Developing a Modeling Framework for Quantifying the Health and Cost Implications of Antibiotic Resistance for Surgical Procedures.

Background. Antimicrobial resistance (AMR) is a global public health threat. The wider implications of AMR, such as the impact of antibiotic resistance (ABR) on surgical procedures, are yet to be quantified. The objective of this study was to produce a conceptual modeling framework to provide a basis for estimating the current and potential future consequences of ABR for surgical procedures in England. Design. A framework was developed using literature-based evidence and structured expert elicitation. This was applied to populations undergoing emergency repair of the neck of the femur and elective colorectal resection surgery. Results. The framework captures the implications of increasing ABR by allowing for higher rates of surgical site infection (SSI) as the effectiveness of antibiotic prophylaxis wanes and worsened outcomes following SSIs to reflect reduced antibiotic treatment effectiveness. The expert elicitation highlights the uncertainty in quantifying the impact of ABR, reflected in the results. A hypothetical SSI rate increase of 14% in a person undergoing emergency repair of the femur could increase costs by 39% (-2% to 108% credible interval [CI]) and decrease quality-adjusted life-years by 11% (0.4% to 62% CI) over 15 y. Conclusions. The modeling framework is a starting point for addressing the implication of ABR on the outcomes and costs of surgeries. Due to clinical uncertainty highlighted in the expert elicitation process, the numerical outputs of the case studies should not be focused on but rather the framework itself, illustration of the evidence gaps, the benefit of expert elicitation in quantifying parameters with limited data, and the potential magnitude of the impact of ABR on surgical procedures. Implications. The framework can be used to support research surrounding the health and cost burden of ABR in England. Highlights: The modeling framework is a starting point for assessing the health and cost impacts of antibiotic resistance on surgeries in England.Formulating a framework and synthesizing evidence to parameterize data gaps provides targets for future research.Once data gaps are addressed, this modeling framework can be used to feed into overall estimates of the health and cost burden of antibiotic resistance and evaluate control policies.

Quantifying the primary and secondary effects of antimicrobial resistance on surgery patients: Methods and data sources for empirical estimation in England.

Antimicrobial resistance (AMR) may negatively impact surgery patients through reducing the efficacy of treatment of surgical site infections, also known as the "primary effects" of AMR. Previous estimates of the burden of AMR have largely ignored the potential "secondary effects," such as changes in surgical care pathways due to AMR, such as different infection prevention procedures or reduced access to surgical procedures altogether, with literature providing limited quantifications of this potential burden. Former conceptual models and approaches for quantifying such impacts are available, though they are often high-level and difficult to utilize in practice. We therefore expand on this earlier work to incorporate heterogeneity in antimicrobial usage, AMR, and causative organisms, providing a detailed decision-tree-Markov-hybrid conceptual model to estimate the burden of AMR on surgery patients. We collate available data sources in England and describe how routinely collected data could be used to parameterise such a model, providing a useful repository of data systems for future health economic evaluations. The wealth of national-level data available for England provides a case study in describing how current surveillance and administrative data capture systems could be used in the estimation of transition probability and cost parameters. However, it is recommended that such data are utilized in combination with expert opinion (for scope and scenario definitions) to robustly estimate both the primary and secondary effects of AMR over time. Though we focus on England, this discussion is useful in other settings with established and/or developing infectious diseases surveillance systems that feed into AMR National Action Plans.

Duration of antibiotic treatment for common infections in English primary care: cross sectional analysis and comparison with guidelines.

OBJECTIVE: To evaluate the duration of prescriptions for antibiotic treatment for common infections in English primary care and to compare this with guideline recommendations. DESIGN: Cross sectional study. SETTING: General practices contributing to The Health Improvement Network database, 2013-15. PARTICIPANTS: 931 015 consultations that resulted in an antibiotic prescription for one of several indications: acute sinusitis, acute sore throat, acute cough and bronchitis, pneumonia, acute exacerbation of chronic obstructive pulmonary disease (COPD), acute otitis media, acute cystitis, acute prostatitis, pyelonephritis, cellulitis, impetigo, scarlet fever, and gastroenteritis. MAIN OUTCOME MEASURES: The main outcomes were the percentage of antibiotic prescriptions with a duration exceeding the guideline recommendation and the total number of days beyond the recommended duration for each indication. RESULTS: The most common reasons for antibiotics being prescribed were acute cough and bronchitis (386 972, 41.6% of the included consultations), acute sore throat (239 231, 25.7%), acute otitis media (83 054, 8.9%), and acute sinusitis (76 683, 8.2%). Antibiotic treatments for upper respiratory tract indications and acute cough and bronchitis accounted for more than two thirds of the total prescriptions considered, and 80% or more of these treatment courses exceeded guideline recommendations. Notable exceptions were acute sinusitis, where only 9.6% (95% confidence interval 9.4% to 9.9%) of prescriptions exceeded seven days and acute sore throat where only 2.1% (2.0% to 2.1%) exceeded 10 days (recent guidance recommends five days). More than half of the antibiotic prescriptions were for longer than guidelines recommend for acute cystitis among females (54.6%, 54.1% to 55.0%). The percentage of antibiotic prescriptions exceeding the recommended duration was lower for most non-respiratory infections. For the 931 015 included consultations resulting in antibiotic prescriptions, about 1.3 million days were beyond the durations recommended by guidelines. CONCLUSION: For most common infections treated in primary care, a substantial proportion of antibiotic prescriptions have durations exceeding those recommended in guidelines. Substantial reductions in antibiotic exposure can be accomplished by aligning antibiotic prescription durations with guidelines.

Identifying English Practices that Are High Antibiotic Prescribers Accounting for Comorbidities and Other Legitimate Medical Reasons for Variation.

BACKGROUND: Seeing one's practice as a high antibiotic prescriber compared to general practices with similar patient populations can be one of the best motivators for change. Current comparisons are based on age-sex weighting of the practice population for expected prescribing rates (STAR-PU). Here, we investigate whether there is a need to additionally account for further potentially legitimate medical reasons for higher antibiotic prescribing. METHODS: Publicly available data from 7376 general practices in England between April 2014 and March 2015 were used. We built two different negative binomial regression models to compare observed versus expected antibiotic dispensing levels per practice: one including comorbidities as covariates and another with the addition of smoking prevalence and deprivation. We compared the ranking of practices in terms of items prescribed per STAR-PU according to i) conventional STAR-PU methodology, ii) observed vs expected prescribing levels using the comorbidity model, and iii) observed vs expected prescribing levels using the full model. FINDINGS: The median number of antibiotic items prescribed per practice per STAR-PU was 1.09 (25th-75th percentile, 0.92-1.25). 1133 practices (76.8% of 1476) were consistently identified as being in the top 20% of high antibiotic prescribers. However, some practices that would be classified as high prescribers using the current STAR-PU methodology would not be classified as high prescribers if comorbidity was accounted for (n = 269, 18.2%) and if additionally smoking prevalence and deprivation were accounted for (n = 312, 21.1%). INTERPRETATION: Current age-sex weighted comparisons of antibiotic prescribing rates in England are fair for many, but not all practices. This new metric that accounts for legitimate medical reasons for higher antibiotic prescribing may have more credibility among general practitioners and, thus, more likely to be acted upon. OUTSTANDING QUESTIONS: Findings of this study indicate that the antibiotic prescribing metric by which practices are measured (and need to implement interventions determined) may be inadequate, and therefore raises the question of how they should be measured. Substantial variation between practices remains after accounting for comorbidities, deprivation and smoking. There is a need for a better understanding of why such variation remains and, more importantly, what can be done to reduce it. While antibiotics are more frequently indicated in patients with comorbidities, it is unclear to what extent antibiotic prescribing can be lowered among that patient population and how this could be achieved.

The relative importance of large problems far away versus small problems closer to home: insights into limiting the spread of antimicrobial resistance in England.

BACKGROUND: To combat the spread of antimicrobial resistance (AMR), hospitals are advised to screen high-risk patients for carriage of antibiotic-resistant bacteria on admission. This often includes patients previously admitted to hospitals with a high AMR prevalence. However, the ability of such a strategy to identify introductions (and hence prevent onward transmission) is unclear, as it depends on AMR prevalence in each hospital, the number of patients moving between hospitals, and the number of hospitals considered 'high risk'. METHODS: We tracked patient movements using data from the National Health Service of England Hospital Episode Statistics and estimated differences in regional AMR prevalences using, as an exemplar, data collected through the national reference laboratory service of Public Health England on carbapenemase-producing Enterobacteriaceae (CPE) from 2008 to 2014. Combining these datasets, we calculated expected CPE introductions into hospitals from across the hospital network to assess the effectiveness of admission screening based on defining high-prevalence hospitals as high risk. RESULTS: Based on numbers of exchanged patients, the English hospital network can be divided into 14 referral regions. England saw a sharp increase in numbers of CPE isolates referred to the national reference laboratory over 7 years, from 26 isolates in 2008 to 1649 in 2014. Large regional differences in numbers of confirmed CPE isolates overlapped with regional structuring of patient movements between hospitals. However, despite these large differences in prevalence between regions, we estimated that hospitals received only a small proportion (1.8%) of CPE-colonised patients from hospitals outside their own region, which decreased over time. CONCLUSIONS: In contrast to the focus on import screening based on assigning a few hospitals as 'high risk', patient transfers between hospitals with small AMR problems in the same region often pose a larger absolute threat than patient transfers from hospitals in other regions with large problems, even if the prevalence in other regions is orders of magnitude higher. Because the difference in numbers of exchanged patients, between and within regions, was mostly larger than the difference in CPE prevalence, it would be more effective for hospitals to focus on their own populations or region to inform control efforts rather than focussing on problems elsewhere.

Cost-effectiveness of national mandatory screening of all admissions to English National Health Service hospitals for meticillin-resistant Staphylococcus aureus: a mathematical modelling study.

BACKGROUND: In December, 2010, National Health Service (NHS) England introduced national mandatory screening of all admissions for meticillin-resistant Staphylococcus aureus (MRSA). We aimed to assess the effectiveness and cost-effectiveness of this policy, from a regional or national health-care decision makers' perspective, compared with alternative screening strategies. METHODS: We used an individual-based dynamic transmission model parameterised with national MRSA audit data to assess the effectiveness and cost-effectiveness of admission screening of patients in English NHS hospitals compared with five alternative strategies (including no screening, checklist-activated screening, and high-risk specialty-based screening), accompanied by patient isolation and decolonisation, over a 5 year time horizon. We evaluated strategies for different NHS hospital types (acute, teaching, and specialist), MRSA prevalence, and transmission potentials using probabilistic sensitivity analyses. FINDINGS: Compared with no screening, mean cost per quality-adjusted life-year (QALY) of screening all admissions was £89,000-148,000 (range £68,000-222,000), and this strategy was consistently more costly and less effective than alternatives for all hospital types. At a £30,000/QALY willingness-to-pay threshold and current prevalence, only the no-screening strategy was cost effective. The next best strategies were, in acute and teaching hospitals, targeting of high-risk specialty admissions (30-40% chance of cost-effectiveness; mean incremental cost-effectiveness ratios [ICERs] £45,200 [range £35,300-61,400] and £48,000/QALY [£34,600-74,800], respectively) and, in specialist hospitals, screening these patients plus risk-factor-based screening of low-risk specialties (a roughly 20% chance of cost-effectiveness; mean ICER £62,600/QALY [£48,000-89,400]). As prevalence and transmission increased, targeting of high-risk specialties became the optimum strategy at the NHS willingness-to-pay threshold (£30,000/QALY). Switching from screening all admissions to only high-risk specialty admissions resulted in a mean reduction in total costs per year (not considering uncertainty) of £2·7 million per acute hospital, £2·9 million per teaching, and £474,000 per specialist hospital for a minimum rise in infections (about one infection per year per hospital). INTERPRETATION: Our results show that screening all admissions for MRSA is unlikely to be cost effective in England at the current NHS willingness-to-pay threshold, and our findings informed modified guidance to NHS England in 2014. Screening admissions to high-risk specialties is likely to represent better resource use in terms of cost per QALY gained. FUNDING: UK Department of Health.

Estimating the effectiveness of isolation and decolonization measures in reducing transmission of methicillin-resistant Staphylococcus aureus in hospital general wards.

Infection control for hospital pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) often takes the form of a package of interventions, including the use of patient isolation and decolonization treatment. Such interventions, though widely used, have generated controversy because of their significant resource implications and the lack of robust evidence with regard to their effectiveness at reducing transmission. The aim of this study was to estimate the effectiveness of isolation and decolonization measures in reducing MRSA transmission in hospital general wards. Prospectively collected MRSA surveillance data from 10 general wards at Guy's and St. Thomas' hospitals, London, United Kingdom, in 2006-2007 were used, comprising 14,035 patient episodes. Data were analyzed with a Markov chain Monte Carlo algorithm to model transmission dynamics. The combined effect of isolation and decolonization was estimated to reduce transmission by 64% (95% confidence interval: 37, 79). Undetected MRSA-positive patients were estimated to be the source of 75% (95% confidence interval: 67, 86) of total transmission events. Isolation measures combined with decolonization treatment were strongly associated with a reduction in MRSA transmission in hospital general wards. These findings provide support for active methods of MRSA control, but further research is needed to determine the relative importance of isolation and decolonization in preventing transmission.

Screening, isolation, and decolonisation strategies in the control of meticillin resistant Staphylococcus aureus in intensive care units: cost effectiveness evaluation.

OBJECTIVE: To assess the cost effectiveness of screening, isolation, and decolonisation strategies in the control of meticillin resistant Staphylococcus aureus (MRSA) in intensive care units. DESIGN: Economic evaluation based on a dynamic transmission model. SETTING: England and Wales. Population Theoretical population of patients on an intensive care unit. MAIN OUTCOME MEASURES: Infections, deaths, costs, quality adjusted life years (QALYs), incremental cost effectiveness ratios for alternative strategies, and net monetary benefits. RESULTS: All decolonisation strategies improved health outcomes and reduced costs. Although universal decolonisation (regardless of MRSA status) was the most cost effective in the short term, strategies using screening to target MRSA carriers may be preferred owing to the reduced risk of selecting for resistance. Among such targeted strategies, universal admission and weekly screening with polymerase chain reaction coupled with decolonisation using nasal mupirocin was the most cost effective. This finding was robust to the size of intensive care units, prevalence of MRSA on admission, proportion of patients classified as high risk, and precise value of willingness to pay for health benefits. All strategies using isolation but not decolonisation improved health outcomes but costs were increased. When the prevalence of MRSA on admission to the intensive care unit was 5% and the willingness to pay per QALY gained was between £20,000 (€23,000; $32,000) and £30,000, the best such strategy was to isolate only those patients at high risk of carrying MRSA (either pre-emptively or after identification by admission and weekly screening for MRSA using chromogenic agar). Universal admission and weekly screening using polymerase chain reaction based detection of MRSA coupled with isolation was unlikely to be cost effective unless prevalence was high (10% of patients colonised with MRSA on admission). CONCLUSIONS: MRSA control strategies that use decolonisation are likely to be cost saving in an intensive care unit setting provided resistance is lacking, and combining universal screening using polymerase chain reaction with decolonisation is likely to represent good value for money if untargeted decolonisation is considered unacceptable. In intensive care units where decolonisation is not implemented, evidence is insufficient to support universal screening for MRSA outside high prevalence settings.