Therapeutic drug monitoring (TDM) of vancomycin is recommended to improve efficacy, minimize toxicity, and prevent the development of resistant microbial strains. International guidelines now recommend the use of an area under the concentration-time curve (AUC)-guided approach to optimize vancomycin dosing.
Objectives
Cefepime-induced neurotoxicity (CIN) has been demonstrated to be associated with cefepime plasma concentrations; however, the toxicity threshold remains unclear. The primary objective of this study was to identify the cefepime plasma trough concentration at which neurotoxicity occurs. Secondary objectives were to determine the incidence of CIN at a large tertiary institution and to identify patient factors associated with the development of CIN.
Methods
A retrospective review of all adult patients administered cefepime between October 2017 and May 2018 in a tertiary hospital was conducted to determine total incidence of CIN. A receiver operating characteristic (ROC) curve was constructed to review the sensitivity and specificity of using various cefepime trough plasma concentrations to predict the development of neurotoxicity. Cefepime plasma concentrations were measured using ultra-HPLC. A regression was conducted to identify patient factors associated with CIN.
Results
In total, 206 patients were administered 259 courses of cefepime, with an overall CIN incidence of 6% (16/259 courses). A total of 64 courses had a cefepime trough concentration measured (24.7%). A cefepime trough concentration of 36 mg/L provided the best differentiation between patients who experienced neurotoxicity and those who did not. No other patient covariates were identified to be significantly associated with neurotoxicity occurring.
Conclusions
A cefepime trough plasma concentration ≥36 mg/L appears to be the most sensitive and specific cut-off to predict CIN occurring. No patient factors were associated with the development of CIN when accounting for cefepime trough plasma concentrations.
The purpose of the study was to assess the status of emerging therapeutic drug monitoring (TDM) of anti-infective agents in Australian hospitals.Methods: A nationwide cross-sectional survey of all Australian hospitals operating in the public and private health sector was conducted between August and September 2019. The survey consisted of questions regarding institutional TDM practice for anti-infective agents and clinical vignettes specific to β-lactam antibiotics.The authors confirm that the Principal Investigator for this paper is Indy Sandaradura and that he had direct responsibility for participant recruitment and the conduct of the study.
Aims
Bayesian forecasting software can assist in guiding therapeutic drug monitoring (TDM)‐based dose adjustments for amikacin to achieve therapeutic targets. This study aimed to evaluate amikacin prescribing and TDM practices, and to determine the suitability of the amikacin model incorporated into the DoseMeRx® software as a replacement for the previously available software (Abbottbase®).
Methods
Patient demographics, pathology, amikacin dosing history, amikacin concentrations and Abbottbase® predicted TDM targets (area under the curve up to 24 hours, maximum concentration and trough concentration) were collected for adults receiving intravenous amikacin (2012–2017). Concordance with the Australian Therapeutic Guidelines was assessed. Observed and predicted amikacin concentrations were compared to determine the predictive performance (bias and precision) of DoseMeRx®. Amikacin TDM targets were predicted by DoseMeRx® and compared to those predicted by Abbottbase®.
Results
Overall, guideline compliance for 63 courses of amikacin in 47 patients was suboptimal. Doses were often lower than recommended. For therapy >48 h, TDM sample collection timing was commonly discordant with recommendations, therapeutic target attainment low and 34% of dose adjustments inappropriate. DoseMeRx® under‐predicted amikacin concentrations by 0.9 mg/L (95% confidence interval [CI] –1.4 to −0.5) compared with observed concentrations. However, maximum concentration values (n = 19) were unbiased (−1.7 mg/L 95%CI –5.8 to 0.8) and precise (8.6% 95%CI 5.4–18.1). Predicted trough concentration values (n = 7) were, at most, 1 mg/L higher than observed. Amikacin area under the curve values estimated using Abbottbase® (181 mg h/L 95%CI 161–202) and DoseMeRx® (176 mg h/L 95%CI 152–199) were similar (P = .59).
Conclusion
Amikacin dosing and TDM practice was suboptimal compared with guidelines. The model implemented by DoseMeRx® is satisfactory to guide amikacin dosing.
We present the first published case of successfully treated disseminated Aspergillus lentulus infection in a solid organ transplant recipient with invasive pulmonary disease, endophthalmitis, and a cerebral abscess. This case highlights important challenges associated with treating Aspergillus lentulus, particularly regarding antifungal resistance and toxicities associated with long-term antifungal therapy.
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