Ceftazidime Plasma Concentrations and Neurotoxicity: The Importance of Therapeutic Drug Monitoring in Patients Undergoing Different Modalities of Renal Replacement Therapy. A Grand Round.

ABSTRACT: Ceftazidime-avibactam (CTZ-AVM) is a novel cephalosporin/beta-lactamase inhibitor with broad-spectrum activity against multidrug-resistant Pseudomonas aeruginosa . Ceftazidime-induced neurotoxicity is a well-described adverse effect, particularly in patients with renal insufficiency. However, appropriate dosing of ceftazidime-avibactam in patients undergoing renal replacement therapy (RRT) is sparsely investigated, and therapeutic drug monitoring to guide dosing remains lacking. Furthermore, when dose adjustment for impaired renal function is based on CTZ-AVM product information, inferior cure rates have been obtained compared with those with the standard therapy for intra-abdominal infections. Maintaining an effective dose while avoiding toxicity in these patients is challenging. Here, the authors describe the case of a critically ill patient, undergoing 2 modalities of RRT, who developed ceftazidime-induced neurotoxicity as confirmed using ceftazidime therapeutic drug monitoring. This case illustrates a therapeutic drug monitoring-based approach for guiding ceftazidime-avibactam dosing in this context and in diagnosing the cause of neurological symptoms and signs.

Long-term medical imaging use in children with central nervous system tumors.

BACKGROUND: Children with central nervous system (CNS) tumors undergo frequent imaging for diagnosis and follow-up, but few studies have characterized longitudinal imaging patterns. We described medical imaging in children before and after malignant CNS tumor diagnosis. PROCEDURE: We conducted a retrospective cohort study of children aged 0-20 years diagnosed with CNS tumors between 1996-2016 at six U.S. integrated healthcare systems and Ontario, Canada. We collected computed topography (CT), magnetic resonance imaging (MRI), radiography, ultrasound, nuclear medicine examinations from 12 months before through 10 years after CNS diagnosis censoring six months before death or a subsequent cancer diagnosis, disenrollment from the health system, age 21 years, or December 31, 2016. We calculated imaging rates per child per month stratified by modality, country, diagnosis age, calendar year, time since diagnosis, and tumor grade. RESULTS: We observed 1,879 children with median four years follow-up post-diagnosis in the U.S. and seven years in Ontario, Canada. During the diagnosis period (±15 days of diagnosis), children averaged 1.10 CTs (95% confidence interval [CI] 1.09-1.13) and 2.14 MRIs (95%CI 2.12-2.16) in the U.S., and 1.67 CTs (95%CI 1.65-1.68) and 1.86 MRIs (95%CI 1.85-1.88) in Ontario. Within one year after diagnosis, 19% of children had ≥5 CTs and 45% had ≥5 MRIs. By nine years after diagnosis, children averaged one MRI and one radiograph per year with little use of other imaging modalities. CONCLUSIONS: MRI and CT are commonly used for CNS tumor diagnosis, whereas MRI is the primary modality used during surveillance of children with CNS tumors.

Therapeutic drug monitoring of commonly used anti-infective agents: A nationwide cross-sectional survey of Australian hospital practices.

When performed according to best-practice principles, therapeutic drug monitoring (TDM) can optimise anti-infective treatment and directly benefit clinical outcomes. We evaluated TDM performance and clinical decision-making for established anti-infective agents amongst Australian hospitals. A nationwide cross-sectional survey was conducted between August and September 2019. The survey consisted of multiple-choice questions regarding TDM of anti-infective agents in general as well as clinical vignettes specific to vancomycin, gentamicin and voriconazole. We sought to survey all Australian hospitals operating both in the public and private health sectors. Responses were captured from 85 unique institutions, from all Australian states and territories. Regarding guidelines, 26% of hospitals did not have endorsed guidelines to advise on the ordering, sampling and interpretation of TDM for any anti-infective agent. Admitting teams were predominantly responsible for ordering TDM (85%) and interpreting results (76%). Only 51% of hospitals had access to dose prediction software, with access generally better amongst principal referral (69%) (P = 0.01) and children's hospitals (100%) (P = 0.04). Whenever a laboratory-derived minimum inhibitory concentration (MIC) was not available to guide dosing decisions, a surrogate target MIC was assumed in 77% of hospitals. This was based on a 'worst-case' scenario infection in 11% of hospitals. The rates of clinical practice consistent with current guideline recommendations across all aspects of TDM were demonstrated to be 0% for vancomycin, 4% for gentamicin and 35% for voriconazole. At present, there is significant institutional variability in the clinical practice of TDM for anti-infective agents in Australia for established TDM drugs.