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					Intraabdominal Infections and MOF - Nicolas V. Christou




      INTRA-ABDOMINAL INFECTIONS
 MULTIPLE ORGAN DYSFUNCTION SYNDROME

          • Pathophysiology of Infection
          • Definitions, Diagnostic Methods
          • Antibiotic Choices in Surgery
          • Host Response to a “trigger”
          • Multiple Organ Dysfunction
            Syndrome
          • New Therapeutic Strategies
Intraabdominal Infections and MOF - Nicolas V. Christou




                 Classification of IA
                     infections

               Primary Peritonitis

               Secondary Peritonitis

               Tertiary Peritonitis
         Intraabdominal Infections and MOF - Nicolas V. Christou




        PATHOPHYSIOLOGY OF FEVER
                                Stimulation of
                                Vasomotor Center



                       Elevation of
                       Hypothalamic
                        Thermostat                            Peripheral Muscles
                                                                                   Peripheral Blood Vessels


(Endogenous
 Pyrogens)    IL-1
                                   STIMULUS                                           Vasoconstriction
                                                                   Shivering




                                                                         F E V E R
               Stimulated
               Macrophage
                                      Resting
                                     Macrophage
Intraabdominal Infections and MOF - Nicolas V. Christou




 Surgeon’s diagnostic approach

    History & Physical Examination

 is the fever real ? Does the patient "look ill" ?

 rule out pneumonia, UTI, phlebitis etc

 examine wound, listen for bowel sounds

 examine abdomen, including rectal exam
Intraabdominal Infections and MOF - Nicolas V. Christou




  Surgeon’s diagnostic approach

                           Laboratory Tests

    leukocytosis, electrolyte or acid-base
     imbalance, anemia ?
    renal or hepatic organ dysfunction ?
    coagulation abnormalities, platelets ?
    specialized tests
Intraabdominal Infections and MOF - Nicolas V. Christou




Surgeon’s diagnostic approach
                          Imaging Studies
• Plain radiographs of the abdomen
      – abdominal series, 3 views of abdomen, ….
      – define location of abscess in ~50% of cases
              Connell et al 1980

• CT scan vs. Ultrasound
      – both offer superior sensitivity and specificity
      – ultrasound better for localized collections
      – CT better in search of an infectious focus in a “septic” patient
               Rotstein and Meakins 1990
Intraabdominal Infections and MOF - Nicolas V. Christou



        Treatment of intra-abdominal
                infections

• prompt surgical intervention
      – stop continuing contamination
      – remove devitalized tissue
      – drain purulent collections

• general supportive measures

• antimicrobial therapy
      – empiric vs. definitive Rx
     Intraabdominal Infections and MOF - Nicolas V. Christou




               Mortality of IA Infections
              80
              70
              60
Mortality %




              50
              40
              30
              20
              10
              0
                   Localized                 Localized           Diffuse      Complicated
                   Abscess                   Peritonitis       Suppurative       Mixed
                                                                Peritonitis    Infections
 Intraabdominal Infections and MOF - Nicolas V. Christou



                   What is Appropriate
                Empiric Antibiotic Therapy?


A single antibiotic or
an antibiotic
combination that
provides broad
spectrum activity
that cover all
suspected pathogens.
Intraabdominal Infections and MOF - Nicolas V. Christou



               SUSPECTED PATHOGENS
                  INTRA-ABDOMINAL INFECTIONS


                        Gm -ve Aerobes
                                                              MUHC-RVH Data
                                Others                            2000
      P. mirabilis
                                 16%
          4%
 Enterobacter
     5%

P. aeruginosa                                             E. coli
     5%                                                    59%
       K. pneumonia
           11%
Intraabdominal Infections and MOF - Nicolas V. Christou



                SUSPECTED PATHOGENS
                   INTRA-ABDOMINAL INFECTIONS


                         Gm +ve Aerobes                    MUHC-RVH Data
                                                               2000

                                Others
                                 15%
    Corynebacteria
         9%

                                                          Enterococci
                                                             52%
                   S. aureus
                      24%
Intraabdominal Infections and MOF - Nicolas V. Christou



                 SUSPECTED PATHOGENS
                    INTRA-ABDOMINAL INFECTIONS

                                                             MUHC-RVH Data
                                   Anaerobes                     2000



                                     Others
                Fusobacteria
                                      9%
                    6%




             B. fragilis                                  Bacteroidis sp.
                27%                                           58%
Intraabdominal Infections and MOF - Nicolas V. Christou



        Potential AIBCS for the Rx of
            Surgical Infections


  Penicillins                          Cephalosporins         Carbapenems


                Aminoglycosides                           Quinolonnes



 Aztreonam                              Clindamycin         Vancomycin
Metronidazole
  Intraabdominal Infections and MOF - Nicolas V. Christou




                         PENICILLINS
            (Penem nucleus)
                                                            • Penicillin G
                                                            • Methicillin
                                                            • Cloxacillin
                                                            • Carboxipenicillins
                                                            • Ureidopenicillins


Basic structure of Penicillins
Intraabdominal Infections and MOF - Nicolas V. Christou


                             In vitro ACTIVITY of
                                    PIPERACILLIN
                         Minimal Inhibitory Concentration (MIC90 in µg/ml) of Antibiotic
                     0        10        20         30        40        50        60        70

  Anaerobic cocci

   Fusobacterium

     Bacteroides

       B. fragilis



     Enterococci

   S. epedermidis

     Streptococci

        S. aureus



   Acinetobacter

     Moerganella

      Citrobacter

          Seratia

         Proteus

    P. aeruginosa

       Klebsiella

    Enterobacter

           E. coli
 Intraabdominal Infections and MOF - Nicolas V. Christou




               AMINOGLYCOSIDES


(gentamycin)
                                                           • Gentamycin
                                                           • Tobramycin
                                                           • Netilmicin
                                                           • Amikacin



          Excellent Gm- activity
Intraabdominal Infections and MOF - Nicolas V. Christou


                             In vitro ACTIVITY of
                                     GENTAMYCIN
                         Minimal Inhibitory Concentration (MIC90 in µg/ml) of Antibiotic

                     0         10        20        30         40        50         60      70

  Anaerobic cocci

   Fusobacterium

     Bacteroides

       B. fragilis



     Enterococci

   S. epedermidis

     Streptococci

        S. aureus



   Acinetobacter

     Moerganella

      Citrobacter

          Seratia

         Proteus

    P. aeruginosa

       Klebsiella

    Enterobacter

           E. coli
Intraabdominal Infections and MOF - Nicolas V. Christou




      “Gold Standard” Therapy
             SURGICAL INFECTIONS


Aminoglycoside                                            e.g. Gentamycin
                                                               2-3 mg/kg q8h
       +
 Antianaerobic                                            e.g. Clindamycin
     Agent                                                     900 mg q8h
Intraabdominal Infections and MOF - Nicolas V. Christou




                 CARBAPENEMS

                                                          Imipenem
                                                          (PBP-2)



                                                          Meropenem
                                                          (PBP-2)
Intraabdominal Infections and MOF - Nicolas V. Christou


                             In vitro ACTIVITY of
                                  CARBAPENEMS
                         Minimal Inhibitory Concentration (MIC90 in µg/ml) of Antibiotic

                     0       10       20       30         40     50       60       70

  Anaerobic cocci

   Fusobacterium

     Bacteroides

       B. fragilis



     Enterococci

   S. epedermidis

     Streptococci

        S. aureus
                                                                                           Meropenem
                                                                                           Imipenem
   Acinetobacter

       P. species

      Citrobacter

          Seratia

         Proteus

    P. aeruginosa

       Klebsiella

    Enterobacter

           E. coli
  Intraabdominal Infections and MOF - Nicolas V. Christou




                          QUINOLONES
                                                            •   Norfloxacin
 Basic Structure of Quinolones                              •   Ciprofloxacin
                                                            •   Enoxacin
                                                            •   Perfloxacin
                                                            •   Ofloxacin
                                                            •   Lomefloxacin
                                                            •   Levoflaxacin
                                                            •   Sparfloxacin
                                                            •   Grepafloxacin
 Classified according to
modifications at X2 and X8
                                                            •   Clinafloxacin
        positions                                           •   Trovafloxacin
Intraabdominal Infections and MOF - Nicolas V. Christou




     In vitro ACTIVITY of Quinolones
                         Minimal Inhibitory Concentration (MIC90 µg/ml) of Antibiotic
                     0        10       20        30        40        50        60       70


  Anaerobic cocci

   Fusobacterium

     Bacteroides

       B. fragilis



     Enterococci

   S. epidermidis

     Streptococci
                                                                                             Trovafloxacin
        S. aureus                                                                            Sparfloxacin
                                                                                             Levofloxacin
   Acinetobacter                                                                             Ciprofloxacin
      Morganella

      Citrobacter

          Seratia

         Proteus

    P. aeruginosa

       Klebsiella

    Enterobacter

           E. coli
Intraabdominal Infections and MOF - Nicolas V. Christou



    Antibiotics for Perforated Colon
• A 70 year old man with known diverticulosis
  presents with LLQ pain and rebound
  tenderness. WBC = 18,000, T=38.5 C.
• Abdominal series shows free intraperitoneal air.
• Dx: perforated sigmoid diverticulitis.


      • A second generation cephalosporin such as Cefoxitin 2 g q4-6h

      • An aminiglycoside such gentamycin 2-3 mg/kg q8-12h plus Clindamycin 900 mg q8h
        or Metronidazole 500 mg q8h
      • A carbapenem such as IMIPENEM 500 mg q6h

      • A 3rd generation cephalosporin such as ceftriaxone 1 g q24h plus Clindamycin 900
        mg q8h or Metronidazole 500 mg q8h
      • A monobactam such Aztreonam + Antianaerobic Coverage.
      • A quinolone+/-Antianaerobic Coverage
      • Piperacillin/Tazobactam or Ticarcillin/Clavulanic Acid
Intraabdominal Infections and MOF - Nicolas V. Christou


    Radical Attempts to cure patients of Intra-
               abdominal Infection




           Packed Open                                    Mesh-Zipper
            Abdomen                                       Laparostomy
Intraabdominal Infections and MOF - Nicolas V. Christou


            Mortality of Certain Intra-abdominal
                 Infections Remains High


35                                                                32.1

30

25

20

15
                                                    10.4
10

  5                  2.3

  0
       Christou et al 1996             Solomkin et al 1996 SIS DSP Study 1992
Intraabdominal Infections and MOF - Nicolas V. Christou




              How does
              infection
                 kill
             the patient?
Intraabdominal Infections and MOF - Nicolas V. Christou




 The patient
  becomes
“SEPTIC” and
    dies!
Intraabdominal Infections and MOF - Nicolas V. Christou



 Importance of correct terminology
  Intraabdominal Infections and MOF - Nicolas V. Christou




           Suggested Terminology


Infection                                                   Sepsis
PROCCESS                                                    RESPONSE
Bacteria invading                                           Pyrexia, tachypnia,
                                                            tachycardia, hypoxia,
normally sterile host                                       hypermetabolism,
tissues                                                     organ(s) dysfunction
Intraabdominal Infections and MOF - Nicolas V. Christou




        ACCP/SCCM Consensus
• Temperature > 38o C or < 36o C
• Heart Rate > 90 bpm
• Tachypnia (RR > 20 bpm, or PaCO2 < 32 torr)
• WBC > 12,000 , < 4,000 /cu. mm, 10% bands"
• Acute Alterations From Baseline

       Systemic Inflammatory Response Syndrome
                                                          Crit. Care Med. 20:864, 1992
Intraabdominal Infections and MOF - Nicolas V. Christou




          ACCP/SCCM Consensus




                                                          Crit. Care Med. 20:864, 1992
Intraabdominal Infections and MOF - Nicolas V. Christou




   CURE INFECTION
   (the microbiologic event)



                                PREVENT
                                 DEATH
 Intraabdominal Infections and MOF - Nicolas V. Christou



                     Host defense against
                           bacteria
Hydrogen Peroxide
Superoxide
Elastase
Proteinases
Lipase
BPI


      Carbuncle




                                                Primitive but Effective
Intraabdominal Infections and MOF - Nicolas V. Christou




       PMN Intravital Microscopy
 Intraabdominal Infections and MOF - Nicolas V. Christou




          Host Response to Bacteria


TRIGGER                                                              RESPONSE
                                                           Activated
                             Resting                       Macrophage
                             Macrophage
    •Bacteria                                                             IL-1
 •LPS
                                                                          TNF-a
    •C5a
                                                                          TGF-ß
         •Ag-Ab                                                            -
                                                                   IL-6   O2
                                                            IL-8
 Intraabdominal Infections and MOF - Nicolas V. Christou


          The “Good”, the “Bad” and the “Ugly” of a
                dysregulated Host Response




“Good”




“Bad”
                                                           “Ugly”
                                                           (MODS)
Intraabdominal Infections and MOF - Nicolas V. Christou

            Pathophysiology of MODS After
                Major Injury/infection


                                                                Persistence of
                                                                 "activation"
                                                                   events


                                                 TRIGGER
                                                                             Activated
                                                                Resting      Macrophage

     Poor tissue
                                                          C5a   Macrophage
                                                                                          IL-1
                                                   LPS
        O22                                       AgAb
                                                                                          TNF-a

      Delivery                                       Bacteria                           .
                                                                                          TGF-ß
                                                                                  IL-2 O2

                                                                                     RESPONSE
Intraabdominal Infections and MOF - Nicolas V. Christou




   Why are we
  seeing MODS
      now?
Intraabdominal Infections and MOF - Nicolas V. Christou




    "Multiple Organ Failure
       is a syndrome of
      surgical progress"



                                                          Arthur E. Baue 1990
Intraabdominal Infections and MOF - Nicolas V. Christou




    Why are we seeing MODS
             now?


     The Threshold
      Hypothesis
Intraabdominal Infections and MOF - Nicolas V. Christou


      Trauma/infectious "insult"
               - B.ICU

                                                      Minor
                                                      Injury




                                                               REST IN


                                                      Major    PEACE




                                                      Injury
Intraabdominal Infections and MOF - Nicolas V. Christou




      Trauma/infectious "insult" -
                A.ICU


                            Major
                            Injury

                                                          4-6 weeks later

                                                                       DIED
  Major Head                                                           from
    Injury                                                             MODS
Intraabdominal Infections and MOF - Nicolas V. Christou




                   Historical Perspective

WW I                      Death from non resuscitated
                          shock
WW II                     Plasma / Saline resuscitation
                          Blood
Korea                     Death from renal failure (single
                          organ failure)
Vietnam                   Pulmonary failure (DaNang Lung)
Intraabdominal Infections and MOF - Nicolas V. Christou




              The
            Genetic
         Heterogeneity
          Hypothesis
      Intraabdominal Infections and MOF - Nicolas V. Christou



                                Clinical Scenarios
     Patient on Left                                            Patient on Right

•   Anasarca                                                          •   No anasarca
•   Intubated                                                         •   Room air
•   Febrile                                                           •   Afebrile
•   Looks sick                                                        •   Looks well




Mesh-Zipper                                                           Packed open
Laparostomy                                                           Abdomen
  Intraabdominal Infections and MOF - Nicolas V. Christou


                            Clinical Scenarios

 Patient on Left                                            Patient on Right

                                                                  No peripheral
    4+                                                               edema
  pitting
  edema




    4+                                                                 No
pulmonary                                                          pulmonary
  edema                                                              edema
  Intraabdominal Infections and MOF - Nicolas V. Christou



                            Clinical Scenarios
 Patient on Left                                            Patient on Right


Mechanical                                                             No
Ventilation                                                         Ventilator
  PEEP




   Jet                                                              Survived
Ventilator
  DIED
Intraabdominal Infections and MOF - Nicolas V. Christou



                                   The Future




                                                          • Genomics
                                                          • Proteomics

				
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