Screening for CPE: sensitivity of serial admission screens Eleonora Dyakova*, Siddharth Mookerjee*, Frances Davies, Kathleen Bamford, Eimear Brannigan, Alison Holmes, Jonathan A. Otter Imperial College Healthcare NHS Trust jon.otter@imperial.nhs.uk @jonotter Blog: www.ReflectionsIPC.com * Joint first authors.

Carbapenemase-producing Enterobacteriaceae (CPE): ‘triple threat’ Resistance Rapid spread Mortality

Carbapenem-resistant organisms, Europe EARS-Net

CPE reported to PHE’s reference lab ESPAUR 2015.

CPE prevention & control Hand hygiene Cleaning / disinfection SDD? Topical CHX? Education? Contact precautions Active screening Antibiotic stewardship Otter et al. Clin Microbiol Infect 2015;21:1057-1066.

CPE screening recommendations Guidelines to prevent the spread of CPE recommend screening to detect asymptomatic carriers.1-3 Public Health England (PHE) issued a Toolkit to prevent the spread of CPE, which includes recommendations for risk-factor based screening of all admissions.4 PHE recommend that patients ‘at-risk’ are screened on three separate occasions, each separated by 48 hours: An inpatient in a hospital abroad An inpatient in UK hospital which has problems CPE spread Previous positive case Wilson et al. J Hosp Infect 2016 in press. Otter et al. Microbiol Infect 2015; 21:1057-1066. Tacconelli et al. Clin Microbiol Infect 2014; 20 Suppl 1:1-55. Public Health England. CPE Toolkit. 2013.

Local screening strategy Risk-factor based admission screening of all admissions Universal admission screening in ‘high-risk’ specialties Weekly screening in high-risk specialties, and around known carriers. Contact tracing screening for newly identified cases. Admission screening and contact tracing was performed using three screens, each separated by 48 hours. Weekly screening was performed using a single screen. Rectal swabs were requested, some perineal swabs were sent; both were included in the analysis. Risk factors = Patients with overnight hospitalisation in any hospital (including our own readmissions) with in the past 12 months, and overseas residents. Universal screening: ICU, renal, vascular and haematology in-patient wards.

New CPE cases, April 2014 – December 2015 Universal risk-factor based admission screening was introduced in June 2015 to extend screening that was being performed in high-risk specialties. The majority of cases are from screens, without evidence of clinical infection.

Aims Determine CPE carriage rate on admission. Establish the value of serial admission screens to confirm negative CPE carriage status. Explore the pattern of apparent carriage to test a “once positive, always positive” approach.

Methods For admission screens, the timelines applied to evaluate the benefit of serial screens were: 1st screen at <24 hours, 2nd between 25-72 hours, and 3rd between 73-120 hours. Screening swabs plated onto chromogenic media (ColorexTM mSuperCARBATM, E&O Laboratories, UK). Suspicious colonies were tested for antimicrobial susceptibility (EUCAST disc diffusion), and carbapenemase gene detection by PCR (Xpert® Carba-R, Cepheid Inc, USA). CPE identified locally and PCR- suspicious isolates sent to the PHE AMRHAI reference unit for confirmation.

Methods – bacterial groups Gram-negative bacteria Enterobacteriaceae Resistant Enterobacteriaceae CPE * Resistant to ertapenem, meropenem, temocillin or tazocin.

Methods Data was de-duplicated separately for each time-point. Carriage rate at the three screening points was tested for a significant trend-change using Chi-squared tests of 2x3 contingency tables for each organism-group. This work was considered a service evaluation, and did not require an application to the NHS Research Ethics Service.

Carriage rate by screening time-point * * = significant trend-change: p<0.05.

Carriage rate by screening time-point (patients who received all 3 screens) n=221. No significant trend-change for any of the organism-groups: p>0.05.

Carriage rate for patients who received 3 screens at any time-point * * * n=1597. * = significant trend-change: p<0.05.

Once positive, always positive? Of 51 that had least three screens, 24 (47.1%) had a ‘+-+’ pattern. 60 / 64 (93.8%) patients had at least one negative surveillance culture during their hospital stay (excluding 6 patients with a single positive screen). Serial CPE screens from 70 patients who were found to be CPE positive by screening cultures during June – December 2015. Red = positive. Green = negative.

Discussion: who’s carrying CPE? Author Year Location Setting n patients n carriers % carriers Lin 2013 Chicago, USA Long term acute care hospitals 391 119 30.4 – Short stay hospital ICU 910 30 3.3 Day Pakistan Patients attending a military hospital 175 32 18.3 Adler 2015 Israel CPE carriage in post-acute hospitals, 2008 1147 184 16.0 CPE carriage in post-acute hospitals, 2013 1287 127 9.9 Girlich 2014 Morocco Hospitalized patients 77 10 13.0 Armand-Lefèvre Paris, France ICU patients 50 6 12.0 Rai East Delhi, India Outpatients 242 24 Birgand Patients repatriated or recently hospitalized in a foreign country 132 9 6.8 Zhao Fujian, China Stool samples from hospitalized patients 303 20 6.6 Swaminathan New York All admissions to 7 units, including ICU, of 2 hospitals 5676 306 5.4 Wiener-Well 2010 Jerusalem, Israel 298 16 Villar Buenos Aires, Argentina Non-hospitalized individuals 164 8 4.9 Kothari New Delhi, India. Healthy neonates 75 1 1.3 Dyakova 2016 London ‘High-risk’ admissions 7666 37 0.5 Mack ‘High-risk’ inpatients and admissions. 2077 7 0.3 Kim Seoul, Korea ICU admissions 347 All hospital admissions 4218 5 0.1 Nüesch-Inderbinen Zurich, Switzerland Healthy community residents and outpatients 605 0.0 Author Setting Location Year % carriers n carriers n patients Israel 2015 Adler1 CPE carriage in post-acute hospitals, 2008 16.0 184 1147 – 1287 CPE carriage in post-acute hospitals, 2013 Mack 9.9 127 ‘High-risk’ inpatients and admissions. London 2014 2077 Rai2 0.3 7 East Delhi, India 24 242 Outpatients Zhao3 Stool samples from hospitalized patients Fujian, China 303 Birgand4 6.6 20 Patients repatriated or recently hospitalized in a foreign country Paris, France 132 Kim5 6.8 9 347 ICU admissions Seoul, Korea 1 Girlich6 Morocco 10 77 Hospitalized patients 2013 Lin7 13.0 391 Long term acute care hospitals Chicago, USA 30.4 119 910 Short stay hospital ICU Villar8 3.3 30 164 Non-hospitalized individuals Buenos Aires, Argentina 8 Kothari9 4.9 New Delhi, India. 75 Healthy neonates Day10 1.3 Patients attending a military hospital Pakistan 175 Swaminathan11 18.3 32 5676 All admissions to 7 units, including ICU, of 2 hospitals New York Nüesch-Inderbinen12 5.4 306 Zurich, Switzerland 605 Healthy community residents and outpatients Armand-Lefèvre13 0.0 ICU patients 12.0 6 50 Jerusalem, Israel 2010 Wiener-Well14 16 298 For refs see: http://reflectionsipc.com/2014/12/22/whos-harbouring-cre/. This study highlighted.

Discussion The carriage rate on admission was low (0.5%), consistent with the few other studies in the UK. Serial admission screens add little value in detecting cases. We are not aware of any other evaluation of the performance of serial admission screens for CPE. Rectal swabs as effective as stool samples, and 2x as effective at detecting resistant Enterobacteriacae than perineal.1,2 A negative CPE screen is not to be trusted for known carriers, as found in other studies.3,4 Lerner et al. Antimicrob Agents Chemother 2013;57:1474-1479. Dyakova et al. IPS 2015, and submitted. O’Fallon et al. Clin Infect Dis 2009;48:1375e1381. Feldman et al. Clin Microbiol Infect 2013;19:E190eE196.

Recommendations Serial screening to confirm negative CPE carriage status when admission screening and contact tracing has ceased. Weekly screening in high-risk areas and around all patients with known CPE. Regular screening of long-stay patients for carriage of resistant Gram-negative bacteria should be considered. “Once positive, always positive” approach.

Simple, stark, sobering sums 0.5% x 186,393 = 932 (!) 0.1% x 186,393 = 186 0.1% x 15.892m* = 15,892 * Admissions to NHS acute hospitals, Financial Year 14/15. NHS Confederation, Key Statistics on the NHS,

Imperial researchers at ECCMID Emergence and clonal spread of colistin resistance during an outbreak of CPE in London, #EP0182. Pivmecillinam; an antibiotic from the past, for the future: a retrospective multicentre observational study of comparative urine susceptibilities in a healthcare network in the United Kingdom. Quantifying where selection occurs: a mathematical modeling approach to better inform resistance control. OS051. Addressing the final hurdle towards the elimination of Hansen’s disease; a critical review of stigma in leprosy #P0596. Refining national surveillance algorithms to facilitate local outbreak detection of carbapenem resistant organisms. Evaluation of different media for introduction of a CPE-screening programme at a UK hospital. Effect of trimethoprim/nitrofurantoin prescribing on the incidence and antibiotic susceptibility patterns of Escherichia coli bacteraemia nationally at the GP practice level (2012-2014). Global antibiotic resistance prevalence in paediatric Escherichia coli urinary tract infections and associations with routine use of primary care antibiotics: a systematic review and meta-analysis. Availability of guidance, decision support tools and education to enable appropriate antimicrobial prescribing in English primary care settings. #P1332. Assessment of cross-specialty engagement in antimicrobial stewardship; a cross-sectional, observational analysis of UK medical specialty curricula. Outbreak of GES-5 carbapenemase-producing Klebsiella oxytoca in a London haematology unit.  Developing a renal antibiotic stewardship round through an education, awareness and feedback methodology to improve specialty engagement and ownership. #EV0682 The Global Point Prevalence Survey of Antimicrobial Consumption and Resistance (Global-PPS): first results of antimicrobial prescribing in English hospitals - quality indicators, #EV0709 Extended stability of antimicrobial agents in devices suitable for OPAT administration, #EV0641 Faecal carriage of antibiotic resistant Escherichia coli in asymptomatic children and associations with primary care antibiotic prescribing: a systematic review and meta-analysis, #3274  (e-Poster)

Screening for CPE: sensitivity of serial admission screens Eleonora Dyakova*, Siddharth Mookerjee*, Frances Davies, Kathleen Bamford, Eimear Brannigan, Alison Holmes, Jonathan A. Otter Imperial College Healthcare NHS Trust jon.otter@imperial.nhs.uk @jonotter Blog: www.ReflectionsIPC.com * Joint first authors.