Objectives. Review basic categories of intra-abdominal infection and their respective treatments. Community acquired intra-abdominal infection

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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 1. IDSA complicated intra-abdominal infection guideline 1 2. IDSA infectious diarrhea guideline 2 3. AASLD ascites guidelines 3 4. ACG pancreatitis guideline 4 5. IDSA SHEA surgical prophylaxis guideline 5 6. ISPD peritoneal dialysis infection guideline 6 7. AGA diverticulitis guidelines 11,12

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 Trend to percutaneous transhepatic cholecystostomy (PTC) in severe cholecystitis with delayed >72h duration of symptoms or unacceptable surgical risk 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 If local cefazolin E. coli susceptibility <90% consider ceftriaxone 2g 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 q6h plus metronidazole 500mg iv q8h Healthcare-associated Use high-risk regimen Can consider empiric addition of vancomycin but RARELY NEEDED

7 Metronidazole dosing T 1/2 = 8h (similar to ceftriaxone) Concentration dependent killing Some institutions use q24h dosing when using IV 1g 1.5g IV q24h in adults 1,7 30 mg/kg/day IV q24h in children 8 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 Suboptimal E. coli and/or B. fragilis activity 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 typically be on a low-risk regimen with plans for early PO conversion

9 Biliary infections These are UPPER GI flora No anaerobic coverage required for non-severe disease unless pre-existing biliary-enteric anastomosis is present Mild-moderate Cefazolin (or ceftriaxone if E. coli susceptibility <90%) 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 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 Treat 24h after cholecystectomy Treat 7 days if treated non-operatively with percutaneous cholecystostomy 31 Complicated established infection with adequate source control 4 7 days

12 Recent duration-oftherapy literature Acute grade II cholecystitis 9 WBC >18, Mass in RUQ, >72h symptoms, or gangrenous/pericholecystic abscess/emphysematous/local peritonitis 4 days of therapy after surgery as effective as >4 days Rx STOP-IT trial 10 NEJM 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 use 11,12 Several new studies show no difference in acute resolution, possible reduced recurrence with antibiotics 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 alone 17,18 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 rates 19-22

15 Spontaneous bacterial peritonitis 3 Defined as PMN 250 cells/mm 3 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 option offers no benefit, limited availability Total daily dose 2g vs. 1g associated with improved outcomes 29 Give SBP prophylaxis in patients with GI bleeding Ceftriaxone 1g IV q24h x 7 days Secondary prophylaxis after 1 st SBP episode 30 if ascites protein <1 Trimethoprim/sulfamethoxazole DS 1 tab 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 antibiotics 4 Without shock, treat as pancreatitis with fluids, NPO etc If antibiotics started, when blood cultures negative and no other source found abx should be discontinued Necrotic pancreatitis is not an indication for antibiotics Earlier trials of PROPHYLACTIC antibiotics 23,24 have been disproven No decrease in infections or sugery, but more RESISTANT organisms when infection develops 25

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 drainage 28 Cephalosporin plus metronidazole or carbapenem

18 Infectious Diarrhea 2 Fever and blood = dysentery Shigella, campylobacter, sometimes salmonella Await stool culture if stable If using rapid diagnostics, be sure to submit culture prior to treatment If septic can give azithromycin 500mg or ciprofloxacin 500mg Traveler s diarrhea Entero-toxigenic E. coli (ETEC), shigella, salmonella Empiric ciprofloxacin 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 (which is another talk entirely)

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 Re-dose based on published intra-operative re-dosing interval 5 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 1. Clinical Infectious Diseases 2010; 50: Clinical Infectious Diseases 2001; 32: Hepatology 2009;49: ). 4. Am J Gastroenterol 2013; 108: ; 5. Am J Health-Syst Pharm. 2013; 70: Peritoneal Dialysis International, Vol. 25, pp J Chemother Aug;19(4): J Pediatr Surg June ; 43(6): J Gastrointest Surg (2013) 17: N Engl J Med 2015;372: Gastroenterology 2015;149: Gastroenterology 2015;149: Colorectal Dis Apr Gastroenterology 2015;149: Br J Surg 2012;99: United European Gastroenterol J 2014;2(1S):A2 17. Tech Coloproctol Feb;19(2): Dis Colon Rectum Oct;49(10): Dis Colon Rectum Mar;59(3): ANZ J Surg Apr Ann Surg Dec;262(6): Dis Colon Rectum Dec;57(12):

22 References 23. Surg Gynecol Obstet 1993 ; 176 : Lancet 1995 ; 346 : Ann Surg 2007 ; 245 : The American Journal of Surgery (2013) 206, Hepatobiliary Pancreat Dis Int 2014;13: Cochrane Database Syst Rev : CD Am J Surg 2009 ; 197 : Gastroenterology 2013 ; 144 : F1000Research 2014, 3: Ann Pharmacother Dec;44(12): World J Surg (2017) 41: