The Changing Face of Transmission Prevention

Eli N. Perencevich, MD MS May 15, 2012 Director, CADRE Iowa City VA HCS Professor, University of Iowa

ALL SCREENING IS HARMFUL

SOME SCREENING IS BENEFICIAL

Overview
• Definitions • Overview of the VHA MRSA Initiative
– Evidence for prediction-targeted screens – Regional control – Novel strains and detection issues

• Other Organisms • Environment • Problems with isolation precautions

Controlling MDROs
(1) ‘Horizontal’ programs that broadly attempt to reduce infections from all pathogens - Hand-hygiene - CLABSI Bundles (2) ‘Vertical’ programs target single pathogens - Screening and isolation - Can include decolonization
FOR MORE INFO...

Wenzel RP, Edmond MB.. Int J Infect Dis. Oct 2010;14 Suppl 4:S3‐5.

http://www.etsy.com/shop/tamarakraft

Importance of MRSA
• 2x mortality vs MSSA1 • 94,000 invasive cases/year2
– 19,000 excess deaths2

• 9.4% annual decline in hospital onset MRSA from 2005 to 20083
– Declines also in England and in Europe4
FOR MORE INFO... 1. Cosgrove S et al Clin Infect Dis 2003 3. Kallen A. et al JAMA 2010 2. Klevens M et al JAMA 2007 4. Perencevich and Diekema, JAMA 2010

VA MRSA Initiative
• VA Pittsburgh (pilot study) • 17 beta-site medical centers (2006) • Bundle:
• (1) admission, in-hospital transfer and discharge active- surveillance swabs for MRSA • (2) contact precautions for patients known or found to be MRSA carriers • (3) efforts targeting improved hand-hygiene and • (4) efforts encouraging culture change • ***Support for site-level MRSA Coordinator
FOR MORE INFO...

Jain R et al. NEJM 2011

Components of VA Bundle
• One vertical intervention:
– Swabs and contact precautions

• Three horizontal interventions:
– Hand-hygiene – Culture change – MRSA Prevention Coordinator

FOR MORE INFO...

Perencevich EN. Clin Infect Disease 2012 (in press)

VA MRSA Initiative Success
• 150 of 153 VA Medical Centers in October 2007
• HA-MRSA infections declined 62% in ICUs and 45% in non-ICUs • MRSA acquisition declined 17% in ICUs and 21% in non-ICUs
FOR MORE INFO...

Jain R et al. NEJM 2011

Other Benefits of the MRSA Initiative
• HA-VRE
– Eliminated in ICUs – 73% decline in non-ICUs

• C. difficile infections declined 61% in nonICU settings
FOR MORE INFO...

Jain R et al. NEJM 2011

Why did MRSA decline in VA?
• National trends in MRSA infections?
– Unlikely since admission prevalence was flat during the period in VA

• Infections declined significantly more than new acquisitions
– Thus, factors other than surveillance swabbing must play a role

Something other than surveillance?
• This is a good thing • Suggests that other changes in VA • These changes are likely – horizontal in nature
– Impact more than just MRSA

• This suggests that VA is better prepared than in 2007 to deal with new emergent pathogens

Why did MRSA decline in VA?
• Math model:
– Vertical intervention (e.g. screening plus isolation) (and/or) – Horizontal intervention (e.g. hand hygiene)

• Two models of hospital-MRSA transmission: (1) All benefits attributable to hand-hygiene (2) All benefits due to contact precautions
FOR MORE INFO...

Gurieva et al. Clin Infect Dis 2012 June 1

Fitting the Model
• Using the data in the Jain NEJM paper estimated:

• Contact precautions and hand hygiene led to: • 1-4% of declines in ICUs • 3-6% in non-ICUs • Neither transmission prevention component of the bundle could explain more than 50% of the reduction in infections
FOR MORE INFO...

Gurieva et al. Clin Infect Dis 2012 June 1

What if newly colonized have 10x the risk of infection?

FOR MORE INFO...

Gurieva et al. Clin Infect Dis 2012 June 1

Editorial
• Systematic analysis of MRSA bundle and challenges conventional wisdom that MRSA control only comes via screening • Models assumed the VA was one aggregate entity, as they didn’t have individual hospital-level data
– Individual VAs might have higher transmission rates and/or lower admission prevalence = larger benefits attributable to contact precautions or hand hygiene

• Benefits of hand hygiene would extend beyond MRSA transmission
– CLABSI insertion and maintenance

Editorial
• Systematic analysis of MRSA bundle and challenges conventional wisdom that MRSA control only comes via screening • Models assumed the VA was one aggregate entity, as they didn’t have individual hospital-level data
– Individual VAs might have higher transmission rates and/or lower admission prevalence = larger benefits attributable to contact precautions or hand hygiene

• Benefits of hand hygiene would extend beyond MRSA transmission
– CLABSI insertion and maintenance
FOR MORE INFO...

Perencevich EN Clin Infect Dis (Editorial): 2012 June 1

Prediction-rule guided surveillance

Previous Admission Beyond Index Hospital
• Prediction rules tend to use electronic sources
– May miss non-index hospital admissions

• University of Maryland, 2003-2004
– Prospective cohort, 697 patients – Nares swab for MRSA + questionnaire + EMR – Self-reported hospital admission <1year = – Electronic record index admission <1 year = 55%
FOR MORE INFO...

Furuno JP et al. Arch Intern Med 2006;166:580-5

Prior admission guided surveillance

FOR MORE INFO...

Riedel S Infect Control Hosp Epidemiol 2008 Oct (29)10: 969-71

Antibiotic exposure guided surveillance
• Prospective cohort 598 patients
– 2007 to 2009 – Baltimore VA – Admission MRSA+ = 10.4%

• CPRS documented antibiotics in past year
– Detected 84% MRSA+ patients days – Only had to swab 51% of patients
FOR MORE INFO...

Morgan D Infect Control Hosp Epidemiol 2010 Dec;31(12):1230-5

Novel strains and detection issues

Persistent S. aureus carriage
• University of Geneva Hospital (2001-2008)
– Used mupirocin + CHG bathing since 1994

• 75 case patients who remained colonized • 75 controls successfully decolonized

FOR MORE INFO... Lee AS et al. Clin Infect Dis 2011:52 (Jun 15): 1422-1430

Low-level mupirocin resistance + genotypic CHG resistance

FOR MORE INFO... Lee AS et al. Clin Infect Dis 2011:52 (Jun 15): 1422-1430

Mupirocin resistance: USA 2009
• 43 medical centers in USA • 100 consecutive clinical cx (no surveillance)

• 4210 S. aureus isolates
– 48% blood – High-level mupirocin R (MIC>256μg/ml) = 2.2% – Linezolid resistance = 0.02%
FOR MORE INFO...

Richter SS et al. 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), September 13, 2010, Boston, MA (abstract E-820)

Resistance profiles: USA 2009

FOR MORE INFO...

Richter SS et al. 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), September 13, 2010, Boston, MA (abstract E-820)

Is mupirocin resistance important?
• Certain centers use mupirocin for transmission control • Evidence supports mupirocin use pre-op

Schweizer ML et al. IDSA 2011

Hogs 2004
Rank State Value ($1000) % US total

1.
2. 3. 4. 5. 6. 7. 8. 9. 10.

Iowa
North Carolina Minnesota Illinois Nebraska Indiana Missouri Oklahoma Ohio Kansas

3,801,018
2,078,800 1,724,512 1,027,628 761,953 738,470 623,260 615,411 402,719 379,048

26.49%
14.49% 12.02% 7.16% 5.31% 5.15% 4.34% 4.29% 2.81% 2.64%

11. SD 12. PA 13. MI 14. CO 15. UT http://stuffaboutstates.com/agriculture/livestock/hogs.htm

Animal-associated ST398 in Humans
• ST398 has been reported in hospitals and in humans without farm exposure
• National Institute for Public Health and the Environment national reference lab in Netherlands • 0% were non-typeable in 20021 • 5.5% in early 2006 to >21% in late 20061
– 32/35 were ST398, 2 were related ST752, ST753

• 30% NT in 20072
FOR MORE INFO...

1. Van Loo I et al. Emerg Infect Dis 2007;13(12):1834-1839 2. Huijsdens XW Euro Surveill 2009 Sep 24;14(38)

MRSA, ST398 in U.S. Swine and Swine Workers
• 299 Swine and 20 Workers in Iowa and Illinois
– Production facilities A and B

• 49% (147/299) swine were MRSA+ • 45% (9/20) of workers were MRSA
– All at facility A

• All isolates SCCmec type V, pvl-negative, ST398
FOR MORE INFO... Smith TC et al. PLoS One, Jan 2009;4(1):e4258

Ireland: novel mecA
• Two clinical MRSA isolates that were PBP2apositive but mecA negative by conventional mecA PCR
– Called MSSA by GeneXpert. – 64-year old in a Dublin acute care hospital – 85 year-old in a South-East Ireland regional hospital – Strains contained a novel SCCmec element (Similar to SCCmec XI) – CC130 suggests bovine origin
FOR MORE INFO... Shore AC et al. Antimicrob Agents Chemother (Published Online June 2, 2011)

UK and Denmark, Novel mecA
• England: MRSA strains from bulk milk
– Novel mecA homologue, mecALGA251

• Undetected by current PCR • Widespread in Scotland, England and Denmark • 54% (13/24) of the bovine isolates • I doubt this could happen here…
FOR MORE INFO... Garcia-Alvarez L et al. Lancet Infect Dis 2011, Published online June 3, 2011

Other issues with molecular testing
• Single targets may remain after loss of mecA (mecA dropouts)
– Found in 5-10% of positive samples (J Clin Microbiol 2011;49:2996-9) – Addressed with mecA primers

• Some MR-CoNS may test positive
– J Clin Microbiol 2010;48:4598

• Positive predictive value lower than culture
– J Clin Microbiol 2009;47:4102

• Don’t eliminate the agar plates

Other Organisms
• Acinetobacter • NDM-1 (US Military Hospital Afghanistan) • KPCs (1st emerged in North Carolina) • ESBLs • C. difficile
FOR MORE INFO... Kumarasamy K et al. Lancet ID 11 August 2010 MMWR June 10, 2011 Yigit H, et al Antimicrob Agents Chemother 2001;45:1151-61.

FOR MORE INFO...

Jason Gale. Bloomberg Markets, June 2012

C. Difficile Prevention Day: March 6

FOR MORE INFO...

MMWR March 9, 2012 / 61(09);157-162

C. Difficile Prevention Day: March 6

94% associated health care
75% had onset outside hospital

52% were present on hospital admission

FOR MORE INFO...

MMWR March 9, 2012 / 61(09);157-162

Acinetobacter
• • • • Gram-negative coccobacillus Was often viewed as a colonizer HAS ARRIVED as a nosocomial pathogen Acinetobacter baumannii is the most common

• Outbreak of imipenem-resistant AB in New York

• Emergence in returning troops from the Middle East

Reference

Clinical Setting

Cases

Attributable Mortality

Acinetobacter Infections Compared to Matched Un-infected Controls
Grupper (2007) Blot (2003) Nosocomial BSI ICU, Israel Nosocomial BSI ICU, Belgium Nosocomial BSI Israel 52 BSI 45 BSI

36.5% 7.8%

Acinetobacter Infections Compared to Matched Controls with Klebsiella Infection
Robenshtok (2006) 112 BSI

22.7%

Multidrug-Resistant Acinetobacter Infections Compared to Matched Susceptible Controls
Kwon (2007)
Sunenshine (2007) Lee (2007)

CR-BSI 3* Care, Korea
MDR-Infections 3* Care; Baltimore MRD-Infections 3* Care, Taiwan MDR-Infections 3* Care, Baltimore

40 CR- Infections
96 MDR-Infections 48 MDR-BSI

25-30%
8.4% 21.8%

Multidrug-Resistant Acinetobacter Infections Compared to Matched Un-infected Controls
Sunenshine (2007) 96 MDR-Infections

14.8%

Playford (2007)

CR-Infection/Colonization ICU, Australia

66 CR-Infections or Colonization

20%

NHSN: impenem-resistance
Bacteria CLABSI VAP CAUTI Pooled (% (% (% (% imipenem imipenem imipenem imipenem resistant) resistant) resistant) resistant)

Pseudomonas
Klebsiella Acinetobacter

23.0%
10.8 29.2

25.1%
10.1 25.6

26.4%
3.6 36.8

25.3%

MDR-Acinetobacter in LTACs
• 180-bed, hospital-afilliated LTAC1 • 147 patient point prevalence survey (12/05) • 28% AB+ (41 patients)
– Sensitivity by site 22% peri-rectal, 68% sputum, 22% wound

• 2010 Survey of 57 Maryland Facilities2

1. Furuno J et al, Am J Infect Control 2008 2. Thom K (unpublished)

Transmissibility and Protection
HCW Room Entries 202 133 94 Hand + Before (%) 1.5% 0% 0% Gown and/or Glove + After % 38.7% 8.2% 9% Hands + After Removal 4.5% 0.7% 0%

Organism A. baumannii1 P. aeruginosa1 VRE2 MRSA2
FOR MORE INFO...

Effectiveness of PPE
88% 90% 100%

81

2%

19%

2.6%

85%

1. Morgan D, et al, Infect Control Hosp Epidemiol July 2010; 31(7):716-21. 2. Snyder G, et al, Infect Control Hosp Epidemiol July 2008; 29(7):584-589

Add in local hand hygiene adherence rates
0
Compliance with Hand-Hygiene 36% 18% 15% 20% 10% 8% 17% 9% 7% 14% 7% 6% 11% 5% 4% 8% 4% 3% 5% 2% 2%

50% 60%

70%
80% 90%

11%
7% 4%

6%
4% 2.% 0

5%
3% 2% 0

4%
3% 1% 0

3%
2% 1% 0

2%
2% 1% 0

1%
1% 1% 0

100% 0 0

50%

60%

70%

80%

90%

100%

Compliance with Gloves (patients on contact precautions)

Environment Equipment

β

β

Patient A

Nosocomial Transmission

Patient B

β
Healthcare Workers

β

Environmental Sampling
• Percent of rooms with positive environmental cultures for organism known to be colonizing patient (PFGE)
– 78% Acinetobacter – 35% VRE – 28% MRSA – 22% P. aeruginosa – 15% KPC
FOR MORE INFO...

1. Morgan D, et al, Society for Healthcare Epidemiology of America (SHEA) 2010

Environmental Sites Cultured

Results
50 Rooms
48% (24/50) of rooms

Identification of A. Baumannii

478 Samples

10% (47/478) of all samples

10%

16%

Environmental Sites POSITIVE

20% 11% 14%

4%
3% 6%

Environmental Sites POSITIVE

9%

FOR MORE INFO...

Thom K et al. Am J Infect Control 2011 Nov;39(9):711-15

4%

Problems with Isolation

Contact Precautions & Care Delivery
Setting Kirkland & Weinstein 1999 Saint et al 2003 Medical ICU Rounds, 2 hospitals Design Cohort (219 room entries) Effect 2.1 vs. 4.2 hourly contacts with HCWs

Cohort (139 35% vs. 73% patients examined by patients, 31 CP) attending physicians Matched cohort (50 hours) 5.3 vs. 10.9 contacts HCWs 22% less contact time overall

Evans et al 2003 Surgical ICUs and wards

Klein et al 1989
Goldszer et al 2002 Stelfox et al 2003 Morgan et al 2012

Pediatric ICU
Ward awaiting Nursing Home Ward 4 hospitals

RCT (50 pts) Observation
Cohort Matched Cohorts Cohort (2,059 hours obs)

No difference in HCW contacts day 1 & 7
4.3 vs. 10.9 delay days 12 vs. 31 or 6 vs. 8 day stay 3.0 vs. 4.6 hourly contacts 18% less time

Psychological Impact of Isolation
•Kennedy & Spinal Contact Isolation tendlimited rehab, More Patients on Cord 16 cases/ 85% believed CP to have Hamilton 1997 rehab unit 16 controls Anger more delirium, depression and anxietyscores (NS) 12.3 vs. 16.5 depression
Gammon 1998 Wards, 3 hospitals Tarzi et al 2001 Rehab unit Wassenberg et Tertiary al. 2010 Hospital Day et al. 2011 Veterans Hospital Day et al. 2011 Tertiary Hospital 20 cases/ 20 controls 20 cases/ 20 controls 42 cases/ 84 controls 20 cases/ 83 controls Cohort of 28,564 30% higher depression and anxiety scores 33% vs. 77% depression 8.6 vs. 15 anxiety scores Small, nonsignificant difference in depression/anxiety at admission Small, nonsignificant difference in depression/anxiety at admission 40% more diagnoses of depression No difference in diagnosis of anxiety Setting Design

Conclusion
• MRSA Initiative has been a success • Given rise of novel strains in MRSA and also increased burden of Gram-negatives and C. difficile, horizontal interventions may become the dominant strategy for control • Environmental cleaning increasingly important • The downsides of screening are costs and clinical impact of isolating patients

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