1. Infectious Disease I: Intraabdominal Infections
Courses in Therapeutics and Disease State Management

2. Learning Objectives (Slide 1 of 3)
Define and describe the difference between primary, secondary, tertiary, complicated, and uncomplicated intraabdominal infections
Define the terms abscess and peritonitis
Describe the typical microbiology of intraabdominal infections

3. Learning Objectives (Slide 2 of 3)
Describe the typical clinical presentation of peritonitis and intraabdominal abscess
Describe the appropriate role of culture and susceptibility information for diagnosis and treatment of intraabdominal infections
Describe the most appropriate drug and nondrug measures to treat intraabdominal infections
Provide examples of antimicrobial agents that would be appropriate to treat a secondary intraabdominal infection such as an appendiceal abscess

4. Learning Objectives (Slide 3 of 3)
Describe the appropriate antimicrobial treatment for a primary intraabdominal infection such as peritonitis associated with liver cirrhosis
Describe the proper duration of treatment of an intraabdominal infection given details of the patient condition and type of infection
Describe the proper assessment of patients during treatment of intraabdominal infections.

5. Required Reading
Gross AE, DiPiro JT, Olsen KM. Chapter 92. Intraabdominal Infections. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 9e. New York, NY: McGraw-Hill; 2014.
Solomkin JS, Mazuki JE, et.al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Clin. Infect. Dis. 210; 50:133–164.

6. Overview (Slide 1 of 2)
Infection contained within the peritoneal cavity or retroperitoneal space
Classification
Generalized or Localized infections
Uncomplicated or Complicated infections
Community or Healthcare associated
The peritoneal cavity extends from the undersurface of the diaphragm to the floor of the pelvis and contains the stomach, small bowel, large bowel, liver, gallbladder, and spleen.
The duodenum, pancreas, kidneys, adrenal glands, great vessels (aorta and vena cava), and most mesenteric vascular structures reside in the retroperitoneum.
Intraabdominal infections may be generalized or localized, complicated or uncomplicated, and community or healthcare-associated
Uncomplicated intraabdominal infections are confined within visceral structure
Complicated intraabdominal infections involve anatomical disruption, extend beyond a single organ, and yield peritonitis and/or abscess
Appendicitis is one of the most common causes of intraabdominal infection.
Most healthcare-associated intraabdominal infections occur as complications following intraabdominal surgeries.

7. Overview (Slide 2 of 2) Peritonitis Abscesses Primary Peritonitis
Spontaneous Bacterial Peritonitis (SBP)
Infection of peritoneal cavity without a source from the abdomen
Secondary Peritonitis
Source of bacteria is evident from within the abdomen
May involve perforation of the GI tract
Tertiary peritonitis
An infection that persists or recurs at least 48 hours after apparently adequate management of primary or secondary peritonitis
Occurs in critically ill patients
Abscesses
Result of chronic inflammation
Located in the peritoneal cavity or in a visceral organ
Risk factors the same as peritonitis
Peritonitis is the acute inflammatory response of the peritoneal lining to microorganisms, chemicals, irradiation, or foreign-body injury
Cirrhosis is one of the most common causes of primary peritonitis is adults.
An abscess is a purulent collection of fluid separated from surrounding tissue by a wall consisting of inflammatory cells and adjacent organs. It usually contains necrotic debris, bacteria, and inflammatory cells.

8. Pathophysiology
Primary Peritonitis is due to bacterial transmigration to the intraabdominal cavity via;
Bloodstream
Lymphatic system
Transmigration through the bowel wall
Indwelling peritoneal dialysis catheter
Fallopian tubes in females
Secondary peritonitis is due to bacterial entry via;
Perforation of the GI tract
Perforation of female genital tract
Contamination during a surgical procedure 
Anastomotic leak
Abscess begins by the combined action of inflammatory cells bacteria, fibrin, and other inflammatory mediators
Intraabdominal infection results from bacterial entry into the peritoneal or retroperitoneal spaces or from bacterial collections within intraabdominal organs
Once bacteria enter into the peritoneal cavity, humoral and cellular defenses are activated and the omentum adheres to the affected area. A small bacterial inoculum is controlled quickly, but higher bacterial loads, the presence of foreign bodies, hematoma, necrotic tissue, continued bacterial contamination can impair the defenses of the body allowing the bacteria to spread.
Bacterial spread through the intraabdominal space leads to widespread inflammation, adhesions, fibrin formation. This along with paralysis of the intestines (ileus) can result in the confinement of the infection to one or more locations within the peritoneum.
Fluid and protein shifts may result in the movement of fluid from the circulating blood volume into the peritoneal space. This often results in a decreased circulating blood volume, decreased cardiac output, and hypovolemic shock
Death from peritonitis is attributed to the combination of fluid shifts, cytokines, and endotoxin causing hypovolemia, hypoperfusion, and shock

9. Causes of Bacterial Peritonitis
Primary (spontaneous) bacterial peritonitis
Peritoneal dialysis
Cirrhosis with ascites
Nephrotic syndrome
Secondary bacterial peritonitis (cont.)
Mechanical GI problems
Any cause of small bowel obstruction (adhesions, hernia)
Vascular causes
Mesenteric arterial or venous occlusion (atrial fibrillation)
Mesenteric ischemia without occlusion
Trauma
Blunt abdominal trauma with rupture of intestine
Penetrating abdominal trauma
Peritoneal contamination during abdominal operation
Secondary bacterial peritonitis (cont.)
Miscellaneous causes
Diverticulitis
Appendicitis
Inflammatory bowel diseases
Salpingitis
Biliary tract infections
Necrotizing pancreatitis
Neoplasms
Intestinal obstruction
Perforation
Iatrogenic intestinal perforation (endoscopy)
Intraoperative events
Solid organ transplant in the abdomen
Leakage from GI anastomosis
Table 92-1 Causes of Bacterial Peritonitis

10. Normal Flora of GI Tract
Approximate Concentration (Log No. Organisms/mL [×103/L])
Site
Commonly Found Bacteria
Aerobes
Anaerobes
Stomacha
Streptococcus, Lactobacillus
10–100
Rare
Biliary tract
Normally sterile (Escherichia coli, Klebsiella, or enterococci in some patients)
Proximal small bowel
Streptococcus (including enterococci), E. coli, Klebsiella, Lactobacillus, diphtheroids
100
Few
Distal ileum
E. coli, Klebsiella, Enterobacter, enterococci, Bacteroides fragilis, Clostridium, peptostreptococci
104–106
105–107
Colon
Bacteroides spp., peptostreptococci, Clostridium, E. coli, Klebsiella, enterococci, Enterobacter, Candida, and many others
105–108
109–1011
Table 92-2 Usual Microflora of the GI Tract
aWith achlorhydria, acid suppressive therapy, gastric cancer, or gastric outlet obstruction, bacterial counts may rise to 105/mL

11. Common Pathogens Nosocomial Infection(%) Secondary Peritonitis(%)
Community-Acquired Infection(%)
Nosocomial Infection(%)
Gram-Negative Bacteria
Escherichia coli
32–61 29
22.5
Enterobacter
8–26
5.2
8.0
Klebsiella
6–26
2.8
4.5
Proteus
4–23
1.7
2.4
Gram-Positive Bacteria
Enterococcus
18–24
10.6 18
Streptococcus
6–55
13.7 10
Staphylococcus
6–16
3.1
4.8
Anaerobic Bacteria
Bacteroides
25–80
10.3
Clostridium
5–18
3.5
3.4
Fungi
2–5 3 4
Table 92-3 Pathogens Isolated from Patients with Intraabdominal Infection
Because of the diverse bacteria present in the GI tract, secondary intraabdominal infections are often polymicrobia

12. Primary Peritonitis Varies greatly between patients Symptoms Signs
Mild complaints
Acute distress
Symptoms
Nausea
Vomiting
Abdominal tenderness
Signs
Hypoactive bowel sounds
Mild fever
Cirrhotic patients may have mental status changes
Cloudy dialysate fluid in patients with
Primary peritonitis can develop over a period of days to weeks and is usually a more indolent process than secondary peritonitis

13. Secondary Peritonitis
Patients are often in acute distress
Symptoms
Nausea and Vomiting
Abdominal guarding
Signs
Fever
Tachypnea
Tachycardia
Faint to absent bowel sounds
Sepsis

14. Laboratory, Radiology, and Microbiology
WBC
Ascitic Fluid
Increase in Leukocytes
Radiology
Abdominal radiographs
Microbiology
Gram stain and Cultures of ascitic fluid
Laboratory studies are not generally helpful in the diagnosis of intraabdominal abscess, although most patients will have leukocytosis
Radiographic methods are used to make the diagnosis of an intraabdominal abscess

15. Goals of Therapy
Correction of the intraabdominal disease processes or injuries that have caused infection
Drainage of purulent collections
Achieve a resolution of infection without major organ system complications
Ameliorate clinical signs and symptoms
Provide supportive care

16. General Approach to Treatment
Surgical intervention and prompt drainage of abscesses
Support of vital functions
Early administration of empiric antibiotics that cover
Gram negatives
Anaerobes

17. Nonpharmacological Treatment
Surgical correction of underlying pathology
Respiratory and circulatory support as needed
Aggressive fluid resuscitation therapy

18. General Approach to Empiric Antibiotic Therapy (Slide 1 of 3)
Primary Bacterial Peritonitis
Cirrhosis
Most Frequent bacteria
E. coli
Klebsiella spp.
Streptococci spp.
Antibiotic Coverage choices
3rd Generation Cephalosporin
Ceftriaxone
Cefotaxime
Ampicillin/Sulbactam
Β-lactam allergy
Ciprofloxacin IV
Trimethoprim/sulfamethoxazole IV
Optional add anaerobic coverage
Metronidazole

19. General Approach to Empiric Antibiotic Therapy (Slide 2 of 3)
Primary Bacterial Peritonitis
Peritoneal Dialysis
Most Frequent bacteria
Staphylococcus aureus
MSSA
MRSA
Streptococci spp.
Gram negative enteric pathogens rare
Antibiotic Coverage choices
Combinations
Cefazolin plus [Cefazidime or Cefepime or Aminoglycoside]
Single Agents
Cefepime
Imipenem/cilastatin
Β-lactam allergy
Vancomycin plus aminoglycoside
Ciprofloxacin (if local susceptibilities allow)

20. General Approach to Empiric Antibiotic Therapy (Slide 3 of 3)
Primary Bacterial Peritonitis
Peritoneal Dialysis
Symptom onset slower which allows for gram stains and cultures
MSSA
Cefazolin IV
Nafcillin/ oxacillin IV
Β-lactam allergy
Vancomycin IV
Linezolid IV
Daptomycin IV
MRSA:
Vancomycin in peritoneal dialysate
Streptococcus or Enterococcus
Ampicillin
Gram negative Bacteria:
Ceftazidime or cefepime

21. Primary Bacterial Peritonitis Treatment Course
Deescalate antibiotics when cultures are finalized
Oral agents can be used to complete the treatment
Treatment Duration
Traditional 10 to 14 days
Peritoneal Dialysis patient should be treated for 14 days
Prevention
High reoccurrence rate of peritonitis in patients with cirrhosis
Decrease in mortality and infection rate
Antibiotic regimens
Trimethoprim/sulfamethoxazole DS 1 tab PO daily for 5 days of the week
Norfloxacin 400 mg PO Daily
Ciprofloxacin 750 mg weekly or 500 mg Daily

22. General Approach to Empiric Antibiotic Therapy: Secondary Bacterial Peritonitis
Perforated GI Tract
Abscess
Appendicitis
Most frequent bacteria depends where perforation/ infection occurs
Antibiotic Coverage choices
Community-Acquired Complicated Intra-abdominal Infections
Mild to Moderate infections
High Severity Infections
Hospital-Acquired Complicated Intra-abdominal Infections

23. Therapy should be active against
Empiric Antibiotics for Mild to Moderate Severity Community Acquired Intraabdominal Infections (Slide 1 of 3)
Therapy should be active against
Enteric gram-negative aerobic and facultative bacilli
Enteric gram-positive streptococci
Coverage for anaerobic bacteria should be provided for distal small bowel, appendiceal, and colon-derived infections
Combination or Monotherapy can be used
Avoid anti-pseudomonal agents

24. Empiric Antibiotics for Mild to Moderate Severity Community Acquired Intraabdominal Infections (Slide 2 of 3)
Mono-therapy
β-lactam/β-lactamase inhibitor therapy
Ticarcillin/ clavulanate
Cephalosporins
Cefoxitin
Carbopenems
Ertapenem
Fluoroquinolones
Moxifloxacin
Glycylcyclines
Tigecycline

25. Empiric Antibiotics for Mild to Moderate Severity Community Acquired Intraabdominal Infections (Slide 3 of 3)
Combination therapy
Cefazolin plus metronidazole
Cefuroxime plus metronidazole
Ciprofloxacin plus metronidazole
Levofloxacin plus metronidazole

26. Empiric Antibiotics for High Risk Community Acquired Intraabdominal Infections (Slide 1 of 3)
High Risk patients should be covered for Pseudomonas aeruginosa
High Risk Patients
High APACHE II Scores
Poor nutritional Status
Cardiovascular disease
Immunosuppression
Prolonged hospital stay

27. Empiric Antibiotics for High Risk Community Acquired Intraabdominal Infections (Slide 2 of 3)
Mono-therapy
Β-lactam/β-lactamase inhibitor therapy
Piperacillin/tazobactam
Carbopenems
Meropenem
Imipenem/cilastatin
Doripenem

28. Empiric Antibiotics for High Risk Community Acquired Intraabdominal Infections (Slide 3 of 3)
Combination Therapy
Cefepime plus metronidazole
Ceftazidime plus metronidazole
Ciprofloxacin plus metronidazole
Levofloxacin plus metronidazole

29. Empiric Antibiotics for High Risk Risk Hospital Acquired Intraabdominal Infections
Patients that have risk factors for Multi drug resistant bacteria
See Empiric Antibiotic lecture for list of risk factors
Pseudomonas aeruginosa
Use antipseudomonal agents
If high resistance at institution consider double coverage
Extended Spectrum β-lactamase producers
MRSA

30. Secondary Bacterial Peritonitis Treatment Course
Deescalate antibiotics when cultures are finalized
Oral agents can be used to complete the treatment
Treatment Duration
Traditional 5 to 10 day courses

31. Clinical Outcomes
Improvement in clinical signs and symptoms 2-3 days after antibiotics initiated
Resolution of WBC
Afebrile

32. Summary Intra-abdominal infections occur in the peritoneal cavity
Empiric antibiotic therapy should be directed at gram negative and anaerobic pathogens
Patient with alcoholic cirrhosis are at high risk for SBP caused by gram negative pathogens
Patients with peritoneal dialysis are at risk for SBP caused by gram positive skin flora
Patients with exposure to health care will require broadened empiric antibiotic coverage

33. References
Gross AE, DiPiro JT, Olsen KM. Chapter 92. Intraabdominal Infections. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 9e. New York, NY: McGraw-Hill; 2014.
Solomkin JS, Mazuki JE, et.al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Clin. Infect. Dis. 210; 50:133–164.