Antibiotic Therapy
Duration of Antimicrobial Therapy for Intra-Abdominal Infections
Traci L. Hedrick, MD; Robert G. Sawyer, MD
Infect Med 21(10):506-510, 2004. © 2004 Cliggott Publishing, Division of CMP
Healthcare Media
Posted 01/24/2005
Abstract and Introduction
Abstract
While intra-abdominal infections account for a significant proportion of patients
admitted to surgical wards, there is relatively little data available regarding appropriate
length of antibiotic treatment for these infections. In the absence of large, prospective,
randomized trials, smaller studies suggest that shorter courses of antibiotics can be used
without increasing the risk of recurrent infection. The severity of the infection and
degree of contamination can help in determining the appropriate length of antibiotic
therapy. Our data from the University of Virginia suggest that we may be using longer
courses of therapy than are necessary, and we speculate that this may be true at other
centers as well.
Introduction
Despite the widespread use of antibiotics for treatment of intra-abdominal infections,
evidence pertaining to optimal duration of treatment is lacking. Although several small,
prospective and retrospective studies have been performed, large, prospective,
randomized trials evaluating the length of antibiotic treatment in this setting have yet to
be published. Historically, surgical patients with significant intra-abdominal infection
were treated with long courses of intravenous antibiotics following definitive surgical
treatment, leading to prolonged hospital stays and significant cost. In an attempt to
shorten hospital stays and reduce costs, the issue of length of antibiotic treatment has
come into question.
In this article, we discuss 3 studies addressing this subject, each of which suggests that
morbidity is unaffected by a shorter length of antibiotic therapy.[1-3] In addition, we
describe 2 separate methods for calculating an appropriate duration of antibiotic
treatment and the evidence related to each. We review current guidelines pertaining to
the suggested length of antibiotic therapy for patients with intra-abdominal infections.
Finally, we summarize our own institutional data on intra-abdominal infections and
assess our compliance with the most current recommendations.
Patient Selection
Before the published literature is reviewed, intra-abdominal infection, as described in
the following studies, must be defined. We will limit our focus to patients with tertiary
peritonitis or intra-abdominal abscess, infections that warrant either surgical or
percutaneous intervention (resection or drainage). Patients with gynecologic or urologic
infections, infections associated with an indwelling catheter (eg, peritoneal dialysis
catheter infections), and infections that do not require intervention (eg, uncomplicated
diverticulitis) are excluded.
Also excluded from our review are patients with viscus perforations repaired before the
onset of peritonitis. For peritonitis to develop, sufficient time must pass to allow the
inflammatory process to progress. Studies based on patients with traumatic perforations
suggest that gastric and enteric perforations repaired within 12 hours of the injury do
not constitute infection and therefore only require perioperative antibiotics.[4-6]
Current Data
As noted above, there have been no randomized prospective studies; therefore, we are
left to rely on retrospective or small prospective studies as the basis for our treatment
decisions regarding patients with intra-abdominal infection.
Several authors have investigated the prospect of limiting the duration of antibiotics in
treating intra-abdominal infections that historically have been treated with 1- to 2-week
courses of intravenous antibiotics.[1-3] Early studies using longer courses of antibiotics
for surgical peritonitis reported a 10% to 20% infectious complication rate after
cessation of antibiotics.[7] This was comparable to the findings of Andäker and
colleagues,[2] who reviewed 99 patients with surgical peritonitis treated with only 5 days
of antibiotics and found an overall infectious complication rate of 8%.
Schein and associates[3] used a treatment protocol for determining duration of antibiotic
administration that was based on the cause of the infection. They reported a 12%
infectious complication rate in 48 patients with localized infection treated with 48 hours
of antibiotics and a 22% infectious complication rate in 23 patients with diffuse
peritonitis treated with 3 to 5 days of antibiotics.
These 2 studies demonstrated infectious complication rates of about 10% to 22% for
patients with localized and diffuse peritonitis, which are similar to the findings in older
studies that used longer courses of antibiotics. These data suggest that antibiotic
duration can safely be limited without increasing patient morbidity.
With the recent trend in shortening the duration of antibiotic therapy, 2 separate
methods for determining the proper length of treatment have emerged. The first
approach relies on studies demonstrating that patients who are afebrile and who do not
show evidence of leukocytosis at the time of antibiotic cessation experience low rates of
treatment failure.
In 2 separate studies, Lennard and coworkers[8,9] were able to demonstrate a correlation
between fever and leukocytosis at the time of antibiotic cessation and treatment failure.
The first study retrospectively examined 31 patients with intra-abdominal sepsis, all of
whom were afebrile when antibiotics were discontinued.[8] Those patients with
leukocytosis (white blood cell [WBC] count greater than 10,000/µL) at the time of
antibiotic cessation experienced a 68% rate of postoperative septic complications, while
those with a normal WBC count demonstrated only an 8% postoperative complication
rate.
These data were reproduced in another retrospective study conducted by the same group
that demonstrated a 30% incidence of intra-abdominal infection in 51 afebrile patients
who had leukocytosis on completion of antibiotic therapy of fixed duration for intraabdominal sepsis (P < .005 compared with patients without fever or leukocytosis at
antibiotic cessation).[9] Among 14 patients who were febrile when antibiotics were
discontinued, there was a 79% incidence of infectious complication. Therefore, because
patients who are afebrile with a normal WBC count experience a low rate of treatment
failure after antibiotic cessation, these measures may be used as a target for duration of
therapy.
The other approach for determining duration of antibiotic therapy relies on
intraoperative findings, specifically the degree of contamination and the organ of origin.
Cases of significant contamination and those involving the liver and pancreas, which are
more difficult to debride or percutaneously drain, are treated with a longer course of
antibiotics than, for example, gangrenous appendicitis.
One small, prospective, randomized trial involving 94 patients with complicated
appendicitis compared the 2 methods of determining antibiotic duration.[10] In all
patients, antibiotics were discontinued after resolution of clinical signs of infection;
however, one group was given a minimum of 5 days of antibiotics, while a second
group had no minimum defined duration of treatment. The first group received an
average of 5.9 days of antibiotic treatment, while the second group received an average
of 4.3 days of treatment (P < .05). Despite the difference in duration of treatment, there
was no significant difference in infectious complications, which were seen in 13% of
the first group and in 12.5% of the second group. These data suggest that a fixed
duration of therapy may lead to needlessly longer treatment with no apparent
improvement in outcome.
Finally, several authors have published guidelines that are focused on the issue of intraabdominal infections and duration of antibiotic treatment.[11,12] The first set of
guidelines comes from Schein and associates,[11] who published recommendations in
1996 to guide clinical decision making in the area of intra-abdominal infections.
According to their recommendations, intra-abdominal infections are separated into 5
categories:



Contamination (as occurs during elective surgery or uncomplicated
appendicitis).
Resectable infection (eg, gangrenous cholecystitis).
Mild infection (eg, localized peritonitis).


Moderate infection (eg, diffuse peritonitis).
Severe infection with poor source control (eg, necrotizing pancreatitis).
The duration of antibiotic therapy is then guided by the degree of infection:
contamination receives single-dose prophylaxis, resectable infections warrant 24 hours
of antibiotics, mild infections are treated for 48 hours, moderate infections are treated
with 2 to 5 days of postoperative antibiotics, and longer courses are reserved for severe
infections.
Most recently, the Surgical Infection Society published its recommendations for
duration of antibiotic treatment, which emphasize the resolution of clinical signs and
symptoms of infection as the target for antibiotic cessation.[12] According to these
recommendations, complicated intra-abdominal infections require 2 to 5 days of
antibiotic therapy that can be terminated after resolution of fever and leukocytosis. For
cases in which a patient has completed a specified course of antibiotics yet still
manifests signs of infection, alternative infectious causes should be investigated and
controlled and antibiotic treatment not prolonged. Finally, if treatment with surgical
debridement/drainage is suboptimal, as in many cases of infected pancreatic necrosis,
antibiotics may be continued for longer than 5 days.
Our Institutional Experience
We recently reviewed our institutional data with regard to intra-abdominal infections
and duration of antibiotic treatment. In the general surgery services at the University of
Virginia, 1343 inpatients with intra-abdominal infection were treated between
December 1996 and July 2003. There were no guidelines for determination of duration
of antibiotic therapy; the decision to stop antibiotics was left up to the individual
treating surgeon and was generally based on the patient's clinical response. The mean
duration of treatment with antibiotics was 14.5 days and depended on the organ of
origin (Figure 1). Infections of the liver and pancreas were treated with the longest
mean duration of antibiotic therapy, 15 and 17 days, respectively, compared with
gastric/appendiceal infections, which were treated with antibiotics for an average of 12
days.
Figure 1. Duration of antibiotic therapy in 1343 patients treated for intra-abdominal
infection at the University of Virginia between 1996 and 2003. The mean duration of
therapy was 14.5 ± 0.4 days.
There was a 22% risk of recurrence of intra-abdominal infection in our series, a
recurrence rate similar to that in the previously described articles, and recurrence
correlated with duration of antibiotic treatment (Figure 2). Those patients treated with
26 to 30 days of antibiotics had a recurrence rate of 50%, while patients treated with 0
to 5 days of antibiotics experienced a recurrence rate of only 12%. Potential
explanations for these differences include the generation of resistant pathogens with
longer antibiotic use and the unwillingness of clinicians to stop antibiotics in critically
ill patients who manifest ongoing evidence of inflammation and are immunologically at
higher risk for infection. In addition, patients with poorer technical control of the initial
source of infection—eg, those with a persistent enteric leak or poorly controlled
fistula—tend to be treated longer yet be at risk for recurrence predominantly because of
persistent contamination by enteric contents.
Figure 2. Correlation between duration of antibiotic therapy and recurrence of intraabdominal infection. As the duration of therapy lengthened, there was a proportional
increase in the likelihood of recurrent infection. This may be attributed to either
underlying severity of infection or a lack of adequate source control (mechanical
diversion of enteric contents from the free peritoneal cavity, whether by resection,
drainage, or diversion).
Not surprisingly, patients with peritonitis as a presenting diagnosis had different
outcomes from those with peritonitis after surgical procedures, since the latter
population includes patients with postoperative complications of significant technical
complexity. Patients with peritonitis as a presenting diagnosis had a mean length of
treatment of 13.1 days with a 16.7% recurrence rate; those with peritonitis after a
surgical procedure had 16.2 days of treatment with a 28.2% recurrence rate.
As we examined risk factors associated with recurrence of infection, the causative
organism and the organ of origin seemed to predict relapse. Although Candida species
were the organisms most commonly isolated in cultures from the 1343 patients with
intra-abdominal infection, Enterococcus species were most commonly isolated in
patients in whom a recurrence subsequently developed. In addition, infections
originating in organs for which it is most difficult to establish adequate local control
(eg, the liver, pancreas, and duodenum) were most likely to recur. From our results, it is
unclear whether infections that were associated with Enterococcus species were
inherently more virulent or whether these infections were merely a marker of severity of
illness and/or immunosuppression.
From these data, it is clear that we, as an institution, are not meeting the standards set
forth by the most current guidelines regarding intra-abdominal infections and duration
of antibiotic therapy. Furthermore, our incidence of recurrent infection is comparable to
those reported in published studies in which there was a significantly shorter duration of
antibiotic treatment.
Finally, we have identified, within our own institution, the organisms and organs of
origin that are most likely to contribute to recurrent infections and can now better
intervene with local control methods rather than prolonged antibiotic therapy. Clearly,
there is room for improvement, and we would be surprised if our practice is
significantly different from that of other medical centers.
We have recently initiated educational efforts to train our house staff to treat most intraabdominal infections with a maximum of 7 days of antibiotics and to consider ongoing
evidence of inflammation as a trigger for investigation rather than further antibiotic
administration. Preliminary evidence suggests that we have been able to reduce
antibiotic use in ward patients but we have had minimal impact in the ICU. We have not
been able to observe any differences in outcomes based on these changes. We are
currently considering more intrusive methods to reduce antibiotic use in patients with
intra-abdominal infection, including automatic stop orders after 5 or 7 days.
Discussion and Conclusions
While patients with intra-abdominal infection make up a significant percentage of the
population in surgical wards, relatively few data have been accumulated concerning the
adequate duration of antibiotic treatment. Although large, prospective, randomized trials
are lacking, smaller trials suggest that shortened antibiotic courses may be used without
increasing the risk of recurrent infection. When determining the length of antibiotic
treatment, the severity of the infection, as suggested by intraoperative findings and
degree of contamination, should be used as a guide.
Contamination during an elective case or in the absence of sufficient time for the
development of peritonitis (less than 12 hours) should be treated with single-dose
prophylactic antibiotics at the time of surgery, whereas resectable infections, such as
gangrenous cholecystitis and appendicitis, warrant 24 hours of perioperative antibiotics.
More significant infections require anywhere from 2 to 5 days of antibiotics or longer if
local control is inadequate (as may be the case with pancreatic, biliary, or
retroperitoneal infections). Antibiotics should be discontinued when the patient's
temperature curve and WBC count have normalized. If clinical signs and symptoms
persist after a reasonable course of antibiotic therapy, an alternative infectious cause
should be sought and controlled rather than continuing antibiotic treatment for the initial
infection.
From our own institutional data, it can be inferred that hepatic, pancreatic, and duodenal
infections are more difficult to control with drain age methods and are therefore more
likely to recur than infections involving other organs. In addition, infections with
Enterococcus species are also associated with recurrence and should, perhaps, be treated
more aggressively than infections with other species.
Theoretically, limiting the duration of therapy for intra-abdominal infections may
prevent the development of resistant organisms, shorten hospital stays (reducing the
likelihood of nosocomial infections), and decrease health care costs. Our data confirm
that we are not yet compliant with the most current recommendations, and discussions
with health care providers at other institutions indicate that we are not unique in this.
Improved standards of care for intra-abdominal infections may be achieved through the
development of guidelines, such as those cited in this article. Furthermore, it is clear
that prospective, randomized trials are needed to address more fully the proper duration
of antibiotic therapy. For now, it is imperative that we continue to monitor our
individual treatment patterns so that we may predict, within our own institutions, the
factors that may predispose our patients with intra-abdominal infections to treatment
failure, and intervene appropriately.
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Dr Hedrick is a resident physician, and Dr Sawyer is associate professor, department
of surgery, at the University of Virginia, Charlottesville.