Evaluation of the cost-effectiveness of strategies claiming to reduce the risk of surgical site infections following primary total hip arthroplasty

Background Total hip arthroplasty (THA) is a commonly performed procedure and numbers are increasing with ageing populations. One of the most serious complications in THA are surgical site infections (SSIs), caused by pathogens entering the wound during the procedure. SSIs are associated with a substantial burden for health services, increased mortality and reduced functional outcomes in patients. Numerous approaches to preventing these infections exist but there is no gold standard in practice and the cost-effectiveness of alternate strategies is largely unknown. Objectives The aim of this project was to evaluate the cost-effectiveness of strategies claiming to reduce deep surgical site infections following total hip arthroplasty in Australia. The objectives were: 1. Identification of competing strategies or combinations of strategies that are clinically relevant to the control of SSI related to hip arthroplasty 2. Evidence synthesis and pooling of results to assess the volume and quality of evidence claiming to reduce the risk of SSI following total hip arthroplasty 3. Construction of an economic decision model incorporating cost and health outcomes for each of the identified strategies 4. Quantification of the effect of uncertainty in the model 5. Assessment of the value of perfect information among model parameters to inform future data collection Methods The literature relating to SSI in THA was reviewed, in particular to establish definitions of these concepts, understand mechanisms of aetiology and microbiology, risk factors, diagnosis and consequences as well as to give an overview of existing infection prevention measures. Published economic evaluations on this topic were also reviewed and limitations for Australian decision-makers identified. A Markov state-transition model was developed for the Australian context and subsequently validated by clinicians. The model was designed to capture key events related to deep SSI occurring within the first 12 months following primary THA. Relevant infection prevention measures were selected by reviewing clinical guideline recommendations combined with expert elicitation. Strategies selected for evaluation were the routine use of pre-operative antibiotic prophylaxis (AP) versus no use of antibiotic prophylaxis (No AP) or in combination with antibiotic-impregnated cement (AP & ABC) or laminar air operating rooms (AP & LOR). The best available evidence for clinical effect size and utility parameters was harvested from the medical literature using reproducible methods. Queensland hospital data were extracted to inform patients’ transitions between model health states and related costs captured in assigned treatment codes. Costs related to infection prevention were derived from reliable hospital records and expert opinion. Uncertainty of model input parameters was explored in probabilistic sensitivity analyses and scenario analyses and the value of perfect information was estimated. Results The cost-effectiveness analysis was performed from a health services perspective using a hypothetical cohort of 30,000 THA patients aged 65 years. The baseline rate of deep SSI was 0.96% within one year of a primary THA. The routine use of antibiotic prophylaxis (AP) was highly cost-effective and resulted in cost savings of over $1.6m whilst generating an extra 163 QALYs (without consideration of uncertainty). Deterministic and probabilistic analysis (considering uncertainty) identified antibiotic prophylaxis combined with antibiotic-impregnated cement (AP & ABC) to be the most cost-effective strategy. Using AP & ABC generated the highest net monetary benefit (NMB) and an incremental $3.1m NMB compared to only using antibiotic prophylaxis. There was a very low error probability that this strategy might not have the largest NMB (<5%). Not using antibiotic prophylaxis (No AP) or using both antibiotic prophylaxis combined with laminar air operating rooms (AP & LOR) resulted in worse health outcomes and higher costs. Sensitivity analyses showed that the model was sensitive to the initial cohort starting age and the additional costs of ABC but the best strategy did not change, even for extreme values. The cost-effectiveness improved for a higher proportion of cemented primary THAs and higher baseline rates of deep SSI. The value of perfect information indicated that no additional research is required to support the model conclusions. Conclusions Preventing deep SSI with antibiotic prophylaxis and antibiotic-impregnated cement has shown to improve health outcomes among hospitalised patients, save lives and enhance resource allocation. By implementing a more beneficial infection control strategy, scarce health care resources can be used more efficiently to the benefit of all members of society. The results of this project provide Australian policy makers with key information about how to efficiently manage risks of infection in THA.

Surgical site infection prevention following total hip arthroplasty in Australia : a cost-effectiveness analysis

Background: Surgical site infection (SSI) is associated with substantial costs for health services, reduced quality of life, and functional outcomes. The aim of this study was to evaluate the cost-effectiveness of strategies claiming to reduce the risk of SSI in hip arthroplasty in Australia. Methods: Baseline use of antibiotic prophylaxis (AP) was compared with no antibiotic prophylaxis (no AP), antibiotic-impregnated cement (AP þ ABC), and laminar air operating rooms (AP þ LOR). A Markov model was used to simulate long-term health and cost outcomes of a hypothetical cohort of 30,000 total hip arthroplasty patients from a health services perspective. Model parameters were informed by the best available evidence. Uncertainty was explored in probabilistic sensitivity and scenario analyses. Results: Stopping the routine use of AP resulted in over Australian dollars (AUD) $1.5 million extra costs and a loss of 163 quality-adjusted life years (QALYs). Using antibiotic cement in addition to AP (AP þ ABC)generated an extra 32 QALYs while saving over AUD $123,000. The use of laminar air operating rooms combined with routine AP (AP þ LOR) resulted in an AUD $4.59 million cost increase and 127 QALYs lost compared with the baseline comparator. Conclusion: Preventing deep SSI with antibiotic prophylaxis and antibiotic-impregnated cement has shown to improve health outcomes among hospitalized patients, save lives, and enhance resource allocation. Based on this evidence, the use of laminar air operating rooms is not recommended.

Most relevant strategies for preventing surgical site infection after total hip arthroplasty : guideline recommendations and expert opinion

BACKGROUND: Numerous strategies are available to prevent surgical site infections in hip arthroplasty, but there is no consensus on which might be the best. This study examined infection prevention strategies currently recommended for patients undergoing hip arthroplasty. METHODS: Four clinical guidelines on infection prevention/orthopedics were reviewed. Infection control practitioners, infectious disease physicians, and orthopedic surgeons were consulted through structured interviews and an online survey. Strategies were classified as "highly important" if they were recommended by at least one guideline and ranked as significantly or critically important by >/=75% of the experts. RESULTS: The guideline review yielded 28 infection prevention measures, with 7 identified by experts as being highly important in this context: antibiotic prophylaxis, antiseptic skin preparation of patients, hand/forearm antisepsis by surgical staff, sterile gowns/surgical attire, ultraclean/laminar air operating theatres, antibiotic-impregnated cement, and surveillance. Controversial measures included antibiotic-impregnated cement and, considering recent literature, laminar air operating theatres. CONCLUSIONS: Some of these measures may already be accepted as routine clinical practice, whereas others are controversial. Whether these practices should be continued for this patient group will be informed by modeling the cost-effectiveness of infection prevention strategies. This will allow predictions of long-term health and cost outcomes and thus inform decisions on how to best use scarce health care resources for infection control.

Control strategies to prevent total hip replacement-related infections : a systematic review and mixed treatment comparison

OBJECTIVE: To synthesise the available evidence and estimate the comparative efficacy of control strategies to prevent total hip replacement (THR)-related surgical site infections (SSIs) using a mixed treatment comparison. DESIGN: Systematic review and mixed treatment comparison. SETTING: Hospital and other healthcare settings. PARTICIPANTS: Patients undergoing THR. PRIMARY AND SECONDARY OUTCOME MEASURES: The number of THR-related SSIs occurring following the surgical operation. RESULTS: 12 studies involving 123 788 THRs and 9 infection control strategies were identified. The strategy of 'systemic antibiotics+antibiotic-impregnated cement+conventional ventilation' significantly reduced the risk of THR-related SSI compared with the referent strategy (no systemic antibiotics+plain cement+conventional ventilation), OR 0.13 (95% credible interval (CrI) 0.03-0.35), and had the highest probability (47-64%) and highest median rank of being the most effective strategy. There was some evidence to suggest that 'systemic antibiotics+antibiotic-impregnated cement+laminar airflow' could potentially increase infection risk compared with 'systemic antibiotics+antibiotic-impregnated cement+conventional ventilation', 1.96 (95% CrI 0.52-5.37). There was no high-quality evidence that antibiotic-impregnated cement without systemic antibiotic prophylaxis was effective in reducing infection compared with plain cement with systemic antibiotics, 1.28 (95% CrI 0.38-3.38). CONCLUSIONS: We found no convincing evidence in favour of the use of laminar airflow over conventional ventilation for prevention of THR-related SSIs, yet laminar airflow is costly and widely used. Antibiotic-impregnated cement without systemic antibiotics may not be effective in reducing THR-related SSIs. The combination with the highest confidence for reducing SSIs was 'systemic antibiotics+antibiotic-impregnated cement+conventional ventilation'. Our evidence synthesis underscores the need to review current guidelines based on the available evidence, and to conduct further high-quality double-blind randomised controlled trials to better inform the current clinical guidelines and practice for prevention of THR-related SSIs.

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).

Synchronous fluorescence and UV–vis spectroscopic studies of interactions between the tetracycline antibiotic, aluminium ions and DNA with the aid of the Methylene Blue dye probe

Synchronous fluorescence spectroscopy (SFS) was applied for the investigation of interactions of the antibiotic, tetracycline (TC), with DNA in the presence of aluminium ions (Al3+). The study was facilitated by the use of the Methylene Blue (MB) dye probe, and the interpretation of the spectral data with the aid of the chemometrics method, parallel factor analysis (PARAFAC). Three-way synchronous fluorescence analysis extracted the important optimum constant wavelength differences, Δλ, and showed that for the TC–Al3+–DNA, TC–Al3+ and MB dye systems, the associated Δλ values were different (Δλ = 80, 75 and 30 nm, respectively). Subsequent PARAFAC analysis demonstrated the extraction of the equilibrium concentration profiles for the TC–Al3+, TC–Al3+–DNA and MB probe systems. This information is unobtainable by conventional means of data interpretation. The results indicated that the MB dye interacted with the TC–Al3+–DNA surface complex, presumably via a reaction intermediate, TC–Al3+–DNA–MB, leading to the displacement of the TC–Al3+ by the incoming MB dye probe.

SNP diversity of Enterococcus faecalis and Enterococcus faecium in a South East Queensland waterway, Australia, and associated antibiotic resistance gene profiles

BACKGROUND: Enterococcus faecalis and Enterococcus faecium are associated with faecal pollution of water, linked to swimmer-associated gastroenteritis and demonstrate a wide range of antibiotic resistance. The Coomera River is a main water source for the Pimpama-Coomera watershed and is located in South East Queensland, Australia, which is used intensively for agriculture and recreational purposes. This study investigated the diversity of E. faecalis and E. faecium using Single Nucleotide Polymorphisms (SNPs) and associated antibiotic resistance profiles. RESULTS: Total enterococcal counts (cfu/ml) for three/six sampling sites were above the United States Environmental Protection Agency (USEPA) recommended level during rainfall periods and fall into categories B and C of the Australian National Health and Medical Research Council (NHMRC) guidelines (with a 1-10% gastrointestinal illness risk). E. faecalis and E. faecium isolates were grouped into 29 and 23 SNP profiles (validated by MLST analysis) respectively. This study showed the high diversity of E. faecalis and E. faecium over a period of two years and both human-related and human-specific SNP profiles were identified. 81.8% of E. faecalis and 70.21% of E. faecium SNP profiles were associated with genotypic and phenotypic antibiotic resistance. Gentamicin resistance was higher in E. faecalis (47% resistant) and harboured the aac(6')-aph(2') gene. Ciprofloxacin resistance was more common in E. faecium (12.7% resistant) and gyrA gene mutations were detected in these isolates. Tetracycline resistance was less common in both species while tet(L) and tet(M) genes were more prevalent. Ampicillin resistance was only found in E. faecium isolates with mutations in the pbp5 gene. Vancomycin resistance was not detected in any of the isolates. We found that antibiotic resistance profiles further sub-divided the SNP profiles of both E. faecalis and E. faecium. CONCLUSIONS: The distribution of E. faecalis and E. faecium genotypes is highly diverse in the Coomera River. The SNP genotyping method is rapid and robust and can be applied to study the diversity of E. faecalis and E. faecium in waterways. It can also be used to test for human-related and human-specific enterococci in water. The resolving power can be increased by including antibiotic-resistant profiles which can be used as a possible source tracking tool. This warrants further investigation.

ASAP ECMO : antibiotic, sedative and analgesic pharmacokinetics during extracorporeal membrane oxygenation : a multi-centre study to optimise drug therapy during ECMO

BACKGROUND: Given the expanding scope of extracorporeal membrane oxygenation (ECMO) and its variable impact on drug pharmacokinetics as observed in neonatal studies, it is imperative that the effects of the device on the drugs commonly prescribed in the intensive care unit (ICU) are further investigated. Currently, there are no data to confirm the appropriateness of standard drug dosing in adult patients on ECMO. Ineffective drug regimens in these critically ill patients can seriously worsen patient outcomes. This study was designed to describe the pharmacokinetics of the commonly used antibiotic, analgesic and sedative drugs in adult patients receiving ECMO. METHODS: This is a multi-centre, open-label, descriptive pharmacokinetic (PK) study. Eligible patients will be adults treated with ECMO for severe cardiac and/or respiratory failure at five Intensive Care Units in Australia and New Zealand. Patients will receive the study drugs as part of their routine management. Blood samples will be taken from indwelling catheters to investigate plasma concentrations of several antibiotics (ceftriaxone, meropenem, vancomycin, ciprofloxacin, gentamicin, piperacillin-tazobactum, ticarcillin-clavulunate, linezolid, fluconazole, voriconazole, caspofungin, oseltamivir), sedatives and analgesics (midazolam, morphine, fentanyl, propofol, dexmedetomidine, thiopentone). The PK of each drug will be characterised to determine the variability of PK in these patients and to develop dosing guidelines for prescription during ECMO. DISCUSSION: The evidence-based dosing algorithms generated from this analysis can be evaluated in later clinical studies. This knowledge is vitally important for optimising pharmacotherapy in these most severely ill patients to maximise the opportunity for therapeutic success and minimise the risk of therapeutic failure

Antibiotic resistance and virulence traits in clinical and environmental Enterococcus faecalis and Enterococcus faecium isolates

This study compared virulence and antibiotic resistance traits in clinical and environmental E. faecalis and E. faecium isolates. E. faecalis isolates harboured a broader spectrum of virulence determinants compared to E. faecium isolates. The virulence traits Cyl-A, Cyl-B, Cyl-M, gel-E and esp were tested and environmental isolates predominantly harboured gel-E (80% of E. faecalis and 31.9% of E. faecium) whereas esp was more prevalent in clinical isolates (67.79% of E. faecalis and 70.37 % of E. faecium). E. faecalis and E. faecium isolated from water had different antibiotic resistance patterns compared to those isolated from clinical samples. Linozolid resistance was not observed in any isolates tested and vancomycin resistance was observed only in clinical isolates. Resistance to other antibiotics (tetracycline, gentamicin, ciprofloxacin and ampicillin) was detected in both clinical and water isolates. Clinical isolates were more resistant to all the antibiotics tested compared to water isolates. Multi-drug resistance was more prevalent in clinical isolates (71.18% of E. faecalis and 70.3 % of E. faecium) compared to water isolates (only 5.66 % E. faecium). tet L and tet M genes were predominantly identified in tetracycline-resistant isolates. All water and clinical isolates resistant to ciprofloxacin and ampicillin contained mutations in the gyrA, parC and pbp5 genes. A significant correlation was found between the presence of virulence determinants and antibiotic resistance in all the isolates tested in this study (p<0.05). The presence of antibiotic resistant enterococci, together with associated virulence traits, in surface recreational water could be a public health risk.

Effect of vitamin D supplementation on antibiotic use : a randomized controlled trial

BACKGROUND: Observational data suggested that supplementation with vitamin D could reduce risk of infection, but trial data are inconsistent. OBJECTIVE: We aimed to examine the effect of oral vitamin D supplementation on antibiotic use. DESIGN: We conducted a post hoc analysis of data from pilot D-Health, which is a randomized trial carried out in a general community setting between October 2010 and February 2012. A total of 644 Australian residents aged 60-84 y were randomly assigned to receive monthly doses of a placebo (n = 214) or 30,000 (n = 215) or 60,000 (n = 215) IU oral cholecalciferol for ≤12 mo. Antibiotics prescribed during the intervention period were ascertained by linkage with pharmacy records through the national health insurance scheme (Medicare Australia). RESULTS: People who were randomly assigned 60,000 IU cholecalciferol had nonsignificant 28% lower risk of having antibiotics prescribed at least once than did people in the placebo group (RR: 0.72; 95% CI: 0.48, 1.07). In analyses stratified by age, in subjects aged ≥70 y, there was a significant reduction in antibiotic use in the high-dose vitamin D compared with placebo groups (RR: 0.53; 95% CI: 0.32, 0.90), whereas there was no effect in participants <70 y old (RR: 1.07; 95% CI: 0.58, 1.97) (P-interaction = 0.1). CONCLUSION: Although this study was a post hoc analysis and statistically nonsignificant, this trial lends some support to the hypothesis that supplementation with 60,000 IU vitamin D/mo is associated with lower risk of infection, particularly in older adults. The trial was registered at the Australian New Zealand Clinical Trials Registry (anzctr.org.au) as ACTRN12609001063202.

Assessment of antibiotic use in children by their parents in Saudi Arabia

This project assessed the factors influencing the parents' use of antibiotics in children in Saudi Arabia. It was conducted through the development and validation of the Parental Perceptions on Antibiotics (PAPA) Scales, which is the first valid and reliable instrument directed to measure these factors on a population-based level. This is also the first population-based study that measures the patterns of antibiotic use in children in Saudi Arabia, where a very high association was found between the use of antibiotics and the number of cold episodes a year, which suggests a potential of overuse of antibiotics in Saudi Arabia. Also, it was found that antibiotic use decreases significantly with parents having higher scores in knowledge and beleifs, behaviors, and eagerness to seek health-related information.

Pharmacist prescribing of venous thromboembolism prophylaxis in a surgical pre-admission clinic

Venous thromboembolism (VTE) is the term used to describe the disease process which presents as either deep vein thrombosis or pulmonary embolism. It is a major cause of death and disability worldwide and places a large financial burden on healthcare systems. Multiple risk factors have been identified for the development of VTE, including hospitalisation for acute medical illness and surgery. Documentation of VTE risk assessment is a critical part of any patient admission, driven by evidence that a risk assessment is a trigger for VTE prophylaxis to be considered. In the United Kingdom, healthcare services have set targets for VTE risk assessment documentation and financial incentives are linked to targets being met...