Assessing Predictive Performance of Published Population Pharmacokinetic Models of Intravenous Tobramycin in Pediatric Patients.

Several population pharmacokinetic models describe the dose-exposure relationship of tobramycin in pediatric patients. Before the implementation of these models in clinical practice for dosage adjustment, their predictive performance should be externally evaluated. This study tested the predictive performance of all published population pharmacokinetic models of tobramycin developed for pediatric patients with an independent patient cohort. A literature search was conducted to identify suitable models for testing. Demographic and pharmacokinetic data were collected retrospectively from the medical records of pediatric patients who had received intravenous tobramycin. Tobramycin exposure was predicted from each model. Predictive performance was assessed by visual comparison of predictions to observations, by calculation of bias and imprecision, and through the use of simulation-based diagnostics. Eight population pharmacokinetic models were identified. A total of 269 concentration-time points from 41 pediatric patients with cystic fibrosis were collected for external evaluation. Three models consistently performed best in all evaluations and had mean errors ranging from -0.4 to 1.8 mg/liter, relative mean errors ranging from 4.9 to 29.4%, and root mean square errors ranging from 47.8 to 66.9%. Simulation-based diagnostics supported these findings. Models that allowed a two-compartment disposition generally had better predictive performance than those that used a one-compartment disposition model. Several published models of the pharmacokinetics of tobramycin showed reasonable low levels of bias, although all models seemed to have some problems with imprecision. This suggests that knowledge of typical pharmacokinetic behavior and patient covariate values alone without feedback concentration measurements from individual patients is not sufficient to make precise predictions.

Antimicrobial stewardship activities: a survey of Queensland hospitals.

OBJECTIVE: In 2011, the Australian Commission on Safety and Quality in Health Care (ACSQHC) recommended that all hospitals in Australia must have an Antimicrobial Stewardship (AMS) program by 2013. Nevertheless, little is known about current AMS activities. This study aimed to determine the AMS activities currently undertaken, and to identify gaps, barriers to implementation and opportunities for improvement in Queensland hospitals. METHODS: The AMS activities of 26 facilities from 15 hospital and health services in Queensland were surveyed during June 2012 to address strategies for effective AMS: implementing clinical guidelines, formulary restriction, reviewing antimicrobial prescribing, auditing antimicrobial use and selective reporting of susceptibility results. RESULTS: The response rate was 62%. Nineteen percent had an AMS team (a dedicated multidisciplinary team consisting of a medically trained staff member and a pharmacist). All facilities had access to an electronic version of Therapeutic Guidelines: Antibiotic, with a further 50% developing local guidelines for antimicrobials. One-third of facilities had additional restrictions. Eighty-eight percent had advice for restricted antimicrobials from in-house infectious disease physicians or clinical microbiologists. Antimicrobials were monitored with feedback given to prescribers at point of care by 76% of facilities. Deficiencies reported as barriers to establishing AMS programs included: pharmacy resources, financial support by hospital management, and training and education in antimicrobial use. CONCLUSIONS: Several areas for improvement were identified: reviewing antimicrobial prescribing with feedback to the prescriber, auditing, and training and education in antimicrobial use. There also appears to be a lack of resources to support AMS programs in some facilities. WHAT IS KNOWN ABOUT THE TOPIC?: The ACSQHC has recommended that all hospitals implement an AMS program by 2013 as a requirement of Standard 3 (Preventing and Controlling Healthcare-Associated Infections) of the National Safety and Quality Health Service Standards. The intent of AMS is to ensure appropriate prescribing of antimicrobials as part of the broader systems within a health service organisation to prevent and manage healthcare-associated infections, and improve patient safety and quality of care. This criterion also aligns closely with Standard 4: Medication Safety. Despite this recommendation, little is known about what AMS activities are undertaken in these facilities and what additional resources would be required in order to meet these national standards. WHAT DOES THE PAPER ADD?: This is the first survey that has been conducted of public hospital and health services in Queensland, a large decentralised state in Australia. This paper describes what AMS activities are currently being undertaken, identifies practice gaps, barriers to implementation and opportunities for improvement in Queensland hospitals. WHAT ARE THE IMPLICATIONS FOR PRACTITIONERS?: Several areas for improvement such as reviewing antimicrobial prescribing with feedback to the prescriber, auditing, and training and education in antimicrobial use have been identified. In addition, there appears to be a lack of resources to support AMS programs in some facilities.

Evaluation of the stability of ceftazidime/avibactam in elastomeric infusion devices used for outpatient parenteral antimicrobial therapy utilizing a national stability protocol framework.

Objectives: To evaluate the stability of ceftazidime/avibactam in elastomeric infusers, utilizing the UK's Yellow Cover Document (YCD) stability testing framework, in conditions representative of OPAT practice. Methods: Ceftazidime/avibactam was reconstituted with sodium chloride 0.9% (w/v) in two elastomeric infusers at concentrations (dose) levels of 1500/375, 3000/750 and 6000 mg/1500 mg in 240 mL. The infusers were exposed to a fridge storage (2°C-8°C) for 14 days followed by 24 h in-use temperature (32°C). Results: After 14 days of fridge storage and subsequent 24 h exposure to 32°C, mean ±â€ŠSD of ceftazidime percent remaining was 75.5% ±â€Š1.8%, 79.9% ±â€Š1.1%, 82.4% ±â€Š0.6%, for Easypump, and 81.7% ±â€Š1.2%, 82.5% ±â€Š0.5%, 85.4% ±â€Š1.1% for Dosi-Fuser devices at the high, intermediate and low doses tested, respectively. For avibactam, mean ±â€ŠSD percent remaining was 83.2% ±â€Š1.8%, 87.4% ±â€Š2.0%, 93.1% ±â€Š0.9% for Easypump, and 85.1% ±â€Š2.0%, 86.7% ±â€Š0.1%, 92.5% ±â€Š0.1% for Dosi-Fuser devices. The cumulative amount of pyridine generated in the devices ranged from 10.4 mg at low dose to 76.9 mg at high dose. Regression-based simulation showed that the degradation of both ceftazidime and avibactam was <10% for at least 12 h of the running phase, if stored in a fridge for not more than 72 h prior to in-use temperature exposure. Conclusions: Whilst not meeting the strict UK YCD criteria for ≤5% degradation, ceftazidime/avibactam may be acceptable to administer as a continuous 12 hourly infusion in those territories where degradation of ≤10% is deemed acceptable.

Building on Antimicrobial Stewardship Programs Through Integration with Electronic Medical Records: The Australian Experience.

Antimicrobial stewardship (AMS) is well established in Australian hospitals. Electronic medical record (EMR) implementation has lagged in Australia, with two Healthcare Information and Management Systems Society (HIMSS) Stage 6 hospitals and one Stage 7 hospital as of September 2020. Specific barriers faced by AMS teams with paper-based prescribing and medical records include real-time identification of antimicrobials orders; the ability to prospectively monitor antimicrobial use; and the integration of fundamental point of prescribing AMS principles into routine clinical practice. There are few local guidelines to assist Australian hospitals and AMS teams beyond "out of the box" EMR functionality. EMR implementation has enormous potential to positively impact AMS teams through more efficient workflows and the ability to expand the reach and coverage of AMS activities. There are inevitable limitations associated with EMR implementation that must be considered. In this paper, four Australian hospitals share their experience with EMR roll out, AMS customisation and how they have overcome specific barriers in local AMS practice.