Therapeutic drug monitoring-guided dosing for pediatric cystic fibrosis patients: recent advances and future outlooks.

INTRODUCTION: Medicine use in children with cystic fibrosis (CF) is complicated by inconsistent pharmacokinetics at variance with the general population, a lack of research into this and its effects on clinical outcomes. In the absence of established dose regimens, therapeutic drug monitoring (TDM) is a clinically relevant tool to optimize drug exposure and maximize therapeutic effect by the bedside. In clinical practice though, use of this is variable and limited by a lack of expert recommendations. AREAS COVERED: We aimed to review the use of TDM in children with CF to summarize recent developments, current recommendations, and opportunities for future directions. We searched PubMed for relevant publications using the broad search terms "cystic fibrosis" in combination with the specific terms "therapeutic drug monitoring (TDM)" and "children." Further searches were undertaken using the name of identified drugs combined with the term "TDM." EXPERT OPINION: Further research into the use of Bayesian forecasting and the relationship between exposure and response is required to personalize dosing, with the opportunity for the development of expert recommendations in children with CF. Use of noninvasive methods of TDM has the potential to improve accessibility to TDM in this cohort.

Antifungal stewardship in solid-organ transplantation: What is needed?

BACKGROUND: Antifungal stewardship (AFS) lags behind antimicrobial stewardship (AMS) in terms of implementation, evidence base, and workforce experience. Solid-organ transplantation (SOT) carries a significant risk of invasive fungal infection, with high associated mortality, and is therefore associated with significant opportunities to optimize antifungal use. METHODS: A literature search for the terms "antifungal stewardship" and "solid-organ transplant" revealed a small evidence base to support AFS programs in this patient group. RESULTS: There is significant overlap in the methodology used in AMS and AFS programs, with notable differences in diagnostics, which are discussed in detail. The primary AFS interventions tested in SOT recipients are implementation of clinical guidelines and care bundles, digital enablers of AFS, and post-prescription review/audit and feedback. CONCLUSION: There is an urgent need for further research to support effective AFS strategies in this highly susceptible population.

A Prospective Real-World Study of the Impact of an Antifungal Stewardship Program in a Tertiary Respiratory-Medicine Setting.

There has been an increase in fungal infections in patients with chronic lung disease over the past decades, which is associated with rapidly increasing costs to health care systems. An antifungal stewardship team was introduced to a tertiary cardiopulmonary hospital, consisting of a medical mycologist and pharmacy support providing weekly stewardship ward rounds, twice-monthly multidisciplinary team meetings, and a dedicated weekly outpatient clinic. A database was set up to record the activity of the stewardship team. During the first 18 months of implementation, the antifungal stewardship team had reviewed 178 patients, with 285 recommendations made to inpatients, and 287 outpatient visits. The commonest diagnoses treated were allergic bronchopulmonary aspergillosis and chronic pulmonary aspergillosis. Cystic fibrosis was the largest patient group treated, followed by asthma and interstitial lung disease. There was a significant sustained reduction in monthly antifungal expenditure (P = 0.005) by £130,000 per month. There was also a significant reduction in antifungal use, measured as the defined daily dose/100 bed days (P = 0.017). There were no significant changes in expenditure on diagnostic tests. There has been a trend toward more patients having therapeutic levels of voriconazole (P = 0.086) and a significant increase in therapeutic levels of posaconazole (P < 0.0001). This study shows that an effective antifungal stewardship program can significantly reduce expenditure in a specialist respiratory service.

Rituximab-induced serum sickness in the treatment of idiopathic membranous nephropathy.

We report a case of rituximab-induced serum sickness in a 50-year-old female with idiopathic membranous nephropathy. Presentation was characterized by a widespread rash 1 week after rituximab administration followed by fever and profound haemodynamic instability, mimicking sepsis. Symptoms resolved over 48 h, although adjunct antibiotics, steroids and inotropes were used. This case is notable for being the first reaction with rituximab for a renal indication as well as the severity of presentation.

Examining Subcortical Infarcts in the Era of Acute Multimodality CT Imaging.

BACKGROUND: Lacunar infarct has been characterized as small subcortical infarct. It is postulated to occur from "in situ microatheroma or lipohyalinosis" in small vessel or lacunar mechanism. Based on this idea, such infarcts by lacunar mechanism should not be associated with large area of perfusion deficits that extend beyond the subcortical region to the cortical region. By contrast, selected small subcortical infarcts, as defined by MR imaging in the subacute and chronic stage, may initially have large perfusion deficit or related large vessel occlusions. These infarcts with "lacunar" phenotype may also be caused by disease in the parent vessel and may have very different stroke mechanism from small vessel disease. Our aim is to describe differences in imaging characteristics between patients with small subcortical infarction with "lacunar phenotype" from those with lacunar mechanism. MATERIALS AND METHODS: Patients undergoing acute CT perfusion/angiography (CTP/CTA) within 6 h of symptom onset and follow-up magnetic resonance imaging (MRI) for ischemic stroke were included (2009-2013). Lacunar infarct was defined as a single subcortical infarct ≤20 mm on follow-up MRI. Presence of perfusion deficits, vessel occlusion, and infarct dimensions was compared between lacunar infarcts and other topographical infarct types. RESULTS: Overall, 182 patients (mean age 66.4 ± 15.3 years, 66% males) were included. Lacunar infarct occurred in 31 (17%) patients. Of these, 12 (39%) patients had a perfusion deficit compared with those with any cortical infarction (120/142, 67%), and the smallest lacunar infarct with a perfusion deficit had a diameter of <5 mm. The majority of patients with lacunar infarction (8/12, 66.7%) had a relevant vessel occlusion. A quarter of lacunar infarcts had a large artery stroke mechanism evident on acute CTP/CTA. Lacunar mechanism was present in 3/8 patients with corona radiata, 5/10 lentiform nucleus, 5/6 posterior limb of internal capsule (PLIC), 3/5 thalamic infarcts, 1/2 miscellaneous locations. There was a trend to significant with regards to finding lacunar mechanism among patients with thalamic and PLIC infarcts versus lentiform nucleus and corona radiata infarcts (p = 0.13). CONCLUSION: Diverse stroke mechanisms were present among subcortical infarcts in different locations. When available acute CTP/CTA should be combined with subacute imaging of subcortical infarct to separate "lacunar phenotype" from those with lacunar mechanism.

Antibiotic surveillance on a paediatric intensive care unit: easy attainable strategy at low costs and resources.

BACKGROUND: Antibiotic surveillance is mandatory to optimise antibiotic therapy. Our objectives were to evaluate antibiotic use in our pediatric intensive care unit (PICU) and to implement a simple achievable intervention aimed at improving antibiotic therapy. METHOD: Prospective, 3 months surveillance of antibiotic use on PICU (phase I) and evaluation according to the CDC 12-step campaign with development of an attainable intervention. 3 months surveillance (phase II) after implementation of intervention with comparison of antibiotic use. RESULTS: Appropriate antibiotic use for culture-negative infection-like symptoms and targeted therapy for proven infections were the main areas for potential improvement. The intervention was a mandatory checklist requiring indication and recording likelihood of infection at start of antibiotic therapy and a review of the continuing need for therapy at 48 h and 5 days, reasons for continuation and possible target pathogen. The percentage of appropriate empiric antibiotic therapy courses for culture-negative infection-like symptoms increased from 18% (10/53) to 74% (42/57; p<0.0001), duration of therapy <3 days increased from 18% (10/53) to 35% (20/57; p=0.05) and correct targeting of pathogen increased from 58% (7/12) to 83% (20/24; p=0.21). CONCLUSIONS: Antibiotic surveillance using the CDC 12-step campaign can help to evaluate institutional antibiotic therapy. Development of an attainable intervention using a checklist can show improved antibiotic use with minimal expense.