Is There Any Role for Oral Antimicrobial Prophylaxis in Colorectal Is There Any Role for Oral Antimicrobial Prophylaxis in Colorectal Surgery? Samuel Eric.

Is There Any Role for Oral Antimicrobial Is There Any Role for Oral Antimicrobial Prophylaxis in ColorectalProphylaxis in Colorectal Surgery?

Samuel Eric Wilson, MD Department of Surgery

University of California, IrvineIrvine, CA

Disclosure

Dr Wilson reports having no financial or advisory relationships with corporate organizations related to this activity.

Adverse Effects in NY Hospitals1133 of 30,195 Hospitalized Patients

Events Disability

Nonoperative 534 (52.3%) 25.3%

Operative 599 (47.7%) 24%

Wound infection 160 18%

Technical 157 12%

Late comp. 137 35.7%

Surgical failure 58 17.5%

Other 87 44%

Harvard Med. Practice Study. Leape LL et al. N Engl J Med. 1991;324:377-384.

Antibiotic Administration in Surgery“The Chaos Continues”*

• New York Methodist Hospital—560 beds• 156/211 inappropriate antibiotic administration• 2 cases Clostridium difficile colitis• Excessive duration of antibiotics• Did not distinguish prophylactic from therapeutic

*Gorecki P et al. World J Surg. 1999;23:429-433.

Timing of Prophylaxis and Surgical Site Infection (SSI) Rate in Colon Surgery

0%

1%

2%

3%

4%

5%

6%

>2 2 1 1 2 3 4 5 6 7 8 9 10 >10

Infe

cti

on

Ra

te (

%)

Hours beforeincision

Incision Hours after incision

Data from University Hospitals Consortium 2004.

National Initiatives to Prevent SSI

• Surgical Care Improvement Program (SCIP)• Save 100,000 Lives Campaign• National Academy of Medicine: “To Err Is Human”• National VA Surgical Quality Improvement Program

(NSQIP) extended to private sector

• Financed by Center for Medicare & Medicaid Services (CMS)

• Reporting of adherence to guidelines required and ? pay for performance

Bowel Preparation for Elective Colon Resection: State of the Art in North America*

Surgeons performing elective colorectal resection with primary anastomosis consider a mechanically cleansed bowel a prerequisite along with oral antimicrobials

*Nichols RL, Smith JW, Garcia RY, et al. Current practices of preoperative bowel preparation among North American Colorectal Surgeons. Clin Infect Dis. 1997;24:609-619.

Wound ClassificationNational Research Council, 1964

• Clean wound—gastrointestinal (GI), genitourinary (GU), or respiratory tract not entered, no apparent inflammation, no break in a septic technique

• Clean contaminated—GI and respiratory tract entered, but no spill of contents

• Contaminated—acute inflammation, gross spillage• Dirty—perforated viscus, pus, abscess

Distribution of Viable Bacteria in the Small Intestine

Prevention of Infection After GI Surgery

Anatomical Site Normal Flora Bacterial Count

Upper GI (esophagus, stomach, duodenum, proximal small bowel)

Streptococci, Lactobacilli, Corynebacteria, oral anaerobes

0–103

Biliary tree Sterile 0

Lower GI (ileum, colon, rectum)

Escherichia coli, Bacteroides fragilis group, Clostridium, Enterococci, anaerobic cocci

108–1012

Type of Procedure Risk of SSI

Clean <2% Clean-contaminated 5–15% Contaminated 15–30% Dirty* >30%

Nichols RL. Am J Surg. 1996;172:68-74.

Traditional Classification of Operative Procedures and Risk of Infection

*Dirty wounds infection—antibiotics indicated as therapy

Surgical Patients at Risk for Infection*

Variable Order P Value

Abdominal operation 1 < .0001

Operation >2 h 2 < .0001

Class III and IV 3 < .0001

3 Diagnoses 4 < .0001

*Study on the Efficacy of Nosocomial Infection Control (SENIC), Centers for Disease Control and Prevention.Haley RW et al. Am J Epidemiol. 1985;121:182-205.

PREVENT Trial Baseline Patient Risk Factors*

Risk FactorsPolyethylene Glycol Sodium Phosphate

P Value(n=303) (n=367)

Obesity (body mass index >30 kg/m2), %

28.5 31.0 .487

Chronic obstructive pulmonary disease, %

9.6 3.0 <.001

Time from dosing to surgery, min

55.923.1 (0–120) 59.624.3 (8–12) .044

Duration of surgery, min 138.863.9 128.156.7 .024

Occurrence of perforation/spillage, %

4.0 1.6 .064

Good to excellent bowel preparation, %

92.7 91.6 .089

*Itani K et al. Am J Surg. 2007;193:190-194.

Is Incidence of Postoperative SSI Within Your Control?

• Postoperative infection rates decrease as residents gain experience

Lau WY et al. Am J Surg. 1988;155:322-326.

• Unique surgeon rates in Portland for colorectal surgeryPeck JJ et al. Am J Surg. 1984;147:633-637.

• In review of 2809 patients, surgeon was independent variableTang R et al. Ann Surg. 2001;234:181-189.

Influence of Surgeons’ Experience on Postappendectomy Sepsis

According to Degree of Appendicitis

Normal Appendix

Acutely Inflamed

Late Appendicitis

Trainees (n=7)

Stage 1 Operations 10 90 40

Infection 1 7 10

Stage 2 Operations 10 91 39

Infection 0 4 5

Stage 3 Operations 19 223 113

Infection 0 9 9

Senior Surgeons (n=6)

Overall Operations 12 71 36

Infection 0 2 2

Lau WY et al. Am J Surg. 1988;155:322-326.

Postappendectomy Sepsis Rates for Seven Individual Trainees

Normal Appendix

Acutely Inflamed

Late Appendicitis

All Appendicitis

1/9 (11.1%) 3/63 (4.8%) 3/30 (10%) 7/102 (6.9%)

0/8 (0%) 2/77 (2.6%) 1/27 (3.7%) 3/112 (2.7%)

0/5 (0%) 1/39 (2.6%) 3/33 (9.1%) 4/77 (5.2%)

0/7 (0%) 2/72 (2.8%) 7/41 (17.1%) 9/120 (7.5%)

0/3 (0%) 4/29 (13.8%) 4/20 (20%) 8/52 (15.4%)

0/2 (0%) 4/52 (7.7%) 5/26 (19.2%) 9/80 (11.3%)

0/5 (0%) 4/72 (5.6%) 1/15 (6.7%) 5/92 (5.4%)

Lau WY et al. Am J Surg. 1988;155:322-326.

Colorectal Surgery: Each Surgeon’s Infection Rate Differs

Surgeon Patients, n Infection, %

B 139 2.2

E 89 5.6

F 64 6.3

I 72 8.3

M 79 11.4

N 105 12.4

O 46 17.4

St. Vincent’s Medical Center, Portland. Peck JJ et al. Am J Surg. 1984;147:633-637.

Antibiotic Effects on Surgeons’ Wound Infection Rates

Percentage

SurgeonsNo. of

PatientsNo or Poor Antibiotics

Effective Antibiotics

P Value

Group I 305 5.3 1.7 NS

Group II 244 12.2 3.6 <.01

Group III 372 20.5 4 <.001

NS=not significant.St. Vincent’s Medical Center, Portland. Peck JJ et al. Am J Surg. 1984;147:633-637.

History of Intestinal Antisepsis

• 1941 Poth—Nonabsorbable sulfas Sulfasuxidine, sulfathalidine

• 1950 Tetracycline—enterocolitis• 1964 Gordon and Finegold

Neomycin—Staphylococcus wound Infections

• 1975 Clarke and Condon VA Cooperative Studies

Mortality 10–12%; Infection 80%Staged resections; Closed anastomoses

Antimicrobial Prophylaxis in Colorectal Surgery

• Antibiotic began preoperatively • Prospective, controlled, randomized• Precise definition of wound infection• Appropriate spectrum for flora

(aerobic and anaerobic)• No established infection

Study Design*

*Guglielmo BJ et al. Arch Surg. 1983;118:943-955.

Wound Infection After Elective Colorectal Resection

• Detailed review of 176 patients/2 years with 3-month follow-up; oral antibiotics

• Age 62 (48–72) years; 57% cancer; 20% diverticulitis

• 40% had ileostomy or colostomy• 45 (25.6%) had SSI: 22 diagnosed after discharge• Mean home health care cost $6200• 3 risk factors: obesity (P = .024); length of operation

(P = .031); ↓blood pressure (P = .1)“A surgeon with considerable intestinal fortitude!”

Smith RL et al. Ann Surg. 2004;239:599-605.

Preventing Infection in Colorectal Surgery

• Field isolation• GIA for bowel division• Clean set (Mayo stand) for wound closure; change

gowns and gloves• Inflammatory bowel disease, active infection, and

perineal wound were exclusions• Independent RN epidemiologist collected outcome data

Technical Methods in VA Cooperative Trials

Oral Antimicrobials Highly Effective in First VA Cooperative Trial

• 116 evaluable patients; 56 erythromycin + neomycin; 60 placebo

• 3-day bowel prep• Septic complications: 43% placebo;

9% erythromycin + neomycin (P < .001)• 4- to 5-log decrease in concentrations of both

aerobes and anaerobes in colonic lumen

Clarke JS et al. Ann Surg. 1977;186:252-259.

Colorectal Prophylaxis: Parenteral Cephalothin Alone Fails

Complication, n (%)

Intravenous Cephalothin

(n = 67)

Erythromycin + Neomycin

± Cephalothin (n = 126)

P Value (chi-square)

Wound infection 20 (30) 7 (6) <.001

Peritonitis/abscess 12 (18) 2 (2) <.001

Anastomotic leak 7 (10) 0 <.001

Septicemia 5 (7) 1 (1) <.04

Death 4 (6) 2 (2) <.2

Total complications 48 12

Total septic patients 26 (39) 7 (6) <.001

Condon RE et al. Am J Surg. 1979;137:68-74.

Efficacy of Oral and Systemic Prophylaxis in Colorectal Operations

• 5-year study of oral neomycin + erythromycin vs orals and parenteral cephalothin

• 1128 patients studied in VA Cooperative Study

• Overall septic complications: orals = 7.8%; orals + cephalothin = 5.7% (NS)

• “…no discernable benefit from adding parenteral antibiotics…”

Condon RE et al. Arch Surg. 1983;118:496-502.

Prophylaxis in Colon Surgery

Baum ML et al. N Engl J Med. 1981; 305:795-799.

Postoperative Infection in Colorectal Surgery

• Protected by mucous blanket from oral antibiotics (Rotstein et al; 1985)

• Colonoscopic biopsies of mucosa; SEM • Greatest suppression with both oral and

parenteral antimicrobials• 3.4 107 1.8 102 mean CFU/g

Musocal-related Microflora

SEM = scanning electron microscope.World J Surg. 1990

Mean Serum Erythromycin Concentration

Wound Infection Rates (% Infections) After Colorectal Surgery: Effect of Combination of Oral and

Parenteral AntimicrobialsPerioperative Antibiotics*

Investigator Oral

Oral and Parenteral

Significance

(P Value) Regimen

Copa et al Copa et al 1983198311

I 18.0%I 18.0% II 6.6%II 6.6% <.01<.01 I Erythromycin (oral) + Neomycin (oral)I Erythromycin (oral) + Neomycin (oral)

II Erythromycin (oral) + Neomycin (oral) + CefoxitinII Erythromycin (oral) + Neomycin (oral) + Cefoxitin

Portnoy et al Portnoy et al 1983198322

I 29.0%I 29.0% II 4.7%II 4.7% <.01<.01 I Erythromycin (oral) + Neomycin (oral)I Erythromycin (oral) + Neomycin (oral)

III 2.3%III 2.3% <.001<.001 II Erythromycin (oral) + Neomycin (oral) + CefazolinII Erythromycin (oral) + Neomycin (oral) + Cefazolin

III Erythromycin (oral) + Neomycin (oral) + CefazolinIII Erythromycin (oral) + Neomycin (oral) + Cefazolin

Condon et al Condon et al 1983198333

I 7.8% I 7.8% septicseptic

II 5.7% II 5.7% septicseptic

NSNS I Erythromycin (oral) + Neomycin (oral) + PlaceboI Erythromycin (oral) + Neomycin (oral) + Placebo

5.6% wound5.6% wound 3.7% wound3.7% wound NSNS II Erythromycin (oral) + Neomycin (oral) + II Erythromycin (oral) + Neomycin (oral) + CephalothinCephalothin

*All patients had mechanical preparation.NS = not significant.

1. Copa et al.

2. Portnoy J et al. Dis Colon Rectum. 1983;26:310-313.

3. Condon RE et al. Arch Surg. 1983;118:496-502.

Colorectal SurgeryEffect of Duration of Operation

Duration, hOrals and Cefazolin, n/total (%)

Cefoxitin, n/total (%)

<3 0/29 0/17

3–4 2/21 (9.5) 2/25 (8.0)

>4 0/13 5/14 (35.7)*

*Cefoxitin IV “on call”: 1 h 40 min before incision

Kaiser AB et al. Ann Surg. 1983;198:525-530.

Antimicrobials for GI/Colorectal Surgery—SIP Guidelines

• ParenteralCefotetan, cefoxitin, ampicillin or cefazolin + metronidazole (if penicillin allergy, use gentamicin, azithromycin, or quinolone)

• OralNeomycin + erythomycin

Resection and Primary Anastomosis of the Colon and Rectum Without Mechanical Bowel Preparation (MBP)

(Controlled, Randomized Series)

Wound Infection, n/total (%)

Leak, n/total (%)

MBP No MBP MBP No MBP

Brownson 19921 5/86 (5.8) 7/93 (7.5) 8/67 (11.9) 1/67 (1.5)

Burke 19922 4/82 (4.9) 3/87 (3.4) 3/82 (3.7) 4/87 (4.6)

Miettmen 20003 5/138 (3.6) 3/129 (2.3) 5.125 (4) 3/117 (2.6)

1. Brownson et al (abstract). Brit J Surg. 1992;77:461-462.2. Burke P et al. Brit J Surg. 1994;81:907-910.3. Miettmen RP et al. Dis Colon Rectum. 2000;43:669-675.

Prevention of Infection in Colorectal Surgery: Status 2007

• Oral antibiotics plus mechanical bowel preparation established in North America

• Broad spectrum, intravenous antibiotics plus oral agents perioperatively in most patients and always in longer procedures (>3 hours)

• Incidence of major wound and intra-abdominal infection approximately 7–10% for elective resection

• Emphasis on avoidance of colostomy, staged operations • New data from Europe question mechanical preparation

given good perioperative antimicrobials

Prevention of Infection in Colorectal Surgery: Next Steps

• Extension of indications for primary colon resection/anastomosis

• Changes in bowel preparation: de-emphasis• Longer procedures (ileoanal, low anterior)

• Demand Parenteral Antimicrobial Highly effective aerobic and anaerobic agent Must have low toxicity Achieve rapid serum MIC90 level No nausea or vomiting Avoid redosing and timing errors accurately with long

half-life

MIC = minimum inhibitory concentration.