Impact of antibiotic allergy labels on patient outcomes in a tertiary paediatric hospital

Aims Antibiotic allergies are reported in 5–15% of children. This study aimed to evaluate the impact of common β‐lactam antibiotic allergy labels (AALs) on hospital treatment, focusing on length of stay and appropriateness of antibiotic prescribing. Methods This was a retrospective cohort study over 21 months at the Royal Children's Hospital Melbourne, Australia. A subset of children with the most common β‐lactam allergies, and who required admission for intravenous antibiotics over a 12‐month period, was analysed for appropriateness of prescribing. Non‐allergic patients were matched to evaluate associations between AALs and hospital treatment. Results There were 98 912 children admitted over the study period, of whom 938 (1%) had at least one AAL on first admission. Of all encounters, 5145 (2.5%) were for children with AALs. The most common AALs were to amoxicillin and amoxicillin‐clavulanic acid combinations (40.8%), cefalexin (14.4%) and trimethoprim‐sulfamethoxazole (9.7%). For the subset, there were 66 admissions for children who required intravenous antibiotics. Documentation was adequate for 27% of AALs. Inappropriate prescribing occurred in almost half (47%). Hospital stay was longer for children with AALs (median 4.7 days; IQR 2.3–9.2) compared to non‐allergic controls (median 3.9 days; IQR 1.9–6.8; P  = .02). Children with AALs were more likely to receive restricted antibiotics (aOR 3.03; 95% CI, 1.45–6.30; P  = .003). Conclusion This is the first study to demonstrate high rates of inappropriate prescribing in children with AALs. Children with AALs were significantly more likely to receive restricted antibiotics and had a longer length of stay compared with non‐allergic controls.</p

Optimizing mycophenolic acid exposure in kidney transplant recipients: time for target concentration intervention

The immunosuppressive agent mycophenolate is used extensively in kidney transplantation, yet dosing strategy applied varies markedly from fixed dosing ("one-dose-fits-all"), to mycophenolic acid (MPA) trough concentration monitoring, to dose optimization to an MPA exposure target (as area under the concentration-time curve [MPA AUC0-12]). This relates in part to inconsistent results in prospective trials of concentration-controlled dosing (CCD). In this review, the totality of evidence supporting mycophenolate CCD is examined: pharmacological characteristics, observational data linking exposure to efficacy and toxicities, and randomized controlled trials of CCD, with attention to dose optimization method and exposure achieved. Fixed dosing of mycophenolate consistently leads to underexposure associated with rejection, as well as overexposure associated with toxicities. When CCD is driven by pharmacokinetic calculation to a target concentration (target concentration intervention), MPA exposure is successfully controlled and clinical benefits are seen. There remains a need for consensus on practical aspects of mycophenolate target concentration intervention in contemporary tacrolimus-containing regimens and future research to define maintenance phase exposure targets. However, given ongoing consequences of both overimmunosuppression and underimmunosuppression in kidney transplantation, impacting short- and long-term outcomes, these should be a priority. The imprecise "one-dose-fits-all" approach should be replaced by the clinically proven MPA target concentration strategy

High-Resolution Twin-Ion Metabolite Extraction (HiTIME) Mass Spectrometry: Nontargeted Detection of Unknown Drug Metabolites by Isotope Labeling, Liquid Chromatography Mass Spectrometry, and Automated High-Performance Computing

The metabolic fate of a compound can often determine the success of a new drug lead. Thus, significant effort is directed toward identifying the metabolites formed from a given molecule. Here, an automated and nontargeted procedure is introduced for detecting drug metabolites without authentic metabolite standards via the use of stable isotope labeling, liquid chromatography mass spectrometry (LC/MS), and high-performance computing. LC/MS of blood plasma extracts from rats that were administered a 1:1 mixture of acetaminophen (APAP) and ¹³C₆-APAP resulted in mass spectra that contained “twin” ions for drug metabolites that were not detected in control spectra (i.e., no APAP administered). Because of the development of a program (high-resolution twin-ion metabolite extraction; HiTIME) that can identify twin-ions in high-resolution mass spectra without centroiding (i.e., reduction of mass spectral peaks to single data points), 9 doublets corresponding to APAP metabolites were identified. This is nearly twice that obtained by use of existing programs that make use of centroiding to reduce computational cost under these conditions with a quadrupole time-of-flight mass spectrometer. By a manual search for all reported APAP metabolite ions, no additional twin-ion signals were assigned. These data indicate that all the major metabolites of APAP and multiple low-abundance metabolites (e.g., acetaminophen hydroxy- and methoxysulfate) that are rarely reported were detected. This methodology can be used to detect drug metabolites without prior knowledge of their identity. HiTIME is freely available from https://github.com/bjpop/HiTIME

Adverse Drug Reactions in Children - International Surveillance and Evaluation (ADVISE) : A Multicentre Cohort Study

Background: A previous meta-analysis reported that 9.5% of hospitalized children suffered from an adverse drug reaction (ADR); however, reported incidences among studies varied. Objective: To enhance the knowledge of ADRs in paediatric hospitalized patients at a global level we investigated the incidence and characteristics of ADRs in hospitalized children in European and non-European countries. Methods: A prospective observational cohort study was conducted in academic and non-academic hospitals in five countries: Australia, Germany, Hong Kong, Malaysia and the UK. Children aged 0-18 years admitted during a 3-month period (between 1 October 2008 and 31 December 2009) were recruited. The main outcome measures were incidence, causality and outcome of ADRs. Results: A total of 1278 patients (1340 admissions) were included [Australia n=146 (149 admissions), Germany n=376 (407), Hong Kong n=143 (149), Malaysia n=300 (314) and the UK n=313 (321)]. The median age was 2 years (interquartile range [TOR] 0-7). Patients received a total of 5367 drugs (median 3; IQR 2-5) and median length of hospital stay was 4 days (IQR 3-7). A total of 380 ADRs were identified in 211 patients. The resultant ADR incidence of 16.5% (95% Cl 14.5, 18.7) varied significantly between countries (p<0.001). The highest incidences were observed in Malaysia and the UK. 65.3% (n=248) of A DRs were found to be probable, and 24% of the ADRs were serious, with one being fatal. Conclusions: By comparing data from five countries in Europe, Asia and Australia we have shown that the incidence of ADRs in hospitalized children is at least as high as incidences published in adults. However, the variation between countries was mainly due to different populations and treatment strategies. Particular attention should be given to opioid use in hospitalized children.Peer reviewe

Prevention and treatment of infant and childhood vitamin D deficiency in Australia and New Zealand : a consensus statement

&bull; Vitamin D deficiency has re-emerged as a significant paediatric health issue, with complications including hypocalcaemic seizures, rickets, limb pain and fracture. &bull; A major risk factor for infants is maternal vitamin D deficiency. For older infants and children, risk factors include dark skin colour, cultural practices, prolonged breastfeeding, restricted sun exposure and certain medical conditions. &bull; To prevent vitamin D deficiency in infants, pregnant women, especially those who are dark-skinned or veiled, should be screened and treated for vitamin D deficiency, and breastfed infants of dark-skinned or veiled women should be supplemented with vitamin D for the first 12 months of life. &bull; Regular sunlight exposure can prevent vitamin D deficiency, but the safe exposure time for children is unknown. &bull; To prevent vitamin D deficiency, at-risk children should receive 400 IU vitamin D daily; if compliance is poor, an annual dose of 150 000 IU may be considered. &bull; Treatment of vitamin D deficiency involves giving ergocalciferol or cholecalciferol for 3 months (1000 IU/day if &lt; 1 month of age; 3000 IU/ day if 1-12 months of age; 5000 IU/day if &gt; 12 months of age). &bull; High-dose bolus therapy (300 000-500 000 IU) should be considered for children over 12 months of age if compliance or absorption issues are suspected.<br /

Antibiotic prophylaxis and recurrent urinary tract infection in children

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