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BACKGROUND: Optimising the management of vancomycin by achieving target therapeutic concentrations early during therapy has been associated with reduced mortality and morbidity. Despite the availability of guidelines and training, the management of vancomycin remains suboptimal. OBJECTIVES: The primary outcome was the development of interventions and associated implementation strategies to optimise the management of vancomycin therapy. This paper describes how co-design process was used to build a theory informed intervention package, which was implemented across a wide range of in-patient hospital settings in Queensland, Australia. METHODS: This multiple methods study was conducted in four phases: 1) a baseline audit to identify the nature of the problem and associated determinants informed by stakeholder interviews 2) mapping these findings to the Theoretical Domains Framework (TDF) to identify behavioural correlates and modifiers 3) prioritising the behavioural modifiers and associated implementation strategies to inform a protype of the intervention in a series of co-design sessions and 4) implementing and evaluating the intervention package. The study was conducted across the four teaching hospitals in a large Queensland Hospital and Health Service across multiple healthcare disciplines namely nurses, doctors, and pharmacists. This intervention package was subsequently implemented across Queensland Health with the support of the local champions under the guidance of the steering group. RESULTS: Clinicians identified that a multifaceted intervention package and training which can be tailored to the health-care professional disciplines, would be best suited to shift clinician behaviour to align with guidelines. The findings from the co-design process aligned with theory-informed intervention package. Each of the intervention strategies varied in their frequency and popularity of use. CONCLUSIONS: The use of theory-informed and participatory approach assisted with the intervention development process and aligned the intervention content with the priorities of stakeholders. The TDF provided a structured process for developing intervention content which is both acceptable and useful to stakeholders and may improve the management of vancomycin.

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BACKGROUND: The area under the curve (AUC) to minimum inhibitory concentration (MIC) ratio is proposed as a therapeutic drug-monitoring parameter for dosing vancomycin continuous infusion in methicillin-resistant Staphylococcus aureus (MRSA) infection. Individualised pharmacokinetic-pharmacodynamic (PK/PD) calculation of AUC24 may better represent therapeutic dosing than current Therapeutic Drug Monitoring (TDM) practices, targeting a Steady State Concentration of 15-25 mg/L. AIM: To compare real world TDM practice to theoretical, individualised, PK/PD target parameters utilising Bayesian predictions to steady state concentrations (Css) for outpatients on continuous vancomycin infusions. METHOD: A retrospective single centre study was conducted at a tertiary hospital on adult patients, enrolled in an outpatient parenteral antimicrobial therapy (OPAT) program, receiving vancomycin infusions for MRSA infection. Retrospective Bayesian dosing was modelled to target PK/PD parameters and compared to real world data. RESULTS: Fifteen patients were evaluated with 53% (8/15) achieved target CSS during hospitalisation, and 83% (13/15) as outpatient. Median Bayesian AUC/MIC was 613 mg.h/L with CSS 25 mg/L. Patients suffering an Acute Kidney Injury (33%) had higher AUC0-24/MIC values. Retrospective Bayesian modelling demonstrated on median 250 mg/24 h lower doses than that administered was required (R2 = 0.81) which achieved AUC24/MIC median 444.8 (range 405-460) mg.h/L and CSS 18.8 (range 16.8-20.4) mg/L. CONCLUSION: Bayesian modelling could assist in obtaining more timely target parameters at lower doses for patients receiving continuous vancomycin infusion as part of an OPAT program, which may beget fewer adverse effects. Utilisation of personalised predictive modelling may optimise vancomycin prescribing, achieving earlier target concentrations as compared to empiric dosing regimens.

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OBJECTIVES: Little is known about the benefits of timely switch from intravenous (IV) to oral antibiotic therapy in children. We evaluated the appropriateness of IV-to-oral switch of antibiotic therapy in remote and regional areas of Australia following the implementation of a multifaceted package of interventions. METHODS: The intervention package, including clinician guidelines, medication review stickers, patient information leaflets and educational resources, was implemented in seven facilities in Queensland, Australia. Children with community-acquired pneumonia and skin and soft-tissue infections were switched to oral therapy if they met the required 'IV-to-oral switch' criteria. Data were collected for a 7-month period from May to November for the baseline (2018) and intervention (2019) phases. RESULTS: A total of 357 patients were enrolled in the study, including 178 in the baseline phase and 179 in the intervention phase. The percentage of patients who switched to oral therapy or stopped IV antibiotics, within 24 h of eligibility, increased from 87.6% (156/178) in the baseline phase to 97.2% (174/179) in the intervention phase (P = 0.003). The average number of extra IV days decreased from 0.45 days in the baseline period to 0.18 days in the intervention period (P < 0.001). The median patient length of stay was 2 days for both phases. The only adverse events recorded were line-associated infiltration, with a decrease from 34.3% (61/178) (baseline) to 17.9% (32/179) (intervention) (P < 0.001). CONCLUSION: A multifaceted intervention package to enhance timely IV-to-oral switch of antibiotic therapy for children in remote and regional facilities is effective.

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A significant portion of healthcare takes place in small hospitals, and many are located in rural and regional areas. Facilities in these regions frequently do not have adequate resources to implement an onsite antimicrobial stewardship programme and there are limited data relating to their implementation and effectiveness. We present an innovative model of providing a specialist telehealth antimicrobial stewardship service utilising a centralised service (Queensland Statewide Antimicrobial Stewardship Program) to a rural Hospital and Health Service. Results of a 2-year post-implementation follow-up showed an improvement in adherence to guidelines [33.7% (95% CI 27.0-40.4%) vs. 54.1% (95% CI 48.7-59.5%)] and appropriateness of antimicrobial prescribing [49.0% (95% CI 42.2-55.9%) vs. 67.5% (95% CI 62.7-72.4%) (P < 0.001). This finding was sustained after adjustment for hospitals, with improvement occurring sequentially across the years for adherence to guidelines [adjusted odds ratio (aOR) = 2.44, 95% CI 1.70-3.51] and appropriateness of prescribing (aOR = 2.48, 95% CI 1.70-3.61). There was a decrease in mean total antibiotic use (DDDs/1000 patient-days) between the years 2016 (52.82, 95% CI 44.09-61.54) and 2018 (39.74, 95% CI 32.76-46.73), however this did not reach statistical significance. Additionally, there was a decrease in mean hospital length of stay (days) from 2016 (3.74, 95% CI 3.08-4.41) to 2018 (2.55, 95% CI 1.98-3.12), although this was not statistically significant. New telehealth-based models of antimicrobial stewardship can be effective in improving prescribing in rural areas. Programmes similar to ours should be considered for rural facilities.

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BACKGROUND: Clinicians who work in primary care are potentially the most influential healthcare professionals to address the problem of antibiotic resistance because this is where most antibiotics are prescribed. Despite a number of evidence based interventions targeting the management of community infections, the inappropriate antibiotic prescribing rates remain high. DISCUSSION: The question is how can appropriate prescribing of antibiotics through the use of Antimicrobial Stewardship (AMS) programs be successfully implemented in primary care. We discuss that a top-down approach utilising a combination of strategies to ensure the sustainable implementation and uptake of AMS interventions in the community is necessary to support clinicians and ensure a robust implementation of AMS in primary care. Specifically, we recommend a national accreditation standard linked to the framework of Core Elements of Outpatient Antibiotic Stewardship, supported by resources to fund the implementation of AMS interventions that are connected to quality improvement initiatives. This article debates how this can be achieved. The paper highlights that in order to support the sustainable uptake of AMS programs in primary care, an approach similar to the hospital and post-acute care settings needs to be adopted, utilising a combination of behavioural and regulatory processes supported by sustainable funding. Without these strategies the problem of inappropriate antibiotic prescribing will not be adequately addressed in the community and the successful implementation and uptake of AMS programs will remain a dream.

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The optimisation of antibiotic dosing therapy with therapeutic drug monitoring is widely recommended. The aim of therapeutic drug monitoring is to help the clinician to achieve target pharmacokinetic/pharmacodynamic parameters, maximising efficacy and minimising toxicity. Computerised programs, utilising the Bayesian estimation procedures, are able to achieve target concentrations in a greater percentage of patients earlier in the course of therapy compared to linear regression analysis and population methods. This article summarises various methods for dose optimisation of antibiotics with a focus on Bayesian programs.

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Vancomycin remains a clinically useful antibiotic despite the advent of several alternative drugs. Optimising vancomycin therapy with therapeutic drug monitoring is widely recommended. The aim of therapeutic drug monitoring is to help the clinician to achieve target pharmacodynamic parameters in the case of vancomycin, an area under the concentration time curve/minimum inhibitory concentration ratio of ≥400. Vancomycin monitoring methods can be categorised into four categories: empiric trough concentrations; linear regression analysis (one-compartment model), population methods and Bayesian estimation procedures. Although the empiric trough concentrations and population methods are easy to use and require minimal resources, there are large differences in the published vancomycin model parameters. This demonstrates that there is great variance in pharmacokinetic parameters between the models and a single vancomycin model cannot be applied to all patient populations. The linear regression and Bayesian methods recommended more accurate dosage regimens; however, they require additional resources such as information technology and healthcare personnel with background training in pharmacokinetics. The Bayesian methods offered additional advantages such as calculation of doses based on a single-serum concentration and optimisation of the patient's previous pharmacokinetic data to determine subsequent dosage regimens. Computerised programs, utilising the Bayesian estimation procedures, are able to achieve target concentrations in a greater percentage of patients earlier in the course of therapy than the empiric trough concentrations and population methods. We recommend the use of these programs providing there is appropriate expertise available to make appropriate recommendations.

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The new Australian Therapeutic Guidelines: Antibiotic, version 14 have revised the recommendations for the use and monitoring of aminoglycosides. The guidelines have clear distinctions between empirical and directed therapy as well as revised recommendations about the monitoring of aminoglycosides. This has led many clinicians to review their current practice with regard to the use of aminoglycosides. This review summarizes why aminoglycosides are still a valid treatment option and discusses the rationale for current dosing regimens in Gram-negative infections. In particular it focuses on the various methods for monitoring aminoglycosides that are currently being used. The aminoglycoside monitoring methods can be categorized into three groups: linear regression analysis (one compartment model), population methods and Bayesian estimation procedures. Although the population methods are easy to use and require minimal resources they can recommend clinically inappropriate doses as they have constant pharmacokinetic parameters and are not valid in special population groups, that is, renal impairment. The linear regression and Bayesian methods recommend more accurate dosage regimens; however, they require additional resources, such as information technology and healthcare personnel with background training in pharmacokinetics. The Bayesian methods offer additional advantages, such as calculation of doses based on a single serum concentration and optimization of the patient's previous pharmacokinetic data, in order to determine subsequent dosage regimens. We recommend the Bayesian estimation procedures be used, wherever feasible. However, they require the expertise of healthcare practitioners with a good understanding of pharmacokinetic principles, such as clinical pharmacists/clinical pharmacologists, in order to make appropriate recommendations.

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This study reviews whether patients with artificial joints need antibiotic cover for dental treatment. Generally in Australia the practice has developed of giving most patients with artificial joints antibiotic prophylaxis for a wide range of dental procedures. This is partly on anecdotal grounds, partly historical and partly for legal concerns. It has been encouraged by some guidelines. Scientifically, the risk and the benefit of each step in the process needs to be analysed. This review shows that the risk of an artificial joint becoming infected from a bacteraemia of oral origin is exceedingly low whereas the risk of an adverse reaction to the antibiotic prophylaxis is higher than the risk of infection. If all patients with artificial joints receive antibiotic prophylaxis then more will die from anaphylaxis than develop infections. Factors which balance the risk benefit are if the patient is seriously immunocompromised, if the joint prosthesis is failing or chronically inflamed and if the dental procedures, such as from extractions and deep periodontal scaling, produce high level bacteraemias. Recommendations to rationalize antibiotic prophylaxis for patients with artificial joints are presented.

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Some cardiac conditions require antibiotic prophylaxis for some types of dental treatment to reduce the risk of infective endocarditis (IE). All medical and dental practitioners are familiar with this practice but tend to use different regimens in apparently similar circumstances. Generally, the trend has been to prescribe antibiotics if in doubt. This review explores the evidence for antibiotic prophylaxis to prevent IE: does it work and is it safe? The changing nature of IE, the role of bacteraemia of oral origin and the safety of antibiotics are also reviewed. Most developed countries have national guidelines and their points of similarity and difference are discussed. One can only agree with the authority who describes antibiotic guidelines for endocarditis as being 'like the Dead Sea Scrolls, they are fragmentary, imperfect, capable of various interpretations and (mainly) missing!' Clinical case-controlled studies show that the more widely antibiotics are used, the greater the risk of adverse reactions exceeding the risk of IE. However, the consensus is that antibiotic prophylaxis is mandatory for a small number of high-risk cardiac and high-risk dental procedures. There are a large number of low-risk cardiac and dental procedures in which the risk of adverse reactions to the antibiotics exceeds the risk of IE, where prophylaxis should not be provided. There is an intermediate group of cardiac and dental procedures for which careful individual evaluation should be made to determine whether IE or antibiotics pose the greater risk. These categories are presented. All medical and dental practitioners need to reconsider their approach in light of these current findings.

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The purpose of this study was to evaluate the effectiveness of early treatment with erythropoietin (EPO) in two different treatment regimes (high vs. low dose) in comparison to the conventional treatment of packed red blood cell (PRBC) transfusions in the management of anaemia of prematurity in a country with limited resources. An open controlled trial was conducted on 93 preterm infants (7 days postnatal age, 900-1500 g birthweight). Patients were randomly assigned either to a low dose (250 IU/kg), a high dose (400 IU/kg), or a control group. EPO was administered subcutaneously three times a week and all infants received 6 mg/kg iron orally from study entry to endpoint of therapy. Haematological parameters were measured and compared. The success was defined as an absence of transfusions and a haematocrit that did not fall below 30 per cent during the time period that the infants were in the study. The three groups were statistically comparable at study entry with respect to gestational age, birthweight, Apgar scores, and haematological values. Over the period that the infants were in the study, 75 per cent of the low dose group and 71 per cent of the high dose group met the criteria for success compared with 40 per cent in the control group (p < 0.001). However, there was no significant difference in the number of transfusions when the low and high EPO dose groups (9.5 per cent) were combined and compared with the control group (26.7 per cent) p = 0.0587. It was concluded that in stable infants, 900-1500 g, where phlebotomy losses are minimized and stringent transfusion guidelines are adhered to, EPO does not significantly decrease the number of transfusions. A conservative approach in the management of anaemia of prematurity, is a viable alternative in areas with limited resources.

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This study compared hematological reference ranges in black very low birth weight infants to previously published values established predominantly on white subjects. Ninety-four healthy, black, premature babies with a birth weight of 800 to 1500 g at 2-7 days of age were enrolled as part of a study comparing blood transfusions and high- versus low-dose recombinant erythropoietin in anaemia of prematurity. Peripheral venous blood was collected for a full blood count and differential, fetal hemoglobin and erythropoietin levels. The hematological parameters observed in black very low birth weight neonates are similar to previously published reference ranges, except that lower limits of normal were observed for hemoglobin and the red cell indices.

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OBJECTIVE: To compare the delivery of an albuterol metered-dose inhaler (MDI) (Ventolin) via an Aerochamber (Monaghan) with an inline adapter (Medicomp Straight Swivel) in an in vitro infant lung model. METHODS: An in vitro infant lung model was modified to compare the delivery of albuterol MDI 10 inhalations via an Aerochamber with an inline adapter. The adapter and Aerochamber were placed at the endotracheal tube. A 1000 mL intravenous bag filled with 500 mL deionized water was attached to a 3.5 mm endotracheal tube (10 cm length). An Infant Bear Cub ventilator was used at the following settings: positive inspiratory pressure 20 cm H2O, intermittent mandatory ventilation 40 breaths/min, positive end expiratory pressure 4 cm H2O, and inspiratory time 0.5 second. Each device was run at least 10 times and assayed in duplicate by HPLC. An unpaired Student's t-test was used to analyze the statistical significance of the data. RESULTS: There was significantly greater delivery of albuterol with the Aerochamber (19.49 +/- 7.23 microg; 2.17% +/- 0.8%) as compared with an inline adapter (1.0625 +/- 1.36 microg; 0.12% +/- 0.15%) (p = 0.001). CONCLUSIONS: The Aerochamber provides a greater delivery of albuterol metered-dose inhalations to the lung than the inline adapter in an in vitro infant lung model.

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OBJECTIVE: To evaluate drug delivery to the lungs of nebulized and metered-dose inhalers (MDIs) in an in vitro infant lung model. METHODS: An in vitro lung model was modified to study drug delivery. A 1000 mL intravenous bag filled with 500 mL deionized water was attached to a 3.5 mm (12 cm length) endotracheal tube. An inline Marquest Whisper Jet infant circuit nebulizer system delivered 2.5 mg/3 mL albuterol sulfate inhalation solution (Ventolin nebules) at a flow rate of 5 L/min. An Aerochamber (Monaghan) was placed at the endotracheal tube for the delivery of the MDIs. Albuterol MDI (Ventolin) 10 inhalations and beclomethasone MDI (Beclovent) 20 inhalations were delivered. A Servo 900C (Siemens-Elma) was used at the following ventilator settings: positive inspiratory pressure 30 cm H2O), intermittent mandatory ventilation 40 breaths/min, positive end expiratory pressure 4 cm H2O, inspiratory time 0.4 sec. Each formulation was run at least 10 times and assayed in duplicate by HPLC. An unpaired Student's t-test was used to analyze the statistical significance of the data. RESULTS: There was a significantly greater percentage of drug delivery with MDI albuterol (1.96 +/- 0.50) as compared with nebulized albuterol (1.26 +/- 0.37) (p = 0.002) or beclomethasone diproprionate (0.51 +/- 0.24) (p = 0.001). CONCLUSIONS: Albuterol MDI provides a more efficient delivery of drug to the lung as compared with nebulized albuterol and MDI beclomethasone diproprionate.

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Bronchopulmonary dysplasia has been well described in premature infants requiring mechanical ventilation. Systemic steroids are one of many treatment modalities used in the management of these infants, but these agents have been associated with a number of adverse effects. Aerosolized therapy has been proposed as an alternative in order to minimize the systemic complications that occur with the parenteral route. The initial reports of inhaled steroids, although limited, have shown promising results with minimal side effects. This article addresses the mechanism of action, the role in therapy, and potential complications associated with the use of inhaled steroids in the treatment of bronchopulmonary dysplasia.

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A case of warfarin-induced intramural hematoma and hemorrhagic infarction of the small intestine is described, and the literature on this adverse effect is reviewed. A 32-year-old white woman who had been receiving warfarin and carbamazepine came to a clinic complaining of lower back and stomach pain. She had a history of iliofemoral deep venous thromboses and seizures. A pelvic sonogram showed a large quantity of fluid present. Her prothrombin time (PT) was 29.2 sec. Her hemoglobin concentration and hematocrit were within the normal ranges. The patient was admitted to the hospital when her back pain increased and she vomited. The warfarin was discontinued. On day 5 the patient was still having abdominal pain and nausea. Her hemoglobin concentration and hematocrit had fallen to 6.6 g/dL and 20%, although her PT had decreased to 12.5 sec. On the same day, the patient underwent an exploratory laparotomy, and an indurated and ischemic area of jejunum was found and resected. The pathology report indicated the presence of hemorrhage and infarction consistent with an anticoagulant-related disorder. About 100 cases of intramural hematoma of the small intestine induced by anticoagulant therapy have been reported. Most patients are white males about 60 years of age. The sites most frequently involved are the duodenum and proximal jejunum. Symptoms include constipation, nausea, vomiting, and abdominal pain. Laboratory test and radiological findings are fairly nonspecific, but when found together in a patient receiving an anticoagulant, the diagnosis can be made with some confidence. Management may be complicated by the bleeding disorder, the intestinal obstruction if present, and the original indication for warfarin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

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Of total of 149 questionnaires distributed to parents, ninety-one were completed and returned (61.1 percent). Overall, six children reported side-effects, including nausea and vomiting, either immediately or within one hour following treatment. Age and weight were not factors in experiencing side-effects.

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