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Plasmid-Mediated Multidrug-Resistant Enterobacteriaceae: Prevalence of Gastrointestinal Colonization and Short-Term Transmission in a Tertiary-Care HospitalMorency-Potvin Philippe1-2 M.D., Lavergne Valery1-2 M.D., Cloutier Chantal1, Pichette Gilbert1-2 M.D., Lefebvre Brigitte3 Ph.D. and Tsimiklis Catherine1-2-3 M.D.1Service de microbiologie médicale et infectiologie, Hôpital du Sacré-Cœur de Montréal, Montréal, Québec, Canada2Département de microbiologie et immunologie, Université de Montréal, Montréal, Québec, Canada3Laboratoire de santé publique du Québec (LSPQ), Sainte-Anne-de-Bellevue, Québec, Canada

All carriersn=34

ESBLn = 22

AmpCn = 7

OXAn = 2

Combinedn = 3

DEMOGRAPHICS

Median age (range) 77 (26-89) 79 (35-89) 64 (50-76) 85 (85-85) 80 (41-81)

Sex masculine 22 (65) 14 (64) 7 (100) 0 (0) 1 (33)

Median Charlson Score (range) 5 (0-11) 5.5 (0-11) 5 (4-9) 7.5 (5-10) 5 (0-7)

Immunosuppression 2 (6) 0 (0) 2 (29) 0 (0) 0 (0)

PRIOR TO HOSPITALIZATION

Hospitalization < 3 months 17 (50) 9 (41) 4 (57) 2 (100) 2 (67)

Antimicrobial therapy < 3 months 20 (59) 12 (55) 4 (57) 1 (50) 3 (100)

From a Long-term Facility 9 (27) 6 (27) 2 (29) 1 (50) 0 (0)

Median hospitalization duration to screening (range)

15 (0-135) 17 (0-59) 12 (2-135) 30 (19-41) 3 (1-7)

Known colonization 2 (6) 1 (5) 1 (14) 0 (0) 0 (0)

DURING HOSPITALIZATION

Active antimicrobial therapy 19 (56) 13 (59) 3 (43) 0 (0) 3 (100)

Instrumentation 14 (41) 9 (40) 5 (71) 0 (0) 0 (0)

Medical Ward 20 (59) 13 (59) 3 (43) 2 (100) 2 (67)

Surgical Ward 12 (35) 7 (32) 4 (57) 0 (0) 1 (33)

Intensive Care Unit 2 (6) 2 (9) 0 (0) 0 (0) 0 (0)

30-day mortality 2 (6) 1 (5) 1 (14) 0 (0) 0 (0)

1. Paterson DL et al. Clin Microbiol Rev. 2005;18(4):657-686.2. Denisuik AJ et al. J Antimicrob Chemother. 2013;68 Suppl 1:i57-65.3. Lowe C et al. Am J Infect Control. 2012;40(9):836-839.4. Harris AD et al. Am J Infect Control. 2007;35(2):97-101.5. Tschudin-Sutter S et al. Clin Infect Dis. 2012;55(11):1505-1511.6. Pérez-Pérez FJ, Hanson ND. J Clin Microbiol. 2002 Jun;40(6):2153-62.7. Rasheed JK et al. Antimicrob Agents Chemother. 1997

Mar;41(3):647-53.8. Monstein HJ et al. APMIS. 2007 Dec;115(12):1400-8.9. Mataseje LF et al. J Antimicrob Chemother. 2012 Jun;67(6):1359-67.10. Magiorakos AP et al. Clin Microbiol Infect. 2012;18(3):268-281.11. Hilty M et al. Clin Infect Dis. 2012;55(7):967-975.12. Hota B. Clin Infect Dis. 2004;39(8):1182-1189.13. Kollef MH et al. Clin Infect Dis. 2011;53 Suppl 2:S33-55; quiz S56-38.14. Savard P, Perl TM. Curr Opin Infect Dis. 2012;25(4):371-377.

Results

Background

Results

Methods

References

Table 1: Carriers’ characteristics

This study established the point prevalence of plasmid-mediated multidrug-resistant Enterobacteriaceae (MDRE) and evaluated transmission to room contact patients in the following month. While 7.4% of patients were colonized, no transmission was demonstrated by culture. This challenges the use of contact precautions for MDRE in non-outbreak settings.

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449 screenings

42 positive screenings

(48 strains)

37 strains

34 strainsconfirmed by PCR

(30 patients)

2 OXA-1

5.9%

3 combined mechanisms

8.8%

7 plasmidic AmpC

20.6%

22 ESBL

64.7%

3 strains not confirmed by PCR

1 strainphenotypically ESBL

11 non-plasmidicphenotypes

(7 rejected after PCR)

39 contacts identified

15 not screened24 screened

9 positive

6 chromosomicAmpC

2 patients already knownto be carriers

1 patient knownto be a carrier

with a new ESBL

15 negative

Discussion and conclusions

Acknolwledgements

NOTE: Comparisons between all resistance mechanisms were not significant (p>0.05). Data are number (%), unless otherwise indicated.

The worldwide steadily increasing occurrence of MDRE is concerning.

Plasmid-mediated resistance mechanisms in MDRE = greater potential for transmission1.

Canadian statistics from 2007 to 20112:• Extended Spectrum Beta-Lactamases (ESBL) prevalence: 3.4% to 7.1%;• AmpC cephalosporinase (AmpC) prevalence: 0.7% to 2.9%;• Carbapenemase-Producing Enterobacteriaceae (CPE) prevalence remains under 0,1%.

Infection control strategies = diverse3 and use of contact precautions are questioned in the literature4-5.

In our institution, a 440-acute care bed University hospital:• No systematic screening for MDRE at admission;• Contact precautions introduced only when a MDRE is isolated from patients with an

increased risk of transmitting the MDRE;• Patients with CPE systematically isolated.

This study aims to determine the prevalence of gastrointestinal colonization of MDRE with plasmid-mediated resistance mechanisms in our hospital and to evaluate their short-term transmission in the aforementioned setting.

POINT PREVALENCE From December 10th to 13th 2012:

• All patients screened by rectal swabbing. ID of mutiresistant strains: ChromID ESBL and ChromID CARBA agar (bioMérieux, France). Species ID and AST: Vitek 2 (bioMérieux, France). MICs interpreted with CLSI criteria (CLSI M100-S23). Confirmation of resistance mechanisms by PCR at the LSPQ with:

• 3 AmpC families: CIT, DHA, and FOX6;• 3 ESBL families: SHV, TEM and CTX-M7-8;• Sequencing of blaSHV and blaTEM (Jacoby classification).

All non-susceptible strains to carbapenems: → β-lactamases PCR at the National Microbiology Laboratory in Winnipeg, MB9.

CONTACT SCREENING Definition: Patients sharing room with a carrier

Screened at discharge from hospital or 1 month after initial screening; ID and AST as above; Molecular biology analyses only in cases of phenotypic similarities.

INFECTION CONTROL MEASURES In the absence of clinical infection, no additional infection control measures were initiated for patients

having a positive MDRE screening.

DATA COLLECTION AND STATISTICAL ANALYSIS Chart reviewing for clinical and demographic data. In addition to descriptive statistics, univariate analysis to compare:

• Resistance mechanisms;• Characteristics from carriers and contact patients.

Fisher’s exact test or Kruskall-Wallis test, as appropriate. Alpha error <0.05 = significant.

Most frequent identified genes: blaCTX-M for ESBL (92%) and blaCIT for AmpC (55.6%). No CPE detected.

2 carriers infected by an MDRE strain (UTI and wound infection).

Average hospital length of stay for the study period: 8 days.

All strains respected the definition of multidrug resistance according to Magiorakos et al. criteria10.

Proportion of MDRE colonization (7.4%) = expected Absence of transmission in low-prevalence in non-outbreak settings also demonstrated in recent

literature4-5-11. Study undertaken during VRE outbreak

• Breaches in standard precautions → transmission by fecal-oral route ↑.• Hand hygiene compliance in a recent audit = 30%.• Nevertheless: no nosocomial MDRE transmission observed.

LIMITATIONS Suboptimal compliance to screening of contact patients at discharge (62%)

• 15% of contact patients died or were sent to a palliative care ward . Prevalence of colonization by plasmid-mediated MDRE only

• Underestimation the overall prevalence of MDRE? Contact screening = room contact

• Shared facilities are still in use in our hospital• Missed cases of transmission? • Acquisition of MDRE from inanimate surfaces does not occur easily12.

Our study supports the hypothesis that systematic isolation of MDRE carriers might not be the optimal strategy in absence of outbreak.

Nosocomial transmission of MDRE = a complex problem. Most cost-effective infection control strategy still understudy. Still possible that these precautions are necessary in situation at high risk of transmission. Optimization of compliance to infection control measures, MDRE infection surveillance and antibiotic

stewardship→ should be the cornerstone of a MDRE infection control program13-14.

Prevalence of MDRE colonization for the study period: 7.4%

This study was partially supported by bioMérieux.

We specially want to thank the work of GinetteBergeron and to all members of our Infection Control team.

1613

76%

15%

3%

3%

3%

Species identified in carriers

Escherichia coli Klebsiella pneumoniae

Klebsiella oxytoca Enterobacter cloacae

Citrobacter koseri

No significant differences between resistance mechanisms nor between characteristics from carriers and contact patients.

No short-term transmission from close contact with MDRE gastrointestinal carriers was observed.

Figure 1: Screening flowchart