Preventing MRSA transmission in the ICUPreventing MRSA transmission in the ICU

What have we learnt?What have we learnt?

Jonathan EdgeworthConsultant Microbiologist Infection and Immunology Unit

Brief overview of local & UK MRSA epidemiology

Describe intervention programme on an ICU

Analysis of a highly invasive MRSA strain

Some science

AcknowledgementsDuncan Wyncoll (Consultant Intensivist) Ben Cooper (HPA)Rahul Batra (Clinical Fellow) Steve Bentley (Sanger Institute)Smriti Pathak (PhD student) Matt Holden (Sanger Institute)

2003 - Top (bottom) of the table…….

Mandatory reporting

*

Declining national rates of MRSA

Government Targets, PMDU, CQC

Board-to-floor accountability, DIPC,assurance framework

Investment, performance management, mandatory training, audits

Raised profile of IPC, clinical championschange in culture and behaviour

So how has this been achieved?

Recommendation SHEA (2003) WIP (2005) Working Party

UK (2006) CDC (2006)

Hand hygiene Y

Contact precautions Y

Education ND ND

System to identify patients with MRSA /Feedback

ND

Cohorting ND ND

Active surveillance testing Y

Environmental Decontamination

Antimicrobial Stewardship

Decolonization therapy

IA, strongly recommended, strongly supported by evidence IB, strongly recommended supported by evidence; Dutch Working party (WIP) Approach recommended for implementation

II Suggested implementation, supported by suggestive studies orS Recommended in specific populations only; ND, not discussed

(adapted from Calfee et al Infect Hosp Epi 2008; 29:S62-80)

MRSA – Control Recommendations for ICU

What evidence is there in the literature?

PubMed search “MRSA control and ICU” (March 17th)531 references (1980-present)201 reviewed (2007-present)

2Controlled study

6Time series analysis

10Surveys / reviews

13Observationalbefore / after

2Cleaning

1Cohorting

3Rapid diagnostics

3AST + isolation

8AST + decolonisation

6 studies from the UK……

*AST = active surveillance testing

An ICU intervention programme

Two 15-bed general ICUs5 side rooms

In 2002….Daily microbiology consults and infection control nurse visitEducation and hand hygiene auditsAlcohol gel at every bed-side

MRSA screening on admission and every Monday (nose, axilla, perineum)

Admitted – MRSA isolated from admission screen or any clinical sample in first 48 hoursAcquired – MRSA isolated from sample taken after first screen and 48 hours on the ICU

No cohorting or use of side rooms for MRSANo decolonisation strategy

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J F M A M J J A S O N D J F M A M J J A S O N D

2002 2003

Admitted Acquired Bacteremia

A B

High level MRSA transmission in intensive care

A = education, audits and hand hygieneB = isolation and cohorting

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J F M A M J J A S O N D J F M A M J J A S O N D J F M A M J

2002 2003 2004N

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TW Non-TW

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810

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2002 2003 2004

Num

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TW Non-TW

Admissions

Acquisitions

TW MRSAResistant to: Pen, Ery, Meth, Cip, Neo, Gent, Tet (T), Trim (W)Susceptible to: Vanc, Rif, Fus, Lzd

Emergence of a new highly resistant MRSA strain Emergence of a new highly resistant MRSA strain ““TWTW””

Holden MTG et al J Bact 2010:192; 888-92

φSaTW - 127 kbSimilar to region in S. epidermidis RP62aAminoglycoside resistanceNovel LPxTG adhesin (homologous to sesI)

TW ST239

Harris S et al Science (2010) 327; 469-474.

TW MRSA – imported from Thailand?

MRSA Positive Patients:• 1% CHX to nostrils, tracheostomy

sites 4x daily• 1% CHX powder to groin, axillae,

skin folds plus 4% CHX whole body wash daily

MRSA Negative Patients:• 1% CHX to nostrils, tracheostomy

sites 2x daily• 1% CHX powder to groin, axillae,

skin folds daily• 2% Triclosan body wash daily

Source control

Colonisation avoidance

Implementation of a chlorhexidine based antiseptic protocol

ADMISSION Confirmed MRSA +ve

KnownMRSA +ve

Unknown

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2002 2003 2004

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TW Non-TW

C

C = Chlorhexidine-based decolonisation strategy

Control of endemic transmission and termination ofthe TW MRSA outbreak

A

Edgeworth J et al Clin Infect Dis (2007) 44;493-501

B

Guy’s & St Thomas’ antimicrobial resistance and transmission database (GSTAR)5.2 million data points from 4,570 patients (2002 to 2006)517 patients admitted with MRSA / 347 patients acquired MRSA>70% MRSA isolates saved

Age, sex, specialty, dates of admission, discharge/death, starting and stopping of: ventilation, antibiotics and haemofiltration, dates of insertion and removal of vascular catheters, Admission & daily APACHE II scores, daily therapeutic intervention scores, collection and results of all microbiology specimens, daily bed placement, staffing levels.

Barnett AG et al Am J Epidemiol 2009:170;1186-1194

Which interventions were associated with a reduction inMRSA transmission?

Interventions:A Educational/Hand hygiene campaign, B Isolation and cohorting, C Antiseptic protocol

Interrupted Time Series analysis of MRSA Transmission

Endemic MRSA TW MRSA

Interventions Incidence Rate Ratio (95% CI) Prob. ≠ 1 Incidence Rate

Ratio (95% CI) Prob. ≠ 1

Education 0.91 (0.53, 1.58) 15 1.12 (0.63, 2.01) 17

Cohorting 1.12 (0.60, 2.09) 18 0.71 (0.18, 2.88) 25

Antiseptics 0.30 (0.19, 0.47) 100 3.85 (0.80, 18.59) 83

Change in trend following Education

1.00 (1.00, 1.00) 4 0.93 (0.85, 1.02) 75

Change in trend following Cohorting

1.00 (1.00, 1.00) 4 0.99 (0.92, 1.06) 15

Change in trend following Antiseptics

1.00 (1.00, 1.00) 4 0.96 (0.88, 1.05) 57

Step change

Trend change

*

* The columns headed “Prob ≠ 1” give estimated probabilities for an effect associated with each parameter. Low values indicate little evidence for an effect and values close to 100 indicate increasingly strong evidence

Batra R, et al Clin Infect Dis 2010 50;210-217.

Step change reduction in endemic TW MRSA transmissionafter introduction of the antiseptic protocol

MRSA Strains Before antiseptic protocol

After antiseptic protocol p value

TW Strainn 82 28Screen sites 28(34)* 11(39) 0.31Respiratory tract 52(63) 15(53) 0.18Skin breaches 45(55) 16(57) 0.42

Endemic Strainsn 480 274Screen sites 359(75) 140(52) <0.001Respiratory tract 261(54) 97(36) <0.001Skin breaches 145(30) 59(22) 0.005

Antiseptic Protocol Reduced Endemic Strain But Not TW Site Colonisation

*n(%) of patients with MRSA isolated at that site at any time during their stay on ICU

MRSA TYPE qacA/B carriagen (%)

TW (n=21)* 21 (100%)

Endemic strains (n=21)* 1 (5%)

qacA/B Carriage

* Representative isolates from cluster acquisitions in the year prior to introduction of the antiseptic protocol

qacA/B are plasmid born multi-component efflux pumps found in 10-20% UK, 65% EU 80% South American and 55% of Asian MRSA strainsPiddock Clin Microbiol Rev 2006; 19: 382-402

MRSA TYPE Triclosan MBC(ug/ml)

Chlorhexidine MBC(ug/ml)

TW (n=5) 25 78±4

Endemic Strains (n=5)* 25 26±8

Increased Chlorhexidine MBCs of TW MRSA

* qacA/B PCR negative

OutcomePopulation and interventionSetting

Acquisitions 21 v 11 Incidence (%) 2.48 v 1.49(p=0.048)

845 v 736 admMRSA 93 (11%) v (69) 9.4%9m AST + contact precautions9m add CHX + mupirocin

Ridenour (2007)Before – after16 bed ICU

Before: 193 (16%) MRSA positive After: 45 (3.1%) adm and 47 (3.4%) acqStep reduction

1232 v 1421 adm. 24m clinical cultures & contact precautions24m AST +CHX baths/nasal treatment

Gould et al (2007)Before - after16 bed ICU

Acquisitions 67 v 45 Incidence (%) 5.04 v 3.44 (p=0.046)

2670 v 2650 admMRSA prevalence 1.6-6.3%6m soap/water v 6m CHX all patients

Climo et al (2009)Before - after6 ICUs

Other studies: Thompson et al J Hosp Infect 2009:71;314-319Raineri et al J Hosp Infect 2007:67;308-315Sandri et al Infect Control Hosp Epidemiol 2006:27;185-187

Studies reporting on the use of chlorhexidine

Summary

Factor contributing to declining UK MRSA transmission have not been clearly defined

Decolonisation/universal antiseptic use may have an important role

MRSA strains carrying qacA/B are resistant to a chlorhexidine based antiseptic protocol

MRSA strains differ in their virulence and response to infectioncontrol interventions in ICU

Intercontinental transmission of a highly invasive, highly antiseptic and antibiotic resistance variant of MRSA (ST239-TW)