The Impact of a Multifaceted Tertiary Pediatric Hospital's Antimicrobial Stewardship Service.

BACKGROUND: Antimicrobials are the most commonly prescribed drug class in children. Overuse through inappropriate prescribing is a key driver of antimicrobial resistance and is recognized as one of the top 10 threats to global health by the World Health Organization. METHODS: A prospective observational cohort study was performed following implementation of a multifaceted Antimicrobial Stewardship (AMS) program (January 2014 to December 2020). Data were collected on AMS and "handshake" ward rounds from patient information sources and directly from clinicians responsible for patient care. Primary outcomes include appropriateness of therapy (drug, dose, antimicrobial spectrum, duration and route), compliance with prescribing guidelines, antimicrobial expenditure, use of high-priority antimicrobials and duration of hospitalization. We compared outcomes across 3 time periods; January 2014-December 2015, January 2016-December 2017 and January 2018-December 2020. RESULTS: The appropriateness of individual antimicrobial orders improved across the study periods from 6111/7040 (79.4%) in the first 2 years following implementation of the AMS program to 17,819/19,229 (92.3%) in the latter period. Guideline compliance increased from 5426/7700 (70.5%) to 17,822/19,316 (92.3%). A reduction in overall antimicrobial expenditure (34% reduction, equivalent to $12.52 per bed day) and a decrease in antifungal expenditure (37% reduction, equivalent to $5.56 per bed day) was observed across the time periods. CONCLUSIONS: This study quantifies a comprehensive pediatric AMS program's sustained impact on reducing inappropriate antimicrobial use and expenditure and improving compliance with guidelines. The effectiveness of these interventions has been demonstrated and should be considered by institutions seeking to improve rational antimicrobial use in children.

Clinical care of children and adolescents with COVID-19: recommendations from the National COVID-19 Clinical Evidence Taskforce.

INTRODUCTION: The epidemiology and clinical manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are different in children and adolescents compared with adults. Although coronavirus disease 2019 (COVID-19) appears to be less common in children, with milder disease overall, severe complications may occur, including paediatric inflammatory multisystem syndrome (PIMS-TS). Recognising the distinct needs of this population, the National COVID-19 Clinical Evidence Taskforce formed a Paediatric and Adolescent Care Panel to provide living guidelines for Australian clinicians to manage children and adolescents with COVID-19 and COVID-19 complications. Living guidelines mean that these evidence-based recommendations are updated in near real time to give reliable, contemporaneous advice to Australian clinicians providing paediatric care. MAIN RECOMMENDATIONS: To date, the Taskforce has made 20 specific recommendations for children and adolescents, including definitions of disease severity, recommendations for therapy, respiratory support, and venous thromboembolism prophylaxis for COVID-19 and for the management of PIMS-TS. CHANGES IN MANAGEMENT AS A RESULT OF THE GUIDELINES: The Taskforce currently recommends corticosteroids as first line treatment for acute COVID-19 in children and adolescents who require oxygen. Tocilizumab could be considered, and remdesivir should not be administered routinely in this population. Non-invasive ventilation or high flow nasal cannulae should be considered in children and adolescents with hypoxaemia or respiratory distress unresponsive to low flow oxygen if appropriate infection control measures can be used. Children and adolescents with PIMS-TS should be managed by a multidisciplinary team. Intravenous immunoglobulin and corticosteroids, with concomitant aspirin and thromboprophylaxis, should be considered for the treatment of PIMS-TS. The latest updates and full recommendations are available at www.covid19evidence.net.au.

Clinical experience with SUBA-itraconazole at a tertiary paediatric hospital.

BACKGROUND: Itraconazole remains a first-line antifungal agent for certain fungal infections in children, including allergic bronchopulmonary aspergillosis (ABPA) and sporotrichosis, but poor attainment of therapeutic drug levels is frequently observed with available oral formulations. A formulation of 'SUper BioAvailability itraconazole' (SUBA-itraconazole; Lozanoc®) has been developed, with adult studies demonstrating rapid and reliable attainment of therapeutic levels, yet paediatric data are lacking. OBJECTIVES: To assess the safety, efficacy and attainment of therapeutic drug levels of the SUBA-itraconazole formulation in children. METHODS: A single-centre retrospective cohort study was conducted, including all patients prescribed SUBA-itraconazole from May 2018 to February 2020. The recommended initial treatment dose was 5 mg/kg twice daily (to a maximum of 400 mg/day) rounded to the nearest capsule size and 2.5 mg/kg/day for prophylaxis. RESULTS: Nineteen patients received SUBA-itraconazole and the median age was 12 years. The median dose was 8.5 mg/kg/day and the median duration was 6 weeks. Indications included ABPA (16 patients), sporotrichosis (1), cutaneous fungal infection (1) and prophylaxis (1). Of patients with serum levels measured, almost 60% (10/17) achieved a therapeutic level, 3 with one dose adjustment and 7 following the initial dose. Adherence to dose-adjustment recommendations amongst the seven patients not achieving therapeutic levels was poor. Of patients with ABPA, 13/16 (81%) demonstrated a therapeutic response in IgE level. SUBA-itraconazole was well tolerated with no cessations related to adverse effects. CONCLUSIONS: SUBA-itraconazole is well tolerated in children, with rapid attainment of therapeutic levels in the majority of patients, and may represent a superior formulation for children in whom itraconazole is indicated for treatment or prevention of fungal infection.

Lessons learned from a hospital-wide review of blood stream infections for paediatric central line-associated blood stream infection prevention.

AIM: Bacteraemia episodes were assessed to calculate a hospital-wide central line-associated blood stream infection (CLABSI) rate per 1000 catheter-days. Secondary objectives were to describe risk factors, microbiology and outcomes of children with CLABSI. METHODS: A retrospective study was conducted at an Australian tertiary paediatric hospital in children <18 years who had blood culture sampling during the 2-year period, 2014-2015. All blood culture results were extracted from the hospital's laboratory information system. National Healthcare Safety Network Centres for Disease Control and Prevention definitions for bacteraemia classification were used. Central venous access device (CVAD) insertion and removal dates were obtained from a surgical electronic database and anaesthetic records and then manually validated. RESULTS: Of 11 774 processed blood culture bottles, 207 episodes of blood stream infection were observed. Eighty-five (41%) episodes were community-acquired bacteraemia (CA-B) and 122 (59%) health care-associated bacteraemia (HA-B), of which 73 (35%) were CLABSI. The hospital-wide CLABSI rate was 0.62 per 1000 catheter-days (95% confidence interval: 0.49-0.77). Conditions associated with CLABSI were malignancy (n = 45, 62%) and gastrointestinal failure (n = 6, 8%). Thirty-three (45%) CLABSI episodes developed in an outpatient setting. CONCLUSIONS: HA-B has a significant impact on child health, exceeding the number of CA-B at our hospital. Children with CVADs are vulnerable in both the inpatient and outpatient settings. Collecting robust data for a hospital-wide CLABSI rate is important to understand the full spectrum of paediatric CLABSI. The value of validating data using both electronic and manual methods is demonstrated.

Dose-Banding of Intravenous Piperacillin-Tazobactam in Pediatric Surgical Inpatients.

BACKGROUND: Antimicrobial doses in children are often prescribed by using an individually calculated dose per weight (e.g., mg/kg) or based on body surface area. Dosing errors are the most commonly reported medication errors in children. A "dose-banding" strategy is frequently used for some over-the-counter drugs to prevent dosing errors. It could also lead to efficiencies by enabling batch preparation of intravenous (IV) medications in hospitals. OBJECTIVES: To evaluate whether use of dose-banding for IV piperacillin-tazobactam results in acceptable dose variation from standard practice of individualized prescription of 100 mg/kg in children. METHODS: We conducted a historically controlled intervention study comparing prescriptions of IV piperacillin-tazobactam before vs. after introduction of dose-banding prescribing guidance for surgical inpatients weighing >5 kg and <16 years of age at the tertiary referral pediatric hospital in Western Australia. RESULTS: Dose-banding of IV piperacillin-tazobactam (with a maximum of 15% departure from the recommended milligram-per-weight dose of 100 mg/kg) resulted in similar overall variation of prescribed dose in comparison to individualized milligram-per-weight (non-dose-banded) prescribing. There was a trend toward fewer prescriptions with large variance (>30% variation from the 100-mg/kg dose) in the dose-banded compared to the non-dose-banded group (1/140 vs. 5/105; p = 0.09). CONCLUSIONS: Our study showed dose-banding of IV piperacillin-tazobactam resulted in acceptable variation when compared to individualized milligram-per-weight dosing in children. Prospectively designed controlled trials are warranted to determine whether dose-banding could reduce medication errors and optimize use of hospital resources. Implications for future practice could include faster batch preparation, shorter checking and dispensing time, and reduction in drug wastage.

The prevention, diagnosis and management of central venous line infections in children.

With advancing paediatric healthcare, the use of central venous lines has become a fundamental part of management of neonates and children. Uses include haemodynamic monitoring and the delivery of lifesaving treatments such as intravenous fluids, blood products, antibiotics, chemotherapy, haemodialysis and total parenteral nutrition (TPN). Despite preventative measures, central venous catheter-related infections are common, with rates of 0.5-2.8/1000 catheter days in children and 0.6-2.5/1000 catheter days in neonates. Central line infections in children are associated with increased mortality, increased length of hospital and intensive care unit stay, treatment interruptions, and increased complications. Prevention is paramount, using a variety of measures including tunnelling of long-term devices, chlorhexidine antisepsis, maximum sterile barriers, aseptic non-touch technique, minimal line accessing, and evidence-based care bundles. Diagnosis of central line infections in children is challenging. Available samples are often limited to a single central line blood culture, as clinicians are reluctant to perform painful venepuncture on children with a central, pain-free, access device. With the advancing evidence basis for antibiotic lock therapy for treatment, paediatricians are pushing the boundaries of line retention if safe to do so, due to among other reasons, often limited venous access sites. This review evaluates the available paediatric studies on management of central venous line infections and refers to consensus guidelines such as those of the Infectious Diseases Society of America (IDSA).