1-37 °C); (4) infection: pulmonary, intracranial, central nervous system, and bronchiectasis infection; (5) history of disease: history of chronic diseases such as diabetes and hypertension, and infectious diseases such as tuberculosis; (6) hospitalization: number of operations and operations performed before each blood concentration measurement, fluid infusion amount, urine amount, whether critical illness occurred during hospitalization, Glasgow coma score (GCS, including blink response, speech response, and limb movement, mild coma: 13-14 points, moderate coma: 9-12 points, severe coma: 3-8 points, normal: >14 points, length of hospital stay, admission department, western medicine fee, antibiotic cost, and antibiotic use during hospitalization, total cost of western medicine; (7) patient medication during hospitalization: vancomycin (dose, frequency of administration, vehicle, and days of drug use), antibiotics and other drugs used in combination with VAN, treatment options are correct, whether there are indications; (8) safety test indicators: ALT: 0-40 IU/L, AST: 0-45 IU/L, alkaline phosphatase (ALP): 40-160 IU/L, glutamyl transpeptidase (GGT): 0-50 IU/L, total protein (TP): 60-80 g/L, albumin (A): 35-55 g/L, G: 9-23 mg/ml, total bilirubin: 1.7-17.1 μmol/L, serum urea: 1.8-7.1 mmol/L, serum creatinine: 44-133 μmol/L, serum creatinine clearance rate: 80-120 ml/min, white blood cell count: 4-10×109/L, hemoglobin: (120-160 g/L), platelets: 100-300 × 109/L; and (9) observed outcome indicators: monitoring values of VAN plasma concentration per patient per time.
Data processing and assignment
Univariate and multivariate logistic regression analyses were used to screen independent risk factors for the compliance of patients receiving VAN. According to the information retrieved for each patient, the assignment of various influencing factors is shown in Table 1.
[Insert Table 1]
Statistical analysis
Data were processed using SPSS 21.0 statistical software (IBM, Armonk, NY, USA). A Pearson’s chi-square test was used to analyze classification data, whereas a t-test was used to analyze continuous data. Univariate risk factors affecting VAN plasma concentration were determined by single factor and multivariate regression analyses. According to the multivariate logistic model analysis results, joint predictors were set and included in the logistic model for analysis. Model equation and ROC curves were then derived. Curve, screen cut points, area under the curve, and the predictive efficacy of various indicators were then derived. All tests were two-sided, and P < 0.05 was considered statistically significant. Unless otherwise stated, results are expressed as the mean ± standard deviation, and lost data is processed using the mean substitution method.