Surgical Infections

Pisake Boontham M.D., Ph.D. Department of Surgery Phramongkutklao Hospital Pathogenesis of Infection •Host defences •Bacterial factors •Bacterial-host interaction •Immune response to infection Host Defences

FEATURES OF INNATE AND ADAPTIVE IMMUNITY

Innate Immunity Adaptive Immunity

Skin Barriers Mucosal epithelium IgA in gut lumen Secretions (skin surface, gut lumen)

Lysozyme Humoral Complement components Antibodies (IgG and IgM) components (C3a, C5a and C3b, C5b) Cytokines (Th1, Th2)* Cytokines

Phagocytic cells (mononuclear cells, Dendritic cells polymorphonuclear cells) T cells (helper*, cytotoxic, Cells Natural killer cells memory) Dendritic cells B cells

*Th1: T helper (type 1) cells; Th2: T helper (type 2) cells Host Defences

Humoral Physical Barriers Acute Phase proteins Skin Complement Mucus Membranes Antibodies Cilia Interferon Gastric Acid Tears HOST DEFENCE SYSTEMS Urine Cellular Neutrophils Macrophages Nkcells B – lymphocytes T - lymphocytes IMMUNE RESPONSE TO INFECTION

IL-8

TNF-α IL-6

IL-1β IL-8

The cells and mediators involved in a local acute inflammatory response Bacterial Factors

• Virulence Factors –Cell Wall Antigens –Serum Resistance –Hemolytic Capability –Growth Dynamics –Iron Scavenging • Adherence Factors –P Fimbriae –Type 1 Fimbriae –DR Fimbriae Bacterial Factors

• Microorganisms show Pathogen-Associated Molecular Patterns (PAMPs), which can be recognized, by so-called ‘Pattern-Recognition Receptors’ (PRRs) by the host: example of PAMPs –LPS of Gram-negative bacteria –Glycolipids of mycobacteria –Peptidoglycans (PGs) and Lipoteichoic acids (LTAs) of Gram-positive bacteria, –Mannans of yeast or fungi –Double-stranded RNAs of viruses –Unmethylated CpG motifs of bacterial DNA Bacterial-Host Interaction

• Bacterial components activate host immune responses via PRRs, which called Toll-like receptors (TLRs) • There are ten TLRs (1-10) had been studied. –TLR-1 z TLR-2 –TLR-3 z TLR-4 –TLR-5 z TLR-6 –TLR-7 z TLR-8 –TLR-9 z TLR-10 Microbial Ligands Recognized by TLR family

Cytokine Productions

Akira and Hashino, JID 2003

Sequence of Immune Response Adaptive Immune Response DEFINITIONS

BACTEREMIA TRAUMA

SIRS INFECTION SEPSIS BURNS SEVERE SEPSIS

PANCREATITIS • Systemic Inflammatory Response Syndrome (SIRS) ≥ 2 of the following: •Temp > 38°C or < 36°C •Heart rate > 90 bpm •Respiratory rate > 20 bpm •WBC > 12,000, < 4,000 or bands > 10% • Sepsis SIRS + documented infection

Bone, et al. 1992. Chest 101:1644-1655 • Severe sepsis –Sepsis with organ dysfunction, hypoperfusion or hypotension • Septic Shock –Sepsis with hypotension and perfusion abnormalities despite adequate volume replacement • MODS –Presence of altered organ function that need intervention

Bone, et al. 1992. Chest 101:1644-1655 PATHOGENESIS OF SEPSIS

• Bacterial components (Cell wall) • Host immune responses; 3 major entities –Cytokine cascade

•Proinflammatory cytokines [T helper 1 (Th1)]

•Antiinflammatory cytokines [T helper 2 (Th2)] - –Mediators: NO, O2 –Apoptosis of immune and non-immune cells ROLE OF CYTOKINES

• Sepsis is associated with the production of many cytokines including: –Pro-inflammatory cytokines (early phase; SIRS) : IFN-γ, TNF-α, IL-1β, IL-6, IL-8, IL-12 –Anti-inflammatory cytokines (late phase; CARS) : IL-4, IL-10, IL-13 ROLE OF CYTOKINES

• Proinflammatory cytokines activate: –Biochemical systems •Complement, coagulation, kinin, etc. –Endothelial cells –PMN / platelets –Release of secondary mediators •NO, prostaglandins, vasoactive agents, endorphins, free-O2 radicals, etc. Arya et al, AJS183 (2002); 268-273 CYTOKINE PROFILE IN SEPSIS

IL-8 Sequential Stages in Sepsis

• Stage 1. In response to injury / infection, the local environment produces cytokines • Stage 2. Small amounts of cytokines are released into the circulation: • Recruitment of inflammatory cells • Acute Phase Response • Normally kept in check by endogenous anti- inflammatory mediators (IL-10, PGE2, Antibodies, Cytokine receptor antagonists)

Bone, et al. 1996 Sequential Stages in Sepsis • Stage 3. Failure to control inflammatory cascade: • Loss of capillary integrity • Stimulation of Nitric Oxide Production • Maldistribution of microvascular blood flow • Organ injury and dysfunction • Stage 4. Compensatory anti-inflammatory response syndrome [CARS]: • Inappropriate and excessive anti-inflammatory responses • Immunosuppression • Multiple organs injuries • Significant morbidity and mortality

Bone, et al. 1996

ROLE OF CYTOKINES

Appropriate cytokine Low bacterial load response Balanced cytokine Minimal SIRS

Inappropriate cytokine High bacterial load response Excessive cytokine SIRS or CARS CYTOKINES AND COAGULATION PATHWAY Gut Liver Axis Theory

Rowlands BJ, 1999 Gut Liver Axis Theory

Rowlands BJ, 1999 MODS Severe sepsis

Dysfunction of host immunity Clinical hypoperfusion

Bacterial products inhibit host immunity Gut barrier dysfunction

Influx of bacterial products (e.g. QSSMs) into systemic circulation Tissue injury Apoptosis

Septic shock Apoptosis

MODS Bacteria Host immune cells

+ Bacterial products Cytokines Apoptosis Bacteria Host immune cells

Cytokines Apoptosis

Antibiotics Neutralization Anti-apoptosis Surgical Infection

Definition • Infections that require operative treatment or result from operative treatment Specific Surgical Infections •Surgical Site Infections •Skin and Soft Tissue Infections •Intra-abdominal Infections •Sepsis •Organ specific Infections •Catheter Related Infections •Post-operative Nosocomial Infections Surgical Site Infection (SSI) Definition An infection that occurs at the incision site within 30 days after surgery or within 1 year if a prosthetic implant is in place. Nosocomial Pathogens NNIS, Jan. 1990 - Mar. 1996

40000

35000

30000

25000

20000

15000

Number of Isolates of Number 10000

5000

0 Urinary Tract Surgical Site Bloodstream Pneumonia Other Sites Infection Infection Infection

Burke JP. N Engl J Med. 2003;348:651-656. Attributable costs of HAI

Systematic review of economic analyses of health care-associated infections: AJIC 2005;33:501 – 9. Impacts of SSIs

ระยะเวลาที่อยโรงพยาบาลนานขู ึ้นเฉลี่ย 12.5 วัน

คายาตานจุลชีพ 4,544 บาท

Prevalence and Impacts of Nosocomial Infection in Thailand 2001 J Med Assoc Thai 2005 Vol. 88 Suppl.10 CLASSIFICATION OF SURGICAL WOUNDS

CLEAN CLEAN- CONTAMINATED DIRTY CONTAMINATED

Uninfected operative Operative wounds in Includes open, fresh Old traumatic wounds in which no which the respiratory, accidental wounds, wounds with inflammation alimentary, genital or operations with major retained devitalised is encountered and the urinary tract is breaks in sterile tissue and those respiratory, alimentary, entered under technique or gross that involve existing genital and uninfected controlled conditions spillage from the GI clinical infection or urinary tract and without unusual tract and incisions in perforated viscera. are not entered. contamination. which acute, non- purulent inflammation is encountered. Skin

Superficial incisional SSI Subcutaneous tissue

Deep soft tissue (fascia & muscle) Deep incisional SSI

Organ/space Organ/space SSI

Mangram AJ et al. Infect Control Hosp Epidemiol. 1999;20:250-278. SSI rate in Thailand

Surgical Wound Risk พ.ศ. พ.ศ. พ.ศ. 2531 (1) 2535 (2) 2544 (3) Classification

Clean 1- 5 % 15.3 % 1.3 % 1.5 % Clean-Contaminated 3-11 % 18.6 % 1.5 % 3.4 % Contaminated 10-17 % 24.7 % 5.1 % 6.3 % Dirty-Infected >27% 30.1 % 9.7 % 7.7 %

(1) A National Prevalence Study on Nosocomial Infections 1988 J Med Assoc Thai July 1989 Vol. 72 Suppl.2 :1-6.

(2) A National Study on Surgical Wound Infections 1992 J Med Assoc Thai July 1995 Vol. 78 Suppl.2 :73-77.

(3) Prevalence and Impacts of Nosocomial Infection in Thailand 2001 J Med Assoc Thai 2005 Vol. 88 Suppl.10 NNIS risk index category Knight R, et al. Am J Surgery 182 (2001) 682–686 SSI rates of different types of procedures and risk index category

Procedures 75th percentile operation NNIS risk NNIS risk NNIS risk time (min) index 0 index 1 index 2,3 Craniotomy 130 0.90 1.67 NA Thyroid surgery 120 0.47 NA NA Cardiac surgery 250 0.70 1.71 2.21 Other thoracic surgery 150 0.65 1.17 3.07 Vascular surgery 140 0.89 1.74 4.51 Mastectomy 140 1.80 2.48 NA Inquinal hernia repair 60 0.77 1.90 3.77 Laparotomy 90 1.71 3.29 5.16 Cholecystectomy 60 0.68 1.93 3.33 Appendectomy 60 1.20 2.55 4.85 Gastric surgery 140 2.79 5.02 10.36 Small bowel surgery 140 5.20 7.33 9.38 Colon surgery 140 4.02 5.76 8.73,11.62 Nephrectomy 180 1.13 1.13 1.13 Open reduction of fracture 90 0.73 1.25 3.51

NNIS. CDC. Am J Infect Control. 2001;29:404-421. American Society of Anesthesiologists(ASA) physical status

1 Normal 2 Mild systemic disease 3 Severe systemic disease 4 Incapacitating systemic disease that is a constant threaten to life 5 Moribund, not expected to survive for 24 hours with/without operation SSI – Wound Class vs NNIS Class

Wound Class All NNIS 0 NNIS 1 NNIS 2 NNIS 3

Clean 2.1% 1.0% 2.3% 5.4% N/A Clean contaminated 3.3% 2.1% 4.0% 9.5% N/A Contaminated 6.4% N/A 3.4% 6.8% 13.2% Dirty infected 7.1% N/A 3.1% 8.1% 12.8%

All 2.8% 1.5% 2.9% 6.8% 13.0%

NNIS. CDC. Am J Infect Control. 2001;29:404-421. Risk Factors for Surgical Site Infections

Age Prolonged preoperative stay Infection at distal site Abdominal site Morbid Obesity Wound classification Malnutrition Surgical/ Duration of surgery Cancer Host Type of procedure Factors Environmental Diabetes Factors Hair removal ASA class Intraoperative contamination Disease severity Prophylactic antibiotics Immunosuppression Surgical technique Surgical volume Multiple operations Poor hemostasis Nasal/skin carriage Microbial Drain/foreign body Virulence Factors Dead space Adherence Urgency of surgery Inoculum Hypothermia Oxygenation

Roy MC, et al. Infect Control Hosp Epidemiol 1997;18:659-68. Possible Risk Factors for Postoperative Wound Infections Host Factors

• Age • Diabetes mellitus • Gender • Estimated prognosis • Severity of disease • Nutritional status • ASA physical status • Serum albumin classification • Weight • Immunocompromising • Presence of other disease infections • Duration of preoperative stay Effect of Aging on Surgical Site Infection

10-year, prospective, cohort study N = 144,485 patients undergoing surgical procedures Age ranged from 17 to 108 years

Age was a strong predictor of infection between 17 and 65 years, the rate of infection increased (~ 1%) per decade peaking at 65 years

At 65, the risk of SSI actually decreased in a linear manner for each additional year; candidate for less risky selected surgical procedures – low risk procedures hardy survivor effect less likely to detect an infection in this patient population Kaye KS. J Infect Dis 2005;191:1056-1062 Hyperglycemia: Hyperglycemia: Diminished Phagocytic Cell Function Impaired Wound Healing - Collagenase

Rayfield et al, Am J Med 1982; 72: 439-450 Hennessey et al, J Pediatr Surg 1990; 25: 75-78 Link Between High Blood Glucose and Poor Outcomes: Potential Mechanisms

Metabolic stress response

↑ Stress hormones and peptides Glucose Insulin

Immune dysfunction FFA Reactive O2 species Ketones Lactate Transcription factors

Cellular injury/apoptosis Infection dissemination Inflammation Secondary mediators Tissue damage Altered tissue/wound repair Acidosis Infarction/ischemia

10 % Infections 5

<200 200-249 250-299 >300

*1,000 cardiothoracic surgery patients

Latham R. Infect Control Hosp Epidemiol. 2001;22:607-12 SSIs Reduced By Tight Peri-op Glucose Control

Type of Surgery Pre-Tight Post_Tight glycemic control Glycemic Control Cardiothoracic 4.6% 2.5%

Vascular 1.9% 0.83%

Hip replacement 1.0% 0.7%

Knee 1.1% 1.0% replacement Bariatric 17.9% 5.3%

Morris Brown MD, Henri Ford Hospital, International Anesthesia Research Society Possible Risk Factors for Postoperative Wound Infections Surgery Factors

• Emergency vs elective • Increased O2 tension procedure • Normothermia • Hair removal technique • Surgeon • Hand washing • Duration of surgery • Surgical skin prep • Drains • Perioperative • Packs & Drapes antibiotics • Glove puncture • Site of surgery • Primary or secondary • Operating room closure environment • Iatrogenic Hair Removal and SSI

• Presence of hair does not does not increase SSI • Razor blades increase SSI • Hair removal with clippers was found to be safer and result in a lower incidence of SSI • Hair removal closer to incision time decrease SSI compared to hair removal the night before surgery.

Alexander et al, Arch surg 1983, 118(3): 347 Shaving, Clipping & SSI

2.5 % Infected

1.5

0.5

0 Shave Clip Neither

Cruse. Arch Surg 1973; 107:206 Ability of Hand Hygiene Agents to Reduce Bacteria on Hands Time after disinfection

% log 0 60 180 minutes 99.9 3.0

99.0 2.0 Alcohol-based handrub (70% Isopropanol)

90.0 1.0 Antimicrobial soap Bacterial Reduction (4% Chlorhexidine)

0.0 0.0 Plain soap

Baseline

Hosp Epidemiol Infect Control, 2nd Edition, 1999 Agent Action Gram + Gram - Tbc Fungi Virus Rapidity Residual toxicity activity Alcohol Denature E E G G G Most rapid None Drying, protein Volatile

Chlorhexidine Disrupt cell E G P F G Intermediate Excellent Ototoxic, membrane Keratitis

Iodine / Oxidation / E G G G G Intermediate Minimal Absroption Iodophore substitution from skin, by free Irritation iodine Chlorhexidine Denature E E G G G Most rapid Excellent Ototoxic, / Alcohol protein Keratitis

E-excellent; F-fair; G-good Effects of Skin Preparative Agents in Foot and Ankle Surgery

200000

180000

160000 140000

120000

100000

80000 Chloroxylenol 60000 Iodophor /alcohol 40000

Total number of bacterial colonies Total number of 20000 Chlorhexidine /alcohol

0 Hallux Toes Controls

Ostrander RV. J. Bone Joint Surg. Am. 2005;87:980-985 Antibiotic Prophylaxis Goals of Surgical Prophylaxis

Prevent postoperative infection of the surgical site Prevent postoperative infectious morbidity and mortality Reduce duration and cost of health care Produce no adverse effects Have no adverse consequences for the microbial flora of patient or hospital Probability of Wound Infection

Houang ET, et al. J Hosp Infect 1991;19:181-9. Guidelines of prophylactic antibiotics Documented beneficial Recommended in: in clean wounds Some Clean wound* Prosthesis is inserted Clean-contaminated wound Vascular surgery Contaminated wound Neurosurgery Dirty wound Bone is incised (craniotomy, sternotomy) High risk patients e.g. old, Controversy on cases of clean DM, co-morbidity surgery of soft tissues (eg, breast, hernia)

Barie PR, et al. Surg Clin N Am 2005;85:1115–35. Mangram AJ, et al. Infect Control Hosp Epidemiol 1999;20:247–80. Which Antibiotics? 1st-gen cephalosporin is the preferred agent Clindamycin and vancomycin preferred for patients with a history of anaphylaxis to penicillin* No evidence of routine use of vancomycin for prophylaxis Vancomycin prophylaxis is appropriate only in institutions where the incidence of MRSA infection is high (>20% of all SSIs caused by MRSA) Vancomycin should be considered for prophylaxis in patients with known MRSA colonization

Barie PR, et al. Surg Clin N Am 2005;85:1115–35. *Bratzler DW, et al. Am J Surg 2005;189:395–404. Procedure-Specific Recommendations for Prophylaxis Procedure Likely organisms Recommended antibiotic Adult dose Cutaneous S. aureus, S. epidermidis No uniform recommendation Head and neck S. aureus, streptococci Cefazolin 1 to 2 g IV Neurosurgery S. aureus, S. epidermidis Cefazolin 1 to 2 g IV Thoracic S. aureus, S. epidermidis Cefazolin 1 to 2 g IV Cardiac S. aureus, S. epidermidis Cefazolin 1 to 2 g IV Gastro-intestinal- Gram-positive cocci, enteric High risk: cefoxitin or cefminox 1 to 2 g IV Appendectomy gram-negative bacilli Alternative: ampicillin/sulbactam 3 g IV amoxicillin/clavulanic acid 1.2 g IV

Colorectal Enteric gram-negative bacilli, Oral: neomycin + erythromycin 1 g oral x 3 anaerobes Parenteral: cefoxitin or cefminox 1 to 2 g IV Alternative: ampicillin/sulbactam 3 g IV amoxicillin/clavulanic acid 1.2 g IV

Biliary tract Enteric gram-negative bacilli High risk: cefoxitin or cefminox 1 to 2 g IV Alternative: ampicillin/sulbactam 3 g IV amoxicillin/clavulanic acid 1.2 g IV

Ob-Gynecologic Enteric gram-neg bacilli, anaerobes Cefazolin, cefoxitin or cefminox 1 to 2 g IV Urologic S. aureus, enteric gram-neg bacilli High risk: ciprofloxacin 400 mg IV Orthopedic S. aureus, S. epidermidis Cefazolin 1 to 2 g IV Vascular surgery S. aureus, S. epidermidis Cefazolin 1 to 2 g IV Breast and hernia S. aureus, S. epidermidis High risk: cefazolin 1 to 2 g IV

The Medical Letter; Dec 2006:83-88 The Medical Letter; Dec 2006:83-88 SSI Rates by Time of Antibiotic Administrations

3 SSI Rate 2

0 >22112346789>10

Classen DC, NEJM 1992; 326:281-6 Single vs Multiple Dose Surgical Prophylaxis: Systematic Review

100

Favors multiple dose 1

0.1 24h All studies, fixed All studies, Multi > 24h Multi < 0.01 random All studies, Favors single dose

McDonald. Aust NZ J Surg 1998;68:388 Antimicrobial Dosing

Agents Renal half-life, h Infusion Standard Weight- Redosing duration dose adjusted interval, h

normal ESRD Cefazolin 1.2–2.5 40–70 3–5 min 1–2 g iv 20–30 mg/kg 2–5 (>80 kg,2g)

Cefuroxime 1–2 15-22 3–5 min 1.5 g iv 50 mg/kg 3-4

Cefoxitin 0.5–1.1 6.5–23 3–5 min 1–2 g iv 20–40 mg/kg 2-3

Clindamycin 2–5.1 3.5–5.0 10–60 600–900 <10 kg, at 3–6 min (not mg iv least 37.5 >30 mg/ mg;>10 min) kg,3–6 mg/kg Vancomycin 4-6 44.1– 1 g >60 1 g iv 10–15 mg/kg 6-12 406.4 min (adult)

Dale W, et al. Clin Infect Dis 2004;38:1706–45. Principles of Antibiotic Prophylaxis

Preop administration, serum levels adequate throughout procedure with a drug active against expected microorganisms.

High Serum Levels Re-doses when: Duration 1. Pre-op timing 1. Operation time 1. None after wound 2. IV route more than 2 half- closed 3. Highest dose life of drug 2. 24 hours maximum of drug 2. Long procedure 4. Long half-life 3. Large blood loss

Mangram AJ et al. Infect Control Hosp Epidemiol. 1999;20:250-278. Prolongation of Antibiotic Prophylaxis

Harmful and no benefit Clostridium difficile-associated disease Increases ris k of later nosocomial infections unrelated to surgical site Pneumonia and catheter-related infection Emergence of multi-drug resistant pathogens MRSA, ESBL Microorganism of SSI

Superficial infection StaphylococcusStaphylococcus StreptococcusStreptococcus

Gram-Gram- negativenegative Deep bacillibacilli infection AnaerobesAnaerobes

Distribution of Bacteria from Superficial to Deep Infection Major Pathogen in SSI % of infections

NNIS 2003 Microbiology of SSI in Ramathibodi Hospital (47 isolates)

A. baumannii P. aeruginosa K. pneumoniae (inc. ESBL) E. coli (inc. ESBL) Proteus spp. Stenotrophomonas spp. MRSA Enterobacter spp. (ESBL) Enterococci Treatment of SSI

Incision and drainage and evacuate infected material of the SSI Tissue specimens or pus collected aseptically (no routine swabs of fluid) Antibiotics is not required for uncomplicated SSI Minimal surrounding evidence of invasive infection and minimal systemic signs of infection Observation-dressing changes-opening the incision site Antibiotics may be indicated in SSI with the presence of systemic toxicity

Barie PR, et al. Surg Clin N Am 2005;85:1115–35. Stevens DL, et al. Clin Infect Dis 2005;41:1373-405. Empiric Antibiotic Therapy

Findings of Gram stain and results of culture of the wound contents Type and site of surgery Resident flora of surgical environment Colonization flora of specific hospital Status of patients’ immune system

Coverage against gram-positive cocci is indicated in most circumstances

Barie PR, et al. Surg Clin N Am 2005;85:1115–35. Antibiotic Treatment Regimens

Type of infection Common infecting bacteria Antibiotic therapy Superficial wound Strep, staph Not used routinely; if needed, 1st and surgical incision gen ceph or oxacillin infections Deep wound infections Strep, staph, Gram- negative 1st-gen ceph or cloxacillin; if mixed other than GI, female enteric bacteria infections are suspected, 2nd or 3rd genital tract, or gen ceph or amoxicillin/clavulanate, oropharyngeal ampicillin/sulbactam, or surgery piperacillin/tazobactam (imipenem or meropenem)

GI, female genital tract, Same as for other deep Same as for mixed infection, above or oropharyngeal wound infections, with surgery addition of Bacteroides species, other anaerobes, enterococci

Nichols RL, et al. Clin Infect Dis 2001;33:S84-93. SSI organism Antibiotic susceptibility Skin wound Staphylococcus aureus •90% remain susceptible to cloxacillin, at any site macrolides and clindamycin Beta-haemolytic •90% remain susceptible to penicillins, streptococci macrolides and clindamycin

Head and Oral anaerobes •95% remain susceptible to metronidazole and neck surgery amoxi/clav. •Penicillin can no longer be relied upon.

Abdominal Anaerobes •95% remain susceptible to metronidazole and surgery amoxi/clav.

E. coli and other •Complex resistance problems. However, 90% enterobacteriaceae of E. coli remain susceptible to 2nd generation cephalosporins or BL/BIs, or gentamicin

Insertion of a Coagulase negative •90% of S. aureus remain susceptible to prosthesis, Staphylococci (CNS) cloxacillin, macrolides or clindamycin. graft or Staphylococcus aureus Although 2/3 of CNS are methicillin-resistant, prophylaxis with beta-lactam antibiotics is still shunt appropriate. ► Environmental controls Operating room environment Maintain > 15 air changes per hour Maintain positive-pressure ventilation with laminar flow Filter all air, recirculated and fresh, through the appropriate filters Keep operating room doors closed

► • Double-blind, randomized, controlled trial • 3 hospitals (2 in Austria, 1 in Germany) • N=500, colorectal resection (cancer, IBD) • July 1996-October 1998 • FiO2 0.8 vs 0.3 during and 2 hours postop • SSI during 14 days postop

Greif R et al. N Engl J Med. 2000;342:161-167. Greif R et al. N Engl J Med. 2000;342:161-167. Supplemental Perioperative Oxygen and the Risk of Surgical Wound Infection

A Randomized Controlled Trial • Double-blind, randomized, controlled trial • 14 Spanish Hospitals • N=300,Colorectal surgery, general anesthesia • March 2003- October 2004

• FiO2 0.8 vs 0.30 during and 6 hours postop • SSI : 35 (24.4%) vs 22 (14.9%), p=0.04

Belda et al, JAMA, 2005; 194: 2035 Effects of Hypothermia and Hypoxia on Wound Healing

Hypothermia Impaired immune function

Vasoconstriction Low Oxygen Tension

↓Collagen deposition ↓Oxidative Killing by neutrophils Perioperative normothermia

Clinical Wound Infections Normothermic Hypothermic Temperature 36.6+0.5 34.7+0.6

Infections (%) 6 19

Hospitalization 12.1+4.4 14.7+6.5 (Days)

*200 colorectal surgical patients

Melling et al., Lancet 2001;358:876 Blood transfusion –Avoid blood transfusion –Prospective cohort study 2003: transfusion of more than 4 units of packed red blood cells was associated with a 9.28-fold increased risk of infection

Hill GE, et al. J Trauma 2003;54:908–14. Surgeon Hand washing Gloves: double gloves 20% of surgical gloves fail during operation Other barriers Caps Masks Gowns Impact of Surgical Masks on Prevention of Microbial Nasopharyngeal Shedding in Healthy Individuals (N = 22) and Subjects with Symptoms of Rhinorrhea (N = 8)

No Mask - Healthy NS Surgical Mask - Healthy 60 No Mask - Rhinorrhea Surgical Mask - Rhinorrhea 50 3 40

p<0.05 NS

cfu/m 30

20 p<0.05

0 90 minutes 180 minutes Test Interval Edmiston et al, Surgery 2005; 138:572-583 Surgical techniques Gentle tissue handling Removal of devitalized tissue or blood or other substances Using drain appropriately Avoid extensive cauterization Avoid anastomosis of intestine under tension Postoperative wound care

• Sterile dressing for 24-48 hrs postoperatively • Wash hands before and after dressing changes • Changed with sterile technique • Educate patient and family regarding proper incision care, symptoms of SSI, and need to report Preoperative Aims Intraoperative z Reduce the inoculums of Postoperative bacteria Surveillance z Improve the host defences

Mangram AJ et al. Infect Control Hosp Epidemiol. 1999;20:250-278. Infection surveillance

Good surveillance program lowered wound infection rate from 4.9 to 1.9 %

Mangram AJ, et al. Infect Control Hosp Epidemiol 1999;20:247–80. Thank you