EMERGING EVIDENCE AROUND SURGICAL PROPHYLAXIS:“the UPSIDES and the DOWNSIDES”
Part 1: EXAMINING CAUSE AND EFFECT Presented by Wendy Runge, RN, BScN, CIC Infection Control Practitioner, Calgary AB
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)
1 2 SURGERY: RISKY OUTCOMES? 3? 4?
SSI AND RISK • RISK INCREASED BY: • PATIENT FACTORS • SURGICAL PROCEDURE • RISK MAY BE DECREASED BY: • COMPLIANCE WITH EVIDENCE-BASED PRACTICE
PROPHYLAXIS: the rationale • SKIN CAN’T BESTERILISED • SKIN FLORA WILL BETRACKED INTO DEEPERTISSUES • PROVIDES SHORT-TERMSUPPORT FOR THE IMMUNE SYSTEM
ASSOCIATED RISKS • INCREASED/IMPROPER USE OF ANTIBIOTICS HAS BEEN IMPLICATED IN: • ANTIMICROBIAL RESISTANCE • Clostridium difficile ASSOCIATED DIARRHEA (CDAD)
Staphylococcus aureus • COMMON SKIN BACTERIUM • PENICILLIN INTRODUCED1943; BY 1960, 80%RESISTANCE REPORTED • 1ST CASE OF METHICILLIN- RESISTANCE WAS SEEN IN 1961 (MRSA) • RELATIVELY SLOW EMERGENCE UNTIL 1990s
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
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
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 doesn’t kill Dr. Michelle Alfa Ph.D, FCCM Diagnostic Services of Manitoba St. Boniface General Hospital Site
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
CDAD • ANTIMICROBIALS MOST OFTEN IMPLICATED: • CLINDAMYCIN • 2ND AND 3RD GENERATION CEPHALOSPORINS • FLUOROQUINOLONES
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
CDAD PREVENTION • ANTIMICROBIAL STEWARDSHIP • ELIMINATING ENVIRONMENTAL RESERVOIRS • CONTACT ISOLATION OF SUSPECT AND CONFIRMED CASES
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”
Paper K-351 ICAAC 2006 Risk Evaluation of Clostridium difficile-Associated Diarrhea Following Antimicrobial Prophylaxis in Patients Undergoing Cardiac, Vascular or Thoracic Surgery in a Tertiary Care Trauma Center 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
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 2001;48:93-97
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
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)
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 2005;353:2442-9. McDonald LC, et al. N Engl J Med 2005;353:2433-41.
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
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
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
Outcomes SECONDARY OUTCOME • Risk factors for CDAD • Surgical site infections • Superficial < 30 days post-op • Deep < 30 days post-op < 1 year post-op if material implant
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)
Baseline characteristics of patients undergoing cardiac, thoracic or vascular surgery SD, standard deviation; COPD, chronic obstructive pulmonary disease; CrCl, creatinine clearance; UC, ulcerative colitis; CD, crohn’s disease.
Rate of CDAD, complications of CDAD, and SSIs in cardiac, thoracic and vascular surgery patients 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
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 (%)
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
Rate of CDAD per year in cardiac, thoracic and vascular surgery Rate (%) n = 1688
Logistic regression of potential risk factors for CDAD among surgical pts a: Renal insufficiency defined as a creatinine clearance less than 30mL/min
Antimicrobial agents used, moment of administration, and duration of antimicrobial prophylaxis 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.
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
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.
Definitions of SSIs • Superficial • < 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
Definitions of SSIs • Deep • < 30 days post-op or • < 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 T>38°C or localized pain • Abcess or evidence of infection by direct or radiological exam, subsequent surgery, or histopathology • Diagnosis of deep SSI
Definition of CDAD complications • ICU admission • Dehydration, electrolyte disorders, hypovolemia, septic shock • Septic shock • Hypotension SBP < 90 mmHg, decrease > 40 mmHg, in the absence of other causes + 2 of the following: • temp > 38°C or < 36°C, HR > 90 bpm, RR > 20/min, pCO2 < 32 mmHg, WBC > 12 000 or < 4000, or > 10% bands • Pseudomembranous colitis: confirmed by endoscopy • Toxic megacolon: > 6 cm dilation, confirmed by X-ray, + 3 of the following: fever > 38.5°C, tachycardia HR>120 bpm, WBC > 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
95% CI Rates of CDAD, complications of CDAD, overall SSIs in cardiac, thoracic and vascular surgery Over a 3 year period (2002-2004) Rate (%)
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.
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
Adverse events - frequency • Gillespie 2000 - Cochrane collaboration • RR 1.83 (0.96 -3.5) • Crabtree TD, et al. Am Surg. 1999. 65:507-511. 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
Summary • Evidence supports the use of prophylactic antibiotics. • the current benefit : harm ratio is favorable • However:
Microorganisms are not boring-change is constant • The healthcare system should not be boring - change needs to be constant.
1945 Penicillinase lactamase Pre Penicillin 1942 Mortality sepsis secondary pneumonia, osteomyelitis, cellulitis > 80% Penicillin 1942 Mortality sepsis secondary pneumonia, osteomyelitis, cellulitis 35% MRSA • An abridged and selected History
1959 semi synthetic penicillins-methicillin 1963 MRSA outbreaks Europe Mid 1940s Penicillin resistance. Mortality rates increase to pre penicillin era 1968 first hospital MRSA outbreak in US 1967 MRSA in US late 1940s - 1950s Staphylococcal epidemics (Golden Staph)- Birth of Hospital Infection Control 1961 MRSA England
1992 aboriginal children western Australia CA MRSA 1975 2.1% ICU S. aureus are MRSA in the US 1986 Cluster of MRSA in Aboriginal community Canada 2000 multiple outbreaks, prisons, schools, schools, athletic teams, Military, increasing prevalence children. (CA MRSA) 55.3 % ICU isolates HA MRSA ∂ ∂ 1999 17% Nosocomial MRSA - Harbor UCLA SCC mec IV (CA MRSA) 1995 -change in sensitivity profiles - Europe 1980 first reports from LTCF
2003 Harbor UCLA 53% Nosocomial MRSA - is CA phenotype SCC mec type IV Interesting times ahead • Change is constant • Surveillance is mandatory