Toronto ethicon lecture jan 2010

© ETHICON, INC. 2007

Index

• Understanding SSIs• Causes

• Risk factors

• Cost and consequences

IRGACARE® MP (triclosan)

Clinical study review

1Confidential. For Internal Use Only.

® Ciba Corporation Inc

*Trademark

© ETHICON, INC. 2008 All Rights Reserved


What Are SSIs?

•SSIs are infections associated with surgical procedures and are a major source of postoperative illness

•These infections are responsible for approximately one quarter of all nosocomial infections and affect 1.4 million people worldwide at any time

•SSIs result in longer hospitalization, increased patient mortality and higher costs for healthcare providers and payers


Nichols RL. Emerg Infect Dis. 2001;7:220-224.

World Health Organization. 2002;1-50.



SSI-causing Pathogens and Frequencies

0%

5%

10%

15%

20%

25%

Staphylococcusaureus

CNS Enterococci Escherichia coli

Pseudomonasaeruginosa

Enterobacterspp

Infe

ctio

ns (

%) Gram positive

Gram negative


CNS=coagulase-negative Staphylococcus.

National Nosocomial Infections Surveillance System. www.cdc.gov.

Mangram AJ et al. Am J Infect Control. 1999;27:97-134.



CDC Surgical Wound Categories

Class I/Clean Uninfected wound in which no inflammation is encountered and respiratory, alimentary, genital, or uninfected urinary tract is not entered.

Class II/Clean-contaminated

Operative wound in which respiratory, alimentary, genital, or urinary tracts are entered under controlled conditions and without unusual contamination.

Class III/Contaminated Open, fresh, accidental wounds.

Class IV/ Dirty-infected

Old traumatic wounds with retained devitalized tissue and those that involve existing clinical infection or perforated viscera.


CDC=Centers for Disease Control and Prevention.




Factors in Bacterial Colonization Leading to SSIs

•Patient-related•Procedure/Techniques•Postoperative• Implants


Hebert CK et al. Clin Orthop. 1996;331:140-145.

Fletcher N et al. J Bone Joint Surg Am. 2007;89:1605-1618.


Fry DE. Medscape Surgery. 2003.



SSI Risk Factors – Patient Related

• Advanced age

• Malnutrition

• Obesity

• Diabetes mellitus

• History of smoking

• Distant infection

• Steroid therapy

• Chronic inflammation

• Open wounds

• Radiation

• Immunosuppressed

• Length of preoperative stay


Sumnicht RW. Med Bull US Army Eur. 1958;15:51-56.





SSI Risk Factors – Procedures/Techniques

• Duration of operation• Duration of surgical scrub• Preoperative shaving,

skin preparation• Inadequate OR ventilation• Inadequate sterilization of

instruments• Surgical technique

• Poor hemostasis• Failure to obliterate dead

space• Tissue trauma• Skin antisepsis• Antimicrobial prophylaxis• Surgical drains





SSI Risk Factors – Procedures/Techniques Cont’d•Length of preoperative hospital stay• Insufficient preoperative preparation•Personal hygiene, hair removal, skin disinfection• Insufficient antibiotic therapy• Intraoperative hypothermia• Intraoperative hypoxemia• Intraoperative hypotension


Nguyen D et al. Infect Cont Hosp Epidemiol. 2001;22:485-492.





SSI Postoperative Issues

• Incision care•Sterile dressing•Dressing changes (use of sterile technique, aseptic precautions)

•Discharge planning•Home incision care





Objective: Control Microbiologic Risk

Personnel

Patient Factors

Surgical SiteSurgical Site

Too

lsO

perating R

oom




Independent Factors Associated With Increased SSI Risk

•Abdominal operation•Operation lasting >2 hours•Surgical site with wound classification of either contaminated or dirty-infected•All wounds are contaminated; the level of contamination determines the severity or presence of an infection

•Operation performed on patient having ≥3 discharge diagnoses


Mangram AJ et al. Am J Infect Control. 1999;27:97-134.© ETHICON, INC. 2008 All Rights Reserved


SSI Rates in Various Surgical Procedures

•Plastic (breast implantations 1964–1991); N=749 women; 2.5%

•Cardiovascular (CABG 1996–1998); N=1,519 procedures; 2.7%

•Orthopedic (1992–1993); N=11,309 hospitalized orthopedic patients; 1.1%– 2.2%

•Gastric (1992–1998); N=1,184 moderate to high-risk procedures; 11%


CABG=coronary artery bypass graft.

Gabriel SE et al. N Engl J Med. 1997;336:677-682.

Hollenbeak CS et al. Chest. 2000;118:397-402.

Gaynes RP et al. Clin Infect Dis. 2001;33(suppl 2):S69-S77.



Additional Factors Affecting SSI Rates

• Growing problems

-Emergence of resistant organisms

-More debilitated, elderly, immunocompromised patients; comorbid disease

-Organ transplants

-Prosthetic implants

• The risk of SSI can be generally defined as the amount of bacterial contamination at the site of the infection combined with the virulence, or degree of pathogenicity, of the bacteria in relation to the immune system resistance of the patient

Dose of Bacterial Contamination Virulence

Resistance of the Host Patient

Risk of SSI=




The Risks of Biofilm

• Biofilm is created when microorganisms like bacteria attach themselves to living or nonliving surfaces in internal or external environments

• For instance, postoperative bacteria may contaminate the tissue in a surgical wound as well as the suture material itself

• Furthermore, the bacteria develop extracellular polymers that promote greater adhesion and resistance to antimicrobial treatment


Donlan RM. Emerg Infect Dis. 2001;7:277-281.

Edmiston CE et al. J Am Coll Surg. 2006;203:481-489.



Consequences & Costs Associated With SSIs

• Increased length of hospital stay (7–10 days), cost, and mortality (doubled)

• 60% more likely to spend time in the intensive care unit

• 5 times more likely to be readmitted to the hospital

• Cost ranges from $400 for superficial incisional SSI to >$30,000 for sternal wound or other serious infection

• Indirect costs (patient, family) are rarely considered• Loss of productivity, functional capacity

• Nearly 90,000 people die annually from healthcare-acquired infections (HAIs). SSIs are the most common HAI among surgical patients

• More people die from HAIs than AIDS, motor vehicle accidents, and breast cancer combined


Bratzler DW et al. Am J Surg. 2005;189:395-404.

Bratzler DW et al. Clin Infect Dis. 2006;43:322-330.

Urban JA. Surg Infect (Larchmt). 2006;7(suppl 1):S19-S22.

Kovach TL. Infect Cont Today. June 1, 2005.



Additional Costs Associated With SSIs

• Indirect costs• Lost productivity (patient, family)• Temporary or permanent impairment of physical/mental function

• Decreased patient satisfaction• Decreased referrals• Increased litigation

• Direct costs• Prolonged hospitalization, readmission

• Outpatient and emergency care visits

• Additional surgical procedures• Incision and drainage• Staged reimplantation

• Prolonged antibiotic therapy• Increased use of ancillary services

• Home health visits• Radiology, laboratory

• Drug costs• Durable medical equipment


Urban JA. Surg Infect (Larchmt). 2006;7(suppl 1):S19-S22.© ETHICON, INC. 2008 All Rights Reserved


Summary• The major pathogens that lead to SSIs are:

• Staphylococcus aureus• Staphylococcus epidermidis• Methicillin-resistant Staphylococcus aureus (MRSA)• Methicillin-resistant Staphylococcus epidermidis (MRSE)

• Staphylococcus aureus is a major pathogen that leads to surgical site infection• There are 4 classes of surgical wound categories• Comprehensive infection-control protocols include dozens of preoperative,

intraoperative, and postoperative components

• SSIs are costly to hospitals and patients: $400 – $30,000• Medicare is restricting the payment of hospital-acquired conditions• SSIs are costly in terms of longer hospitalization and increased mortality for

patients, and higher costs for hospitals


Nichols RL. Emerg Infect Dis. 2001;7:220-224.© ETHICON, INC. 2008 All Rights Reserved


IRGACARE® MP (triclosan) Properties

• IRGACARE MP• 2,4,4′-tri-chloro-2′-hydroxydiphenyl ether

• High-purity material that meets USP specifications for triclosan, with minimal residue content

• IRGACARE MP is safe• Biocompatible, nontoxic

• Consumer products

• IRGACARE MP is effective• Active against methicillin-sensitive and methicillin-resistant S aureus and S epidermidis (most common for device infections)

• Active against Escherichia coli and Klebsiella pneumoniae

• IRGACARE MP is compatible with suture processing• Maintains excellent suture properties


USP=United States Pharmacopeia.

Zurita R et al. Macromol Biosci. 2006;6:58-69.

Ming X et al. Surg Infect (Larchmt). 2007;8:201-207.


Barbolt TA. Surg Infect (Larchmt). 2002;3(suppl 1):S45-S53.




IRGACARE® MP (triclosan): Mode of Action

•Chlorinated phenolic biocide—a “phenol” with multitargeted biocidal mechanisms•Actions widely unknown•Nonspecific effects on cell membrane activities and cell membrane integrity

•Blocks active site of the enoyl-acyl carrier protein reductase—an essential enzyme in fatty acid synthesis—building cellular components and reproduction


Zurita R et al. Macromol Biosci. 2006;6:58-69.




Why IRGACARE® MP (triclosan)?

•Able to withstand the manufacturing process•Cost-effective•Effective, safe, and compatible•Performance/function properties

•Handling•Absorption profile, breaking-strength retention


Storch M et al. Surg Infect (Larchmt). 2002;3(suppl 1):S65-S77.




IRGACARE® MP (triclosan): Pharmacokinetics

•Well absorbed after oral administration•Well distributed in the body•Rapidly metabolized in liver to the glucuronide/sulfate conjugate•T½=10 to 13 hours

•Excreted through kidneys






IRGACARE® MP (triclosan) and Microbial Resistance

• IRGACARE MP is very effective against S aureus, S epidermidis, and E coli, which are the 3 most important bacteria related to SSIs

• There is no connection between the use of IRGACARE MP and significant antibiotic resistance

• The use of IRGACARE MP may lead to the overall reduction of the antibiotic burden•Decreases the risk of SSIs and the resulting application of stronger antibiotics against SSIs

•The use of IRGACARE MP is not associated with increased bacterial

virulence that raises the antibiotic burden




Ford HR et al. Surg Infect (Larchmt). 2005;6:313-321.




Triclosan-Coated Sutures for the Reduction of Sternal Wound Infections: Economic Considerations

Fleck T, Moidl R, Blacky A, et al. Ann Thorac Surg. 2007;84:232-236.




Results• Total patients enrolled 479

•103 closed with Coated VICRYL* Plus Antibacterial (polyglactin 910) Suture

•376 closed with non-coated sutures• Reported a cost of infection of $11,200

•“24 patients had superficial infections (n=10) or deep (n=14) sternal wound infections”

• “In the triclosan group, no wound infection or dehiscence was observed during hospital stay and follow-up visits”

• This information concerns a use that has not been cleared by the FDA (Infection Reduction Claim)

24

Fleck T et al. Ann Thorac Surg. 2007;84:232-236.

*Trademark



Antimicrobial Suture Wound Closure for Cerebrospinal Fluid Shunt Surgery: a Prospective, Double-blinded, Randomized Controlled Trial

Rozzelle CJ, Leonardo J, Li V. J Neurosurg Pediatrics. 2008;2:111-117.




Results and Conclusions

•Total patients enrolled = 61•Total procedures performed = 84

•Over 21 months

•Shunt infection rate•2 (4.3%) infections in 46 procedures for study group•8 (21%) infections in 38 procedures for control group (P=0.038)

•This information concerns a use that has not been cleared by the FDA (Infection Reduction Claim)


Rozzelle CJ et al. J Neurosurg Pediatrics. 2008;2:111-117.



Antibiotic coating of abdominal closure sutures and wound infection

Dr Justinger (Germany) from department of General, Visceral, Vascular and Pediatric Surgery


Results and Conclusions

• Objective: Dr Justinger compared the use of Coated VICRYL* Plus Antibacterial (polyglactin 910) Suture with PDS*II (polydioxanone) Suture (loop suture) for the closure of midline laparotomy to evaluate the reduction in wound infections.

• Patients: 2088 operations between October 2004 and September 2006

• Procedures: Abdominal wall closure (midline incision)• Findings: with PDS Suture (loop suture) for abdominal wall

closure, 10.8% of patients with wound infections were detected. The number of patients with infections using Coated VICRYL Plus Suture decreased to 4.9% despite no changes in protocols of patient care.

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Toronto ethicon lecture jan 2010