Making decisions about antibiotic use in the Australian primary healthcare sector

Introduction Australia is contributing to the global problem of antimicrobial resistance with one of the highest rates of antibiotic use amongst OECD countries. Data from the Australian primary healthcare sector suggests unnecessary antibiotics were prescribed for conditions that will resolve without it. If left unchecked, this will result in more resistant micro-organisms, against which antibiotics will be useless. There is a lack of understanding about what is influencing decisions to use antibiotics – what factors influences general practitioners (GPs) to prescribe antibiotics, consumers to seek antibiotics, and pharmacists to fill old antibiotic prescriptions? It is also not clear how these individuals trade-off between the possible benefits that antibiotics may provide in the immediate/short term, against the longer term societal risk of antimicrobial resistance. Method This project will investigate (a) what factors drive decisions to use antibiotics for GPs, pharmacists and consumers, and (b) how these individuals discount the future. Factors will be gleaned from published literature and from a qualitative phase using semi-structured interviews, to inform the development of Discrete Choice Experiments (DCEs). Three DCEs will be constructed – one for each group of interest – to allow investigation of which factors are more important in influencing (a) GPs to prescribe antibiotics, (b) consumers to seek antibiotics, and (c) pharmacists to fill legally valid but old or repeat prescriptions of antibiotics. Regression analysis will be conducted to understand the relative importance of these factors. A Time Trade Off exercise will be developed to investigate how these individuals discount the future, and whether GPs and pharmacists display the same extent of discounting the future, as consumers. Expected Results Findings from the DCEs will provide an insight into which factors are more important in driving decision making in antibiotic use for GPs, pharmacists and consumers. Findings from the Time Trade Off exercise will show what individuals are willing to trade for preserving the miracle of antibiotics. Conclusion The emergence of antibiotic resistance is inevitable. This research will expand on what is currently known about influencing desired behaviour change in antibiotic use, in the fight against antibiotic resistance. Real World Implications Research findings will contribute to existing national programs to bring about a reduction in inappropriate use of antibiotic in Australia. Specifically, influencing (1) how key messages and public health campaigns are crafted to increase health literacy, and (2) clinical education and empowerment of GPs and pharmacists to play a more responsive role as stewards of antibiotic use in the community.

Genome Sequence of Acinetobacter baumannii Strain A1, an Early Example of Antibiotic-Resistant Global Clone 1

Acinetobacter baumannii isolate A1 was recovered in the United Kingdom in 1982 and belongs to global clone 1 (GC1). Here, we present its complete 3.91-Mbp genome sequence, generated via a combination of short-read sequencing (Illumina), long-read sequencing (PacBio), and manual finishing.

Nutritional impact of antipseudomonas intravenous antibiotic courses in cystic fibrosis

Editor,—In their study of cystic fibrosis patients who were nutritionally assessed at the start and end of a 14 day period of home intravenous antibiotic treatment for chest disease, Vicet al concluded that increased weight was a result of increased fat storage.1 While this may in part be true, their methodology dictates caution in drawing conclusions....

Antibiotic resistance in Campylobacter jejuni and Campylobacter coli isolated from poultry in the South-East Queensland region

Objectives: The aim of this study was to determine the antimicrobial resistance patterns of 125 Campylobacter jejuni and 27 Campylobacter coli isolates from 39 Queensland broiler farms. Methods: Two methods, a disc diffusion assay and an agar-based MIC assay, were used. The disc diffusion was performed and interpreted as previously described (Huysmans MB, Turnidge JD. Disc susceptibility testing for thermophilic campylobacters. Pathology 1997; 29: 209–16), whereas the MIC assay was performed according to CLSI (formerly NCCLS) methods and interpreted using DANMAP criteria. Results: In both assays, no C. jejuni or C. coli isolates were resistant to ciprofloxacin or chloramphenicol, no C. coli were resistant to nalidixic acid, and no C. jejuni were resistant to erythromycin. In the MIC assay, no C. jejuni isolate was resistant to nalidixic acid, whereas three isolates (2.4%) were resistant in the disc assay. The highest levels of resistance of the C. jejuni isolates were recorded for tetracycline (19.2% by MIC and 18.4% by disc) and ampicillin (19.2% by MIC and 17.6% by disc). The C. coli isolates gave very similar results (tetracycline resistance 14.8% by both MIC and disc; ampicillin resistance 7.4% by MIC and 14.8% by disc). Conclusions: This work has shown that the majority of C. jejuni and C. coli isolates were susceptible to the six antibiotics tested by both disc diffusion and MIC methods. Disc diffusion represents a suitable alternative methodology to agar-based MIC methods for poultry Campylobacter isolates.

Conformation of antibiotic X-537A (lasalocid-A) and its calcium complex in acetonitrile solvent using circular dichroism spectroscopy

The calcium binding characteristics of antibiotic X-537A (lasalocid-A) in a lipophilic solvent, acetonitrile (CH3CN), have been studied using circular dichroism (CD) spectroscopy. The analysis of the data indicated that in this medium polar solvent, X-537A forms predominantly the charged complexes of stoichiometries 2:1 and 1:1, the relative amounts of the two being dependent on [Ca2+]. The conformation of the complexes, arrived at on the basis of the data, seem to indicate a rigid part encompassing Ca2+, liganded to 3 oxygens of the molecule, viz., the carbonyl, the substituted tetrahydrofuran ring and the substituted pyran ring oxygens (apart from possibly, the liganding provided by nitrogen atoms of the solvent molecules), and a flexible part consisting of the salicylic acid group of the molecule.

Crystal and molecular structure of the quinoxaline antibiotic analog TANDEM (des-N-tetramethyltriostin A)

The crystal structure of TANDEM (des-N-tetramethyltriostin A), a synthetic analogue of the quinoxaline antibiotic triostin A, has been determined independently at -135 and 7 'C and refined to R values of 0.088 and 0.147, respectively. The molecule has approximate 2-fold symmetry, with the quinoxaline chromophores and the disulfide cross-bridge projecting from opposite sides of the peptide ring. The quinoxaline groups are nearly parallel to each other and separated by about 6.5 A. The peptide backbone resembles a distorted antiparallel 13 ribbon joined by intramolecular hydrogen bonds N-H(LVal)--O(L-Ala). At low temperatures, the TANDEM molecule is surrounded by a regular first- and second-order hydration sphere containing 14 independent water molecules. At room temperature, only the first-order hydration shell is maintained. Calculations of the interplanar separation of the quinoxaline groups as a function of their orientation with respect to the peptide ring support the viability of TANDEM to intercalate bifunctionally into DNA.

Antibiotic Sensitivity Testing

Respiratory bacterial pathogens in pigs are currently treated with antibiotics. Intervet - Schering Plough markets an antibiotic called Nurflor (Florfenicol) targeting respiratory pathogens. This project tests the effectiveness of this antibiotic against a series of respiratory pathogens. 6 isolates will be tested per serovar/strain and the isolates will be from 4 different farms using MIC testing. The sensitivity of Florfenicol will be compared to sensitivity of the organisms to Tilmicosin and Amoxicillin. Development of resistance to certain antibiotics have been reported, so it is important to have alternative antibiotics available to treat the respiratory pathogens on farms.

The persistence of biofilm-associated antibiotic resistance of Staphylococcus aureus isolated from clinical bovine mastitis cases in Australia

The aim of this investigation was to determine the persistence of biofilm-associated antibiotic resistance developed by methicillin-sensitive Staphylococcus aureus (MSSA), of different capsular types, during biofilm formation. Because of superiority of the tissue culture plate (TCP) over the Congo Red Agar (CRA) method for measuring biofilm formation, it was used to determine the persistence of the antibiotic resistance developed by the isolates in biofilms. The antibiotic resistance was found to persist for 3-4 wk post-propagation as planktonic subcultures. Interestingly, some strains even developed resistance to vancomycin and/or teicoplanin. However, no association of either biofilm formation or persistent antibiotic resistance with the major capsular phenotype was observed. These observations highlight the potential significance of (a) determining the antibiograms of S. aureus subcultured from biofilms developed in vitro using the TCP method as well as from planktonic cultures for formulation of an optimal therapeutic strategy, and (b) continuing to identify predominant non-capsular antigens contributing to biofilm formation, regardless of the capsular phenotype for the development of an effective potentially broad-spectrum vaccine for prevention of bovine mastitis caused by S. aureus.

Effect of the antitumor antibiotic chromomycin A3 on the humoral immune response in rats

Chromomycin A3 (250 mug/kg) suppressed the humoral immune response in rats against sheep erythrocytes when administered 48 h or later after antigenic stimulus. The antibiotic at this dose enhanced immunity when given along with or before antigen administration. The natural heterohemagglutinin levels in rabbits and guinea pigs were not affected by the antibiotic (10 mug/kg per day x 7).

Making decisions about antibiotic use in the Australian primary healthcare sector

Background Australia has one of the highest rates of antibiotic use amongst OECD countries. Data from the Australian primary healthcare sector suggests unnecessary antibiotics were prescribed for self-resolving conditions. We need to better understand what drives general practitioners (GPs) to prescribe antibiotics, consumers to seek antibiotics, and pharmacists to fill repeat antibiotic prescriptions. It is also not clear how these individuals trade-off between the possible benefits that antibiotics may provide in the immediate/short term, against the longer term societal risk of antimicrobial resistance. This project investigates what factors drive decisions to use antibiotics for GPs, pharmacists and consumers, and how these individuals discount the future. Methods Factors will be gleaned from published literature and from semi-structured interviews, to inform the development of Discrete Choice Experiments (DCEs). Three DCEs will be constructed – one for each group of interest – to allow investigation of which factors are more important in influencing (a) GPs to prescribe antibiotics, (b) consumers to seek antibiotics, and (c) pharmacists to fill legally valid but old or repeat prescriptions of antibiotics. Regression analysis will be conducted to understand the relative importance of these factors. A Time Trade Off exercise will be developed to investigate how these individuals discount the future. Results Findings from the DCEs will provide an insight into which factors are more important in driving decision making in antibiotic use for GPs, pharmacists and consumers. Findings from the Time Trade Off exercise will show what individuals are willing to trade for preserving the miracle of antibiotics. Conclusion Research findings will contribute to existing national programs to bring about a reduction in inappropriate use of antibiotic in Australia. Specifically, influencing how key messages and public health campaigns are crafted, and clinical education and empowerment of GPs and pharmacists to play a more responsive role as stewards of antibiotic use in the community.

What consumers think, do and say about antibiotic use

Objective The objectives of this study were to investigate (1) the attitudes and behaviours of Australian consumers in antibiotic use, and (2) their understanding of antibiotic resistance. Methods Semi-structured interviews were conducted with consumers in May/June 2015. Convenience sampling was used to recruit consumers between 18–54 years old. Thirty-two consumers were interviewed. Transcripts were analysed to identify themes. Lessons Learned Dominant themes for attitudes and behaviours regarding antibiotics were (a) avoidance of antibiotic use unless clinically warranted; (b) antibiotics were useful but “weakened the body”; and (c) use of complementary medicines as adjuncts to antibiotics or to strengthen the immune system. Key information needs were (a) unambiguous instructions from GPs when prescribed antibiotics, to avoid inappropriate medicine-taking behaviour; (b) rationale for antibiotic selection; and (c) treatment duration. Antibiotic resistance was conceptualised in three ways: as a property of the body (body becomes resistant to antibiotics); the medication (antibiotic no longer effective); and the bacteria (bacteria is resistant). Antibiotic resistance was perceived as an issue that would only affect the wider community in the future, although most recognised that it is a current challenge for hospitals. Personal good health and/or avoidance of antibiotics were perceived as insurance against being adversely affected by antibiotic resistance. Implications A structured survey (discrete choice experiment) will be developed from these findings to investigate how consumers trade-off on factors influencing antibiotic use. Public health campaigns promoting conservation of antibiotics can benefit from these findings.

Questionable antibiotic practices: Obtaining reliable estimates of consumer behaviours

Background: Significant recent attention has focussed on the role of antibiotic prescribing and usage with the aim of combating antibiotic resistance, a growing worldwide health concern. A significant gap in this literature concerns the consumption patterns and beliefs of consumers about antibiotics and their effects. We seek to remedy this gap by exploring a range of questionable antibiotic practices and obtaining reliable estimates of their prevalence as well as their normative status. Methods: We conducted an online survey of over 100 consumers. We used a new incentive compatible technique, the Bayesian Truth Serum (BTS), to elicit more truthful responding than standard self-report measures. We asked participants to indicate whether they engaged in a number of practices including whether they had: taken antibiotics when they are out of date and stored antibiotics at home for later use. We then sought estimates of the percentage of other patients (like them) who had engaged in each behaviour, as well as asking them among those patients who had, the percentage that would admit to having done so. We also asked about social acceptability and responsibility of the practices. Results: These results will show for each type of questionable practice how prevalent it is and whether consumers view it as both socially acceptable and socially responsible. We will gain the relative prevalence of each of these practices. Conclusion: These findings are of paramount importance in gaining a better understanding of consumers’ antibiotic consumption patterns. These will be vital for better targeting educational campaigns to lower inappropriate antibiotic consumption.

Benefits and challenges of antivirulence antimicrobials at the dawn of the post-antibiotic era

In April 2014, the World Health Organization announced the beginning of a post-antibiotic era and declared antimicrobial resistance (AMR) a public health priority demanding global action. If no action is taken, by 2050 AMR will kill more people each year than cancer, with 10 million estimated annual deaths at a cost of $100 trillion to the global economy. New therapies to tackle multidrug resistant bacterial pathogens are urgently needed. Unlike traditional antibiotics, antivirulence drugs inhibit bacterial virulence instead of growth promising to offer a new class of superior therapeutics that will be ‘evolution-proof’ and ‘tailored-spectrum’. This mini-review discusses the latest emerging evidence on the promised benefits of antivirulence drugs over conventional antibiotics, also highlighting the challenges in evaluating these properties for each of the diverse virulence targets that are currently under investigation. The author argues that overcoming such challenges early in the development process constitutes an important step towards successfully progressing each of the expanding number of antivirulence strategies into next-generation therapies for common human and animal infections that are becoming increasingly refractory to all available antibiotics.