EMERGING EVIDENCE AROUND SURGICAL PROPHYLAXIS:

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EMERGING EVIDENCE AROUND SURGICAL
PROPHYLAXISthe UPSIDES and the DOWNSIDES
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Part 1 EXAMINING CAUSE AND EFFECT
Presented by Wendy Runge, RN, BScN, CIC Infection
Control Practitioner, Calgary AB
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HEALTH CARE ASSOCIATED INFECTIONS (HCAI)

• THE BIG 3 SSI, CLI, VAP
• PREVENTION RESEARCH HAS IDENTIFIED EVIDENCE-BASED
  INTERVENTIONS(CLASS 1 EVIDENCE)
• HOWEVER,
• NO GOOD DEED GOES UNPUNISHED
• (Clare Boothe Luce)

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• SURGERY RISKY OUTCOMES?

3?
4?
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SSI AND RISK

• RISK INCREASED BY
• PATIENT FACTORS
• SURGICAL PROCEDURE
• RISK MAY BE DECREASED BY
• COMPLIANCE WITH EVIDENCE-BASED PRACTICE

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PROPHYLAXIS the rationale

• SKIN CANT BESTERILISED
• SKIN FLORA WILL BETRACKED INTO DEEPERTISSUES
• PROVIDES SHORT-TERMSUPPORT FOR THE IMMUNE SYSTEM

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ASSOCIATED RISKS

• INCREASED/IMPROPER USE OF ANTIBIOTICS HAS BEEN
  IMPLICATED IN
• ? ANTIMICROBIAL RESISTANCE
• Clostridium difficile ASSOCIATED DIARRHEA (CDAD)

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Staphylococcus aureus

• COMMON SKIN BACTERIUM
• PENICILLIN INTRODUCED1943 BY 1960,
  80RESISTANCE REPORTED
• 1ST CASE OF METHICILLIN- RESISTANCE WAS SEEN IN
  1961 (MRSA)
• RELATIVELY SLOW EMERGENCE UNTIL 1990s

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MRSA

• ADAPTS AND SHARES GENETIC INFORMATION
• ANTIMICROBIAL PRESSURE WILL SELECT FOR RESISTANT
  STRAINS
• RECENT EPIDEMIOLOGY
• COMMUNITY ACQUISITION
• POOR ADHERANCE TO HAND HYGIENE IN HEALTH CARE

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Presented at the CNISP 2006 Annual Meeting
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Clostridium difficile

• FOUND IN LOWER BOWEL, CAN BE PART OF RESIDENT
  FLORA
• SPORE-FORMER SURVIVES FOR EXTENDED PERIODS IN
  THE ENVIRONMENT
• EXCRETES TOXINS WHICH CAN CAUSE TISSUE DAMAGE

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C.difficile Vegetative vs Spore
Vegetative form metabolically active -
Produces Toxin A B (? Other)- Killed by some
antibiotics only- Oxygen exposure kills
Spores not metabolically active- No Toxin
production, - Not affected by antibiotics-
Oxygen exposure doesnt kill
Dr. Michelle Alfa Ph.D, FCCM Diagnostic Services
of Manitoba St. Boniface General Hospital Site
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CDAD (C. difficile associated diarrhea)

• ANTIMICROBIAL PRESSUREMAY ALLOW FOR OVERGROWTH
• RECOGNIZED AS PRIMARY CAUSE OF ANTIBIOTIC
  ASSOCIATED DIARRHEA IN 1978
• RECENT EMERGENCE OF NEW STRAINS CAUSING MORE
  SEVERE DISEASE

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CDAD

• ANTIMICROBIALS MOST OFTEN IMPLICATED
• CLINDAMYCIN
• 2ND AND 3RD GENERATION CEPHALOSPORINS
• FLUOROQUINOLONES

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CDAD MORE TO THE STORY?

• 2000 2001 LARGEST MULTICENTRE OUTBREAK TO DATE
  REPORTED IN CALGARY
• INVESTIGATIONAL FINDINGS
• FRAIL ELDERLY WITH MULTIPLE COMORBIDITIES
• ENVIRONMENTAL CONTAMINATION
• UNRESTRICTED USE OFCLINDAMYCIN

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CDAD PREVENTION

• ANTIMICROBIAL STEWARDSHIP
• ELIMINATING ENVIRONMENTAL RESERVOIRS
• CONTACT ISOLATION OF SUSPECT AND CONFIRMED CASES

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PROPHYLAXIS DONE RIGHT!

• TARGETS THE ORGANISMS MOST LIKELY AT THE SURGICAL
  SITE
• DELIVERED AT THE OPTIMAL TIME
• PROPHYLAXIS VS TREATMENT
• BUGS DRUGS 2006 ANTIMICROBIAL REFERENCE
  BOOK

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Risk Evaluation of Clostridium
difficile-Associated Diarrhea Following
Antimicrobial Prophylaxis in Patients Undergoing
Cardiac, Vascular or Thoracic Surgery in a
Tertiary Care Trauma Center
Paper K-351 ICAAC 2006
D.J.G. Thirion, M.Sc., Pharm.D., BCPS Clinical
Assistant Professor, Pharmacist Hôpital du
Sacré-Cœur de Montréal Faculty of Pharmacy,
Université de Montréal
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Background

• Antimicrobial prophylaxis (AP) is standard of
  practice for
• Cardiac, thoracic, vascular surgery
• AP decreases surgical site infections (SSIs)
• Risk of C. difficile associated diarrhea (CDAD)
  has been low historically (1.2)

Harbarth et al. J Hosp Inf 20014893-97
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Antibiotic prophylaxis protocol

• Promoting rational use of antibiotic prophylaxis
  in surgery can
• Surgical Site Infections
• length of stay
• therapeutic use of antimicrobials
• Improve costs

Thirion DJG et al. Applied Therapeutics. 2004
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Appropriate use to decrease risks (pitfalls!)

• Adverse reactions
• Allergic or toxic reactions
• Clostridium difficile (superinfection)
• (Spencer RC. AAC 1998)
• Development of resistance
• Vancomycin resistant enterococci (VRE)

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CDAD

• Outbreak in Quebec, Canada associated with new
  strain (BI/NAP1 toxinotype III)
• Average rate of up to 20 cases/1000 admissions
• Increased mortality, morbidity
• Increased severity of disease
• Onset of disease closely related to antimicrobial
  exposure
• Outbreak of CDAD may expose pts to higher adverse
  risk with AP

Loo V, et al. N Engl J Med 20053532442-9. McDona
ld LC, et al. N Engl J Med 20053532433-41.
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Assessment

• Adverse outcomes with CDAD may surpass benefits
  of AP
• Purpose
• To evaluated the risk of CDAD and its
  complications
• Following AP
• In cardiac, thoracic, and vascular surgery

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Methodology

• Retrospective cohort study
• University affiliated tertiary trauma center
• Pts who underwent
• Cardiac surgery
• Thoracic surgery
• Vascular surgery
• January 1st 2002 to December 31st 2004
• AP 4 hours prior to and up to 2 hours after
  beginning of surgery
• 2 surgeries in the same patient were considered
  as separate events
• Pts who did not receive AP were excluded

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Outcomes

• PRIMARY OUTCOME
• Occurrence of CDAD (post-op. up to 1 mo.
  post-op.)
• Positive C. difficile toxin A and/or B assay and
  3 or more episodes of diarrhea/day
• Endoscopic evidence of pseudomembranous colitis
• Histopathological evidence of C. difficile
  colitis
• Complications of CDAD
• (from hospitalisation and up to 3 months post
  CDAD)
• Pseudomembranous colitis
• Toxic megacolon
• Perforation
• Surgery or colectomy
• Relapse
• Death

1 of 3

• Septic choc
• ICU admission for
• Dehydration
• Electrolyte disorders
• Hypovolemia
• Septic shock

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Outcomes

• SECONDARY OUTCOME
• Risk factors for CDAD
• Surgical site infections
• Superficial
• lt 30 days post-op
• Deep
• lt 30 days post-op
• lt 1 year post-op if material implant

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Statistical analysis

• Rates of CDAD (95 CI)
• Risk of complications with CDAD
• Rates of SSIs (95 CI)
• Logistic regression for influence of different
  risk factors on the incidence of CDAD (OR, 95
  CI)

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Baseline characteristics of patients undergoing
cardiac, thoracic or vascular surgery
Baseline characteristics Global n 1688 Cardiac n 832 Thoracic n 350 Vascular n 506
Mean age (years) 64.1 63.6 60.9 67.0
Percentage of women 31.0 27.2 39.1 31.8
Hospital stay Mean duration (days ? SD) 15.9 ? 19.3 15.1 ? 11.5 19.6 ? 22.3 14.7 ? 25.9
Median days (range) 11 (1-187) 12 (1-144) 13 (2-236) 8 (1-387)
Co-morbidities
Mean number of co-morbidities 3.3 3.8 3.3 2.5
Diabetes () 22.3 26.9 13.4 20.9
COPD () 19.8 9.0 49.7 16.8
Active malignancy () 17.1 1.4 76.9 1.6
Anemia () 7.0 6.6 8.6 6.7
Renal insufficiency (CrCl ?30 mL/min) () 3.6 3.4 1.1 5.7
Heart failure () 2.4 3.7 0.9 1.4
Rhumatoid Arthritis () 0.9 0.8 0.9 1.2
Gastro-intestinal disease (CD, UC) () 0.5 0.6 0 0.6
SD, standard deviation COPD, chronic obstructive
pulmonary disease CrCl, creatinine clearance
UC, ulcerative colitis CD, crohns disease.
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Rate of CDAD, complications of CDAD, and SSIs in
cardiac, thoracic and vascular surgery patients
Global Cardiac Thoracic Vascular
Number of patients 1688 832 350 506
Number of CDADsa 82 35 24 23
Number of complicationsb 21 9 8 4
Number of superficial SSIs 47 25 3 19
Number of deep SSIsc 12 8 0 4
a CDAD was evaluated up to 30 days after
surgery b Complications were evaluated up to 3
months post-CDAD c SSIs were evaluated up to 1
year post surgery
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Rates of CDAD, complications of CDAD, superficial
SSIs and deep SSIs in cardiac, thoracic and
vascular surgery
Over a 3 year period (2002-2004)
Rate ()
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Observations

• Pts developed CDAD on average 9 d (range 2-30 d)
  post-surgery
• CDAD pts had longer hospital stay (32.1 d vs 15.1
  d) than non-CDAD pts
• AP was the only antibiotic received in
  perioperative care
• 45.1 of patients with CDAD
• from 3 months before surgery until diagnosis of
  CDAD
• No CDAD related deaths reported

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Rate of CDAD per year in cardiac, thoracic and
vascular surgery
Rate ()
n 1688
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Logistic regression of potential risk factors for
CDAD among surgical pts
Potential risk factors Odd ratio 95 C.I. 95 C.I. P-value
Lower Upper
Parenteral nutrition 6.4 2.7 15.0 lt0.001
Enteral nutrition 4.3 2.3 8.2 lt0.001
Diabetes 0.9 0.5 1.5 0.6
COPD 2.0 1.2 3.4 0.01
UC/CD 3.7 0.4 31.4 0.2
Renal insufficiencya 1.6 0.6 4.3 0.3
Heart failure 1.8 0.6 5.7 0.3
Anemia 1.4 0.6 2.9 0.4
Malignancy 1.3 0.7 2.4 0.4
Immunosupression 0 0 - 1.0
H2 antagonists 2.5 0.8 7.4 0.1
PPI 1.0 0.6 1.7 1.0
RA 0 0 - 1.0
a Renal insufficiency defined as a creatinine
clearance less than 30mL/min
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Antimicrobial agents used, moment of
administration, and duration of antimicrobial
prophylaxis
Cardiac () (n 832) Thoracic () (n 350) Vascular () (n 506)
Cefazolin 43.9 74.9 91.1
Cloxacillin Ampicillin 52.5 2.4 4.2
Vancomycine 3.4 3.5 3.2
Other 0.2 19.2 1.5
Moment of administration a, b 34.1 12.3 16.3
Duration of AP ? 24 hours 45.3 78.1 83.1
Duration of AP gt 24 hours 54.7 21.9 16.9
a Administration of antimicrobial prophylaxis
between 30 minutes to 1 hour before the surgical
incision. b Documentation of the moment of
administration was absent from charts in 25.7 of
charts overall.
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Discussion

• AP is not without risk, especially in epidemic
  areas of CDAD
• AP exposes patients to a high risk of CDAD, which
  can lead to additional morbidity, length of stay,
  and hospital costs.
• The risk of CDAD with AP use outweighs the
  benefits in thoracic surgery.
• AP in surgeries at low risk of SSIs needs to be
  re-evaluated in the context of CDAD outbreaks.
• Confirms other reports that enteral and
  parenteral nutrition, and COPD are risks for
  development of CDAD

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Acknowledgements

• David Banon, B. Pharm.1, 2
• Catherine Ferland, B. Pharm. 1, 2
• Anik Thibodeau, B. Pharm. 1, 2
• Karine Wilhelmy , B. Pharm. 1, 2
• Pierre J. Laflamme, MD1
• Gilbert Pichette, MD1
• Thérèse Bigras, M.Sc.Inf., MBA1
• Anne Filion, B.Pharm., M.Sc. 1
• Lucie Blais, Ph.D. 1, 2

1.
2.
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Definitions of SSIs

• Superficial
• lt 30 days post-op
• Skin or soft tissue involvment only
• One of the following
• Purulent drainage
• S/sx of infection and opening of the wound by the
  surgeon
• Diagnosis of superficial surgical site infection
• Positive culture from site using aseptic
  technique

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Definitions of SSIs

• Deep
• lt 30 days post-op or
• lt 1 year post-op if material implants
• Infection seems related to surgery
• Affects deep tissue including fascia and muscle
• One of the following
• Purulent drainage from deep wound ( but not
  cavity or organ)
• Spontaneous dehiscance opening of the deep wound
  by the surgeon when Tgt38C or localized pain
• Abcess or evidence of infection by direct or
  radiological exam, subsequent surgery, or
  histopathology
• Diagnosis of deep SSI

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Definition of CDAD complications

• ICU admission
• Dehydration, electrolyte disorders, hypovolemia,
  septic shock
• Septic shock
• Hypotension SBP lt 90 mmHg, decrease gt 40 mmHg, in
  the absence of other causes
• 2 of the following
• temp gt 38C or lt 36C, HR gt 90 bpm, RR gt 20/min,
  pCO2 lt 32 mmHg, WBC gt 12 000 or lt 4000, or gt 10
  bands
• Pseudomembranous colitis confirmed by endoscopy
• Toxic megacolon gt 6 cm dilation, confirmed by
  X-ray,
• 3 of the following
• fever gt 38.5C, tachycardia HRgt120 bpm, WBC gt 10
  500, anemia, dehydration, confusion, electrolyte
  disorders, hypotension
• Colon perforation confirmed by radiography
• Relapse readmissioin to the hospital for CDAD
  following initial remission
• Death as confirmed on death certificate

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Rates of CDAD, complications of CDAD, overall
SSIs in cardiac, thoracic and vascular surgery
Over a 3 year period (2002-2004)
Rate ()
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Prevention and Change
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Questions to consider in Prevention

• What is the burden of disease
• Is there any proven benefit from the
  intervention?
• If there is, how great is it ?
• Are there any adverse effects of the
  intervention?
• If there are, what are they, how serious are
  they, and how frequently do they occur?
• Informed consent.

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Burden of SSI

• 2-5 of patients undergoing clean extraabdominal
  operations
• up to 20 intraabdominal procedures will develop
  an SSI.
• SSI results in increased morbidity - increased
  length of stay, increased ICU admissions,
  increased readmissions, and increased mortality.
• Norton and Baker -

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Assessing benefit

• Type of outcome ( Surrogate v. clinically
  significant)
• The interval between the intervention and the
  bnenefit
• The duration of intervention required to achieve
  the benefit.
• The application of a benefit for one variant of a
  disease to another variant
• Lower benefits in community settings than in
  clinical trials
• Publication bias

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Proven intervention

• Multiple studies demonstrated a decrease in SSI
  if prophylactic antibiotics. administered within
  one(1) hour of incision.
• Multiple studies demonstrated no additional
  benefit in decreasing SSI if prophylactic
  antibiotics continued post surgery.
• Many guidelines exist for selecting the
  appropriate agent, for the surgical procedure.

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Size of benefit

• Multiple studies actual results varied however OR
  in ranges of 0.30 to 0.5 in antibiotic vs placebo
  trials
• Number needed to treat (NNT) approximately 6

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Adverse effects

• Individual level
• adverse reactions to agent
• super infection
• Population level
• change the ecology
• Antibiotic resistance

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Adverse events - frequency

• Gillespie 2000 - Cochrane collaboration
• RR 1.83 (0.96 -3.5)
• Crabtree TD, et al. Am Surg. 1999. 65507-511.
  In16 of post surgical patients with C. difficile
  colitis the antibiotics were prophylactic.
• Antibiotic resistance - associated with
  antibiotic use - ? relevance to a single dose
  regimen

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Summary

• Evidence supports the use of prophylactic
  antibiotics.
• the current benefit harm ratio is favorable
• However

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• Microorganisms are not boring-change is constant
• The healthcare system should not be boring -
  change needs to be constant.

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MRSA

• An abridged and selected History

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(No Transcript)
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(No Transcript)
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Interesting times ahead

• Change is constant
• Surveillance is mandatory

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Evolution in Health Care Systems

• Surgical Infection Prevention(SIP) project.
• Antibiotic selection suspended as a publically
  reported measure of hospital quality.
• Reasons
• MRSA - guidelines not in agreement on when
  Vancomycin should be used as prophylaxis-what is
  a high prevalence of MRSA?
• Antibiotic shortages.
• Conflicting guidelines regarding preventing SSI
  and endocarditis in surgical patients.

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Remember

• Organisms change.
• New knowledge is accumulating.
• There is an absolute need to monitor what is
  happening in your institution.
• There is a need for organizations such as Safer
  Healthcare Now to regularly review the
  recommendations in their guidelines.

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Thank you and have a good day