New Issues in bacteria we thought we knew
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 n n n n ID specialist with training in epidemiology GP who worked in outport NFLD 1981 -1983 Worked in Kenya doing HIV in the late ’ 80 s 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 n I have done talks for all the companies re: antibiotics and HIV n n n 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, Neuroges. X, 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 Objectives Methicillin resistant Staphylococcus aureus MRSA 1. 2. 3. 4. 5. How have Staphylococcus aureus infections changed? What is the prevalence of MRSA in the CHR Infection vs colonization Treatment- who, what , and when? What will the future look like?
With Many Thanks n n n 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 n n 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 n Soft tissue infections n n n n 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 n food poisoning, toxic shock
My Jan 28 th case Why is my patient not improving? n n 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 n the usual bacterial suspects that cause uncomplicated soft tissue infection are n Group A Streptococcus n S. aureus Cultures rarely done n 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 are a) Oral S. aureus antibiotics b) IV S. aureus antibiotics
15 Classes of anti-S. aureus drugs Class Oral (n=9 ) IV (n=12) Penicillin Cephalosporin Carbapenum Cloxacillin Keflex Cloxacillin Ancef Meropenum Sulfa Macrolides Lincomycins “septra” All Clindamycin “septra” Azithromycin Clindamycin Tetracyclines Glycopeptide Quinolones Others All Not cipro* Linezolid Fusidic Acid Rifampin Vancomycin Levo, Moxi 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
My Jan 28 th case Why is my patient not improving? n n n 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 n Story of the Spider bite n Large often complex abscesses n Multiple skin lesions n Co-infection with Group A Streptococcus n Patients have multiple infections despite good treatment n Patients come from the community
Carbuncle Furuncle (boil) Abscess Folliculitis Courtesy Melissa Tobin-D’Angelo, Georgia DHR
We are seeing a new spectrum of disease ~10% infections creating critical illnesses n 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 2 nd bacterial infection n 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
My Jan 28 th case Why is my patient not improving? n n n 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 three beta lactam classes
MRSA = resistance to all of current beta lactam antibiotics n n n 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) Penicillin Cephalosporin Cloxacillin Keflex Cloxacillin Ancef Carbapenum Meropenum Sulfa Macrolides Lincomycins “septra” All Clindamycin Tetracyclines Glycopeptide Quinolones Others All Not cipro* Linezolid Fusidic Acid Rifampin “septra” Azithromycin Clindamycin Vancomycin Levo, Moxi 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
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) Penicillin Cephalosporin Cloxacillin Keflex Cloxacillin Ancef Carbapenum Meropenum Sulfa Macrolides Lincomycins “septra” All Clindamycin Tetracyclines Glycopeptide Quinolones Others All Not cipro* Linezolid Fusidic Acid Rifampin “septra” Azithromycin Clindamycin Vancomycin Levo, Moxi Linezolid, Tigecycline, Daptomycin, Synercid **Rifamycins work but not alone
Betalactam antibiotics work by interfering with the penicillin binding proteins (PBP). This prevents the bacteria cell wall from being built
Think Cement Retaining Wall n S. aureus builds cross links in the bacteria cell wall that strengthen the wall (think rebar) n If beta lactams can bind to the cell wall, the beta lactams prevent the cross links n The cell wall has no “ribar” and collapses n The bacteria die MRSA 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) n When S. aureus changes PBP 2 to PBP 2’ (also called PBP 2 a) 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 n
A short history of S. aureus Resistance Penicillin (the drug not the class) n 1928 - Penicillin discovered n 1939 - Penicillin first used as treatment n 1945 - Resistance to penicillin identified n 1980’s < 1% susceptible to penicillin
A short history of S. aureus Resistance: Solving Penicillin Resistance n 1959 Vancomycin created and looked like drug of choice n 1959 Methicillin introduced followed by many “copycat” semi synthetic penicillins (i. e. , cloxacillin, nafcillin) n 1964 first cephalosporins introduced (Ancef)
A Short History of S. aureus resistance: Develops Resistance to Semi-synthetic penicillins and cephalosporins n 1961 - First identified MRSA (UK) n 1981 - MRSA appears in Canada n 1995 - MRSA begins to escalate in Canada n 1999 – 6% of S. aureus are MRSA in Canada
Antimicrobial Resistance among Nosocomial Infections with Gram-Positive Pathogens, Canada (yellow) & US (green) and by ICU Status (pink) United States Canada Source: NNIS Data: Fridkin and Gaynes Clinics in Chest Medicine June ‘ 99 303 -16 CNISP 2000 (colonization/infection)
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 bars Data from CNISP Jan 2008
To all organisms Resistance is not futile, Resistance is survival S. aureus has 4 different alphabet soup names to describe resistance MRSA, h. VISA, GISA (not VISA), VRSA Look up Staphylococcus aureus in Infection Control manual
S. Aureus resistance to “methicillin” and Vancomycin 1 use methicillin 1959 1 MRSA 1961 1 MRSA US Outbreak Vancomycin st st st Europe, UK Aus, India USA , Aus Ireland intermediate resistance 1997 Vancomycin Resistance 2002 Worldwide
What is happening to S. aureus Calgary?
Odd year
Calgary Health Region, Adult Nosocomial Blood Stream Infections SA Total BSI Stable rate of BSI per 1000 patient days (0. 8)
Comparison of Organisms Having Multiple Drug Resistances 2004 to 2007 (Fiscal Year) 2004 fiscal year (n=41) 2006 fiscal year (n=56) 2005 fiscal year (n=43) 2007 fiscal year (n=82)
S. aureus in CHR Emergency Room: prior to 2004 slow but steady increase in per cent
From 2004 to Dec 2007, MRSA took off
MRSA seems to have changed
Before 2004, MRSA was acquired in n Acute Care Hospitals n n n Long term care n n 75% of cases Specific clones 10% of cases Community n 8%
As a resident at FMC I meet my first “Hospital MRSA” n n This MRSA was the one in the journals Was associated with Thames, Australia, U. S. Burn Units Only available antibiotic was Vancomycin Occurred in n n 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 n n Private room Standard + contact
After that first patient my MRSA experience changed “Prairie” MRSA n n n 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 n n 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 MRSA EIP Active Bacterial Core(ABCs) MRSA Surveillance 2004 – 2005 New% Old% (n=865) (n=5522) Skin / soft tissue infection Pneumonia 33. 8† 16. 3 10. 2 14. 1 Endocarditis (? New biofilm gene(s)) Internal / deep seated abscess Osteomyelitis Septic arthritis, native joint Septic shock Endocarditis and / or metastatic complications (? New biofilm gene(s)) Bacteremia, uncomplicated (no source)^ 11. 5† 9. 0† 8. 3 5. 1† 4. 3 21. 3† 5. 0 4. 4 7. 5 2. 3 4. 4 9. 9 80. 5† 23. 8† 88. 2 47. 4 †Difference tested by Chi Square with p value <0. 0001 Ray SM et al. IDSA 2005
Type of MRSA causing bacteremia n n 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
GISA Boyce JM (2003), Clin Updates ID
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 n n “Old question” Do you a lot of contact with the hospital system Do you volunteer, work or live at the jail the drop in center n n n 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? n Hospital (Old) Elderly or renal patients n Community (New) Young people, jail, drugs, homeless n n Many visits to hospital Lots of positive nasal swabs n Few visits to hospital <50% of nasal swabs positive n Not a lot of infection n Lots of infection Called “hospital” acquired MRSA n n n Called “community” acquired MRSA
Risk Factors for Neonatal MRSA Infection in a Well-infant Nursery Nguyen 2007 ACHE 28(4): 407 -411 n Risk for newborn infants to have MRSA n n n Circumcision 2 nd outbreak had multi-dose lidocaine vial Surgical instruments uncovered n Infections often looked like diaper rashes n 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 n n n beta lactam antibiotics work by interfering with the penicillin binding proteins (PBP) MRSA organism change the PBP 2 i. e. , PBP 2 becomes PBP 2’ Resistance comes on a cassette called staphylococcal chromosomal cassette Mec (SCCmec). Cassette has n Mec A n Two regulatory genes (Mec I and Mec R 1) n Two site specific recombinases n +/- other antibiotic resistances
The size of the cassette (SCC) suggests if resistance to other antibiotics might be present Larger cassettes have more room to carry more than “just” beta lactam antibiotic resistance
bp MW SCCmec I (613) II (398) III IVa IVb IVc IVd V (280) (776) (493) (200) (880) (325) MW CLS M-PCR typing scheme for SCCmec 100 080 0 60 0 50 0 40 0 30 0 20 0 10 0 mec. A
Current SCCmec types and Type IV subtypes SCCmec types and subtypesa I Class B mec Type 1 ccr Hospital Gen. Bank No. and Reference AB 033763 (1) II Class A mec Type 2 ccr N 315 D 86934 (1) III Class A mec Type 3 ccr Hospital AB 37671 (1) IVa Class B mec Type 2 ccr Community AB 063172 (3) IVb Class B mec Type 2 ccr Community AB 063173 (3) IVc Class B mec Type 2 ccr Community AB 096217 (4) IVd Class B mec Type 2 ccr Community AB 097677 V Class C mec Type 5 ccr mec- complexb ccr- complexc Where found AB 12121 (5)
SCCmec types: mec complex ccr complex (A, B, C, D) (1, 2, 3 & 5: ccr. A 1 -4, ccr. B 1 -4 & ccr. C) J (Junkyard) Type IVc Type IVd Type V type 5 ccr (ccr. C) ccr. C: single copy of a new gene encoded cassette chromosome recombinase Modified from Okuma et al J Clin Micro 2
Other MRSA naming schemes Simple Hospital Acquired Community acquired* Canada NML 2, 6, 8 United States 10, 7 300, 400 100, 200 *Very complex wording. . Hospital associated community acquired MRSA National Lab has now changed to spa
Why is CA-MRSA 10 different? n n No one is sure Some ideas have been put forward n PVL (presence increases from 1. 6% to 18%) n agr gene changes n Enterotoxin H and 15 superantigens n 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
My Jan 28 th case Why is my patient not improving n n 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 h. VISA, GISA n 1. 2. Paper after paper is saying how important it is to drain the abscesses. . This takes time What PPE should we use? Should you wear a procedure mask to open an abscess How do we clean the room?
Background n n 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). Methicillinresistant 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 n n 290 kids with osteomylitis 1999 -2001 22. 6% MRSA 2001 -2003 31. 1% MRSA 33/290 kids had MRSA osteomyelitis n n 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 n n 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) Alberta Government Guidelines
Strain specific rates (per 100, 000), by Health Region for MRSA in Alberta (Jan 1, 2006 -Dec 31, 2007) CMRSA Strain Type Health Region 2 4 6 7 8 10 Chinook 53. 0 0. 3 14. 4 0. 6 25. 2 Palliser 45. 4 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 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 92. 0 ALBERTA 24. 7 0. 1 4. 2 5. 5 0. 8 48. 0 Alberta Government Guidelines
MRSA has attracted a lot of government interest n n 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 n Try to limit risk to others re transmission n n Admitted to take part in a program n n n Some would have us lock MRSA positive patients in their rooms 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
Framework for Intervention Infectious agent What is the ability of the host to stop invasion Portal of entry Reservoirs Chain of Transmission Portal of exit Means of transmission
AHW acknowledges these risk factors for Community MRSA: the 5 C’s n n n 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 n Cleanliness n n Crowding n n n The “old” MRSA was polite with few family members ill. The “new” MRSA also affects family members. Sharing Contaminated articles n n Over capacity is hard We need 116 -170 isolation beds per day in CHR Contact n n Can not conduct study because asks pts to be bathed every day Staphylococcus is a ubiquitous organism. Toys, computers, hand rails, pagers, cell phones etc Compromised skin
APEC 2006 study n n n 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 n n 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 culture 19% by surveillance culture Site n n 37% skin and soft tissue 63% other
CHR Prevalence study Or did we have all the MRSA patients correctly isolated? n n n 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 n n n ? 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 n n Aug-Dec 2007 All children presenting to ER with cellulitis or abscess n 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 n Some bacteria stay on our skin for long time periods n n 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 Local infection Systemic infection Colonization Only temporarily on skin “normal” flora, not invading Local redness, pain, swelling, heat, pus Systemically ill with fever, chills, rigors sometimes ICU serious
Definitions of infection Invasion and multiplication of micro-organisms in body tissues associated with tissue destruction or host inflammatory response Criteria 1. Two local findings (redness, warmth, purulent secretions, pain, tenderness) or 2. Superficial soft tissue infection must have cellulitis (redness of the surrounding skin) or 3. Deep infection. . Presence of abscess, septic arthritis, osteomyelitis, septic tenosynovitis or 4. Systemic symptoms
If transient bacteria become resident bacteria Deciding what the bacteria on our skin are doing May colonize i. e. , present but not invading May cause an infection Mom’s criteria Ø 105 organism/ gm of tissue redness, warmth, purulent secretions, pain, tenderness > 1 ml of pus
If you order a swab Why are you ordering it Remember chronic ulcers will chronically grow bacteria GO BACK 1 SLIDE if do not know if colonization or infection To see if Colonized i. e. , present but not invading To identify the cause of an infection MRSA surveillance swab Order Wound swab Report will say Yes MRSA present or No MRSA found Report will tell what Antibiotics you can use
Lab report says MRSA positive What does that mean? Patient needs to be placed under contact precautions Why was the swab taken? Clinically what does the pt look like No obvious infection Patient colonized You do not need To order any further MRSA screening swabs IPC will order Mom says infected Use results to help guide therapy for an infected wound Use information to treat infection (infectious disease
What does Treatment look like for MRSA 10? n Septra n n n Population has 8% rash rate Causes problems with breast feeding moms Premies do not do well Issues with G-6 PD deficiency Clindamycin: n n Not good if local C. difficile happens to be F strain (very high association with Clindamycin Tastes terrible as liquid
n What does Treatment look like for MRSA 10? Tetracyclines n n Vancomycin n n Are not given to young children IV medication Linezolid n n n PO or IV Currently must fail Vancomycin to get Issues re hemogloblin
In the Adult HPTP World n Ancef n n Ancef + Septra (Tetracycline, clindamycin) n n Ancef + clindamycin works well with the “aggressive MSSA + Group A strep” cellulitis + Group A Ancef + Vancomycin n Some people fail on Day 3 ? ? ? Had mixed MSSA and MRSA infection. Ancef kills MSSA but leaves MRSA untouched Cellulitis in face ICU patient with Staph in blood Vancomycin n Pt known to have MRSA
Colonization has been associated with subsequently developing infection n n 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) n Decrease by 78% risk of BSI in hemodialysis patients n Decrease by 66% risk of BSI in peritonneal dialysis patients n Tacconelli 2003 Clin Infect Dis
Should we decolonize patients because colonized patients have a high risk of developing an active infection
What is Decolonization? n n n 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 Yes Associated with 1530% chance risk of infection n May prevent re-current infections n Good for public health because decrease transmission No n n Cochrane review 2003 did n n not support use of decolonization Not recommended by AMMI, PHAC, CDC Patients fail Patients will reacquire S. aureus will develop resistance to chemicals/drugs we use Will not change genetics that result in person being colonized
Who should we try to decolonize n n All patients? Choose subsets of patients n n All patients with access lines? All patients with more than 3 infections in six months? All patients who will be compliant No patient n 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 n Most reviews do not support intranasal mupirocin alone UNLESS n n n 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 n n Most groups have used nasal mupirocin + 2% CHG body washes Some groups have used n n PO Vancomycin to resolve GI carriage Some have treated positive urine n n n 2 nd 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 Study Clin Infect Dis 2007 n n n 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 n Significant eradication at 3 months n n 75% with program, 32% without At 8 months n 54% still negative (so 21% returned to be positive)
My roadside conversations with Tom Louie n Yes you can decolonize MRSA 2 n n Interesting because are the folks with the “holes” (stasis ulcer, PEGs etc) Very hard to decolonize MRSA 10 n 2% CHG in nares works better than mupirocin
The “core” patients are not in easy to do locations n n n 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 Recommendations For Decolonization n n No group or organization has supported decolonization for all patients Some support for selected Decolonization (if mupirocins) n n Dialysis patients Recurrent infections Infection control measure Do Not use routine decolonization in preop or non-surgical patients
Resident flora Transient flora Good Hand Hygiene as prevention remains good plan but can we do it
Good Hand Hygiene for everyone Start of activity, End of activity Staff Patients Volunteers Visitors
Are we now where we were in the early 1980 s 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
n n n MRSA prevalence rates are growing in the community Risk factor are breaking down No magic way to detect MRSA Should we assume that everyone and everything is MRSA positive?
Here are four actions you can take to protect your children from MRSA 1. 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.
Here are four actions you can take to protect your children from MRSA 2. 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 wound Clean 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.
Here are four actions you can take to protect your children from MRSA 3. 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 towelsnapping! Also, tell kids not to share clothes or other personal items.
Here are four actions you can take to protect your children from MRSA 4. 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.
Will MRSA always be an Antibiotic Resistant Organism?
12 Classes of anti-S. aureus drugs Class Penicillin Cephalosporin Oral (n=9 ) Cloxacillin Keflex Carbapenum IV (n=12) Cloxacillin Ancef Meropenum Sulfa Macrolides Lincomycins “septra” All Clindamycin Tetracyclines Glycopeptide Quinolones Others All Not cipro* Linezolid Fusidic Acid Rifampin “septra” Azithromycin Clindamycin Vancomycin Levo, Moxi Linezolid, Tigecycline, Daptomycin, *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
New Anti Staph Agents Antimicrobial Agent Class 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 n n n Infectious diseases is hoping that the new IV cephalosporins and carbapenem are as good as we think The new cephalosporins target the PBP 2’ 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 n n n 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” MRSA Pro n Scientifically, likely yes n The system does not have enough beds or staff to deal with private rooms needs Con n Would likely die in the media n Government has a lot at stake n We should not be transmitting organisms
MRSA Outbreak reporting n Any person who knows or has reason to suspect the existence of MRSA: n n 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 Alberta Government Guidelines
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 profile There will be more n abscesses and soft tissue infection n More person to person transmission (gene(s) from Co. NS) n 10% of the infections will be very serious (? new pathogen markers) n Repeat infection since MRSA 10 seems to result in a poor antibody response n Very high rate of colonization becoming infection Very different from MRSA 2, 6, 8
I do not believe we have seen all that MRSA 10 will do n n 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 n n 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.
CANADIAN PAEDIATRIC SURVEILLANCE PROGRAM n n n 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 K 1 G 4 J 8 Tel: 613 -526 -9397, ext. 239 Fax: 613 -526 -3332 cpsp@cps. ca or www. cps. ca/cpsp http: //www. cps. ca/English/surveillance/cp sp/studies/Questionnaire/MRSA. pdf
Questions?
References Guidelines for the prevention and management of CAMRSA: a perspective for Canadian health care practitioners n Can J Infect Dis Med Microbiol 2006 (suppl. C): 4 c-24 c Control and treatment of MRSA in Canadian paediatric health care institutions. n Paediar Child Health 2006; 11: 163 -165 Ca-MRSA: Implications for the Care of Children n Paediatrics and Child Heatlh 2007; 12(4) 323 -324 Consensus Statement for the management of MRSA infections in Neonatal ICUs Susan Gerber n ICHE Feb 2006 27(2): 139 -145 CDC Sept 8, 2008 launched program to teach parents about MRSA
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