S. aureus

conference.cast.com

S. aureus

The Skin Microbiome -

Clinical Laboratory Impact on

Hospital Acquired Infections Affecting

Patient Outcomes

ASM, New Orleans

May 22, 2011

Lance R. Peterson, MD

Director of Microbiology and

Infectious Disease Research

Epidemiologist, NorthShore University HealthSystem

Clinical Professor

University of Chicago, Chicago, IL USA


• Research Grants

Potential COI

– Bayer, Cepheid, NorthShore, GeneOhm, GSK, Johnson and

Johnson, Merck, MicroPhage, Nanogen, Nanosphere,

NIAID, Roche, 3M, Washington Square Health Foundation,

Wyeth (Pfizer), AHRQ

• Consultations (in conjunction with research projects

and new diagnostics)

– Cepheid, GeneOhm, GSK, MicroPhage, Nanogen,

Nanosphere, Roche, 3M, Wyeth (Pfizer)

• Industry support for this presentation

– None


Objectives

• Review the relevance of the skin Microbiome to

infections impacted by the clinical laboratory

• Discuss the application of MRSA surveillance

• Summarize the literature on pre-surgical testing

for S. aureus to lower surgical site infection


Skin Ecology

• Hairy, moist underarms lie a short distance

from smooth dry forearms

– “These two niches are as ecologically dissimilar as

rainforests are to deserts”

• Molecular approaches (as opposed to

traditional culture) have revealed a greater

diversity of skin microbiota within and

between distinct topographical regions

• Methicillin-resistant S. aureus acquired genes

that promote growth on skin from the symbiont

S. epidermidis

EA Grice et al. Science 324:1190-2, 2009

EA Grice et al. Nature Rev Microbiol: 9:244-253, 2011


Skin Ecology - Dominance

• Propionibacteria and Staphylococcus species

predominate in sebaceous sites

• Corynebacteria spp. predominate in moist

sites, although staphylococci also are present

• A mixed population of bacteria reside in dry

sites, with a greater prevalence of

β-Proteobacteria and Flavobacteriales

• Unique microenvironment of the anterior

nares consists of moist, epithelia contiguous

with noncornified nasal mucosa and drier

keratinized skin EA Grice et al. Science 324:1190-2, 2009

EA Grice et al. Nature Rev Microbiol: 9:244-253, 2011


Microbiome of the Nose

• Studied 5 healthy carriers and 42 hospital patients

– Culture-independent analysis of 16S rRNA

• Healthy nares had only two bacterial phyla

– Actinobacteria (i.e., High-G+C Gram positive organisms

such as corynebacteria - 68% of sequences)

– Firmicutes (i.e., Low-G+C Gram positive organisms such

as staphylococci - 27% of sequences)

– S. aureus found in the nares (of 2/5 individuals)

– Nares samples similar mostly to each other (p


Microbiome of the Nose

• S. aureus was most abundant in patients classified

as S. aureus-carriers by femA PCR

– Confirms the diagnostic utility of the femA PCR assay

used to classify patients with staphylococcal species

DN Frank et al. PLoS ONE 5(5):

e10598. doi:10.1371, 2010


What Does this Suggest for the

Clinical Laboratory?


Risk for S. aureus Infection

• Systematic review (10 studies) to estimate of

the risk of infection following colonization with

MRSA compared with colonization by MSSA

• Random effects model was used to obtain

pooled odds ratio estimates

• Overall, colonization by MRSA was

associated with a 4-fold increase in the risk of

infection (odds ratio 4.08, 95% confidence

interval, 2.10-7.44) N Safdar et al. Am J Med 121:310-15, 2008


Risk for S. aureus Infection

• Measured 1-year risk of MRSA infection

following detection of nasal colonization

– 4 hospitals over 4.5 years with 211,339 episodes

• 1-year risk of MRSA infection was 11.8% for

nasally colonized persons

• 1-year risk of MRSA infection was 0.7% for

non-colonized persons

D Ridgway et al. IDSA meeting, 2011

• Suggests 1-year risk of MSSA infection is

2.9% for nasally colonized persons


Review of Mupirocin

Decolonization

• Nasal carriage of S. aureus is a defined risk

factor for subsequent infection in patients

• 8 studies compared mupirocin with placebo

or with no treatment: Statistically significant

reduction in the rate of S. aureus infection

associated with intranasal mupirocin (RR

0.55, 95% CI = 0.43 to 0.70)

M van Rijen et al. Cochrane Database of Systematic Reviews 2008,

Issue 4. Art.No.:CD006216.


Critical Review of MRSA

Screening by Rapid Methods

• Review and meta-analysis of randomized, nonrandomized,

and observational studies

– Random-effect model was used

– Ten studies (nine interventional studies and one

unblinded, cluster-randomized, crossover trial) reviewed

• Between wards applying rapid screening tests and

those without screening, noted a significantly

decreased risk for MRSA bloodstream infections

• Overall, concluded that active screening for MRSA

is more important than the type of test used

E Tacconelli et al. Lancet Infect Dis 9: 546–54, 2009


CDC Surveillance (2005)

• Prospective study on MRSA risk

• Nearly 9,000 cases from 9 sites (ABC surveillance)

– 77% of HAI* were blood infections (2-fold rise in 6 years)

– 31.8 invasive infections/100,000 persons

– Nationally translates to 94,360 cases of invasive disease

– 18,650 annual US deaths (greater than HIV-AIDS)

• No longer well defined risk groups

• 85% healthcare associated

– “It is a major health problem primarily related to health care

but no longer confined to intensive care units . . ”

* HAI = Healthcare Associated Infection

- RM Klevens, JAMA 298:1763-71, 2007


Comparative Mortality of MSSA

and MRSA Bacteremia

• Meta-analysis of 31 reports from 1980-2000

– 3963 MSSA and 2603 MRSA cases

– Significant increase in mortality noted for MRSA

» OR 1.93; 95%

CI = 1.54-2.42,

p


US Infection Mortality 2005

FR DeLeo &

HF Chambers

JCI 119:2464, 2009


Do Colonized Patients Spread MRSA?

• Compared 58 patients with MRSA disease to

57 with nasal colonization to determine risk for

skin and environmental contamination

– Skin and environment contaminated 50 vs 47%

– Various skin sites 38-66% vs 30-63%

– Various environment sites 27-60% vs 21-63%

• Glove acquisition from skin 14-45% vs 16-38%

• “Strategies to limit transmission must address

colonized patients”

S Chang et al, CID 48: 1423-8, 2009


Percent Positive on Admission

25.0

20.0

15.0

10.0

5.0

0.0

MRSA Prevalence by Age

n=18,898

Disease risk* = 3.7%/year Disease risk = 8.2%/year; P=0.067

0-9 10-19 20-29 30-39 40-49 50-59 60-69 70-79 80-89 90-99

*Risk of invasive disease if MRSA colonized; N=993

A Robicsek et al, ICHE 30:623-32, 2009

Age

CMS Recipients


MRSA Screening Program

• Intervention: Admission MRSA screening and

isolation to assure new admissions we are doing

our best so they will not get MRSA from

NorthShore

– Start with >90% compliance

• Admission order set for PCTs and nursing

– Admission MRSA Screen

– Choice for response either yes or refused

• Treatment order package (nasal mupirocin twice

daily for 5 days with chlorhexidine bathing)

– Type in MRSA, and order MRSA Decolonization Panel

LR Peterson et al, Jt Com J Qual Pt Safety, 33:732-8, 2007


NorthShore MRSA Program

Began on August 1, 2005

• Observational study in a 3-hospital, 850-bed

organization with 40,000 annual admissions

comparing rates of MRSA clinical disease

during and 30 days after hospital admission

• Real-time PCR-based nasal surveillance for

MRSA followed by topical decolonization

therapy and contact isolation of patients who

tested positive for MRSA


Prevalence Density

(Cases/10,000 patient-days)

10.0

9.0

8.0

7.0

6.0

5.0

4.0

3.0

2.0

1.0

0.0

P = 0.15

Total MRSA Healthcare Infections

8/03 - 7/04 9/04 - 7/05 9/05 - 7/06 8/06 - 7/07 8/07 - 7/08 8/08 - 7/09

ICU surveillance Universal surveillance

P ≤ 0.001

Years

A Robicsek et al, Ann Int Med 148:409-18, 2008

70% reduction in

total MRSA disease

during hospitalization

and 30 days post-discharge

2 BSI in 3 hospitals

LR Peterson et al, Decennial Meeting on

Nosocomial Infections, Atlanta, 2010

Total


Includes all admissions (Community and Hospital onset)

Data generated solely by capturing

positive clinical cultures from LIS:

Chart review (n=1,194) of all positive

cultures found that 77.1% represented

actual infection

Universal surveillance begins

P


How Much Does MRSA HAI Cost?

No MRSA HAI

(n=5796)

LOS ≥8d

MRSA HAI

(n=178)

Mean Total

Cost

$50,013 $42,363,

$57,662

$73,795 $63,743,

$83,847

Excess $23,783 $16,771,

$30,794

95% CI Mean Profit/Loss 95% CI

-$25,000 -$28,883,

-$21,116

-$35,479 -$42,034,

-$28,923

-$10,479 -$16,110,

-$4,848

LR Peterson et al, Jt Com J Qual Pt Safety, 33:732-8, 2007


Medical and Economic Outcome

• Excess expense of MRSA infection

(compared to no infection) = $24,000

– Actual cost data from 178 cases/5,796 controls

• During first four years of NorthShore MRSA

containment program avoided 406 infections

– Net expense reduction = $8.8 million

– Number of deaths avoided = 72

LR Peterson, JCM 48:683-9, 2010

LR Peterson et al, Jt Comm J Qual Patient Saf 33:732-8, 2007

RM Klevens et al, JAMA 298:1763-71, 2007


Veterans Administration

Healthcare System (153 Hospitals)

• Reported 21-month results of all admission

screening for MRSA based on 1,312,840

admissions covering 8,318,675 patient days

• 45% reduction in MRSA disease in non-ICU

patients (P = 0.001) throughout the system

• 62% reduction in MRSA disease for ICU

patients (P < 0.001)

– 2 year baseline in ICU patients had no change in

disease

R Jain et al. NEJM 364:1419-30, 2011

• Testing primarily (92%) with rtPCR methods


Cluster Randomized Trial of ICU:

Demonstrated non-Utility of Culture

• Assessed VRE and MRSA surveillance plus

enhanced barrier precautions in the ICU

• 5,434 admissions to 10 intervention ICUs, and 3,705

to 8 control ICUs over 6 months

– Centralized, broth enriched culture used for testing

• Incidence of colonization or infection with MRSA or

VRE per 1000 patient-days at risk did not differ

significantly (P = 0.35)

• Mean (±SD) number of days from when surveillance

swab obtained until it was reported was 5.2±1.4

– 41% of patient days captured after reporting

WC Huskins et al. NEJM 364:1407-18, 2011


% of isolation days missed

50

45

40

35

30

25

20

15

10

5

0

Missed Isolation Day Percentage: Method Comparison

† = Failed Programs

* = Successful Program


Program † likely successful if capture

>80% of MRSA potential isolation days

*

*

0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78 81 84

Turnaround Time (hours)

Traditional or Chrom Agar

Enrichment + Chrom Agar

rtPCR

Ari Robicsek, ICAAC/IDSA 2008; A Robicsek et al, An Int Med, 48:409-18, 2008; D Jeyaratnam et al, BMJ ,

336;927-30, 2008; S Harbarth et al, Crit Care 10:R25, 2006; Ari Robicsek, ICAAC/IDSA 2008; K Hardy et al,

Clin Microbiol Infect 10.1111/j.1469-0691.2009; WA Bowler et al. ICHE 31:269-75, 2010; WC Huskins et al.

NEJM 364:1407-18, 2011


*



Changing Prevalence of

S. aureus in Surgery

• Percentage of S. aureus as a cause of

Surgical Site Infection in Coronary Artery

Bypass Grafting, Cholecystectomy,

Colectomy and Total Hip Arthroplasty rose

from 17% to 31% between 1992-2002

JA Jernigan, Maryland Patient Safety Center (NNIS), January 12, 2006


NorthShore Program for Detection of

Staphylococcus aureus Colonization:

Process Overview

• The patient is screened for S. aureus in the

nose 0-28 days prior to surgery

• If the test is positive, the physician will then

prescribe a 5-day course of mupirocin ointment

• The patient administers the nasal ointment

twice a day for the 5 days in the month prior to

surgery DM Hacek et al. Clin Orthop Relat Res 466:1349-55, 2008


Results of Preoperative Screening

for NorthShore Hip and Knee Surgery

Patients (n = 1,495)

• S. aureus SSI rate of decolonized S. aureus

carriers was reduced 3.8-fold (P≤0.05)

• Overall S. aureus infection rate in screened

versus unscreened group was 0.8% versus

1.7% DM Hacek et al, Clin Orthop Relat Res. 466:1349-55, 2008


Results of Preoperative Screening

for NorthShore Hip and Knee Surgery

Patients (n = 1,495)

• Mean readmission cost for 4 patients requiring

second hospitalization $17,122 (total=$68,500)

• 7 SSI from other pathogens (compared to 17 from

S. aureus)

– No change in rate from other bacteria over time

– All non-S. aureus considered superficial

– None required hospitalization

DM Hacek et al, Clin Orthop Relat Res. 466:1349-55, 2008


Prospective, Randomized Trial of

S. aureus decolonization

• Multicenter, prospective placebo controlled trial of

6,771 patients between 2005 and 2007

– Intervention was rtPCR screening with nasal

mupirocin/chlorhexidine bath for positive patients

• 808 positive patients had surgery

– 4 deep infections (0.9%) occurred in the treated group

– 16 infections (4.4%) occurred in the placebo group

» RR 0.21; 95% CI = 0.07-0.62

– LOS 1.8 days shorter in the treated group (p=0.04)

– Time to infection was shorter in the placebo group

(p=0.005) LGM Bode et al. NEJM 362: 9-17, 2010


Summary

• The nares is an essential site for

staphylococcal colonization

• Surveillance for S. aureus is helpful for

preventing infection in the pre-surgical setting

as well as for MRSA control

• The role of active surveillance is most

important when:

– Clinical disease is significant

– Colonization precedes clinical infection

– Clonal spread is important in disease escalation

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