Transcript Choice of Antibiotics in Uncomplicated and Complicated

Choice of Antibiotics in
Diverticulitis
Jeff Poynter
University of Michigan Medical School
The Problem: Uncomplicated
Diverticulitis
 Uncomplicated diverticulitis represents
a localized infection, primarily by Gramnegative rods and anaerobes, mostly E.
coli and B. fragilis. (Ambrosetti P, et al.)
 Conservative (medical) treatment of
acute uncomplicated diverticulitis is
successful in 70-100% of patients.
(Janes, et al. and Detry, et al.)
Some Common Choices of
Antibiotics: Dual-Agent Coverage
 Quinolone with metronidazole (Ciprofloxacin,
500 mg PO BID plus metronidazole, 500 mg
PO BID)
 Ciprofloxacin 400 mg IV q 12 hours plus
metronidazole 500 mg PO/IV q 6-8 hours
 Levofloxacin 500 mg IV daily plus
metronidazole 500 mg PO/IV q 6-8 hours
 Choices made in part with regard to history of
drug allergies
Some Common Choices of
Antibiotics: Single-Agent Therapy
 Amoxicillin-clavulanate 875/125 mg PO
BID
 Ampicillin-sulbactam 3 g IV q 6 hours
 Piperacillin-tazobactam 3.375 or 4.5 g
IV q 6 hours
 Ticarcillin-clavulanate 3.1 g IV q 4 hours
 Imipenem 500 mg IV q 6 hours
 Meropenem 1 g IV q 8 hours
Single- versus Dual-Antibiotic
Therapy
 Single and multiple antibiotic regimens
are equally effective as long as both
Gram-negative rods and anaerobes are
covered adequately. (Kellum, et al.)
The Problem: Complicated
Diverticulitis
 Complications include obstruction,
abscess formation, fistula formation or
perforation.
 Requires IV antibiotics plus surgery
(usually Hartmann operation).
Antibiotics in Complicated
Diverticulitis
 Ampicillin 2 g IV q 6 hours plus gentamicin 1.5-2.0 g IV q 8
hours plus metronidazole 500 mg IV q 8 hours
 Imipenem/cilastin 500 mg IV q 6 hours
 Piperacillin-tazobactam 3.375 mg IV q 6 hours
 Moxifloxacin
 Tigecycline, a new drug, has recently been approved for the
treatment of intra-abdominal infections; it has not been shown to
be superior to the traditional regimens.
 Lots of choices- the goal is to cover GNRs and anaerobes and
proceed to definitive surgery. No single regimen has been
shown to be definitely superior to the others.
Krobot K, et al
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425 patients who required surgery for community-acquired secondary
peritonitis, including patients with complicated diverticulitis.
13% of patients did not receive appropriate antibiotics, defined as not
covering all bacteria later isolated or not empirically covering typical
aerobic and anaerobic organisms in the absence of culture results.
26% of appropriately treated patients and 30% of inappropriately
treated patients had colonic sources of infection.
Resolution of infection with initial or step-down therapy after primary
surgery was significantly less likely to occur (53% vs. 79%).
Failure of resolution of infection due to inadequate choice of antibiotics
resulted in six-day prolongation of stay in hospital (20 versus 14 days
total).
Schechter S, et al
 Survey of 373 Fellows of the American Society of Colon and
Rectal Surgeons surveyed regarding diagnosis and treatment of
acute uncomplicated diverticulitis
 Half of responders chose a single-drug regimen: secondgeneration cephalosporin (27%) or ampicillin/sulbactam (16%).
 Single-therapy oral antibiotics at discharge were ciprofloxacin
(18%), amoxicillin/clavulanate (14%), metronidazole (7%) and
doxycycline (6%).
 Combinations chosen were ciprofloxacin/metronidazole (28%)
and TMP-SMX/metronidazole (6%). 21% chose various other
antibiotics.
Summary
 Antibiotic coverage must cover both Gram-negative rods and
anaerobes, or infections will persist longer and prolong length of
stay in hospital.
 Single or multiple antibiotic regimens are equally effective as
long as coverage is adequate- this equivalency amongst
choices is probably why there aren’t any recent studies
attempting to identify superior drugs!
 Top choices by ASCRS Fellows include: ciprofloxacin plus
metronidazole, ciprofloxacin alone and amoxicillin/clavulanate.
 The dominant consideration regarding choice of antibiotics is
coverage of GNRs and anaerobes!
References
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Krobot K, et al. Eur J Clin Microbiol Infect Dis 2004 Sep;23(9):682-7.
Papi C, et al. Aliment Pharmacol Ther 9:33-39.
Schechter S, et al. Dis Colon Rectum 1999; 42:470.
Up-to-Date, “Diverticulitis”.
Imbembo, AL, Bailey, RW. Diverticular disease of the colon. In: Textbook of Surgery, 14th
ed, Sabiston, DC Jr (Ed), Churchill Livingstone 1992. p.910.
Rafferty, J, Shellito, P, Hyman, NH, Buie, WD. Practice parameters for sigmoid diverticulitis.
Dis Colon Rectum 2006; 49:939.
Ambrosetti P, et al. Dis Colon Rectum 2000; 43:1363-7.
Janes S, et al. Br J Surg 2005; 92:133-42.
Detry R, et al. Int J Colorectal Dis 1992; 7:38-42.
Kellum JM, et al. Clin Ther 1992; 14:376-84.
Solomkin JS, et al. Clin Infect Dis; 37(8): 997-1005.
Goldstein EJ, et al: In vitro activity of moxifloxacin against 923 anaerobes isolated from
human intra-abdominal infections. Antimicrob Agents Chemother 50. (1): 148-155.2006.
Olivia ME, et al: A multicenter trial of the efficacy and safety of tigecycline versus
imipenem/cilastatin in patients with complicated intra-abdominal infections. BMC Infect Dis
5. 88.2005.