1. Module 5: Stewardship in intra-abdominal infections
Benjamin Westley MD FAAP FACP
4120 Laurel St Suite 204
Anchorage, AK 99508

2. Objectives
Review basic categories of intra-abdominal infection and their respective treatments
Community acquired intra-abdominal infection
Mild/Moderate
Severe
Acute biliary tract infections
Nosocomial intra-abdominal infection
Consider other abdominal processes associated with antibiotic use
Spontaneous bacterial peritonitis
Pancreatitis with and without necrosis
Infectious diarrhea
Mention of prevention of surgical infections during colorectal surgery

3. Useful guidelines
IDSA complicated intra-abdominal infection guideline1
IDSA infectious diarrhea guideline2
AASLD ascites guidelines3
ACG pancreatitis guideline4
IDSA SHEA surgical prophylaxis guideline5
ISPD peritoneal dialysis infection guideline6
AGA diverticulitis guidelines11,12

4. Intra-abdominal infection
Enteric contents enter the peritoneal cavity leading to abscess or peritonitis
Obtaining adequate early source control is the rule
Localized- Appendicitis, diverticulitis, cholecystitis with or without perforation
Contained perforation without hemodynamic instability
Carefully selected patients with appendiceal perforation OCCASIONALLY treated medically without an open or percutaneous source control procedure
Trend to non-operative management of perforated diverticulitis utilizing percutaneous drainage only
Diffuse peritonitis- after perforation
THESE PATIENTS ARE SICK AND NEED TO GO TO THE OR

5. “High risk” infection1

6. Treatment
Mild-moderate severity: perforated appendicitis, diverticulitis, intra-abdominal abscess.
Cefazolin 1-2g iv q8h plus metronidazole 500mg iv q8h
High-risk severity: hemodynamic instability, advanced age, immune-compromised state (Table 1 on prior slide)
Piperacillin/tazobactam 3.375g iv q8h over 4h, or
Cefepime 1g iv q8h plus metronidazole 500mg iv q8h
Healthcare-associated
Use high-risk regimen
Can consider empiric addition of vancomycin but rarely needed

7. Metronidazole dosing T1/2 = 8h (similar to ceftriaxone)
Concentration dependent killing
Some institutions use q24h dosing when using IV
1g – 1.5g IV q24h in adults1,7
30 mg/kg/day IV q24h in children8
When given PO, nausea is limiting so q8h dosing more appropriate

8. Basic points Cultures not mandatory for mild-moderate infections
Do not use ampicillin/sulbactam, clindamycin, aminoglycosides, or cephamycins
Empiric enterococcus therapy not needed for mild-moderate infections but favored for severe infections
If recovered in culture in severe or healthcare associated infection then treat
Empiric antifungal therapy is not recommended
Give fluconazole if recovered in culture until identified
Patients to be treated non-operatively for low-risk infections should be on a low-risk regimen with plans for early PO conversion

9. Biliary infections These are UPPER GI flora Mild-moderate Severe
No anaerobic coverage required for non-severe disease unless pre-existing biliary-enteric anastomosis is present
Mild-moderate
Cefazolin
Severe
Piperacillin-tazobactam, or
Cefepime plus metronidazole

10. De-escalation and alteration of initial regimen
Low-risk patients with adequate source control who are improving nicely DON’T have to be broadened if untreated pathogens are later reported in culture
In high risk or persistently ill patients, try to optimize regimen to predominant flora and generally avoid narrowing

11. Duration of therapy
Stomach or proximal jejunal perforation repaired within 24h and with adequate source control
Cefazolin prophylaxis x24h then discontinue
If on PPI or malignancy, give high-risk regimen x4-7d
Penetrating/blunt or iatrogenic perforation repaired within 12 hours
Treat for ≤24h
Acute appendicitis without perforation
Treat ≤24h
Acute cholecystitis without perforation
Complicated established infection with adequate source control
4 – 7 days

12. Recent duration of therapy literature
Acute grade II cholecystitis9
WBC >18, Mass in RUQ, >72h symptoms, or gangrenous/pericholecystic abscess/emphysematous/local peritonitis
≤4 days of therapy was as effective as >4 days Rx
STOP-IT trial10
NEJM 2015
518 patients with complicated intra-abdominal infection
Randomized to fixed 4 day Rx vs. 10 days or “clinical resolution”
Results: intervention group got 4 days, control 8 days
Equivalent 21% recurrence rates

13. Acute uncomplicated diverticulitis
Antibiotics may not be needed after all!?
If no perforation or sepsis
AGA guidelines allow for “selective” use11,12
Several new studies show no difference in acute resolution, possible reduced recurrence with antibiotics13- 16
Too early to know what to recommend, but argues for less-aggressive trend to current approach

14. Approach to perforated diverticular abscess
Patients with diffuse fecal peritonitis require emergent surgery
Localized small abscesses <4-6cm may be amenable to antimicrobial therapy alone17,18
Larger abscesses are generally drained by CT guidance percutaneously
Failure to improve with medical or CT drainage after 3 days suggests need for surgery
Patients with successful drainage may require delayed elective sigmoid resection due to high recurrence rates19-22

15. Spontaneous bacterial peritonitis3
Defined as PMN ≥250 cells/mm3 in ascitic fluid of cirrhotic patient with signs or symptoms suggestive of ascitic fluid infection
Tap and treat if PMN criteria reached
Ceftriaxone 1g iv q12h x5 days
Narrow if a single pathogen is isolated in culture
Cefotaxime E. coli activity is inferior to ceftriaxone at our institutions so no longer recommended
Total daily dose 2g vs. 1g associated with improved outcomes29
Give SBP prophylaxis in patients with variceal bleeding
Ceftriaxone 1g IV q24h x 7 days
Secondary prophylaxis after 1st SBP episode30 if ascites protein <1
Trimethoprim/sulfamethoxazole DS 1 tab daily
Daily ciprofloxacin 500mg PO daily if tmp/smx not feasible

16. Acute pancreatitis
These patients have high WBC, fever, and tachycardia; they look septic
Patients with shock need blood cultures and antibiotics4
Without shock, treat as pancreatitis with fluids, NPO etc
If antibiotics started, when blood negative and no other source found abx should be discontinued
Necrotic pancreatitis is not an indication for antibiotics
Earlier trials of PROPHYLACTIC antibiotics23,24 have been disproven25-27
No decrease in infections or sugery, but more RESISTANT organisms when infection develops25

17. Infected pancreatic necrosis
Patients failing to improve or worsening after 7-10 days of conservative management
CT guided fine needle aspiration (FNA) can be used to diagnose
Preferred from stewardship standpoint over empiric abx
Prolonged IV antibiotics if infected
Surgery can be avoided in ~3/4 of patients and only ~1/3 required percutaneous drainage28
Cephalosporin plus metronidazole or carbapenem

18. Infectious Diarrhea2 Fever and blood = dysentery Traveler’s diarrhea
Shigella, campylobacter, sometimes salmonella
Await stool culture if stable
If septic can give azithromycin 500mg or Cipro 500mg
Traveler’s diarrhea
Entero-toxigenic E. coli (ETEC), shigella, salmonella
Empiric cipro 500 bid x3d or 750 x1; azithromycin 500 x3d
Blood and NO fever
Enterohemorrhagic E. coli (EHEC): NO ANTIBIOTICS
Recent hospitalization, ED visit, or antibiotics
CDIFF, CDIFF, CDIFF

19. Peri-operative prophylaxis for colorectal surgery
Our protocols mimic our treatment guidelines
Cefazolin 2g (3g if >120kg) plus metronidazole 500mg
Immediately prior to incision
Can be mixed and given in same bag as “cefanidazole”
Cefazolin redosing interval 4h; metronidazole not redosed
Levofloxacin 750mg plus metronidazole if anaphylactic penicillin allergy
No redosing
If known MRSA colonized can consider adding vancomycin though literature supports primarily for orthopedic and cardiac surgery

20. If already on antibiotics and going to OR
Redose based on published intra-operative redosing interval5
4h for cefazolin
2h for piperacillin/tazobactam
Using cefazolin/metronidazole is effective, easy, and logistically simple vs. alternative regimens
We do NOT endorse use of ertapenem for prophylaxis
Extremely broad , ESBL coverage
If surgeons insist on q24h regimen can use daily dosed ceftriaxone plus metronidazole 1g

21. References Clinical Infectious Diseases 2010; 50:133–64
Hepatology 2009;49: ).
Am J Gastroenterol 2013; 108:1400–1415;
Am J Health-Syst Pharm. 2013; 70:
Peritoneal Dialysis International, Vol. 25, pp. 107–131
J Chemother Aug;19(4):410-6
J Pediatr Surg June ; 43(6): 981–985
J Gastrointest Surg (2013) 17:1947–1952
N Engl J Med 2015;372:
Gastroenterology 2015;149:1944–1949
Gastroenterology 2015;149:1950–1976
Colorectal Dis Apr 18
Gastroenterology 2015;149:1650–1651
Br J Surg 2012;99:532–539.
United European Gastroenterol J 2014;2(1S):A2
Tech Coloproctol Feb;19(2):97-103
Dis Colon Rectum Oct;49(10):1533-8
Dis Colon Rectum Mar;59(3):208-15
ANZ J Surg Apr 8.
Ann Surg Dec;262(6):
Dis Colon Rectum Dec;57(12):

22. References Surg Gynecol Obstet 1993 ; 176 : 480 – 3
Lancet 1995 ; 346 : 663 – 7
Ann Surg 2007 ; 245 : 674 – 83
Cochrane Database Syst Rev : CD002941
Am J Surg 2009 ; 197 : 806 – 13
Gastroenterology 2013 ; 144 : 333 – 40
F1000Research 2014, 3:57
Ann Pharmacother Dec;44(12):