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.

Antimicrobial stewardship in Victorian hospitals: a statewide survey to identify current gaps.

OBJECTIVE: To determine antimicrobial stewardship (AMS) activities currently being undertaken at Victorian hospitals, identifying gaps when assessed against the Australian Commission on Safety and Quality in Health Care criteria for effective AMS. DESIGN, SETTING AND PARTICIPANTS: A survey open to all Victorian health services, conducted between January and March 2012. MAIN OUTCOME MEASURES: Availability of the endorsed prescribing guidelines, antimicrobial prescribing policies, formularies, approval systems for restricted antimicrobials, procedures for postprescription review, auditing and selective reporting of sensitivities. RESULTS: Response rates were 96.4% for public health services and 67.7% for private hospitals. Guidelines were available at all public and 88.1% of private hospitals, and 90.6% of public metropolitan, 45.7% of public regional and 21.4% of private hospitals had antimicrobial prescribing policies. Antimicrobial approval systems were used in 93.8% of public metropolitan, 17.3% of public regional and 4.8% of private hospitals. Prescribing audits were conducted by 62.5% of public metropolitan, 35.8% public regional and 52.4% of private hospitals. Nearly all hospitals had selective laboratory reporting of antimicrobial sensitivities. Few hospitals had dedicated funding for AMS personnel. CONCLUSIONS: We identified wide differences between hospital AMS activities. Additional support for AMS is particularly required in the public regional and private hospital sectors, principally in the key areas of policy development, antimicrobial approval systems, prescription review and auditing. Further research is required to develop recommendations for implementation of AMS within the regional and private hospital settings.

A quality improvement initiative to improve adherence to national guidelines for empiric management of community-acquired pneumonia in emergency departments.

OBJECTIVE: The objective of this study was to improve the concordance of community-acquired pneumonia management in Australian emergency departments with national guidelines through a quality improvement initiative promoting concordant antibiotic use and use of a pneumonia severity assessment tool, the pneumonia severity index (PSI). DESIGN: and INTERVENTIONS: Drug use evaluation, a quality improvement methodology involving data collection, evaluation, feedback and education, was undertaken. Educational interventions included academic detailing, group feedback presentations and prescribing prompts. SETTING AND PARTICIPANTS: Data were collected on 20 consecutive adult community-acquired pneumonia emergency department presentations by each hospital for each of three audits. MAIN OUTCOME MEASURES: Two process indicators measured the impact of the interventions: documented PSI use and concordance of antibiotic prescribing with guidelines. Comparisons were performed using a Chi-squared test. RESULTS: Thirty-seven hospitals, including public, private, rural and metropolitan institutions, participated. Twenty-six hospitals completed the full study (range: 462-518 patients), incorporating two intervention phases and subsequent follow-up audits. The baseline audit of community-acquired pneumonia management demonstrated that practice was varied and mostly discordant with guidelines. Documented PSI use subsequently improved from 30/518 (6%, 95% confidence interval [CI] 4-8) at baseline to 125/503 (25%, 95% CI 21-29; P < 0.0001) and 102/462 (22%, 95% CI 18-26; P < 0.0001) in audits two and three, respectively, while concordant antibiotic prescribing improved from 101/518 (20%, 95% CI 16-23) to 132/462 (30%, 95% CI 26-34; P < 0.0001) and 132/462 (29%, 95% CI 24-33; P < 0.001), respectively. CONCLUSIONS: Improved uptake of guideline recommendations for community-acquired pneumonia management in emergency departments was documented following a multi-faceted education intervention.

Identification of an antimalarial synthetic trioxolane drug development candidate.

The discovery of artemisinin more than 30 years ago provided a completely new antimalarial structural prototype; that is, a molecule with a pharmacophoric peroxide bond in a unique 1,2,4-trioxane heterocycle. Available evidence suggests that artemisinin and related peroxidic antimalarial drugs exert their parasiticidal activity subsequent to reductive activation by haem, released as a result of haemoglobin digestion by the malaria-causing parasite. This irreversible redox reaction produces carbon-centred free radicals, leading to alkylation of haem and proteins (enzymes), one of which--the sarcoplasmic-endoplasmic reticulum ATPase PfATP6 (ref. 7)--may be critical to parasite survival. Notably, there is no evidence of drug resistance to any member of the artemisinin family of drugs. The chemotherapy of malaria has benefited greatly from the semi-synthetic artemisinins artemether and artesunate as they rapidly reduce parasite burden, have good therapeutic indices and provide for successful treatment outcomes. However, as a drug class, the artemisinins suffer from chemical (semi-synthetic availability, purity and cost), biopharmaceutical (poor bioavailability and limiting pharmacokinetics) and treatment (non-compliance with long treatment regimens and recrudescence) issues that limit their therapeutic potential. Here we describe how a synthetic peroxide antimalarial drug development candidate was identified in a collaborative drug discovery project.

Alteration of the intravenous pharmacokinetics of a synthetic ozonide antimalarial in the presence of a modified cyclodextrin.

The pharmacokinetic profile and renal clearance of a novel synthetic ozonide antimalarial (1) was found to be significantly altered when intravenously administered to rats as a cyclodextrin-based formulation (0.1 M Captisol, a sulfobutylether beta-cyclodextrin derivative (SBE(7)-beta-CD)) compared to a cyclodextrin-free isotonic buffered glucose formulation. There was an 8.5-fold decrease in the steady-state blood volume of distribution, a 6.6-fold decrease in the mean residence time and a greater than 200-fold increase in renal clearance of 1 when administered in the cyclodextrin formulation. Analysis of the whole blood and plasma concentration profiles revealed an essentially constant blood to plasma ratio when 1 was administered in the cyclodextrin-free formulation, whereas this ratio changed as a function of time when administered in the presence of the cyclodextrin derivative. It is postulated that the observed differences were due to a very strong complexation interaction between 1 and the cyclodextrin, resulting in a slow dissociation of the complex in vivo, and altered distribution and excretion profiles. Preliminary studies using isothermal titration calorimetry (ITC) indicated that the association constant for the 1/Captisol complex was approximately two orders of magnitude higher than reported for typical drug/cyclodextrin complexes.

New manzamine alkaloids from an Indo-Pacific sponge. Pharmacokinetics, oral availability, and the significant activity of several manzamines against HIV-I, AIDS opportunistic infections, and inflammatory diseases.

12,28-Oxamanzamine A (1), 12,28-oxa-8-hydroxymanzamine A (2), and 31-keto-12,34-oxa-32,33-dihydroircinal A (3) were isolated from two collections of an Indo-Pacific sponge, and their structures were assigned on the basis of 1D and 2D NMR spectroscopic data. These compounds possess a novel manzamine-type ring system generated through a new ether bridge formed between carbons 12 and 28 or between carbons 12 and 34 of the typical manzamine structure and add to our growing understanding of manzamine SAR and metabolism. Based on molecular modeling studies, the formation of these oxidation products is highly sterically favored. The potent antiinflammatory, antifungal, and anti-HIV-1 activity for a number of previously reported manzamines is also presented in addition to the pharmacokinetic studies of manzamine A (5). Oral and intravenous pharmacokinetic studies of manzamine A in rats indicated the compound to have low metabolic clearance, a reasonably long pharmacokinetic half-life, and good absolute oral bioavailability of 20.6%, which supports the value of these compounds as potential leads for further preclinical assessment and possible development.

Orally active antimalarials: hydrolytically stable derivatives of 10-trifluoromethyl anhydrodihydroartemisinin.

New fluoroartemisinin derivatives containing polar or water-soluble functionalities at C-16 (11a-j, 12a-g) were synthesized using the key intermediate 16-bromo-10-trifluoromethyl anhydrodihydroartemisinin 10. The substitution reaction from 10 was more selective than that from the nonfluorinated parent bromide; the allylic bromide 10 underwent no allylic rearrangement and provided only nucleophilic substitution products in high yields with N-, O-, and C-nucleophiles. Among them, amines 11a-c appeared to be highly in vivo efficient antimalarials on mice infected with Plasmodium berghei, more than the reference sodium artesunate 1d. In particular, the most effective piperazinoethanol derivative 11b cured all mice after oral treatment at a dose lower than 10 mg/kg. Further pharmacokinetic studies showed that the bioavailability in rats following oral administration was 25 times greater for 11b than for artemether 1b.

Empiric management of community-acquired pneumonia in Australian emergency departments.

OBJECTIVE: To describe empiric community-acquired pneumonia (CAP) management in Australian hospital emergency departments (EDs) and evaluate this against national guidelines, including use of the pneumonia severity index and antibiotic selection. DESIGN: A multicentre, cross-sectional, retrospective audit, April 2003 to February 2005. SETTING: 37 Australian hospitals: 22 principal referral hospitals, six large major city hospitals, four large regional hospitals, four medium hospitals and one private hospital. PARTICIPANTS: Adult patients with a diagnosis of CAP made in the ED. Data on 20 consecutive CAP ED presentations were collected in participating hospitals. OUTCOME MEASURES: Documented use of the pneumonia severity index, initial antibiotic therapy prescribed in the ED, average length of stay, inpatient mortality, and concordance with national guidelines. RESULTS: 691 CAP presentations were included. Pneumonia severity index use was documented in 5% of cases. Antibiotic therapy covering common bacterial causes of CAP was prescribed in 67% of presentations, although overall concordance with national guidelines was 18%. Antibiotic prescribing was discordant due to inadequate empiric antimicrobial cover, allergy status (including contraindication to penicillin), inappropriate route of administration and/or inappropriate antibiotic choice according to recommendations. There was no significant difference between concordant and discordant antibiotic prescribing episodes in average length of stay (5.0 v 5.7 days; P = 0.22) or inpatient mortality (1.6% v 4.1%; chi2 = 1.82; P = 0.18). CONCLUSIONS: Antibiotic therapy for CAP prescribed in Australian EDs varied. Concordance with national CAP guidelines was generally low. Targeted interventions are required to improve concordance.