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Treatment Guidelines for Intra-abdominal Infections • CID 2003:37 (15 October) • 997
Table 1. Recommended agents for treatment of community-acquired complicated intra-abdominal infections.
Community-acquired infections. For patients with com- physicians before local publication of selected regimens; use of
munity-acquired infections of mild-to-moderate severity, lectures and publications; small-group interactive sessions; and
agents that have a narrower spectrum of activity and that are computer-assisted care. Compliance may be monitored through
not commonly used for nosocomial infections, such as am- pharmacy-based drug utilization reviews and through review
picillin/sulbactam, cefazolin or cefuroxime plus metronidazole, of microbiology records.
ticarcillin/clavulanate, ertapenem, and quinolones plus me-
tronidazole, are preferable to agents that have broader coverage
INTRODUCTION
against gram-negative organisms and/or greater risk of toxicity.
Cost is an important factor in the selection of a specific regimen. Complicated intra-abdominal infections are problems in clin-
Patients with more-severe infections, as defined by accepted ical practice and consume substantial hospital resources. These
physiologic scoring systems, or patients deemed to have im- resources include emergency department services, imaging ser-
munosuppression resulting either from medical therapy or vices, operating room time, laboratory services, antibiotic ther-
from acute or chronic disease, might benefit from regimens apy, and in-hospital care of variable intensity. Outcomes are
with a broader spectrum of activity against facultative and aer- heavily influenced by the rapidity of diagnosis and appropriate
obic gram-negative organisms. Recommended regimens in- intervention and by the timeliness and efficacy of anti-infective
clude meropenem, imipenem/cilastatin, third- or fourth-gen- therapy.
eration cephalosporins (cefotaxime, ceftriaxone, ceftizoxime, A wide range of individual antimicrobial agents and com-
ceftazidime, and cefepime) plus metronidazole, ciprofloxacin binations of agents is available for use in complicated intra-
plus metronidazole, and piperacillin/tazobactam. abdominal infections. There are convincing data that absent or
Health care–associated infections. Postoperative (noso- inadequate empirical and definitive antibiotic therapy results
comial) infections are caused by more-resistant flora, which in both increased failure rates and increased mortality [1–5].
may include Pseudomonas aeruginosa, Enterobacter species, Pro- Conversely, unnecessary or needlessly broad therapy is asso-
teus species, methicillin-resistant Staphylococcus aureus, enter- ciated with its own problems. Cost remains an important issue
ococci, and Candida species. For these infections, complex mul- in antimicrobial agent selection. Various patient- and agent-
tidrug regimens are recommended, because adequate empirical specific toxicities may occur, including superinfection and or-
therapy appears to be important in reducing mortality. Local gan toxicity. Acquisition of intrinsically drug-resistant organ-
nosocomial resistance patterns should dictate empirical treat- isms and selective pressure for resistance within the unit,
ment, and treatment should be altered on the basis of the results hospital, or community is of increasing concern [6, 7].
of a thorough microbiologic workup of infected fluid. These Development of these guidelines. These evidence-based
infections remain an important area for clinical research. guidelines were developed by an expert panel using the IDSA
Multiple implementation strategies should be used to max- Guidelines Development process and have been endorsed by
imize adherence to these recommendations. These include ob- the IDSA, the Surgical Infection Society, the American Society
taining feedback from microbiologists, nurses, pharmacists, and for Microbiology, and the Society of Infectious Disease Phar-
Treatment Guidelines for Intra-abdominal Infections • CID 2003:37 (15 October) • 999
Table 2. Infectious Diseases Society of America–United States Public Health Service grading system for
rating recommendations in clinical guidelines.
taneous intervention. Evidence of established infection includes terococci are also commonly present. By far the most common
the presence of a systemic and local inflammatory response, gram-negative facultative organism is Escherichia coli.
the latter as indicated by the presence of a purulent exudate Antibiotics used for empirical treatment of community-
and inflamed tissue. acquired intra-abdominal infections should, therefore, be active
Once the diagnosis of intra-abdominal infection is suspected, against enteric gram-negative aerobic and facultative bacilli
it is appropriate to begin antimicrobial therapy before an exact and b-lactam–susceptible gram-positive cocci (A-1). Coverage
diagnosis is established and before results of appropriate cul- against obligate anaerobic bacilli should be provided for distal
tures are available. The goals of antibiotic therapy for intra- small-bowel and colon-derived infections and for more-
abdominal infection are to eliminate infecting microorganisms, proximal gastrointestinal perforations when obstruction is pre-
to decrease the likelihood of recurrence, and to shorten the sent (A-1).
time to resolution of signs and symptoms of infection. Infecting Table 3 details agents and regimens that may be used to treat
microorganisms heavily contaminate surgical wounds, and it intra-abdominal infections and that have been adequately stud-
is important that effective antimicrobial therapy be begun be- ied in clinical trials [45]. We note that studies in which sample
fore any intervention, so that subsequent surgical-site infection sizes are too small to define equivalence or detect differences
can be prevented. between various regimens provide little useful data. Studies that
Antibiotics should be administered after fluid resuscitation are not subject to peer review are, similarly, of little use.
has been initiated, so that adequate visceral perfusion can be The expanded gram-negative bacterial spectrum of some
restored and better drug distribution is possible. Particularly agents shown to be effective in clinical trials is not advantageous
in the case of aminoglycosides, nephrotoxicity is exacerbated for patients with community-acquired infections, and unnec-
by impaired renal perfusion [17]. essary use of such agents may contribute to the emergence of
antimicrobial resistance. In particular, agents that are used to
treat nosocomial infections in the intensive care unit should
SELECTION OF EMPIRICAL
not be routinely used to treat community-acquired infections
ANTIBIOTIC REGIMENS
(B-2) [7, 46].
Infections derived from the stomach, duodenum, biliary sys- For patients with mild-to-moderate community-acquired in-
tem, and proximal small bowel can be caused by gram-positive fections, agents that have a narrower spectrum of activity, such
and gram-negative aerobic and facultative organisms. Infections as ampicillin/sulbactam, cefazolin or cefuroxime/metronida-
derived from distal small-bowel perforations can be caused by zole, ticarcillin/clavulanate, and ertapenem are preferable to
gram-negative facultative and aerobic organisms with variable more costly agents that have broader coverage against gram-
density. Perforations of this type often evolve into localized negative organisms and/or greater risk of toxicity (A-1). Generic
abscesses, with peritonitis developing only after rupture of the agents have cost advantages.
abscess. Anaerobes, such as B. fragilis, are commonly present. Aminoglycosides have relatively narrow therapeutic ranges
Colon-derived intra-abdominal infections can be caused by fac- and are associated with ototoxicity and nephrotoxicity. Because
ultative and obligate anaerobic organisms. Streptococci and en- of the availability of less toxic agents demonstrated to be of
Treatment Guidelines for Intra-abdominal Infections • CID 2003:37 (15 October) • 1001
or recurrent intra-abdominal infections, additional interven- anaerobic isolates should be considered when there is persistent
tion likely will be required to achieve source control. If a patient isolation of the organism, when bacteremia is present, and when
has persistent clinical symptoms and signs, but no evidence of prolonged therapy is needed.
a new or persistent infection is uncovered after a careful in-
vestigation, termination of antimicrobial therapy is warranted.
HEALTH CARE–ASSOCIATED
INTRA-ABDOMINAL INFECTIONS
LABORATORY CONSIDERATIONS
In infections occurring after elective or emergent operations,
In community-acquired infections, the encountered flora is a more resistant flora is routinely encountered [66]. Further-
routinely susceptible to recommended regimens. There is a more, there is evidence that not providing empirical therapy
strong case to be made against culturing samples from patients active against the subsequently identified pathogens is associ-
with perforated or gangrenous appendicitis. Several retrospec- ated with significant increases in mortality and treatment failure
tive studies have examined the impact of performance of such
(C-3) [66]. The organisms seen are similar to those seen in
cultures on outcome and have failed to identify any beneficial
other nosocomial infections, and anaerobes are not frequently
effect [56–58].
encountered. Antibiotic therapy for such infections should be
There are, however, several concerns that prevent easy ex-
guided by knowledge of the nosocomial flora seen at the par-
trapolation of this observation to other types of intra-abdom-
ticular hospital and its antimicrobial susceptibilities. This may
inal infection [55, 59]. The listed studies have been confined
require the use of multidrug regimens (e.g., an aminoglycoside
to pediatric populations with perforated, not abscessed, ap-
or quinolone or a carbapenem and vancomycin).
pendicitis. Treatment failure in this situation leading to recur-
rent infection is extremely uncommon. This is due in part to
excision of the inflamed viscus; there remains no abscess rim
WHAT MATERIAL SHOULD BE SENT
or other infected tissue.
FOR CULTURE?
For other intra-abdominal infections, particularly those in-
volving the colon, failure rates are substantially higher if em-
Blood cultures do not provide additional clinically relevant in-
pirical therapy is not active against any identified isolate [1, 2,
formation for patients with community-acquired intra-abdom-
5]. Altering the regimen to cover identified isolates improves
inal infections and are, therefore, not recommended for such
outcome (C-3) [4].
patients (A-1). Specimens collected from the intra-abdominal
There are marked differences in susceptibility patterns within
focus of infection should be representative of the material as-
and between different communities. These epidemiologic data
sociated with the clinical infection, and there is no benefit to
are of considerable value in defining the most suitable anti-
obtaining multiple specimens. Both aerobic and anaerobic cul-
microbial therapy for intra-abdominal infections. Certain com-
munities have an inexplicably high incidence of P. aeruginosa tures can be performed using a single specimen, provided it is
in community-acquired appendicitis [2]. Therefore, local hos- of sufficient volume (at least 0.5 cc of fluid or tissue) and is
pital antimicrobial susceptibility patterns should be heeded in transported to the laboratory in an anaerobic transport system,
selecting initial empirical therapy. rather than on a swab. Swabs do not provide appropriate spec-
Identification and susceptibility testing of anaerobes (a te- imens for anaerobic cultures.
dious and expensive undertaking) appear to be unnecessary if
broadly active anaerobic agents are used to treat infections in
which anaerobes are frequently encountered (those with distal WHEN SHOULD GRAM STAINING
intestinal, appendiceal, and colonic sources) and if adequate BE PERFORMED?
drainage or debridement is achieved. Resistance repeatedly has
been identified and found to be increasing for clindamycin, For community-acquired infections, there is no value in making
cefoxitin, cefotetan, piperacillin, and the quinolones [60–63]. a Gram stain of the infected material (B-2). For health care–
Published multicenter surveys of anaerobic susceptibility that associated infections, Gram staining may be valuable in defining
used the methods currently recommended by the NCCLS may the need for specific therapy for methicillin-resistant gram-
be used as guides for therapy directed at the B. fragilis group positive organisms [66]. Local susceptibility patterns for S. au-
[63, 64]. This statement is not intended to discourage hospitals reus and for enterococci might warrant addition of vancomycin
from monitoring local resistance trends. If this is undertaken, to the regimen until results of cultures and susceptibility testing
the results should be published annually and compared with are available. For enterococci, local susceptibilities should be
those for previous years [65]. Susceptibility testing of individual monitored for ampicillin and vancomycin resistance.
Treatment Guidelines for Intra-abdominal Infections • CID 2003:37 (15 October) • 1003
comparison of gentamicin and clindamycin versus cefamandole versus 23. Allo MD, Bennion RS, Kathir K, et al. Ticarcillin/clavulanate versus
cefoperazone. Am J Surg 1982; 144:8–13. imipenem/cilistatin for the treatment of infections associated with gan-
2. Yellin AE, Heseltine PN, Berne TV, et al. The role of Pseudomonas grenous and perforated appendicitis. Am Surg 1999; 65:99–104.
species in patients treated with ampicillin and sulbactam for gangre- 24. Dougherty SH, Sirinek KR, Schauer PR, et al. Ticarcillin/clavulanate
nous and perforated appendicitis. Surg Gynecol Obstet 1985; 161: compared with clindamycin/gentamicin (with or without ampicillin)
303–7. for the treatment of intra-abdominal infections in pediatric and adult
3. Solomkin JS, Dellinger EP, Christou NV, Busuttil RW. Results of a patients. Am Surg 1995; 61:297–303.
multicenter trial comparing imipenem/cilastatin to tobramycin/clin- 25. Solomkin JS, Yellin AE, Rotstein OD, et al. Ertapenem versus piper-
damycin for intra-abdominal infections. Ann Surg 1990; 212:581–91. acillin/tazobactam in the treatment of complicated intraabdominal in-
4. Mosdell DM, Morris DM, Voltura A, et al. Antibiotic treatment for fections: results of a double-blind, randomized comparative phase III
surgical peritonitis. Ann Surg 1991; 214:543–9. trial. Ann Surg 2003; 237:235–45.
5. Falagas ME, Barefoot L, Griffith J, Ruthazar R, Snydman DR. Risk 26. Solomkin JS, Reinhart HH, Dellinger EP, et al. Results of a randomized
factors leading to clinical failure in the treatment of intra-abdominal trial comparing sequential intravenous/oral treatment with ciproflox-
or skin/soft tissue infections. Eur J Clin Microbiol Infect Dis 1996; 15: acin plus metronidazole to imipenem/cilastatin for intra-abdominal
913–21. infections. The Intra-Abdominal Infection Study Group. Ann Surg
6. Wilton P, Smith R, Coast J, Millar M. Strategies to contain the emer- 1996; 223:303–15.
gence of antimicrobial resistance: a systematic review of effectiveness 27. Solomkin JS, Wilson SE, Christou NV, et al. Results of a clinical trial
and cost-effectiveness. J Health Serv Res Policy 2002; 7:111–7. of clinafloxacin versus imipenem/cilastatin for intraabdominal infec-
7. Shlaes DM, Gerding DN, John JF Jr, et al. Society for Healthcare tions. Ann Surg 2001; 233:79–87.
Epidemiology of America and Infectious Diseases Society of America 28. Angeras MH, Darle N, Hamnstrom K, et al. A comparison of imi-
Joint Committee on the Prevention of Antimicrobial Resistance: guide- penem/cilastatin with the combination of cefuroxime and metroni-
lines for the prevention of antimicrobial resistance in hospitals. Clin dazole in the treatment of intra-abdominal infections. Scand J Infect
Infect Dis 1997; 25:584–99. Dis 1996; 28:513–8.
8. Kish MA. Guide to development of practice guidelines. Clin Infect Dis 29. Barie PS, Vogel SB, Dellinger EP, et al. A randomized, double-blind
2001; 32:851–4. clinical trial comparing cefepime plus metronidazole with imipenem-
9. Mazuski JE, Sawyer RG, Nathens AB, et al. The Surgical Infection cilastatin in the treatment of complicated intra-abdominal infections.
Society guidelines on antimicrobial therapy for intra-abdominal in- Cefepime Intra-Abdominal Infection Study Group. Arch Surg 1997;
fections: an executive summary. Surgical Infections 2002; 3:161–74. 132:1294–302.
10. Mazuski JE, Sawyer RG, Nathens AB, et al. The Surgical Infection 30. Brismar B, Malmborg AS, Tunevall G, et al. Meropenem versus imi-
Society guidelines on antimicrobial therapy for intra-abdominal in- penem/cilastatin in the treatment of intra-abdominal infections. J An-
fections: evidence for the recommendations. Surg Infect 2002; 3: timicrob Chemother 1995; 35:139–48.
175–234. 31. Brismar B, Malmborg AS, Tunevall G, et al. Piperacillin-tazobactam
11. Bohnen JM, Solomkin JS, Dellinger EP, Bjornson HS, Page CP. Guide-
versus imipenem-cilastatin for treatment of intra-abdominal infections.
lines for clinical care: anti-infective agents for intra-abdominal infec-
Antimicrob Agents Chemother 1992; 36:2766–73.
tion. A Surgical Infection Society policy statement. Arch Surg 1992;
32. Christou NV, Turgeon P, Wassef R, Rotstein O, Bohnen J, Potvin M.
127:83–9.
Management of intra-abdominal infections: the case for intraoperative
12. Boey J, Wong J, Ong GB. Bacteria and septic complications in patients
cultures and comprehensive broad-spectrum antibiotic coverage. The
with perforated duodenal ulcers. Am J Surg 1982; 143:635–9.
Canadian Intra-Abdominal Infection Study Group. Arch Surg 1996;
13. Fong IW. Septic complications of perforated peptic ulcer. Can J Surg
131:1193–201.
1983; 26:370–2.
33. Colardyn F, Faulkner KL. Intravenous meropenem versus imipenem/
14. Westphal JF, Brogard JM. Biliary tract infections: a guide to drug treat-
cilastatin in the treatment of serious bacterial infections in hospitalized
ment. Drugs 1999; 57:81–91.
patients. Meropenem Serious Infection Study Group. J Antimicrob
15. Rau B, Pralle U, Mayer JM, Beger HG. Role of ultrasonographically
guided fine-needle aspiration cytology in the diagnosis of infected pan- Chemother 1996; 38:523–37.
creatic necrosis. Br J Surg 1998; 85:179–84. 34. Donahue PE, Smith DL, Yellin AE, Mintz SJ, Bur F, Luke DR. Tro-
16. Kramer KM, Levy H. Prophylactic antibiotics for severe acute pan- vafloxacin in the treatment of intra-abdominal infections: results of a
creatitis: the beginning of an era. Pharmacotherapy 1999; 19:592–602. double-blind, multicenter comparison with imipenem/cilastatin. Tro-
17. Kacew S, Bergeron MG. Pathogenic factors in aminoglycoside-induced vafloxacin Surgical Group. Am J Surg 1998; 176:53S-61S.
nephrotoxicity. Toxicol Lett 1990; 51:241–59. 35. Poenaru D, De Santis M, Christou NV. Imipenem versus tobramycin—
18. Walker AP, Nichols RL, Wilson RF, et al. Efficacy of a beta-lactamase antianaerobe antibiotic therapy in intra-abdominal infections. Can J
inhibitor combination for serious intraabdominal infections. Ann Surg Surg 1990; 33:415–22.
1993; 217:115–21. 36. Basoli A, Meli EZ, Mazzocchi P, Speranza V. Imipenem/cilastatin (1.5
19. Cohn SM, Lipsett PA, Buchman TG, et al. Comparison of intravenous/ g daily) versus meropenem (3.0 g daily) in patients with intra-abdom-
oral ciprofloxacin plus metronidazole versus piperacillin/tazobactam inal infections: results of a prospective, randomized, multicentre trial.
in the treatment of complicated intraabdominal infections. Ann Surg Scand J Infect Dis 1997; 29:503–8.
2000; 232:254–62. 37. Berne TV, Yellin AE, Appleman MD, Heseltine PN, Gill MA. Mero-
20. Ohlin B, Cederberg A, Forssell H, Solhaug JH, Tveit E. Piperacillin/ penem versus tobramycin with clindamycin in the antibiotic manage-
tazobactam compared with cefuroxime/metronidazole in the treatment ment of patients with advanced appendicitis. J Am Coll Surg 1996;
of intra-abdominal infections. Eur J Surg 1999; 165:875–84. 182:403–7.
21. Eklund AE, Nord CE. A randomized multicenter trial of piperacillin/ 38. Condon RE, Walker AP, Sirinek KR, et al. Meropenem versus tobra-
tazobactam versus imipenem/cilastatin in the treatment of severe intra- mycin plus clindamycin for treatment of intraabdominal infections:
abdominal infections. Swedish Study Group. J Antimicrob Chemother results of a prospective, randomized, double-blind clinical trial. Clin
1993; 31(Suppl A):79–85. Infect Dis 1995; 21:544–50.
22. Jaccard C, Troillet N, Harbarth S, et al. Prospective randomized com- 39. Geroulanos SJ. Meropenem versus imipenem/cilastatin in intra-
parison of imipenem-cilastatin and piperacillin-tazobactam in noso- abdominal infections requiring surgery. Meropenem Study Group. J
comial pneumonia or peritonitis. Antimicrob Agents Chemother Antimicrob Chemother 1995; 36(Suppl A):191–205.
1998; 42:2966–72. 40. Huizinga WK, Warren BL, Baker LW, et al. Antibiotic monotherapy
Treatment Guidelines for Intra-abdominal Infections • CID 2003:37 (15 October) • 1005