New Issues in bacteria we thought we knew so well. Meet the new Staphylococcus aureus

New Issues in bacteria we thought we knew so well.

Meet the new Staphylococcus aureus

Donna Holton,

Infectious Diseases, CHR

Oct 23, 2008

HARBOUR BRETON NEWFOUNDLAND

Who am I ID specialist with training in epidemiology

GP who worked in outport NFLD 1981-1983 Worked in Kenya doing HIV in the late ’80s Worked for Health Canada as epidemiologist

(created the TB Guidelines for Canadian Hospitals) Self employed epidemiologist (organized the 1997

Canadian Antimicrobial Resistance Conference) Worked in Regina as Infectious Diseases doctor Work in Calgary as ID and do HIV and Infection

Control

Who am I I have done talks for all the companies re:

antibiotics and HIV Abbott, BMS, Wyeth-Ayerst, GSK

Interested in biofilm infections and hospital building design

HIV trials with a wide variety of companies Tibotec, GSK, Abbott, Boehringer-Ingelheim, NeurogesX, Argos Therapeutics, Gilead, Pzifer, Merck

I sit on three boards for new HIV drugs (Abbott, Kaletra: Merck, Raltegrevir: Pzifer, Maraviroc)

I am part of the committee writing Canadian HIV treatment guidelines

Learning ObjectivesMethicillin resistant Staphylococcus

aureusMRSA

1. How have Staphylococcus aureus infections changed?

2. What is the prevalence of MRSA in the CHR3. Infection vs colonization4. Treatment- who, what , and when?5. What will the future look like?

With Many Thanks

To all the IPCs who collect the bloodstream infections and to Stephanie who enters the data

To CLS and Provincial Lab especially Drs. Dan Gregson, Deirdre Church and Marie Louie

To all IPCs who took part in the Mark of Zoro study

Staphylococcus aureus

Very successful bacteria: can infect anyone bacteria

Ubiquitous

In the days before antibiotics whole wings of hospitals were filled with people who had chronic S. aureus infections

2% of lactating women died of S. aureus mastitis

S. aureus causes Soft tissue infections

Basically any, impetigo, cellulitis, muscle abscess

Joint infections Surgery site infections Endocarditis Osteomyelitis Prosthetic device infections Others: pneumonia, organ abscesses

Produces toxins that cause different diseases food poisoning, toxic shock

My Jan 28th caseWhy is my patient not

improving? 40 yr female with abscess in her left

thigh WBC 22 with 20 neutrophils Blood cultures negative Not toxic, just not getting better

Clinical issues the usual bacterial suspects that cause

uncomplicated soft tissue infection are Group A Streptococcus S. aureus

Cultures rarely done

Because this lady has a large abscess, the pathogen is more likely to be S. aureus rather than Group A Streptococcus

Staphylococcus aureus is a common cause of infection

Name five drugs from five different antibiotics classes

that area) Oral S. aureus antibiotics

b) IV S. aureus antibiotics

15 Classes of anti-S. aureus drugs Class Oral (n=9 ) IV (n=12)

Penicillin Cloxacillin Cloxacillin

Cephalosporin Keflex Ancef

Carbapenum Meropenum

Sulfa “septra” “septra”

Macrolides All Azithromycin

Lincomycins Clindamycin Clindamycin

Tetracyclines All

Glycopeptide Vancomycin

Quinolones Not cipro* Levo, Moxi

Others LinezolidFusidic AcidRifampin

Linezolid, Tigecycline, Daptomycin, Synercid

*CIPRO has an MIC that just works but that also means it often fails against S. aureus. Spain has a > 30% resistance rate

**Rifamycins work but not alone


improving? 40 yr female with abscess in her left

thigh WBC 22 with 20 neutrophils Blood cultures negative Nasal and rectal cultures negative for

MRSA Superficial wound (skin intact) swab

grew Cloxacillin susceptible S. aureus

In your practice, what kind of soft tissues infections are you

seeing?If you are aware of several patients have MRSA, do they have the same spectrum of disease?

In HPTP we are seeing a new spectrum of disease

90% are variations of soft tissue themes Story of the Spider bite Large often complex abscesses Multiple skin lesions Co-infection with Group A Streptococcus Patients have multiple infections despite

good treatment Patients come from the community

Courtesy Melissa Tobin-D’Angelo, Georgia DHR

Carbuncle

Furuncle (boil))

AbscessFolliculitisFolliculitis

We are seeing a new spectrum of disease

~10% infections creating critical illnesses Necrotizing pneumonia

-Vayalumkal (new ped ID staff) article CJEM 2007:9(4):300-3.. Pt died-CDC is investigating 2 deaths (11 yr old and 13 year children) who died when MRSA complicated a viral “flu” like illness (2008)

22/73 kids who died of influenza in 2006-7 had Staphylococcus 2nd bacterial infection

Rare cases where it caused necrotizing fasciitis, purpura fulmanans

This type of MRSA seems to have acquired new abilities to cause critically serious disease

Courtesy of M. Farley

BMJ 2006;332;838-841


improving? 40 yr female with abscess in her left thigh WBC 22 with 20 neutrophils Blood cultures negative Nasal and rectal cultures negative for MRSA Superficial wound swab grew Cloxacillin

susceptible S. aureus Smart hospitalists are concerned this

patient has an antibiotic resistant S. aureus

Hospitalist was concerned patient had Methicillin

resistant Staphylococcus aureus (MRSA)

Which of the 15 class(es) of Staphylococcal Drugs can not

be used if a patient has MRSA?

MRSA has developed resistance to ALL current

Beta Lactams

Name the three beta lactam classes

MRSA = resistance to all of current beta lactam antibiotics

All of the penicillin class regardless of generation or complexity i.e., can not use Cloxacillin, Clavulin or Tazocin

All of the current cephalosporins regardless of generation

All of the current carbapenum (meropenum, imipenum, ertapenum)

And MRSA usually comes with even MORE resistance than this!!!

12 non-Beta lactam S. aureus drugs Class Oral (n=9 ) IV (n=12)







Tetracyclines All







Why is this resistance so important that the

Alberta Government has declared war on it?

Because the loss of the Betalactam = the loss of

bactercidal antibiotics

If the Betalactms are gone so are the Fluroquinolones

What is an Antibiotic Resistant Organism?

An organism that We can no longer use our first string (bactercidal) antibiotics

We still have antibiotics but we are sending in the second

string (bacteriostatic)

12 non-Beta lactam S. aureus drugs Class Oral (n=9 ) IV (n=12)







Tetracyclines All






Betalactam antibiotics work by interfering with

the penicillin binding proteins (PBP).

This prevents the bacteria cell wall from being built

Think Cement Retaining Wall

S. aureus builds cross links in the bacteria cell wall that strengthen the wall (think rebar)

If beta lactams can bind to the cell wall, the beta lactams prevent the cross links

The cell wall has no “ribar” and collapses The bacteria dieMRSA means that S. aureus has worked out

how to prevent Beta lactams from binding

Mechanism of Staphylococcus aureus Methicillin Resistance

Beta lactam antibiotics bind to penicillin binding protein 2 (PBP 2)

When S. aureus changes PBP 2 to PBP 2’ (also called PBP 2a) all currently licensed for use in Alberta beta lactam antibiotics become useless. -Change occurs via the Mec A gene.

In the presence of the Mec A gene, the beta lactam antibiotics can not attach to the PBP and so the bacteria grow because the bacteria cells walls are cross linked and strong

A short history of S. aureus Resistance

Penicillin (the drug not the class)

1928 - Penicillin discovered

1939 - Penicillin first used as treatment

1945 - Resistance to penicillin identified

1980’s < 1% susceptible to penicillin

A short history of S. aureus Resistance:

Solving Penicillin Resistance 1959 Vancomycin created and looked like

drug of choice

1959 Methicillin introduced

followed by many “copycat” semi synthetic

penicillins (i.e., cloxacillin, oxacillin, nafcillin)

1964 first cephalosporins introduced (Ancef)

A Short History of S. aureus resistance:

Develops Resistance to Semi-synthetic penicillins and

cephalosporins 1961 - First identified MRSA (UK)

1981 - MRSA appears in Canada

1995 - MRSA begins to escalate in

Canada

1999 – 6% of S. aureus are MRSA in

Canada

Antimicrobial Resistance among NosocomialInfections with Gram-Positive Pathogens, Canada (yellow) & US (green) and by ICU

Status (pink)

Source: NNIS Data:Fridkin and Gaynes Clinics in Chest Medicine June ‘99 303-16CNISP 2000 (colonization/infection)

Canada

United States

Figure 1. Incidence and rate per 1,000 patient admissions for MRSA (infections and colonizations) from 1995 to 2006 in Canadian hospitals participating in CNISP

Rate is blue line

# of cases = red barsData from CNISP Jan 2008

To all organisms Resistance is not futile, Resistance is survival

S. aureus has 4 different alphabet soup names to

describe resistanceMRSA, hVISA,

GISA (not VISA), VRSA

Look up Staphylococcus aureus in Infection Control manual

S. Aureus resistance to “methicillin” and

Vancomycin

0

10

20

30

40

1940 1950 1960 1970 1975 1980 1985 1990 1995 2000 2003

Year

% R

esis

tan

ce

Methicillin

Vancomycin

1st use methicillin 1959

1st MRSA 1961

Europe, UK Aus, India

Vancomycin Resistance2002

1st MRSA US Outbreak

USA ,AusIreland Worldwide

Vancomycin intermediate resistance 1997

What is happening to S. aureus

Calgary?

MRSA isolates (in and out patients) ACH

1 15 5 3 4 5 4 6 8

11

24

38

59

05

101520253035404550556065

1986 1992 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008

Years

Nu

mb

er

S. aureus Bacteremias

0

20

40

60

80

100

120

140

160

2003 2004 2005 2006 2007 Year

Nu

mb

er

of

ca

se

s

MSSA

MRSA

10.6 13.4 16.7 23.9 34.3 %MRSA

Odd year

Calgary Health Region, Adult Nosocomial Blood Stream

Infections

Stable rate of BSI per 1000 patient days (0.8)

Total BSI

SA

Comparison of Organisms Having Multiple Drug Resistances 2004 to 2007 (Fiscal Year)

Organisms Having Mulitple Drug Resistances

MRSA

VREEscherichia

Klebsiella

PseudomonasMRSA

VRE

Escherichia

Klebsiella

Pseudomonas

Organisms Having Multiple Resistances

MRSA

VREoth Gram Negative

Escherichia

Klebsiella

Pseudomonas MRSA

VRE

oth Gram Negative

Escherichia

Klebsiella

Pseudomonas

Organisms Having Multiple Drug Resistances 2006

58%

0%

14%

5%

4%

7%

7%5%

MRSA

VRE

E. coli

Enterobacter

Klebsiella

Pseudo

Steno

Other GramNegative

Organisms Having Multiple Drug Reisistances 2007

59%

1%

15%

13%

1%

2%

4%

5%MRSA

VRE

E. coli

Enterobacter

Klebsiella

Pseudo

Steno

Other Gram Negative

2004 fiscal year (n=41)




S. aureus in CHR Emergency Room: prior to 2004 slow but steady increase

in per cent

0

1

2

3

4

5

6

% M

RSA in E

R iso

late

s

1985 1990 1995 2000 2005

Year

MRSA

0

5

10

15

20

25

30

% M

RSA

in E

R

isol

ates

1985 1990 1995 2000 2005 2007

Year

From 2004 to Dec 2007,From 2004 to Dec 2007, MRSA took offMRSA took off

MRSA seems to have changed

Before 2004, MRSA was acquired in

Acute Care Hospitals 75% of cases Specific clones

Long term care 10% of cases

Community 8%

As a resident at FMC I meet my first “Hospital MRSA”

This MRSA was the one in the journals Was associated with Thames, Australia, U.S.

Burn Units Only available antibiotic was Vancomycin Occurred in

elderly, frail hospital patients burn, ICU and dialysis units

Caused infection (bacteremias) but a lot of people just seemed to be colonized

This organism plus VRE were the basis of creating increased isolation in acute care settings Private room Standard + contact

After that first patient my MRSA experience changed

“Prairie” MRSA caused simple skin infections had an effective oral agents (TMP-SMX,

clindamycin) occurred in an isolated population (First Nations) was found on the Prairies Was not a research project, no one was able to

get any traction for research on this type of MRSA

So we treated the kids and young people with Septra and they got better.

2005

Until 2005, the majority of MRSA isolates came from the hospital environment

Since mid 2005, most of the MRSA isolates came from the community

Clinical Syndromes – Invasive MRSAEIP Active Bacterial Core(ABCs) MRSA

Surveillance2004 – 2005New%

(n=865)Old%

(n=5522)

Skin / soft tissue infection 33.8† 10.2

Pneumonia 16.3 14.1

Endocarditis (? New biofilm gene(s)) 11.5† 5.0

Internal / deep seated abscess 9.0† 4.4

Osteomyelitis 8.3 7.5

Septic arthritis, native joint 5.1† 2.3

Septic shock 4.3 4.4

Endocarditis and / or metastatic complications (? New biofilm gene(s))

21.3† 9.9

Bacteremia 80.5† 88.2

Bacteremia, uncomplicated (no source)^ 23.8† 47.4

†Difference tested by Chi Square with p value <0.0001 Ray SM et al. IDSA 2005

Type of MRSA causing bacteremia

Prior to 2006, most of the nosocomial bacteremias were caused by MRSA 2, 6, and 8 i.e, the “hospital” or “old” MRSAs

Since 2006, the “new” or Community or “10” MRSA is the major cause of the MRSA bacteremias

My previous antibiotic suspectibility patterns

persisted

Boyce JM (2003), Clin Updates ID

GISA

Since 2004 epidemiological questions

became important.

What are the five current CHR risk factors for MRSA?

I tell the clerks and residents in HPTP if they can not answer this question for each patient with soft tissue infections I will

fail them

MRSA Risk Factor Questions

“Old question” Do you a lot of contact with the hospital system

Do you volunteer, work or live atthe jail

the drop in center Do you smoke, inject, snort any

recreational drugs? Are you or anyone you know MRSA

positive? secondary questions “do you work on the rigs, in

construction, do you work out at a gym”

Who are the MRSA patients now?

Hospital (Old) Elderly or renal

patients

Many visits to hospital Lots of positive nasal

swabs

Not a lot of infection

Called “hospital” acquired MRSA

Community (New) Young people, jail,

drugs, homeless

Few visits to hospital <50% of nasal swabs

positive

Lots of infection

Called “community” acquired MRSA

Risk Factors for Neonatal MRSA Infection in a Well-infant

NurseryNguyen 2007 ACHE 28(4): 407-

411 Risk for newborn infants to have MRSA

Circumcision 2nd outbreak had multi-dose lidocaine vial Surgical instruments uncovered

Infections often looked like diaper rashes

Investigation of moms. No MRSA in nose

The lab has now worked some of my previous epi

questions

The Staphylococcal resistance is much more than “just” a MEC A

gene

Methicillin Resistance in Staphylococcus aureus

beta lactam antibiotics work by interfering with the penicillin binding proteins (PBP)

MRSA organism change the PBP2 i.e., PBP2 becomes PBP2’

Resistance comes on a cassette called staphylococcal chromosomal cassette Mec (SCCmec). Cassette has

Mec A Two regulatory genes (Mec I and Mec R1) Two site specific recombinases +/- other antibiotic resistances

The size of the cassette (SCC) suggests if resistance to other antibiotics might be

presentLarger cassettes have more

room to carry more than “just” beta lactam antibiotic

resistance

CLS M-PCR typing scheme for SCCmec

MW

MW

300

400

800600500

bp

200

1000

(613) (398) (280) (776) (493) (200) (880) (325)

I II III IVa IVb IVc IVd VSCCmec

100

mecA

AB12121 (5)Type 5 ccrClass C mecV

AB097677CommunityType 2 ccrClass B mecIVd

AB096217 (4)CommunityType 2 ccrClass B mecIVc

AB063173 (3)CommunityType 2 ccrClass B mecIVb

AB063172 (3)CommunityType 2 ccrClass B mecIVa

AB37671 (1)HospitalType 3 ccrClass A mecIII

D86934 (1)N315Type 2 ccrClass A mecII

AB033763 (1)HospitalType 1 ccrClass B mecI

GenBank No. and

Reference

Where found

ccr-complexc

mec-complexb

SCCmec types and subtypesa

Current SCCmec types and Type IV subtypes

Modified from Okuma et al J Clin Micro 2002Modified from Okuma et al J Clin Micro 2002

mec complex (A,

B, C, D)

ccr complex (1, 2, 3 & 5: ccrA1-4, ccrB1-4 & ccrC)

type 5 ccr (ccrC)Type V

Type IVcType IVd

ccrC: single copy of a new gene encoded cassette chromosome recombinase

SCCmec types:

J (Junkyard)

Other MRSA naming schemes

Simple CanadaNML

United States

Hospital Acquired

2, 6, 8 100, 200

Community acquired*

10, 7 300, 400

*Very complex wording ..

Hospital associated community acquired MRSA

National Lab has now changed to spa

Why is CA-MRSA 10 different?

No one is sure Some ideas have been put forward

PVL (presence increases from 1.6% to 18%) agr gene changes Enterotoxin H and 15 superantigens Combinations of changes

But from your practice point of view, it is different..

The U.S have very rapidly moved to 59% (Morgan 2006 NEJM) S. aureus infections are MRSA and the “risk” groups are not holding

My patient uses crack cocaine daily and

her partner is MRSA positive

and She says she had an MRSA buttock abscess last year in

Edmonton


improving Smart hospitalists: Start Cloxacillin,

Vancomycin

Why is she not getting better?

U/S show 15 cm!!!! Abscess. Culture grows MRSA. No source control. No control of infection

We will need to get smarter about treating abscess to avoid hVISA,

GISA Paper after paper is saying how

important it is to drain the abscesses.. This takes time

1. What PPE should we use? Should you wear a procedure mask to open an abscess

2. How do we clean the room?

Background MRSA infections can cause worse clinical

outcomes than MSSA infections CNISP reported increased rate of MRSA in

Canadian hospitals from 0.46 to 5.90 per 1000 admissions 1995-2004

Health care costs of MRSA in Canada estimated at $82 million in 2004

Patients with MRSA require prolonged hospitalization (average 26 days)

Goetghebeur M, Landry PA, Han D, Vicente C. (2007). Methicillin-resistant Staphylococcus aureus: A public health issue with economic consequences. Can J Infect Dis Med Microbiol. Vol. 18. No 1. January/February Alberta Government Guidelines 2007

MRSA changes face of oseomyelitis

Gever, June 30, 2008 290 kids with osteomylitis

1999-2001 22.6% MRSA2001-2003 31.1% MRSA

33/290 kids had MRSA osteomyelitis 69% of MRSA had bone abscesses vs 11-

39% of other cause (p < 0.05) Significantly longer median days with

fever, complications, days to normal CRP and Sed rate, days of hospitalization

In the Adult World

Some paper have shown that so long as you anticipate MRSA, that outcomes are similar. My concern is that the patient description makes me think MRSA 2, 6, 8 i.e, the “old” MRSA

Will come back to this in the future section

Strain specific rates (per 100,000), by Month for MRSA in Alberta

(Jan 1, 2006 -Dec 31, 2007)

0 . 0 0

1 . 0 0

2 . 0 0

3 . 0 0

4 . 0 0

5 . 0 0

6 . 0 0

7 . 0 0

8 . 0 0

J a n - 0 7 F e b - 0 7 M a r - 0 7 A p r - 0 7 M a y - 0 7 J u n - 0 7 J u l - 0 7 A u g - 0 7 S e p - 0 7 O c t - 0 7 N o v - 0 7 D e c - 0 7

Rate

(per

100

,000

)

C M R S A 2 ( n = 8 5 5 ) C M R S A 6 ( n = 1 5 8 ) C M R S A 7 ( n = 2 1 8 ) C M R S A 8 ( n = 3 1 ) C M R S A 1 0 ( n = 2 , 0 8 9 )

Alberta Government Guidelines

Strain specific rates (per 100,000), by Health Region for MRSA in Alberta (Jan 1, 2006 -Dec 31, 2007)

Health RegionCMRSA Strain Type

2 4 6 7 8 10

Chinook 53.0 0.0 0.3 14.4 0.6 25.2

Palliser 45.4 0.0 0.0 1.5 0.5 34.7

Calgary 32.0 0.1 0.4 5.8 1.5 59.9

DTHR 62.8 0.3 3.3 3.3 0.3 30.0

East Central 12.1 0.4 5.8 4.5 0.4 15.7

Capital 7.1 0.0 9.4 4.6 0.3 45.5

Aspen 7.0 0.6 8.5 9.0 1.1 32.1

Peace Country 5.4 0.0 2.9 1.8 0.0 59.0

Northern Lights 3.3 0.7 2.0 11.3 1.3 92.0

ALBERTA 24.7 0.1 4.2 5.5 0.8 48.0


MRSA has attracted a lot of government interest

Poster bug for adequacy of infection control

Demonstration project to show effectiveness of government oversight of health care

Much responsibility has been passed along

Limited resources provided

A Balancing Act Try to limit risk to others re transmission

Some would have us lock MRSA positive patients in their rooms

Admitted to take part in a program Day care, schools Rehabilitation Psych Elderly programs

Acute Care, Long Term Care schools have different goals for clients

AHW states

Primary mechanism for transmission of MRSA is via HCWs who are temporarily

colonized with MRSA

But infection control rarely has a single

action that effectively stops an event

Infectious agent

Reservoirs

Portal of exit

Portal of entry

Means of transmission

What is the ability of the host to stop invasion Chain of

Transmission

Framework for Intervention

AHW acknowledges these risk factors for Community

MRSA: the 5 C’s Cleanliness Crowding Contact Sharing Contaminated articles Compromised skin

These are “community risk factors”.

What do they look like as health care risk factors?

AHW acknowledges these risk factors for Community MRSA: the

5 C’s Cleanliness

Can not conduct study because asks pts to be bathed every day

Crowding Over capacity is hard We need 116-170 isolation beds per day in CHR

Contact The “old” MRSA was polite with few family

members ill. The “new” MRSA also affects family members.

Sharing Contaminated articles Staphylococcus is a ubiquitous organism. Toys,

computers, hand rails, pagers, cell phones etc etc Compromised skin

APEC 2006 study

One day prevalence study In 1237 sites or 21% of US healthcare

facilities Looking for all patients know to have

MRSA i.e., patient could be colonized or have an active infection

APEC study results

Rate 16-48 (avg 34) MRSA positive/ 1000 patients or 1.6 to 4.8% of patients (11 x higher than expected) (10-17% of colonized)

Gender 54% male, 46% female Identified by

81% detected by clinical culture19% by surveillance culture

Site 37% skin and soft tissue 63% other

CHR Prevalence studyOr did we have all the MRSA patients correctly isolated?

IPC did a quick study looking at 3 adult units. One unit per site

RGH medicine, FMC orthopedics, PLC palliative and “overflow” medicine

Did Nasal and “Mark of Zoro” on admission and at specified intervals

MRSA is already common in U.S.

MRSA is already here

PLC had the most positives by a long shot

? Exposure in hospital, health care We realized that PLC was different in that

we had 2 individual (Jan and Leah) doing the swabs on the prevalence days and they did GROIN “z” swabs (my fault, I said groin) while FMC and RGH ended “z” at belt level.

? If difference is difference in real life v.s. technique

ACH ER Study

Aug-Dec 2007 All children presenting to ER with

cellulitis or abscess 9/50 (18%) shown to be MRSA positive

If you culture MRSA someone’s skin do they

have an infection?

We all have bacteria on our skin Some bacteria stay on our skin for long time

periods Persistent 20% (range 12-30%) Intermittent 30% (range 16-70%) Non-carrier 50% (range 16-69%)

Some bacteria may be only transiently present and if we do proper hand hygiene (alcohol hand rubs or soap and water) these organisms will not become part of the “normal” organisms on skin-the bacteria are “bounced” off the skin like a rubber ball off a surface

Finding bacteria does not

necessarily mean there is an infection

Only temporarily on skin

“normal” flora, not invading

Local redness, pain, swelling, heat, pus

Systemically ill with fever, chills, rigors sometimes ICU serious

Colonization

Local infection

Systemic infection

Definitions of infectionInvasion and multiplication of micro-organisms

in body tissues associated with tissue destruction or host inflammatory response

Criteria1. Two local findings (redness, warmth,

purulent secretions, pain, tenderness) or2. Superficial soft tissue infection must have

cellulitis (redness of the surrounding skin) or3. Deep infection.. Presence of abscess, septic

arthritis, osteomyelitis, septic tenosynovitis or

4. Systemic symptoms

Deciding what the bacteria on

our skin are doingIf transient bacteria become resident bacteria

May colonizei.e., present but

not invadingMay cause an infection

Mom’s criteria105 organism/ gm

of tissue> 1 ml of pus

redness, warmth, purulent secretions,

pain, tenderness

If you order a swabWhy are you ordering it

To see if Colonizedi.e., present but

not invading

To identify the cause of an infection

MRSA surveillanceswab

Report will say Yes MRSA present or

No MRSA found

Order Wound swab

Report will tell what Antibiotics you can use

Remember chronic ulcers will chronically grow bacteria GO BACK 1 SLIDE if do not know if colonization or infection

Lab report says MRSA positive

What does that mean?

Why was the swab taken?Clinically what does the pt look like

No obvious infectionPatient colonized

Mom says infectedUse results to help guide

therapy for an infected wound

Patient needs to be placed under contact precautions

You do not need To order any further

MRSA screening swabsIPC will order

Use informationto treat infection

(infectious diseases)

What does Treatment look like for MRSA 10?

Septra Population has 8% rash rate Causes problems with breast feeding

moms Premies do not do well Issues with G-6PD deficiency

Clindamycin: Not good if local C. difficile happens to

be F strain (very high association with Clindamycin

Tastes terrible as liquid

What does Treatment look like for MRSA 10? Tetracyclines

Are not given to young children Vancomycin

IV medication Linezolid

PO or IV Currently must fail Vancomycin to get Issues re hemogloblin

In the Adult HPTP World

Ancef Some people fail on Day 3 ??? Had mixed MSSA and

MRSA infection. Ancef kills MSSA but leaves MRSA untouched

Ancef + Septra (Tetracycline, clindamycin) Ancef + clindamycin works well with the “aggressive

MSSA + Group A strep” cellulitis + Group A Ancef + Vancomycin

Cellulitis in face ICU patient with Staph in blood

Vancomycin Pt known to have MRSA

Colonization has been associated with subsequently developing

infection Reported rates have varied

Low 15% High > 30% Nosocomial bacteremia rate RR 30 (NEJM 2001, von Eiff) SSI 2-9 fold increase risk of infection (but decolonization

pre-op mupirocin did not decrease risk) Renal patients (meta-analysis)

Decrease by 78% risk of BSI in hemodialysis patients

Decrease by 66% risk of BSI in peritonneal dialysis patients

Tacconelli 2003 Clin Infect Dis

Should we decolonize patients because colonized patients have a high risk of

developing an active infection

What is Decolonization?

Use of topical and/or systemic agents to eradicate/reduce MRSA carriage on skin and mucus membranes

Purpose is to reduce risk of transmission in healthcare settings

Efficacy dependent on multiple factors related to the patient e.g. health status, wounds, foreign bodies, feeding tubes, compliance

To Decolonize or Not

Who should we try to decolonize

All patients? Choose subsets of patients

All patients with access lines? All patients with more than 3 infections in six

months? All patients who will be compliant

No patient Cazaban 2007 ICHE looked at outcomes. If had

non-pneumonia MRSA infection in hospital no worse outcome than MSSA. Just be smarter when we treat

How Has Decolonization Been Done

Most reviews do not support intranasal mupirocin alone UNLESS short term use for patients about to undergo major surgery

(e.g. cardiac, ortho) OR conventional methods have failed to control an outbreak

(e.g. NICU) Multiple agent intervention more successful and

generally used for very selected patient populations or HCWs (e.g. surgeons). Generally use combinations of mupirocin, CHG, and if susceptible combos of clindamycin or SXT or rifampin

How Has Decolonization Been Done

Most groups have used nasal mupirocin + 2% CHG body washes

Some groups have used PO Vancomycin to resolve GI carriage Some have treated positive urine

2nd commonest first clinical isolate in CHR is urine (Dan Gregson)

Some have treated positive vaginal culture Some have treated positive throat cultures

Andy Simor’s StudyClin Infect Dis 2007

2% CHG wash 2% intranasal mupirocin Rifampin x 7 days Doxycycline x 7 days

(can TB land tolerate this medical use of their VERY IMPORTANT drug)

Andy’s results

Significant eradication at 3 months 75% with program, 32% without

At 8 months 54% still negative (so 21% returned to

be positive)

My roadside conversations with Tom Louie

Yes you can decolonize MRSA 2 Interesting because are the folks with

the “holes” (stasis ulcer, PEGs etc) Very hard to decolonize MRSA 10

2% CHG in nares works better than mupirocin

The “core” patients are not in easy to do locations

Can you do this in the high risk areas of jails, drop in centers, ER, Urgent Care

Can you do this in high risk clinical areas (HPTP, SAC, STI)

We couldn’t do it the acute care settings and Tom responded by making an outpatient clinic

Summary RecommendationsFor Decolonization

No group or organization has supported decolonization for all patients

Some support for selected Decolonization (if mupirocins) Dialysis patients Recurrent infections Infection control measure

Do Not use routine decolonization in pre-op or non-surgical patients

Good Hand

Hygiene as

prevention

remains good

plan but can we

do it

Transient floraResident flora

Good Hand Hygiene for everyone

Start of activity, End of activity

StaffPatients

VolunteersVisitors

Are we now where we were in the early 1980s with HIV?In the 1980’s we learnt that we could

not tell if someone is HIV positive or not

VIEW ALL BLOOD AND BODY SUBSTANCES as potentially carrying BLOODBORNE PATHOGENS

Should we assume that everyone and everything is

MRSA positive?

MRSA prevalence rates are growing in the community

Risk factor are breaking down No magic way to detect MRSA

Here are four actions you can take to protect your children

from MRSA1. If your child has a booboo, put a

bandage on it. MRSA is usually spread by skin-to-skin contact. Bandages protect broken skin from MRSA and also reduce the risk of spreading MRSA to family members and friends if a wound already is infected.


from MRSA2. Wash your hands with soap and water, and don't be timid about nagging kids to wash their hands, too. Boring, but it works.

If you are cleaning a woundClean potentially contaminated surfaces with ¼ cup bleach(5.25%) to 4 gallons of water)

Wear gloves when cleaning a wound but REMEMBER you MUST ALSO WASH your hands.


from MRSA3. Discourage sharing of towels,

razors, and other hygiene items, which are often implicated in MRSA outbreaks. That's one reason MRSA outbreaks have been more common in school athletic teams. This could be the best way ever to scare boys off towel-snapping! Also, tell kids not to share clothes or other personal items.


from MRSA4. Call the doctor ASAP if a family

member has a skin infection and also a fever. Most staph infections look like a bump or infected area that is red, swollen, painful, and warm to the touch. Rapid treatment with the right antibiotics makes it easier to get rid of the bug.

http://usnews.healthline.com/adamcontent/fever?utm_medium=usnews&utm_campaign=article&utm_source=hlinks&utm_term=fever

http://usnews.healthline.com/adamcontent/mrsa?utm_medium=usnews&utm_campaign=article&utm_source=hlinks&utm_term=staph-infections

http://usnews.healthline.com/adamcontent/mrsa?utm_medium=usnews&utm_campaign=article&utm_source=hlinks&utm_term=staph-infections

Will MRSA always be anAntibiotic Resistant Organism?

12 Classes of anti-S. aureus drugs Class Oral (n=9 ) IV (n=12)







Tetracyclines All







New Anti Staph AgentsAntimicrobial

AgentClass Route of

Administration

Ceftobiprole Cephalosporin IV

Ceftaroline Cephalosporin IV

Cethromycin Ketolide Oral

Dalbavancin Lipoglycopeptide IV

Doripenem Carbapenem

IV

Iclaprim Diaminopyrimidine IV

Oritavancin Glycopeptide IV

Prulifloxacin Quinolone Oral

Telavancin Lipoglycopeptide IV

The Future Infectious diseases is hoping that the new

IV cephalosporins and carbapenem are as good as we think

The new cephalosporins target the PBP2’ i.e., the PBP that Mec A makes

Side effects-Ceftobiprole (rash, nausea, bad taste) -Ceftaroline (mild headache)

We hope that at some of the other drugs in development pan out, a new oral agent would be wonderful

These are very broad spectrum antibiotics

Question for 2010-2012

At some point in the not distant future we will have more MRSA than MSSA. MRSA will become our new “Norm” of S. aureus

We will have at least 3 new antibiotics from 2 classes that will be bactercidal for MRSA

Could we “de ARO” MRSA as we did in the 1960’s re penicillin resistant S. aureus?

Could we “de-ARO” MRSAPro Scientifically, likely yes The system does not have enough beds

or staff to deal with private rooms needsCon Would likely die in the media Government has a lot at stake We should not be transmitting organisms

MRSA Outbreak reporting

Any person who knows or has reason to suspect the existence of MRSA: In epidemic form; Occurring at an unusually high rate; or That is caused by a nuisance or other

threat to public health, Shall immediately notify the regional

MOH by the fastest means possible


Summary

Failure to quickly and appropriately treat serious infections will result in poor

patient outcomes.

In mid 2007, 35% of ER isolates of S. aureus were MRSA

18% kids MRSA swab positive 2007

CA-MRSA 10 will likely permanently alter S. aureus’

disease profileThere will be more abscesses and soft tissue infection More person to person transmission

(gene(s) from CoNS) 10% of the infections will be very serious (?

new pathogen markers) Repeat infection since MRSA 10 seems to

result in a poor antibody response Very high rate of colonization becoming

infection

Very different from MRSA 2, 6, 8Very different from MRSA 2, 6, 8

I do not believe we have seen all that MRSA 10 will

do CHR had a really nasty episiotomy MRSA

infection. I think we may see MRSA looking like Group B Streptococcus and Listeria in newborns because I think the Europeans are correct, MRSA 10 is carried in the vagina

There is an increasing sense that MRSA 10 are sexually transmitted infections

I do not believe we have seen all that MRSA 10 will

do S. aureus causes secondary bacterial

pneumonias after influenza infections. We have not yet had a bad influenza year to go sour with secondary MRSA pneumonia

We have not really seen MRSA prosthetic joint infections yet. The paper on osteomyelitis suggests this may be very true.

http://www.cps.ca/English/surveillance/cpsp/studies/Questionnaire/MRSA.pdf

CANADIAN PAEDIATRIC SURVEILLANCE PROGRAM

Please complete the following sections for the case identified above. Reporting to the CPSP does not preclude

a responsibility to report cases of MRSA directly to the province according to each province’s legislation

on notifiable disease reporting. Patient and reporter information will be kept confidential.

2305 St. Laurent Blvd.Ottawa, ON K1G 4J8

Tel: 613-526-9397, ext. 239 Fax: 613-526-3332 [email protected] or www.cps.ca/cpsp

mailto:[email protected]

Questions?

ReferencesGuidelines for the prevention and management of

CA-MRSA: a perspective for Canadian health care practitioners

Can J Infect Dis Med Microbiol 2006 (supplC): 4c-24c

Control and treatment of MRSA in Canadian paediatric health care institutions.

Paediar Child Health 2006;11:163-165

Ca-MRSA: Implications for the Care of Children Paediatrics and Child Heatlh 2007;12(4) 323-324

Consensus Statement for the management of MRSA infections in Neonatal ICUs Susan Gerber

ICHE Feb 2006 27(2): 139-145

CDC Sept 8, 2008launched program to teach parents about MRSA

Documents

New Issues in bacteria we thought we knew so well. Meet the new Staphylococcus aureus