Voriconazole is widely used in the treatment and prevention of invasive fungal diseases. Common drug-induced liver injuries increase the economic burdens and the risks of premature drug withdrawal and disease recurrence. This study estimated the disposal cost of voriconazole-related liver injury, explored the risk factors of voriconazole-related liver injury in hospitalized patients, and established a predictive model of liver injury to assist clinicians and pharmacists in estimating the probability or risk of liver injury after voriconazole administration to allow for early identification and intervention in patients at high risk of liver injury. A retrospective study was conducted on the selected inpatients whose blood concentration of voriconazole was measured in the West China Hospital of Sichuan University from September 2016 to June 2020. The incidence and disposal cost of voriconazole-related liver injuries were calculated. The incidence of voriconazole-related liver injury was 15.82% (217/1372). The disposal cost has been converted to 2023 at a discount rate of 5%. The median (P₂₅, P₇₅) disposal cost of severe liver injury (n = 42), general liver injury (n = 175), and non-liver injury (n = 1155) was 993.59 (361.70, 1451.76) Chinese yuan, 0.00 (0.00, 410.48) yuan, and 0.00 (0.00, 0.00) yuan, respectively, with a statistically significant difference (p < 0.001). Single factor analysis and multiple factor logistic regression were used to analyze the risk factors of voriconazole-related liver injury. The voriconazole-related liver injury was related to the trough concentration (C_min, OR 1.099, 95% CI 1.058–1.140), hypoproteinemia (OR 1.723, 95% CI 1.126–2.636), and transplantation status (OR 0.555, 95% CI 0.325–0.948). The prediction model of liver injury was Logit (P)= −2.219 + 0.094 × C_min + 0.544 × H_{ydroproteinemia} − 0.589 × Transplantation, and the prediction model nomogram was established. The model validation results showed that the C-index of the derivation set and validation set was 0.706 and 0.733, respectively. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was 0.705 and 0.733, respectively, indicating that the model had good prediction ability. The prediction model will be helpful to develop clinical individualized medication of voriconazole and to identify and intervene in the cases of patients at high risk of voriconazole-related liver injury early on, in order to reduce the incidence of voriconazole-related liver injuries and the cost of treatment.

Background and Aims: Eculizumab is expected to lead to increased susceptibility to infection. We performed a meta-analysis of data from randomized controlled trials (RCTs) to determine the risk of infection in eculizumab-treated patients.Methods: We searched PubMed, EMBASE, Web of Science and ClinicalTrials.gov (up to 8 Oct 2024) to identify published RCTs that focused on the occurrence of infection in patients treated with eculizumab regardless of the indications of the patients. Relative risks and 95% confidence intervals (95% CIs) were calculated via the random effects model. (PROSPERO Code No. CRD42024562470).Results: Nine RCTs including 691 patients were eligible. Compared with the control (placebo or standard of care), eculizumab did not significantly increase the overall risk of infection (RR = 1.07; 95% CI, 0.89–1.28; I² = 44%), regardless of whether the infection was a general infection (RR = 1.07; 95% CI, 0.86–1.34; I² = 39%) or a serious infection (RR = 1.05; 95% CI, 0.75–1.47; I² = 11%). Analyses of subgroups revealed that eculizumab significantly increased the risk of general urinary system infection (RR = 1.33; 95% CI, 1.00–1.77; I² = 46%) and severe bacteremia (RR = 2.31; 95% CI, 1.04–5.13; I² = 0%).Conclusion: Compared with placebo or standard of care, although eculizumab did not significantly increase the overall risk of infection, it was associated with 33% and 131% increases in the risk of general urinary system infection and severe bacteremia, respectively.Systematic Review registration: PROSPERO CRD42024562470

Vancomycin-induced bleeding has been reported, attributed to the mechanism of immune thrombocytopenia. A rare case of vancomycin-induced gastrointestinal hemorrhage in a young patient with no underlying disease, receiving intravenous vancomycin for methicillin-resistant Staphylococcus aureus (MRSA) infection, is presented. This occurrence occurred without thrombocytopenia. Relevant cases reported in the literature were also reviewed. A 34-year-old male patient presented with maxillofacial multiple spaces infection accompanying left temporal abscess, bilateral lung abscesses. Culture results from both blood and secretion indicated that the infection was caused by MRSA. The patient received standard-dose vancomycin (1 g q12h intravenously guttae) for treatment. On the 5th day of therapy, he presented with bright red blood in his stool; however, vancomycin treatment was continued. By the 9th day, a decrease in hemoglobin level to 76 g/L and a platelet (PLT) count of 424 × 109/L raised concerns about gastrointestinal hemorrhage. The hemoglobin level decreased to 62 g/L on day 12. Due to the high tissue concentration of linezolid, administration of linezolid at a dose of 600 mg q12h intravenously guttae commenced on the 13th day as an alternative to vancomycin(D13-D17). Subsequently, on the 17th day, there was an improvement in hemoglobin level to 78 g/L. However, despite treatment with linezolid, the patient’s fever showed no significant improvement, prompting a switch back to vancomycin at a dosage of 1 g q12h intravenously guttae(D18-D22). On the 21st day, there was a recurrence of gastrointestinal hemorrhage, accompanied by a hemoglobin level of 42 g/L and a PLT count of 224 × 109/L. Gastroscopy revealed the presence of a gastroduodenal ulcer. The patient had no prior history of hemorrhoids, gastrointestinal ulcers, liver cirrhosis, or purpura. Prior to admission, he had not been administered non-steroidal anti-inflammatory drugs (NSAIDs) or steroids. During hospitalization, the only medications given were vancomycin, ambroxol and lidocaine. Additional tests ruled out immunological disorders as the cause of gastrointestinal ulcers, and a positive vancomycin rechallenge test indicated an association between vancomycin and bleeding. After discontinuation of vancomycin, no further bleeding occurred. This case highlights a rare occurrence of vancomycin-induced bleeding without thrombocytopenia, classified as “Certain” according to the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) scale for standardized case causality assessment. This case represents the first documented instance of vancomycin-induced bleeding without thrombocytopenia, as confirmed by a positive rechallenge test. This discovery will aid in the early detection of this rare adverse reaction in future cases.

Objective: To systematically evaluate the impact of pharmacist interventions on the implementation and clinical efficacy of vancomycin therapeutic drug monitoring (TDM). Methods: A Cochrane systematic review methodology was employed. Databases including PubMed, Medline, Embase, Cochrane Library, CNKI, and Sinomed were searched. After quality assessment and data extraction of eligible clinical studies, Meta-analysis was performed using Stata 18.0 to compare the differences between the pharmacist intervention group and the non-pharmacist intervention group in terms of the incidence of acute kidney injury, clinical effective rate, 30-day mortality, correct blood sampling time rate, target blood concentration attainment rate, TDM sampling rate, etc. Results: A total of 63 studies were included in the Meta-analysis. The results showed that pharmacist interventions reduced the incidence of acute kidney injury (RR = 0.67, 95% CI = 0.57, 0.78, P < 0.05), improved the clinical effective rate (RR = 1.11, 95% CI = 1.06, 1.17, P < 0.05), reduced 30-day mortality (RR = 0.52, 95% CI = 0.33, 0.82, P < 0.05), increased the correct TDM blood sampling time rate (RR = 1.52, 95% CI = 1.25, 1.83, P < 0.05), increased the target blood concentration attainment rate (RR = 1.60, 95% CI = 1.49, 1.72, P < 0.05), increased the TDM sampling rate (RR = 1.65, 95% CI = 1.34, 2.04, P < 0.05), increased the proportion of dosage regimen adjustments based on TDM results (RR = 2.68, 95% CI = 1.93, 3.70, P < 0.05). There was no significant effect on the duration of medication, length of hospital stay or TDM timeliness. Subgroup analysis showed that In the 10–20 mg/L group and the group with no specified target range, the serum concentration attainment rate was improved under pharmacist intervention (RR = 1.61, 95% CI = 1.50, 1.73, P < 0.05; RR = 1.49, 95% CI = 1.07, 2.08, P < 0.05). In the groups defined by serum creatinine increase ≥0.5 mg/dL or ≥50% from baseline, and serum creatinine increase ≥0.3 mg/dL or ≥50% from baseline, pharmacist interventions reduced the incidence of acute kidney injury (RR = 0.58, 95% CI = 0.45, 0.74, P < 0.05; RR = 0.64, 95% CI = 0.48, 0.85, P < 0.05). Conclusion: This study indicates that in patients treated with vancomycin under TDM, pharmacist interventions can promote the standardization of vancomycin TDM, reduce the incidence of acute kidney injury, and improve clinical outcomes. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261301721 , identifier CRD420261301721.