ANTIBIOTICS IN COLORECTAL SURGERY

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THE CURRENT ROLE OF ANTIBIOTICS IN COLON AND RECTAL SURGERY IS PRESENTED IN A BRIEF AND CONCISE MANNER- ON AN EVIDENCE BASED APPROACH.

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ANTIBIOTICS IN COLORECTAL SURGERY

  1. 1. DR SANOOP K ZACHARIAH Consultant Surgeon & Assistant Professor MOSC Medical College Kolenchery Kerala, India
  2. 2. <ul><li>“ SINCE ANTIQUITY THE PROBLEM OF INFECTION HAS BEEN CLOSELY LINKED WITH SURGICAL THERAPY” </li></ul>
  3. 3. <ul><li>COLORECTAL SURGEONS </li></ul><ul><li>HAVE TO DEAL WITH A LOT OF BOWEL BACTERIA </li></ul>
  4. 4. ONE DROP OF FEACES = 400 SPECIES OF BACTERIA 10 12 BACTERIA PER GRAM OF WET FEACES 40-50% OF SOLID FEACES=BACTERIA
  5. 5. COLORECTAL SURGERY= LOT OF BACTERIA
  6. 6. <ul><li>PATIENTS IMMUNE SYSTEM </li></ul><ul><li>PROPER SURGICAL TECNIQUE & SKILL </li></ul><ul><li>KNOWLEDGE OF PREDICTABLE GUT MICROFLORA </li></ul><ul><li>OUR WEAPON------ ANTIBIOTICS </li></ul>
  7. 7. <ul><li>1992-CENTRE FOR DISEASE CONTROL, USA (CDC) (REVISED DEFNITION ) </li></ul><ul><li>SURGICAL INFECTIONS </li></ul><ul><li>RESULT OF A SURGICAL PROCEDURE (SSI) </li></ul><ul><li>REQUIRES A SURGICAL PROCEDURE ( eg.ABSCESS DRAINAGE ) </li></ul><ul><li>SURGICAL SITE INFECTIONS(SSI ) </li></ul><ul><li>DEFN : INFECTIONS ALONG THE SURGICAL TRACT WITHIN 0 TO 30 DAYS OF SURGERY OR ONE YEAR FOLLOWING IMPLANTS </li></ul><ul><li>SECOND MOST COMMON NOSOCOMIAL INFECTION (20%) </li></ul><ul><li>INCREASES MORBITIDY,HOSPITALIZATION COSTS,MORTALITY(3%) </li></ul>ARCHIVES OF SURGERY ,OCT 2006;141:1014-1018
  8. 8. SUPERFICIAL SSI DEEP SSI ORGAN SPACE SSI SKIN SUBCUTANEOUS DEEP SOFT TISSUE FASCIA&MUSCLE INTRAPERITONEAL 1)HORAN ET AL,INFECT CONTROL HOSP EPIDEMOL 1992;13(10);606-8 2)AMJ INFECT CONTROL,2008:36:309-32
  9. 9. NUMBER OF RISK FACTORS PROCEDURE 0 1 2 3 GASTRIC SURGERY 1.84 2.64 4.86 APPENDICECTOMY 1.49 2.68 3.49 SMALL BOWEL SURGERY 2.62 6.31 COLON SURGERY 4.18 6.07 8.01 10.86 BREAST SURGERY .80 2.74 HERNIA SURGERY 1.02 2.47 4.36
  10. 10. <ul><li>Without Antibiotic Prophylaxis= 40% SSI </li></ul><ul><li>The Risk Of Death Is Doubled (Relative Risk (RR) 2.2, 95% Confidence Interval (CI) 1.1 To 4.5) </li></ul><ul><li>Intensive Care Unit Admission Is More Likely (RR 1.6, 95% Ci 1.3 To 2.0) </li></ul><ul><li>Average Hospital Stay Is Lengthened By Five Days </li></ul><ul><li>the risk of hospital readmission is greatly increased (RR 5.5, 95% CI 4.0 to 7.7) </li></ul>Baum 1981, (Kirkland 1999), (Smith 2004),
  11. 11.
  12. 12. <ul><li>ENDOGENOUS-SKIN & GIT </li></ul><ul><li>EXOGENOUS </li></ul>SKIN STAPHYLOCOCCUS sp CORNYFORMS MICROCOCCI
  13. 13. MICROBIOLOGICAL COMPOSITION AND DISTRIBUTION OF THE GUT 10 3 10 8 10 12 Aerobes To Predominantly Anaerobes
  14. 14. <ul><li>COMMENSALS </li></ul><ul><li>SYMBIOTIC </li></ul><ul><li>PRIMARILY LARGE BOWEL R >L </li></ul><ul><li>>4OO SPECIES </li></ul>CONCENTRATION OF BACTERIA PRESENT IN HUMAN COLON <ul><li>ANAEROBES </li></ul><ul><li>BACTERIODES SP </li></ul><ul><li>LACTOBACILLUS </li></ul><ul><li>CLOSTRIDIUM SP </li></ul>10 9 -10 12 10 6 -10 12 10 3 -10 10 <ul><li>AEROBES </li></ul><ul><li>COLIFORMS </li></ul><ul><li>LACTOBACILLUS </li></ul><ul><li>STAPHYLOCOCCUS SP </li></ul>10 5 -10 8 10 3 -10 7 10 2 -10 4
  15. 15.
  16. 16. LYMPHATICS,BLOOD BOWEL EXTRA INTESTINAL SITES
  17. 17. >10 5 =INFECTION
  18. 18. <ul><li>THERAPEUTIC - FOR ESTABLISHED INFECTION </li></ul><ul><li>PROPHYLATIC - ADMINISTERED IN ABSENCE OF INFECTION TO REDUCE SEVERITY OR PREVENT INFECTION FOLLOWING SURGICAL INTERVENTION </li></ul>
  19. 19. <ul><li>TO PREVENT INFECTION FOR A DEFINED PERIOD </li></ul>VULNERABLE/GOLDEN PERIOD INCISION TO CLOSURE ANYTHING BEYOND SKIN CLOSURE =THERAPY
  20. 20. <ul><li>PROVIDE, AS FAR AS POSSIBLE ,THE PRECISE COVERAGE </li></ul><ul><li>MINIMAL EFFECT ON PTS NORMAL BACTERIAL FLORA </li></ul><ul><li>MINIMAL ADVERSE EFFECTS </li></ul><ul><li>MINIMAL CHANGE ON HOST DEFENCES </li></ul><ul><li>USAGE SHOULD BE SUPPORTED BY EVIDENCE OF EFFECTIVENESS </li></ul>
  21. 21. <ul><li>SHOULD I USE ANTIBIOTICS ? </li></ul><ul><li>WHICH ANTIBIOTIC? </li></ul><ul><li>SINGLE OR COMBINATION? </li></ul><ul><li>WHEN TO START? </li></ul><ul><li>HOW LONG TO CONTINUE? </li></ul><ul><li>ROUTE-IV/ORAL? </li></ul><ul><li>WHAT OTHER FACTORS SHOULD I CONSIDER? </li></ul>
  22. 22. NATIONAL RESEARCH COUNCIL GROUP 1964(NRC) TAXONOMY OF SURGICAL WOUNDS WOUND TYPE DESCRIPTION 1 CLEAN ELECTIVE,NON TRAUMATIC,NOBREAK IN TECNIQUE,RESPIRATORY,GI,GENITOURINARY TRACT NOT ENTERED 2 CLEAN CONTAMINATED ELECTIVE OPENING OF RS,GI,GENITURINARY TRACT WITHOUT SIGNIFICANT SPILLAGE 3 CONTAMINATED TRAUMATIC WOUND,GROSS SPILLAGE FROM GI TRACT,ENCOUNTERING INFECTED URINE/BILE. 4 DIRTY SUPPORATIVE-INFLAMMATION,PRE-OP PERFORATION OF RS,GI,GTU ,TRACTS
  23. 23. ABSENCE OF ANTIMICROBIAL PROPHYLAXIS- WOUND INFECTION-32-58% INFECTIOUS COMPLICATIONS-UPTO 75% CATEGORY WITHOUT PROHYLATIC ANTIBIOTICS PROHYLATIC ANTIBIOTICS 1 CLEAN 1-2% 1-2% 2 CLEAN CONTAMINATED 6-11% 3.3% 3 CONTAMINATED 13-20% 6.4% 4 DIRTY 27-40% 7.1%
  24. 24. ??PENICILLIN AMINOGLYCOSIDE CEPHALOSPORINS METRONIDAZOLE,…….?????????
  25. 25. <ul><li>THE COMMONEST BACTERIA ISOLATED FROM POST-OP WOUND INFECTIONS AFTER VARIOUS COLORECTAL PROCEDURES - E.COLI ,BACTERIODES FRAGILIS AND STAPH. </li></ul><ul><ul><ul><li>ENDOTOXIN GENERATING FACULTATIVE AND GM –IVE AEROBES E.COLI ,OBLIGATE ANAEROBES- BACTERIODES </li></ul></ul></ul>
  26. 26. CHOOSE ONE FROM EACH EMPIRICALLY AEROBIC COVERAGE GENTAMICIN TOBRAMYCIN AMIKACIN CEFOTAXIM CEFTIZOXIME CRFTRIAXONE AZTREONAM CIPROFLOXACIN ANEROBIC COVERAGE CLINDAYCIN METRONIDAZOLE CHLORAMPHENICOL
  27. 27. <ul><li>THE RISK FOR INFECTIONS BEGINS WITH THE INCISION </li></ul><ul><li>ANTIBIOTICS SHOULD ALREADY BE PRESENT IN THE TISSUES AT THE TIME OF INSCISION(SKIN,COLON) </li></ul><ul><li>FIRST DOSE-ATLEAST WITHIN 30 MINUTES OF INDUCTION </li></ul><ul><li>ANTIBIOTICS STARTED 3HRS AFTER CONTAMINATION ARE LESS EFFECTIVE </li></ul><ul><li>THE GOAL –TO ACHIEVE CONCENTRATION THAT EXCEEDS MIC BY 3-4 TIMES AT LEAST ¾ OF THE TIME BETWEEN SUCCESSIVE DOSES </li></ul><ul><li>PROLONGED SURGERIES-RPT DOSES AT INTERVALS OF 1-2 HALF LIFES OF THE DRUG </li></ul>
  28. 28. HALF-LIVES OF SELECTED ANTIBIOTICS COMMONLY USED FOR PROPHYLAXIS Antibiotic Half-life (hours) Cefazolin Vancomycin Cefoxitin Cefotetan Aminoglycosides Metronidazole Clindamycin Ciprofloxacin 1.8 6 0.6 to 1 3 to 4.6 2 8 2.4 to 3 3 to 5
  29. 29. <ul><li>AVOID –BLIND,INDISCRIMINATE,PROLONGED POST OP ANTIBIOTICS </li></ul><ul><li>THE DURATION OF AN ADEQUATE TISSUE LEVEL OF THE ANTIBIOTIC NEED NOT EXCEED THE OPERATIVE PERIOD . </li></ul><ul><li>EVOLVING POLICY- MINIMAL ANTIBIOTIC ADMINISTRATION </li></ul><ul><li>SURGEONS SHOULD UNDERSTAND DIFFERENCE BETWEEN CONTAMINATION ,INFLAMMATION, INFECTION </li></ul><ul><li>STERILE INFLAMMATION IS COMMON AFTER ANY OPERATION </li></ul><ul><li>MANIFESTS AS LOCAL INFLAMMATORY RESPONSE( LIRS ) </li></ul><ul><li>SO,PYREXIA OR LEUKOCYTOSIS NEED NOT MEAN INFECTION </li></ul><ul><li>LIRS RESOLVES WITHOUT ANTIBIOTICS </li></ul>
  30. 30. ONLY CONDITIONS APPLICABLE TO COLORECTAL SURGERY ARE INCLUDED CONTAMINATION- NO POSTOPERATIVE ANTIBIOTICS Traumatic enteric perforations-12 hrs Peritoneal contamination with bowel contents in elective/emg surgery Appendectomy – early/phlegmonous RESECTABLE INFECTION- UPTO 24 HRS Gangrenous (appendicitis) Resection of ischemic/strangulated necrotic bowel without perforation MILD INFECTION-UPTO 48HRS Intra abdominal infection with localized pus formation Late(>12 hrs)perforation without established infection MODERATE INFECTION-UPTO 5 DAYS Diffuse established intra abdominal infection from any source SEVERE INFECTION->5 DAYS Intra abdominal infection with a source not easily controllable Post op intraabdominal infection
  31. 31. <ul><li>DEBATED TOPIC </li></ul><ul><li>IMPAIRED GI FUNCTION- INTRAVENOUS ROUTE IS PREFERRED </li></ul><ul><li>PROPHYLAXIS BY I.V IS THE ONLY METHOD SUPPORTED BY A SUBSTANTIAL BODY OF EVIDENCE </li></ul><ul><li>ADDITION OF ORAL TO PARAENTERAL---NO PROVEN BENEFIT </li></ul>A SINGLE DOSE OF ANTIBIOTIC AT THERAPUETIC COMBINATION USUALLY SUFFICES FOR PROPHYLAXIS FOR LONGER PROCEDURES, READMINISTRATION OF THE DRUG AT INTERVALS OF 1-2 TIMES THE HALF-LIFE OF THE DRUG (USING THE SAME DOSE).)
  32. 32. <ul><li>ERYTHROMYCIN AND NEOMYCIN </li></ul><ul><li>1GM OF EACH </li></ul><ul><li>1PM,2PM &11 PM </li></ul><ul><li>FIRST DOSE 19 HRS BEFORE SURGERY </li></ul><ul><li>METRONIDAZOLE =ERYTHROMYCIN </li></ul><ul><li>KANAMYCIN=NEOMYCIN </li></ul>
  33. 33. <ul><li>1)BLOOD LOSS & 2) FLUID REPLACEMENT </li></ul><ul><li>HERE SERUM ANTIBIOTIC CONCENTRATIONS --REDUCED </li></ul><ul><li>BLOOD LOSS>1500ml </li></ul><ul><li>HAEMODILUTION >15ml/kg </li></ul>ADDITIONAL DOSE <ul><li>DIABETES </li></ul><ul><li>CORTICOSTEROIDS </li></ul><ul><li>OBESITY </li></ul><ul><li>EXTREMES OF AGE </li></ul><ul><li>MALNUTRITION </li></ul><ul><li>MASSIVE TRANSFUSION </li></ul><ul><li>3 OR MORE COMORBID CONDITIONS </li></ul><ul><li>ASA CLASS 3,4,5 </li></ul>
  34. 34. <ul><li>A new simple risk stratification for SSI-BY ( NATIONAL NOSOCOMIAL INFECTION SURVEILENCE SYSTEM ) </li></ul>
  35. 35.
  36. 36. IN ANORECTAL ABCESS, FISTULA, PILONIDAL ABCESS COMMONEST ORGANISMS ISOLATED WERE GUT SPECIFIC ORGANISMS & STAP.AUREUS Whitehead et al 1982 BJS
  37. 37.
  38. 38. HA-MRSA, CA-MRSA VRSA,VISA ESBL
  39. 39. Suppression of normal gut flora Overgrowth of toxigenic strains of C.Difficile Effects- toxin a-mildly cytopathic toxin b-highly cytopathic Strain-bi/na1/027-new highly toxigenic strain-a,b toxins- Common antibiotics- penicillin, clindamycin, cephalosporin
  40. 40. YEAR AUTHORS RESULT 1985 Lozaro et al Iv metronidazole to be highly effective against anaerobes 1991 Tsimyianu et al Ornidazole 1g+cetrioxone =metronidazole+amikacin 1993 Rohwedher et al Ciprofloxacin 750mg single dose +met > gentamicin 8omg+met 1995 Nyam et al Amoxicllin-clavulanic acid > ceftrioxone+metronidazole 1996 Akuell Single dose ceftotam2gm+met > multiple doses(3) 2000 Zanella et al Single dose cefipime/ceftrioxone +met =other alternative regimens 2000 Zelenitsky et al Single high dose gentamicin+met>multiple standard doses 2005 Epsin et al Oral antibiotics have no additional benefits when added to paraenteral prophylatics
  41. 41. DNA mRNA DNA GYRASE PENICILLIN CEPHALOSPORIN VANCOMYCIN AMPHOTERICIN BACITRACIN GENTAMICIN METRONIDAZOLE CIPROFLOXACIN t-RNA LINEZOLID
  42. 42. MECHANICAL PREP REMOVES FEACAL BULK NOT BACTERIA RISK OF INFECTION WITH MEC.PREP ALONE=25-30% ROUTINE USE OF MECHANICAL PREP HAS BEEN QUESTIONED
  43. 43. <ul><li>Cochrane Database of Systematic Reviews 2010 Issue 3, </li></ul><ul><li>(Data Source-medline, Pubmed ,Cochrane Data Base, embase </li></ul><ul><li>January, 1980 to December, 2007 </li></ul><ul><li>Objective –To Evaluate Efficacy Of Antimicrobial Prophylaxis In Pts Undergoing Colorectal Surgery </li></ul><ul><li>DATA - </li></ul><ul><li>182-RCT trials, </li></ul><ul><li>30,880patients </li></ul><ul><li>>70 different antibiotic regimens, </li></ul><ul><li>50 different antibiotics </li></ul>Nelson RL, Glenny AM, Song -ANTIMICROBIAL PROPHYLAXIS IN COLORECTAL SURGERY ,SYST REWIEW OF RCT–HEALTH TECH ASSMT 1998/2010-updated
  44. 44. <ul><li>Antimicrobial prophylaxis versus no treatment control/placebo </li></ul><ul><li>Short- versus long-term use of an antimicrobial </li></ul><ul><li>Regimen with additional aerobic coverage versus same regimen with no additional aerobic coverage </li></ul><ul><li>Regimen with additional anaerobic coverage versus same regimen with no additional anaerobic coverage </li></ul><ul><li>Orally versus intravenous administration </li></ul><ul><li>Orally and intravenous (iv) versus iv alone </li></ul><ul><li>Antibiotic prophylaxis of any antibiotic compared to an established gold-standard prophylaxis regimen( oral </li></ul><ul><li>neomycin/erythromycin base, iv cefoxitin or cefotetan, and iv doxycycline.) </li></ul>DESCRIPTION OF STUDIES
  45. 45. <ul><li>Without prophylaxis SSI= 40% </li></ul><ul><li>No advantage with longer dosing (RR1.06, 95%CI 0.89 to 1.27 (P value 0.51) </li></ul><ul><li>Addition of aerobic coverage to anaerobic coverage significantly reduced the incidence of SWI (RR 0.41, 95% CI 0.23 to 0.71 (P value 0.002)) </li></ul><ul><li>Addition of anaerobic coverage to aerobic coverage resulted in a statistically significant reduction in SWI rates (RR 0.55, 95% CI 0.35 to 0.85 (P value 0.008) </li></ul><ul><li>ORAL VS IV- no statistically significant difference in SWI incidence </li></ul><ul><li>A statistically significant benefit in favour of combined oral and intravenous, compared to intravenous alone (RR 0.55, 95% CI 0.41 to 0.74 (P value less than 0.0001) </li></ul><ul><li>A statistically significant benefit for combined oral and intravenous, compared to oral prophylaxis alone (RR 0.34, 95% CI 0.13 to 0.87 (P value 0.02 ) </li></ul>RESULTS
  46. 46. <ul><li>Without prophylaxis SSI= 40% </li></ul><ul><li>Overall rate of SSI-11.1%(prophylaxis) </li></ul><ul><li>Prophylactic antibiotics reduce the risk of postoperative SSI by 75% </li></ul><ul><li>Single dose as effective as multidose-no significant diff in SSI </li></ul><ul><li>Oral combined with iv is better. </li></ul><ul><li>No convincing evidence -2/3 gen cephalosporin's better than 1 gen. </li></ul><ul><li>Efficacy of different regimens similar –difficult to identify best regimen </li></ul><ul><li>Monotherapy with metronidazole,piperacillin,-ineffective </li></ul><ul><li>Further research is required to establish adverse effects such as Clostridium difficile pseudomembranous colitis. </li></ul>SONG F,GLENNY AM-ANTIMICROBIAL PROPHYLAXIS IN COLORECTAL SURGERY ,SYST REWIEW OF RCT–HEALTH TECH ASSMT 1998 CONCLUSIONS
  47. 47. <ul><li>SIGN (SCOTTISH INTERCOLLEGIATE GUIDELINES NETWORK) </li></ul><ul><li>PROPHYLATIC ANTIBIOTICS IS HIGHLY RECOMMENDED </li></ul><ul><li>AHSP (AMERICAN SOCIETY OF HEALTH SYSTEM PHARMACISTS </li></ul><ul><li>CEFUROXIME WITH METRONIDAZOLE- PREFERRED COMBINATION </li></ul>
  48. 48. <ul><li>Antibiotic prophylaxis proven septic complications ,-definitely required in colorectal surgery </li></ul><ul><li>It is unethical to perform colorectal surgery without prophylaxis </li></ul><ul><li>The target coverage-aerobes & anaerobes </li></ul><ul><li>GOLD STANDARD REGIMEN is yet to be defined </li></ul><ul><li>Paraenteral and oral combination are preferred choice </li></ul><ul><li>Mono/combination therapy –active –anaerobes+aerobes </li></ul><ul><li>Timing of first dose is important </li></ul><ul><li>Further doses depend on operative findings </li></ul><ul><li>Avoid misuse/prolonged use-additional dosing=resistance/colitis </li></ul><ul><li>Should consider basing practice on updated guidelines, evidence based medicin e </li></ul>

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