Julie V. Robotham

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;

Using a Longitudinal Model to Estimate the Effect of Methicillin-resistant Staphylococcus aureus Infection on Length of Stay in an Intensive Care Unit

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.

Targeted versus universal screening and decolonization to reduce healthcare-associated meticillin-resistant Staphylococcus aureus infection.

Health-care-associated methicillin-resistant Staphylococcus aureus (MRSA) infection may cause increased hospital stay, or sometimes death. Quantifying this effect is complicated because the exposure is time dependent: infection may prolong hospital stay, while longer stays increase infection risk. In this paper, the authors overcome these problems by using a multinomial longitudinal model to estimate the daily probability of death and discharge. They then extend the basic model to estimate how the effect of MRSA infection varies over time and to quantify number of excess days in the intensive care unit due to infection. They found that infection decreased the relative risk of discharge (relative risk ratio = 0.68, 95% credible interval: 0.54, 0.82). Infection on the first day of admission resulted in a mean extra stay of 0.3 days (95% credible interval: 0.1, 0.5) for a patient with an Acute Physiology and Chronic Health Evaluation II score of 10 and 1.2 days (95% credible interval: 0.5, 2.0) for a patient with a score of 30. The decrease in the relative risk of discharge remained fairly constant with day of MRSA infection but was slightly stronger closer to the start of infection. Results confirm the importance of MRSA infection in increasing stay in an intensive care unit but suggest that previous work may have systematically overestimated the effect size.

Antimicrobial stewardship: English Surveillance Programme for Antimicrobial Utilization and Resistance (ESPAUR)

BACKGROUND The benefits of universal meticillin-resistant Staphylococcus aureus (MRSA) admission screening, compared with screening targeted patient groups and the additional impact of discharge screening, are uncertain. AIMS To quantify the impact of MRSA screening plus decolonization treatment on MRSA infection rates. To compare universal with targeted screening policies, and to evaluate the additional impact of screening and decolonization on discharge. METHODS A stochastic, individual-based model of MRSA transmission was developed that included patient movements between general medical and intensive care unit (ICU) wards, and between the hospital and community, informed by 18 months of individual patient data from a 900-bed tertiary care hospital. We simulated the impact of universal and targeted [for ICU, acute care of the elderly (ACE) or readmitted patients] MRSA screening and decolonization policies, both on admission and discharge. FINDINGS Universal admission screening plus decolonization resulted in 77% (95% confidence interval: 76-78) reduction in MRSA infections over 10 years. Screening only ACE specialty or ICU patients yielded 62% (61-63) and 66% (65-67) reductions, respectively. Targeted policies reduced the number of screens by up to 95% and courses of decolonization by 96%. In addition to screening on admission, screening on discharge had little impact, with a maximum 7% additional reduction in infection. CONCLUSIONS Compared with universal screening, targeted screening substantially reduced the amount of screening and decolonization required to achieve only 12% lower reduction in infection. Targeted screening and decolonization could lower the risk of resistance emerging as well as offer a more efficient use of resources.

Impact of mupirocin resistance on the transmission and control of healthcare-associated MRSA

The clinical, public health and economic implications of antimicrobial resistance present a major threat to future healthcare. Antimicrobial use is a major driver of resistance, and antimicrobial stewardship programmes are increasingly being advocated as a means of improving the quality of prescribing. However, to increase their impact and assess their success, a better understanding of antimicrobial usage, both in primary and secondary care, and linkage with antimicrobial resistance data are required. In England, national summaries of primary care dispensing data are issued annually by the Health and Social Care Information Centre. However, there is currently no routine public reporting of antimicrobial usage in hospitals. In response to the threat posed by antimicrobial resistance, as highlighted in the Report of the Chief Medical Officer and on the request of the Department of Health, Public Health England has developed a new national programme, the English Surveillance Programme for Antimicrobial Utilization and Resistance (ESPAUR). The programme will bring together the elements of antimicrobial utilization and resistance surveillance in both primary and secondary care settings, alongside the development of quality measures and methods to monitor unintended outcomes of antimicrobial stewardship and both public and professional behaviour interventions. This article reports on the background to the programme development, the current oversight group membership and the public reporting structure.

The National One Week Prevalence Audit of Universal Meticillin-Resistant Staphylococcus aureus (MRSA) Admission Screening 2012

Objectives The objectives of this study were to estimate the relative transmissibility of mupirocin-resistant (MupR) and mupirocin-susceptible (MupS) MRSA strains and evaluate the long-term impact of MupR on MRSA control policies. Methods Parameters describing MupR and MupS strains were estimated using Markov chain Monte Carlo methods applied to data from two London teaching hospitals. These estimates parameterized a model used to evaluate the long-term impact of MupR on three mupirocin usage policies: ‘clinical cases’, ‘screen and treat’ and ‘universal’. Strategies were assessed in terms of colonized and infected patient days and scenario and sensitivity analyses were performed. Results The transmission probability of a MupS strain was 2.16 (95% CI 1.38–2.94) times that of a MupR strain in the absence of mupirocin usage. The total prevalence of MupR in colonized and infected MRSA patients after 5 years of simulation was 9.1% (95% CI 8.7%–9.6%) with the ‘screen and treat’ mupirocin policy, increasing to 21.3% (95% CI 20.9%–21.7%) with ‘universal’ mupirocin use. The prevalence of MupR increased in 50%–75% of simulations with ‘universal’ usage and >10% of simulations with ‘screen and treat’ usage in scenarios where MupS had a higher transmission probability than MupR. Conclusions Our results provide evidence from a clinical setting of a fitness cost associated with MupR in MRSA strains. This provides a plausible explanation for the low levels of mupirocin resistance seen following ‘screen and treat’ mupirocin usage. From our simulations, even under conservative estimates of relative transmissibility, we see long-term increases in the prevalence of MupR given ‘universal’ use.

Reconstructing transmission trees for communicable diseases using densely sampled genetic data.

Introduction The English Department of Health introduced universal MRSA screening of admissions to English hospitals in 2010. It commissioned a national audit to review implementation, impact on patient management, admission prevalence and extra yield of MRSA identified compared to “high-risk” specialty or “checklist-activated” screening (CLAS) of patients with MRSA risk factors. Methods National audit May 2011. Questionnaires to infection control teams in all English NHS acute trusts, requesting number patients admitted and screened, new or previously known MRSA; MRSA point prevalence; screening and isolation policies; individual risk factors and patient management for all new MRSA patients and random sample of negatives. Results 144/167 (86.2%) trusts responded. Individual patient data for 760 new MRSA patients and 951 negatives. 61% of emergency admissions (median 67.3%), 81% (median 59.4%) electives and 47% (median 41.4%) day-cases were screened. MRSA admission prevalence: 1% (median 0.9%) emergencies, 0.6% (median 0.4%) electives, 0.4% (median 0%) day-cases. Approximately 50% all MRSA identified was new. Inpatient MRSA point prevalence: 3.3% (median 2.9%). 104 (77%) trusts pre-emptively isolated patients with previous MRSA, 63 (35%) pre-emptively isolated admissions to “high-risk” specialties; 7 (5%) used PCR routinely. Mean time to MRSA positive result: 2.87 days (±1.33); 37% (219/596) newly identified MRSA patients discharged before result available; 55% remainder (205/376) isolated post-result. In an average trust, CLAS would reduce screening by 50%, identifying 81% of all MRSA. “High risk” specialty screening would reduce screening by 89%, identifying 9% of MRSA. Conclusions Implementation of universal screening was poor. Admission prevalence (new cases) was low. CLAS reduced screening effort for minor decreases in identification, but implementation may prove difficult. Cost effectiveness of this and other policies, awaits evaluation by transmission dynamic economic modelling, using data from this audit. Until then trusts should seek to improve implementation of current policy and use of isolation facilities.

Seasonal changes in the incidence of Escherichia coli bloodstream infection: variation with region and place of onset

Whole genome sequencing of pathogens from multiple hosts in an epidemic offers the potential to investigate who infected whom with unparalleled resolution, potentially yielding important insights into disease dynamics and the impact of control measures. We considered disease outbreaks in a setting with dense genomic sampling, and formulated stochastic epidemic models to investigate person-to-person transmission, based on observed genomic and epidemiological data. We constructed models in which the genetic distance between sampled genotypes depends on the epidemiological relationship between the hosts. A data augmented Markov chain Monte Carlo algorithm was used to sample over the transmission trees, providing a posterior probability for any given transmission route. We investigated the predictive performance of our methodology using simulated data, demonstrating high sensitivity and specificity, particularly for rapidly mutating pathogens with low transmissibility. We then analyzed data collected during an outbreak of methicillin-resistant Staphylococcus aureus in a hospital, identifying probable transmission routes and estimating epidemiological parameters. Our approach overcomes limitations of previous methods, providing a framework with the flexibility to allow for unobserved infection times, multiple independent introductions of the pathogen, and within-host genetic diversity, as well as allowing forward simulation.

Antibiotics in primary care in England: which antibiotics are prescribed and for which conditions?

Previous research has shown that Escherichia coli infection rates peak in the summer; however, to date there has been no investigation as to whether this is seen in both hospital and community-onset cases, and how this differs across regions. We investigated and quantified E. coli bloodstream infection (BSI) seasonality. A generalized additive Poisson model was fitted to mandatory E. coli BSI surveillance data reported in England. There was no impact of seasonality in hospital-onset cases; however, for the community-onset cases, there was statistically significant seasonal variation over time nationally. When examined regionally, seasonality was significant in the North of England only. This variation resulted in an absolute increase of 0.06 (95% CI 0.02-0.1) cases above the mean (3.25) in each hospital trust for each week of the peak summer season, and a decrease of (-) 0.07 (95% CI -0.1 to -0.03) in the autumn. We estimate that fewer than one hospital bed-day per week per hospital is lost because of seasonal increases during the summer. Our findings highlight the need to understand the distinct community and hospital dynamics of E. coli BSI, and to explore the regional differences driving the variation in incidence, in order to design and implement effective control measures.

Potential for reducing inappropriate antibiotic prescribing in English primary care

Objectives To analyse antibiotic prescribing behaviour in English primary care with particular regard to which antibiotics are prescribed and for which conditions. Methods Primary care data from 2013-15 recorded in The Health Improvement Network (THIN) database were analysed. Records with a prescription for systemic antibiotics were extracted and linked to co-occurring diagnostic codes, which were used to attribute prescriptions to clinical conditions. We further assessed which antibiotic classes were prescribed and which conditions resulted in the greatest share of prescribing. Results The prescribing rate varied considerably among participating practices, with a median of 626 prescriptions/1000 patients (IQR 543-699). In total, 69% of antibiotic prescriptions (n = 3 156 507) could be linked to a body system and/or clinical condition. Of these prescriptions, 46% were linked to conditions of the respiratory tract, including ear, nose and throat (RT/ENT); leading conditions within this group were cough symptoms (22.7%), lower respiratory tract infection (RTI) (17.9%), sore throat (16.7%) and upper RTI (14.5%). After RT/ENT infections, infections of the urogenital tract (22.7% of prescriptions linked to a condition) and skin/wounds (16.4%) accounted for the greatest share of prescribing. Penicillins accounted for 50% of all prescriptions, followed by macrolides (13%), tetracyclines (12%) and trimethoprim (11%). Conclusions The majority of antibiotic prescriptions in English primary care were for infections of the respiratory and urinary tracts. However, in almost one-third of all prescriptions no clinical justification was documented. Antibiotic prescribing rates varied substantially between practices, suggesting that there is potential to reduce prescribing in at least some practices.