Who’s carrying CPE? Universal admission screening in London Jonathan A. Otter, Eleonora Dyakova, Karen N. Bisnauthsing, Antonio Querol-Rubiera, Amita Patel, Chioma Ahanonu, Olga Tosas Auguet, Jonathan D. Edgeworth, Simon D. Goldenberg Centre for Clinical Infection and Diagnostics Research (CIDR), Guy’s and St. Thomas’ NHS Foundation Trust & King’s College London jon.otter@imperial.nhs.uk @jonotter www.ReflectionsIPC.com You can download these slides from www.jonotter.net

Disclosures I am a consultant to Gama. I have received payment for producing educational material for 3M. Research funding from Pfizer and the Guy’s & St Thomas’ Charity.

What’s the problem? “CRE are nightmare bacteria.” Dr Tom Frieden, CDC Director “If we don't take action, then we may all be back in an almost 19th Century environment where infections kill us as a result of routine operations.” Dame Sally Davies, Chief Medical Officer “If we fail to act, we are looking at an almost unthinkable scenario where antibiotics no longer work and we are cast back into the dark ages of medicine where treatable infections and injuries will kill once again.” David Cameron, Prime Minister, UK “The rise of antibiotic-resistant bacteria, however, represents a serious threat to public health and the economy.” Barack Obama, President USA

Rising threat from MDR-GNR % of all HAI caused by GNRs. % of ICU HAI caused by GNRs. Non-fermenters Acinetobacter baumannii Pseudomonas aeruginosa Stenotrophomonas maltophilia Enterobacteriaceae Klebsiella pneumoniae Escherichia coli Enterobacter cloacae CPO CPE Hidron et al. Infect Control Hosp Epidemiol 2008;29:966-1011. Peleg & Hooper. N Engl J Med 2010;362:1804-1813.

What’s the problem? Resistance

What’s the problem? Mortality Enterobacteriaceae Non fermenters Organism AmpC / ESBL CPE A. baumannii Attributable mortality Moderate Massive (>50%) Minimal Shorr et al. Crit Care Med 2009;37:1463-1469. Patel et al. Iinfect Control Hosp Epidemiol 2008;29:1099-1106. Falagas et al. Emerg Infect Dis 2014;20:1170-1175.

What’s the problem? Global domination! Rapid spread Clonal expansion GI carriage Horizontal gene transfer

Emergence of CPE in the UK PHE.

Introduction Few cases of CPE locally Carriage rate unknown PHE risk factors * not evidence based Questions over the best anatomic site to screen Importance of PCR vs. culture unknown * an inpatient in a hospital abroad, or an inpatient in a UK hospital which has problems with spread of CPE (if known), or a ‘previously’ positive case.

Methods * PCR+ samples repeated on Cepheid PCR. All patients within the first 72 hrs of admission (excluding paediatrics) Rectal swab CRO cultured on MacConkey plus erta (reference method) CRE culured on Chrome plate CPE detected by PCR (Check Direct CPE*) Perineal swab ESBL cultured on Chrome plate Each patient approached and verbal consent obtained; risk factor questionnaire completed. Target sample size: 4500. * PCR+ samples repeated on Cepheid PCR. The study was approved by the NHS Research Ethics Committee.

Results 4843 patients enrolled. Rectal swabs collected from 4207 patients. CPE cultured from 5 (0.1%) patients. All were positive by Cepheid, 4/5 positive by CheckDirect. Samples from 2 patients were PCR+/culture negative by both PCR systems (Cepheid and CheckDirect). CPO identified in 7 (0.2%) patients. Samples from a further 75 patients were culture negative, and PCR+ by CheckDirect but negative by Cepheid. Working hypothesis: false positives.

Results ESBL were cultured from 354 (8.1% of patients overall). Rectal swabs were significantly more sensitive for detecting ESBL than perineal swabs: 331 (7.5%) vs. 165 (3.8%), p<0.001 (Fisher’s exact test). None of the CPE positives swabs had visible faecal matter; those with visible faecal matter were more likely to fail PCR. The reference lab method (MacConkey plus an erta disc) failed to identify any of the CPEs.

Results Designation CheckDirect (Ct) Cepheid (Ct) Direct culture/PCR Ref lab CPE OXA (31.8) OXA (30.2) E.coli OXA+ OXA (29.0) OXA (27.8) NDM (23.1) NDM (25.6) E.coli NDM+ Negative OXA (34.1) C.freundii OXA+   NDM 2(8.2) NDM (28.2) K.pneumoniae NDM+ CPO OXA (31.1) OXA (24.8) - VIM (30.5) VIM (31.7)

Prevalence of risk factors n pts % pts Non-UK residents 55 1.2% Overseas travel in the past 12 months 1524 32.4% Overnight hospital stay in the past 12 months - GSTT 1658 35.3% Overnight hospital stay in the past 12 months - within M25 1964 41.8% Overnight hospital stay in the past 12 months - North West 8 0.2% Overnight hospital stay in the past 12 months - any UK hospital (including London) 2187 46.5% Overnight hospital stay in the past 12 months - overseas hospital (CRE risk countries) 20 0.4% Overnight hospital stay in the past 12 months - overseas hospital (any country) 49 1.0% Antibiotics in the past 6 months - any 2628 55.9% Antibiotics in the past 6 months - one course 1399 29.8% Antibiotics in the past 6 months - more than one course 1229 26.1% At least one risk factor 3618 77.0% At least one risk factor (excluding antibiotics) 2961 63.0% n=4701.

%CPO+ without risk factor Risk factors for CPO Risk factors % CPO+ with risk factor %CPO+ without risk factor p value Overnight hospital stay in the past 12 months - overseas hospital (any country) 6.4% 0.1% <0.01 Overnight hospital stay in the past 12 months - overseas hospital (CPE risk countries as defined by PHE) 5.0% Risk factors excluding antibiotics 0.2% 0.0% 0.07 Antibiotics in the past 6 months - any 0.12 Overnight hospital stay in the past 12 months - within M25 0.13 Overseas travel in the past 12 months 0.3% 0.16 Antibiotics in the past 6 months - more than one course 0.19 Overnight hospital stay in the past 12 months - GSTT 0.23 All risk factors Antibiotics in the past 6 months - one course 0.28 Overnight hospital stay in the past 12 months - any UK hospital (including London) 0.60 Non-UK residents 0.78 Overnight hospital stay in the past 12 months - North West 0.91

Standard of care screens, and isolation Risk factors Number of approached patients Patients in isolation % Standard of care screening* Number of patient with at least one risk factor (out of all approached patients) 3874 253 6.5% 250 Non-UK residents 55 0.0% 4 7.3% Overseas travel in the past 12 months 1524 77 5.1% 78 Overnight hospital stay in the past 12 months - GSTT 1658 135 8.1% 88 5.3% Overnight hospital stay in the past 12 months - within M25 1964 153 7.8% 112 5.7% Overnight hospital stay in the past 12 months - North West 8 1 12.5% Overnight hospital stay in the past 12 months - any UK hospital (including London) 2187 167 7.6% 165 7.5% Overnight hospital stay in the past 12 months - overseas hospital (CRE risk countries) 20 2 10.0% 5 25.0% Overnight hospital stay in the past 12 months - overseas hospital (any country) 49 10.2% * Within the first 48 hours of admission.

Discussion How do we interpret a PCR+ culture-? Questions over the quality of risk factor data collection. Is all the extra screening worth it? Economic analysis to follow! Implementation of the PHE Toolkit is challenging: only 8% of the admissions that met the PHE screening trigger were in pre-emptive isolation, and only 6% were screened..

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

Summary The first study to evaluate the rate of CPE carriage in a non-selected acute hospital cohort. Carriage rate of CPE is extremely low at GSTT (around 0.1%). PCR may be useful, but no way of differentiating CPE from non-fermenters if an organism cannot be grown. If you’re interested in resistant Enterobacteriaceae, only rectal swabs will do. Be careful when using “the brown test”; properly collected rectal swabs may not have any faecal matter. Overseas hospitalisation seemed to be the most important risk factor for CPO (but difficult to be certain with so few cases).

Imperial researchers at IPS Oral presentations Abstract ID: 3865 - Otter J, Dyakova E, Bisnauthsing K, Querol-Rubiera A, Girdham S, Patel A, Ahanonu C, Tosas Auguet O, Edgeworth J, Goldenberg S. Who’s carrying CRE? Universal admission screening in London Abstract ID: 3866 - Dyakova E, Bisnauthsing K, Querol-Rubiera A, Girdham S, Patel A, Ahanonu C, Tosas Auguet O, Edgeworth J, Goldenberg S, Otter J. “Can I swab your rectum, please?”: Improving compliance with rectal screening for CRE Abstract ID: 3860 - Mookerjee S, Sullivan J, Davies F, Donaldson H, Brannigan E, Holmes A, Otter J. Risk factors for patients with carbapenemase-producing Enterobacteriaceae (CPE) in a Northwest London hospital Trust, 2014 – 2015 Posters Abstract ID: 3785 - Ahmad R, Castro-Sanchez E, Iwami M, Husson F, Holmes A. Knowledge, perceptions and decision making: What matters to patients? Abstract ID: 3798 - Record C, Gilchrist M, Patel D, Jiao L. Infection prevention in splenectomy patients: An audit of practice in a regional hepatobiliary centre Abstract ID: 3799 - Turnbull A, Moore L, Azadian B. To PPE or not to PPE Abstract ID: 3858 - Batten L, Holmes A, Otter J, Castro-Sanchez E. Estimating the isolation burden if overseas residents are pre-emptively isolated during CRE admission screening Abstract ID: 3859 - Mookerjee S, Sullivan J, Davies F, Donaldson H, Brannigan E, Holmes A, Otter J. Real-time surveillance of carbapenem-resistant Enterobacteriaceae (CRE) using live microbiology culture data in a North-West London Hospital Trust, 2014–2015 Abstract ID: 3861 - Alexander M, Mookerjee S, Nelson D, Holmes A, Otter J. An audit of single room capacity for isolation at a London hospital Trust   Abstract ID: 3862 - Galletly T, Bateman A, Brannigan E, Holmes A, Otter J. Thematic analysis of post 48-hour bloodstream infections: What did we learn? Abstract ID: 3863 - Acharya A , Samarasinghe D , Singleton J, Brannigan E, Galletly T, Donaldson H, Holmes A, Otter J. Pilot evaluation of environmental hygiene using fluorescent markers and microbiological cultures Abstract ID: 3864 - Gilchrist M , Galletly T, Brannigan E, Holmes A, Otter J. How much Clostridium difficile is preventable? Abstract ID: 3867 - Goldberg S, Dyakova E, Bisnauthsing K, Querol-Rubiera A, Girdham S, Patel A, Ahanonu C, Tosas Auguet O, Edgeworth J, Otter J. Poor sensitivity of perineal compared with rectal swabs for detecting ESBL Enterobacteriaceae

Who’s carrying CPE? Universal admission screening in London Jonathan A. Otter, Eleonora Dyakova, Karen N. Bisnauthsing, Antonio Querol-Rubiera, Amita Patel, Chioma Ahanonu, Olga Tosas Auguet, Jonathan D. Edgeworth, Simon D. Goldenberg Centre for Clinical Infection and Diagnostics Research (CIDR), Guy’s and St. Thomas’ NHS Foundation Trust & King’s College London jon.otter@imperial.nhs.uk @jonotter www.ReflectionsIPC.com You can download these slides from www.jonotter.net

% ESBL (without risk factor) ESBL risk factor data Risk factor N pts with risk factor % ESBL (risk factor) % ESBL (without risk factor) p value Non-UK residents 47 10.6% 8.4% 0.6171 Overseas travel in the past 12 months 1358 9.1% 8.1% 0.3489 Overnight hospital stay in the past 12 months - GSTT 1459 9.9% 7.7% 0.0242 Overnight hospital stay in the past 12 months - within M25 1703 10.0% 7.4% 0.0059 Overnight hospital stay in the past 12 months - any UK 1895 9.3% 0.0936 Overnight hospital stay in the past 12 months – overseas 42 23.8% 8.3% 0.0019 Antibiotics in the past 6 months - one course 1269 7.6% 8.8% 0.2697 Antibiotics in the past 6 months - >1 course 1103 11.8% 7.2% 0.00002