1. 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
@jonotter
Blog:
* Joint first authors.

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

3. Carbapenem-resistant organisms, Europe
EARS-Net

4. CPE reported to PHE’s reference lab
ESPAUR 2015.

5. 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:

6. 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:
Tacconelli et al. Clin Microbiol Infect 2014; 20 Suppl 1:1-55.
Public Health England. CPE Toolkit

7. 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.

8. 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.

9. 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.

10. Methods
For admission screens, the timelines applied to evaluate the benefit of serial screens were:
1st screen at <24 hours,
2nd between hours, and
3rd between 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.

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

12. 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.

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

14. 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.

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

16. 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 Red = positive. Green = negative.

17. 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: This study highlighted.

18. 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:
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.

19. 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.

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

21. 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 ( ).
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)

22. 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
@jonotter
Blog:
* Joint first authors.