Background: Tigecycline and cefoperazone/sulbactam can cause coagulation disorders; tigecycline may also lead to hypofibrinogenemia, raising safety concerns. This study aimed to investigate whether tigecycline plus cefoperazone/sulbactam increases the risk of bleeding compared with other tigecycline-based combination therapies and identify risk factors for tigecycline-associated hypofibrinogenemia.Methods: In this multi-method, multicenter, retrospective study, coagulation and other baseline variables were compared using a cohort study, and risk factors for hypofibrinogenemia using a case-control study.Results: The 451 enrolled participants were divided into three group: tigecycline plus cefoperazone/sulbactam (Group A, 193 patients), tigecycline plus carbapenems (Group B, 200 patients) and tigecycline plus β-lactams without N-methylthio-tetrazole (NMTT) side chains (Group C, 58 patients). Activated partial thromboplastin time and prothrombin time were prolonged, and fibrinogen declined for all patients after tigecycline-based medication (all p < 0.05). Prothrombin time in Group B was significantly longer than in other groups (p < 0.05), but there were no significant differences in bleeding events between the three groups (p = 0.845). Age greater than 80 years (OR: 2.85, 95% CI: 1.07–7.60), treatment duration (OR: 1.29, 95% CI: 1.19–1.41), daily dose (OR: 2.6, 95% CI: 1.29–5.25), total bilirubin (OR: 1.01, 95% CI: 1.01–1.02) and basal fibrinogen (OR: 1.32, 95% CI: 1.14–1.63) were independent risk factors of hypofibrinogenemia. The optimal cut-off for treatment course was 6 days for high-dose and 11 days for low-dose.Conclusion: Tigecycline plus cefoperazone/sulbactam did not increase the risk of bleeding compared with tigecycline plus carbapenem, or tigecycline plus β-lactam antibiotics without NMTT-side-chains. Coagulation function should be closely monitored in patients receiving tigecycline treatment.
Backgrounds Tigecycline has a broad spectrum of antimicrobial activity and has been approved for the treatment of complicated intra-abdominal infections. However, it is debatable whether tigecycline should be used alone or in combination. This study aimed to investigate whether tigecycline plus β-lactam antibiotics (combination therapy [CT] group) are superior to tigecycline alone (monotherapy [MT] group) in non-critically ill intra-abdominal infection patients after tumor surgery. Methods This was a multicenter, retrospective cohort study. The primary outcome was mortality during the hospital stay. Secondary outcomes were clinical success rate, microbial eradication rate, relapse rate within one week, course of treatment, and adverse effects. Propensity score matching (PSM) was used to adjust the degree of infection before medication between the MT and CT groups. Univariate comparisons were performed using the chi-squared test for qualitative variables and Student’s t-test or the Mann-Whitney U-test for continuous variables, as appropriate. Multivariate logistic regression analysis was performed to examine the relationship between antimicrobial treatments and mortality during hospitalization. The paired samples Wilcoxon test was used to compare the parameters before and after medication. Results In total, 291 patients were included in the final analysis: 128 in MT group and 163 in CT group. Mortality rate was 6.25% in the MT group and 6.13% in the CT group (P = 0.97). Multivariate logistic regression model showed that carbapenem-resistant organisms (OR: 4.35, 95% CI: 2.36 ~ 61.70) and age > 65 (OR: 1.32, 95% CI:1.19 ~ 3.01) were independent risk factors for death. CT group had a shorter defervescence time (P < 0.05), with less likelihood of relapse (P < 0.05) but had a more significant effect on activated partial thromboplastin and prothrombin time. Conclusions Tigecycline plus β-lactam wasn’t superior to tigecycline monotherapy for the treatment of non-critically ill patients with intra-abdominal infection. But for advanced age patients with cancer, tigecycline combination therapy maybe a better choice in terms of mortality.
Introduction This study aimed to investigate the relationship between gene polymorphisms and clinical factors with the concentrations of valproic acid (VPA) in adult patients who underwent neurosurgery in China. Methods A total of 531 serum concentration samples at steady state were collected from 313 patients to develop a population pharmacokinetic (PPK) model. Data analysis was performed using nonlinear mixed effects modeling. Covariates included demographic parameters, biological characteristics, and genetic polymorphism. Bootstrap evaluation showed that the final model was stable. Sensitive analysis was performed to verify the relationship between gene polymorphisms and concentrations of VPA. Linear regression was used to analyze the relationship between VPA concentration, ANKK1 , and daily dosage. Results In the recruited patients, 17 of 25 single-nucleotide polymorphism distributions were consistent with the Hardy–Weinberg equilibrium. A one-compartment model with first-order absorption and elimination was developed for VPA injections. VPA clearance was significantly influenced by three variables: sex (17.41% higher in male than female patients), body weight, and the ANKK1 gene. Typical values for the elimination clearance and the volume of central compartment were 0.614 L/min and 23.5 L, respectively. The model evaluation indicated the stable and precise performance of the final model. After sensitive analysis using Kruskal–Wallis and Mann–Whitney U tests, we found that patients with AA alleles had higher VPA concentrations than those with GG and AG alleles. Linear regression models showed that gene polymorphisms of ANKK1 had little effects on VPA concentration. Conclusion A PPK model of VPA in Chinese Han patients was successfully established; this can be helpful for model-informed precision-dosing approaches in clinical patient care, and for exploring the mechanism of VPA-induced weight gain. Supplementary Information The online version contains supplementary material available at 10.1007/s40120-022-00419-8.
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