Alison Holmes, Jonathan Otter Risk factors for patients with carbapenemase-producing Enterobacteriaceae (CPE) at Imperial College Healthcare NHS Trust, 2014 – 2015 Siddharth Mookerjee, Jonathan Sullivan, Frances Davies, Hugo Donaldson, Eimear Brannigan, Alison Holmes, Jonathan Otter Jon.Otter@imperial.nhs.uk

What’s this talk about? Introduction Methods: What we did at Imperial Let’s talk CPE!! European picture Methods: What we did at Imperial Live surveillance Analysis Summary What did we learn?

Why do they pose a threat? What are CPEs? Anyone? C – Carbapenemase P – Producing E – Enterobacteriaceae CPO! CRE! CRO?! Why do they pose a threat? Key resistance mechanisms acquired – HGT Establish community reservoir – asymptomatic carriage Prior hospital stay – key risk factor Large at-risk group Carbapenem resistance conferred by carbapenemase production, ESBL –encoding genes, AmpC

European picture Carbapenemase-producing Enterobacteriaceae (CPE) present an important and emerging threat to healthcare facilities worldwide (Schwaber MJ et al . Containment of a Country-wide Outbreak of Carbapenem-Resistant Klebsiella pneumoniae in Israeli Hospitals via a Nationally Implemented Intervention) The prompt identification and subsequent isolation of CPE carriers is vital to preventing the transmission of CPE (Schwaber MJ et al . Containment of a Country-wide Outbreak of Carbapenem-Resistant Klebsiella pneumoniae in Israeli Hospitals via a Nationally Implemented Intervention) Risk factors for CPE include hospitalisation abroad, but the role of overseas travel or residence without direct healthcare contact, and the important of hospitalisation in the UK are less certain (ECDC. Risk assessment on the spread of Carbapenemase-producing Enterobacteriaceae (CPE) through patient transfer between healthcare facilities, with special emphasis on cross-border transfer. Stockholm, ECDC. 2011) Enterobacteriaceae are fermentative GNB, who with a combination of inherent and primarily acquired antibiotic resistant mechanisms are responsible for increased mortality among patients in acute care settings (Schwaber MJ, et al. Predictors of carbapenem-resistant Klebsiella pneumoniae acquisition among hospitalized adults and effect of acquisition on mortality. Antimicrob Agents Chemother 2008; 52:1028–33.) Recent situation report from PHE (PHE. Level 3 Situation Report 4: Carbapenemase Resistant Enterobacteriacaea. June 2015) noted that in Q4 of 2014, 71% of CRE were from patients in NHS Trusts. And reflecting the important of CPE – PHE have launched the Enhanced Surveillance system for Carbapenemase-producing Gram-negative bacteria. ECDC

Methods: What we did at Imperial Live surveillance system established in May 2014 56 positive CPO isolates (May 14 – Mar 15) 43 patients Enterobacteriaceae 38 isolates 28 patients Non – fermenters 18 isolates 15 patients

Previous hospitalisation within UK/abroad Travel abroad Patient hospital number PHE reference no DOB Previous hospitalisation within UK/abroad Travel abroad Gender Ward location where specimen taken VNTR Patient name Specimen collection date Isolate Ethnicity Co-morbidities, hospital diagnosis High dependency care history Molecular mechanism MICROBIOLOGY results fed LIVE to INFECTION CONTROL server + send sample to PHE lab MICROBIOLOGY informing INFECTION CONTROL TEAM We began recording detailed risk factor information for each new case of CPE from May 2014 to April 2015. Risk factors included, within the year prior to the first CPE specimen, hospitalisation abroad, travel abroad without hospitalisation, hospitalisation in the UK, and known epidemiological contact with another CPE case.  Microbiology sent out emails to Infection control team of high suspect cases of CRE, detailing patient current ward location, specimen detail (whether screen or clinical sample), specimen number, patient number, confirmation of in-house PCR result (confirm what is done in-house) Microbiology sent sample to PHE AMRHAI (confirm what exactly is done at PHE). Infection control team commencing gathering of risk factor information for that patient – awaiting confirmation as CPE Once PHE send confirmation of mechanism by which Carbapenemase resistant – then confirmed as a CPE All details stored on a centrally available database New software programmes like ICNET can do this for you Sample type Lab number for specimen

Distribution of CPO (May-14 to Mar-15) – based on 56 isolates, as per slide 5

Distribution of CPE by isolate and mechanism of resistance May 14 to Mar 15 – 38 CPE – as per slide 5

Comparison of risk factors – Enterobacteriaceae vs. Non-fermenters May 14 – Mar 15 – 38 isolates CPE – 28 patients – 25 on which RF information available May 14 – Mar 15 - 18 isolates NF – 15 patients – 12 on which RF information available Detailed risk factor data was not available for all patients.

K. pneumoniae NDM outbreak Most of the CPE isolates were K. pneumoniae, with either OXA-48 or NDM carbapenemases, in line with other UK hospitals. 88% of 25 CPE patients for whom risk factor data was available had one or more of the risk factors that we recorded. It was notable that more than half of the patients had been hospitalised in the UK and 12% had been hospitalised abroad, supporting previous findings that hospitalisation is the most important risk factor for CPE. A greater understand of CPE risk factors is crucial for developing effective and efficient screening strategies Add to notes – Ask Jon about key points we learnt from the outbreak – note the Live surveillance system helped us identify an outbreak of Kleb NDM at a couple of wards at Imperial Implementation of CRE screening Live surveillance Getting those side rooms up and ready Staff awareness Key linkages between microbiology infection control and staff on the wards Epi curve in the right direction Equals an Epi curve going in the right direction!

Summary: What did we learn? CPE are emerging at ICHT We experienced a clonal outbreak in the background of sporadic cases Sporadic cases have the ‘classic’ CPE risk factors (related to overseas travel etc), which do not seem to be shared by non-fermenters Real-time surveillance proved used in detecting and tracking the outbreak and wider CPE picture at ICHT Most of the CPE isolates were K. pneumoniae, with either OXA-48 or NDM carbapenemases, in line with other UK hospitals. 88% of 25 CPE patients for whom risk factor data was available had one or more of the risk factors that we recorded. It was notable that more than half of the patients had been hospitalised in the UK and 12% had been hospitalised abroad, supporting previous findings that hospitalisation is the most important risk factor for CPE. A greater understand of CPE risk factors is crucial for developing effective and efficient screening strategies Add to notes – Ask Jon about key points we learnt from the outbreak – note the Live surveillance system helped us identify an outbreak of Kleb NDM at a couple of wards at Imperial Implementation of CRE screening Live surveillance Getting those side rooms up and ready Staff awareness Key linkages between microbiology infection control and staff on the wards Epi curve in the right direction

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

Alison Holmes, Jonathan Otter Risk factors for patients with carbapenemase-producing Enterobacteriaceae (CPE) at Imperial College Healthcare NHS Trust, 2014 – 2015 Siddharth Mookerjee, Jonathan Sullivan, Frances Davies, Hugo Donaldson, Eimear Brannigan, Alison Holmes, Jonathan Otter Jon.Otter@imperial.nhs.uk jonotter.net