Preventing infections following caesarean section

Surgical site infections following caesarean section are a serious and costly adverse event for Australian hospitals. In the United Kingdom, 9% of women are diagnosed with a surgical site infection following caesarean section either in hospital or post-discharge (Wloch et al 2012, Ward et al 2008). Additional staff time, pharmaceuticals and health supplies, and increased length of stay or readmission to hospital are often required (Henman et al 2012). Part of my PhD investigated the economics of preventing post-caesarean infection. This paper summarises a review of relevant infection prevention strategies. Administering antibiotic prophylaxis 15 to 60 minutes pre-incision, rather than post cordclamping, is probably the most important infection prevention strategy for caesarean section (Smaill and Gyte2010, Liu et al 2013, Dahlke et al 2013). However the timing of antibiotic administration is reportedly inconsistent in Australian hospitals. Clinicians may be taking advice from the influential, but out-dated RANZCOG and United States Centers for Disease Control and Prevention guidelines (Royal Australian and New Zealand College of Obstetricians and Gynaecologists 2011, Mangram et al 1999). A number of other important international clinical guidelines, including Australia's NHMRC guidelines, recommend universal prophylactic antibiotics pre-incision for caesarean section (National Health and Medical Research Council 2010, National Collaborating Centre for Women's and Children's Health 2008, Anderson et al 2008, National Collaborating Centre for Women's and Children's Health 2011, Bratzler et al 2013, American College of Obstetricians and Gynecologists 2011a, Antibiotic Expert Group 2010). We need to ensure women receive preincision antibiotic prophylaxis, particularly as nurses and midwives play a significant role in managing an infection that may result from sub-optimal practice. It is acknowledged more explicitly now that nurses and midwives can influence prescribing and administration of antibiotics through informal approaches (Edwards et al 2011). Methods such as surgical safety checklists are a more formal way for nurses and midwives to ensure that antibiotics are administered pre-incision (American College of Obstetricians and Gynecologists 2011 b). Nurses and midwives can also be directly responsible for other infection prevention strategies such as instructing women to not remove pubic hair in the month before the expected date of delivery and wound management education (Ng et al 2013). Potentially more costly but effective strategies include using a Chlorhexidine-gluconate (CHG) sponge preoperatively (in addition to the usual operating room skin preparation) and vaginal cleansing with a povidone-iodine solution (Riley et al 2012, Rauk 2010, Haas, Morgan, and Contreras 2013).

The antigen 43 structure reveals a molecular velcro-like mechanism of autotransporter-mediated bacterial clumping

Aggregation and biofilm formation are critical mechanisms for bacterial resistance to host immune factors and antibiotics. Autotransporter (AT) proteins, which represent the largest group of outer-membrane and secreted proteins in Gram-negative bacteria, contribute significantly to these phenotypes. Despite their abundance and role in bacterial pathogenesis, most AT proteins have not been structurally characterized, and there is a paucity of detailed information with regard to their mode of action. Here we report the structure–function relationships of Antigen 43 (Ag43a), a prototypic self-associating AT protein from uropathogenic Escherichia coli. The functional domain of Ag43a displays a twisted L-shaped β-helical structure firmly stabilized by a 3D hydrogen-bonded scaffold. Notably, the distinctive Ag43a L shape facilitates self-association and cell aggregation. Combining all our data, we define a molecular “Velcro-like” mechanism of AT-mediated bacterial clumping, which can be tailored to fit different bacterial lifestyles such as the formation of biofilms.

B-lactamase-mediated resistance to antimicrobials : the relationship between genotype and phenotype

This thesis examined the ability to predict the emergence of bacteria resistant to antibiotics using genetic markers in the bacteria. Bacteria containing the genetic markers were able to become resistant to antibiotics, whereas bacteria that did not have the genetic markers remained susceptible. Existing techniques can identify the presence of resistance by looking at the characteristics of the bacteria during growth. However, having the ability to predict antibiotic resistance before it emerges could improve the preservation of currently available antibiotics and minimise treatment failure.

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.

A conjugative plasmid carrying the carbapenem resistance gene blaOXA-23 in AbaR4 in an extensively resistant GC1 Acinetobacter baumannii isolate

OBJECTIVES: To locate the acquired bla(OXA-23) carbapenem resistance gene in an Australian A. baumannii global clone 1 (GC1) isolate. METHODS: The genome of the extensively antibiotic-resistant GC1 isolate A85 harbouring bla(OXA-23) in Tn2006 was sequenced using Illumina HiSeq, and the reads were used to generate a de novo assembly. PCR was used to assemble relevant contigs. Sequences were compared with ones in GenBank. Conjugation experiments were conducted. RESULTS: The sporadic GC1 isolate A85, recovered in 2003, was extensively resistant, exhibiting resistance to imipenem, meropenem and ticarcillin/clavulanate, to cephalosporins and fluoroquinolones and to the older antibiotics gentamicin, kanamycin and neomycin, sulfamethoxazole, trimethoprim and tetracycline. Genes for resistance to older antibiotics are in the chromosome, in an AbaR3 resistance island. A second copy of the ampC gene in Tn6168 confers cephalosporin resistance and the gyrA and parC genes have mutations leading to fluoroquinolone resistance. An 86 335 bp repAci6 plasmid, pA85-3, carrying bla(OXA-23) in Tn2006 in AbaR4, was shown to transfer imipenem, meropenem and ticarcillin/clavulanate resistance into a susceptible recipient. A85 also contains two small cryptic plasmids of 2.7 and 8.7 kb. A85 is sequence type ST126 (Oxford scheme) and carries a novel KL15 capsule locus and the OCL3 outer core locus. CONCLUSIONS: A85 represents a new GC1 lineage identified by the novel capsule locus but retains AbaR3 carrying genes for resistance to older antibiotics. Resistance to imipenem, meropenem and ticarcillin/clavulanate has been introduced into A85 by pA85-3, a repAci6 conjugative plasmid carrying Tn2006 in AbaR4.

Bone-anchored prosthesis: Evidence that “gains” overcome the “pain”

Most of socket related discomforts leading to a significant decrease in quality of life of individuals with limb amputation can be overcome by surgical techniques enabling bone-anchored prostheses. To date, the OPRA two-stage procedure (i.e., S1, S2) is the most acknowledged treatment. However, surgical implantations of osseointegrated fixations are developing at an unprecedented pace worldwide.[1-18] Clearly, this option is becoming accessible to a wide range of individuals with limb amputations. The team led by Dr Rickard Branemark has published a number of landmark articles each focusing on a particular aspect (e.g., health related quality of life, functional outcomes, bone remodelling, infection rate). [1-3, 19-32] However, evidences presented in this prospective study are remarkable. Functional outcome, health-related quality of life and complications were considered concurrently for a large population (i.e., 51 participants) over an extended period of time (i.e., up to year follow up). Therefore, the “gain” and “pain” of the whole procedure were truly contrasted for the first time. The results confirmed that OPRA surgical and rehabilitation procedures improved significantly prosthetic use, mobility, global situation and fewer problems. Furthermore, the authors reported 47 episodes of infections for 63% (32) participants between post-op S1 and two years follow up. A total of 87% (41) were superficial infections recorded for 28 participants between post-op S2 and two years follow up, while 13% (6) were deep infections occurring for 4 participants during post-op S1 and S2. As expected, post-op S2 phase was the most prone to both infections. More importantly, the vast majority of infections were effectively treated with oral antibiotics. Clearly, this study provided definitive evidence that the benefits of OPRA fixation overcome complications. This article is also establishing reporting standards and benchmark data for future studies focusing on bone-anchored prostheses.

Safety of OPRA procedure for individuals with upper limb amputation

Surgical implantations of osseointegrated fixations for bone-anchored prosthesis are developing at an unprecedented pace worldwide while initial skepticism in the orthopedic community is slowly fading away. Clearly, this option is becoming accessible to a wide range of individuals with limb loss. [1-18] The team led by Dr Rickard Branemark has previously published a number of landmark articles focusing on the benefits and safety of the OPRA fixation mainly for individual with lower limb loss, particularly those with transfemoral amputation. [1-3, 19-32] However, similar information is lacking for those with upper limb amputation. This team is once again taking a leading role by sharing a retrospective study focusing on the implant survival, adverse events, implant stability, and bone remodelling for 18 individuals with transhumeral amputation over a 5-year post-operative period. Therefore, a comprehensive analysis of the safety of the procedure is accessible for the first time. In essence, the results showed an implant survival rate of 83% and 80% at 2 and 5 year follow ups, respectively. The most frequent adverse events were superficial skin infections that occurred for 28% (5) participants while the least frequent was deep bone infection that happened only once. More importantly, 38% of complications due to infections were effectively managed with nonoperative treatments (e.g., revision of skin penetration site, local cleaning, antibiotics, restriction of soft tissue mobility). Implant stability and bone remodelling were satisfactory. Clearly, this study provided better understanding of the safety of the OPRA surgical and rehabilitation procedure for individuals with upper limb amputation while establishing standards and benchmark data for future studies. However, strong evidences of the benefits are yet to be demonstrated. However, increase in health related quality of life and functional outcomes (e.g., range of movement) are likely. Altogether, the team of authors are providing further evidence that bone-anchored attachment is definitely a promising alternative to socket prostheses.

Scoping study into wound management nurse practitioner models of practice

Objectives The primary objective of this research was to investigate wound management nurse practitioner (WMNP) models of service for the purposes of identifying parameters of practice and how patient outcomes are measured. Methods A scoping study was conducted with all authorised WMNPs in Australia from October to December 2012 using survey methodology. A questionnaire was developed to obtain data on the role and practice parameters of authorised WMNPs in Australia. The tool comprised seven sections and included a total of 59 questions. The questionnaire was distributed to all members of the WMNP Online Peer Review Group, to which it was anticipated the majority of WMNPs belonged. Results Twenty-one WMNPs responded (response rate 87%), with the results based on a subset of respondents who stated that, at the time of the questionnaire, they were employed as a WMNP, therefore yielding a response rate of 71% (n≤15). Most respondents (93%; n≤14) were employed in the public sector, with an average of 64 occasions of service per month. The typical length of a new case consultation was 60min, with 32min for follow ups. The most frequently performed activity was wound photography (83%; n≤12), patient, family or carer education (75%; n≤12), Doppler ankle-brachial pressure index assessment (58%; n≤12), conservative sharp wound debridement (58%; n≤12) and counselling (50%; n≤12). The most routinely prescribed medications were local anaesthetics (25%; n≤12) and oral antibiotics (25%; n≤12). Data were routinely collected by 91% of respondents on service-related and wound-related parameters to monitor patient outcomes, to justify and improve health services provided. Conclusion This study yielded important baseline information on this professional group, including data on patient problems managed, the types of interventions implemented, the resources used to accomplish outcomes and how outcomes are measured.

Investigating the population structure of Queensland invasive Streptococcus pneumoniae isolates in children: Using a modified multi-locus variable number of tandem repeat analysis and a novel minimum SNPs capsular typing method

This research investigated the use of DNA fingerprinting to characterise the bacteria Streptococcus pneumoniae or pneumococcus, and hence gain insight into the development of new vaccines or antibiotics. Different bacterial DNA fingerprinting methods were studied, and a novel method was developed and validated, which characterises different cell coatings that pneumococci produce. This method was used to study the epidemiology of pneumococci in Queensland before and after the introduction of the current pneumococcal vaccine. This study demonstrated that pneumococcal disease is highly prevalent in children under four years, that the bacteria can `switch' its cell coating to evade the vaccine, and that some DNA fingerprinting methods are more discriminatory than others. This has an impact on understanding which strains are more prone to cause invasive disease. Evidence of the excellent research findings have been published in high impact internationally refereed journals.

Vaccination of koalas (Phascolarctos cinereus) with a recombinant chlamydial major outer membrane protein adjuvanted with poly I:C, a host defense peptide and polyphosphazine, elicits strong and long lasting cellular and humoral immune responses

Chlamydial infections are wide spread in koalas across their range and a solution to this debilitating disease has been sought for over a decade. Antibiotics are the currently accepted therapeutic measure, but are not an effective treatment due to the asymptomatic nature of some infections and a low efficacy rate. Thus, a vaccine would be an ideal way to address this infectious disease threat in the wild. Previous vaccine trials have used a three-dose regimen; however this is very difficult to apply in the field as it would require multiple capture events, which are stressful and invasive processes for the koala. In addition, it requires skilled koala handlers and a significant monetary investment. To overcome these challenges, in this study we utilized a polyphosphazine based poly I:C and a host defense peptide adjuvant combined with recombinant chlamydial major outer membrane protein (rMOMP) antigen to induce long lasting (54 weeks) cellular and humoral immunity in female koalas with a novel single immunizing dose. Immunized koalas produced a strong IgG response in plasma, as well as at mucosal sites. Moreover, they showed high levels of C. pecorum specific neutralizing antibodies in the plasma as well as vaginal and conjunctival secretions. Lastly, Chlamydia-specific lymphocyte proliferation responses were produced against both whole chlamydial elementary bodies and rMOMP protein, over the 12-month period. The results of this study suggest that a single dose rMOMP vaccine incorporating a poly I:C, host defense peptide and polyphosphazine adjuvant is able to stimulate both arms of the immune system in koalas, thereby providing an alternative to antibiotic treatment and/or a three-dose vaccine regime.

Antimicrobial treatment of non-cystic fibrosis bronchiectasis

Bronchiectasis unrelated to cystic fibrosis is characterized by chronic wet or productive cough, recurrent exacerbations and irreversible bronchial dilatation. After antibiotics and vaccines became available and living standards in affluent countries improved, its resulting reduced prevalence meant bronchiectasis was considered an ‘orphan disease’. This perception has changed recently with increasing use of CT scans to diagnose bronchiectasis, including in those with severe chronic obstructive pulmonary disease or ‘difficult to control’ asthma, and adds to its already known importance in non-affluent countries and disadvantaged Indigenous communities. Following years of neglect, there is renewed interest in identifying the pathogenetic mechanisms of bronchiectasis, including the role of infection, and conducting clinical trials. This is providing much needed evidence to guide antimicrobial therapy, which has relied previously upon extrapolating treatments used in cystic fibrosis and chronic obstructive pulmonary disease. While many knowledge gaps and management challenges remain, the future is improving for patients with bronchiectasis.

Prediction of the fate of oxytetracycline and oxolinic acid in a fish pond using simulation model: A preliminary study

The fate of two popular antibiotics, oxytetracycline and oxolinic acid, in a fish pond were simulated using a computational model. The VDC model, which is designed based on a model for predicting pesticide fate and transport in paddy fields, was modified to take into account the differences between the pond and the paddies as well as those between the fish and the rice plant behaviors. The pond conditions were set following the typical practice in South East Asia aquaculture. The two antibiotics were administered to the animal in the pond through medicated feed during a period of 5 days as in actual practice. Concentrations of oxytetracycline in pond water were higher than those of oxolinic acid at the beginning of the simulation. Dissipation rate of oxytetracycline is also higher as it is more readily available for degradation in the water. For the long term, oxolinic acid was present at higher concentration than oxytetracycline in pond water as well as pond sediment. The simulated results were expected to be conservative and can be useful for the lower tier assessment of exposure risk of veterinary medicine in aquaculture industry but more data are needed for the complete validation of the model.

Synthesis of Unnatural C-2 Amino Acid Nucleosides Using NIS-Mediated Ring Opening of 1,2-Cyclopropane Carboxylated Sugar Derivatives

We have developed a general and efficient method for the stereoselective construction of pyrimidine-based pyranosyl C-2 amino acid nucleosides using NIS-mediated ring opening of 1,2-cyclopropanated sugar derivatives. This methodology has been successfully extended to the synthesis of furanosyl nucleosides, Which have potential applications in the development of novel, nontoxic antifungal therapeutics.