Appendectomy procedures
Background. Cases of appendicitis
can be described as complicated
or uncomplicated on the basis of the
pathology. Patients with uncomplicated
appendicitis have an acutely
inflamed appendix. Complicated
appendicitis includes perforated or
gangrenous appendicitis, including
peritonitis or abscess formation.
Because complicated appendicitis
is treated as a complicated intraabdominal
infection,303 it has not
been addressed separately in these
guidelines. All patients with a suspected
clinical diagnosis of appendicitis,
even those with an uncomplicated
case, should receive appropriate preoperative
i.v. antimicrobials for SSI
prevention, which, due to the common
microbiology encountered, requires
similar antimicrobial choices
to those used to treat complicated
appendicitis.
Approximately 80% of patients
with appendicitis have uncomplicated
disease.59 SSI has been reported
in 9–30% of patients with uncomplicated
appendicitis who do not
receive prophylactic antimicrobials,
though some reports suggest lower
complication rates in children with
uncomplicated appendicitis.165,360-365
Mean SSI rates for appendectomy
reported in the most recent NHSN
report (2006–08) were 1.15% (60 of
5211) for NHSN risk index categories
0 and 1 versus 3.47% (23 of 663)
for NHSN risk index categories 2 and
3.165 Laparoscopic appendectomy has
been reported to produce lower rates
of incisional (superficial and deep)
SSIs than open appendectomy in
adults and children in multiple metaanalyses
and several randomized
clinical trials.292,310,366-371 However, the
rate of organ/space SSIs (i.e., intraabdominal
abscesses) was significantly
increased with laparoscopic
appendectomy.
Organisms. The most common
microorganisms isolated from SSIs
after appendectomy are anaerobic
and aerobic gram-negative enteric
organisms. Bacteroides fragilis is the
most commonly cultured anaerobe,
and E. coli is the most frequent aerobe,
indicating that the bowel flora
constitute a major source for pathogens.
59,372,373 Aerobic and anaerobic
streptococci, Staphylococcus species,
and Enterococcus species also have
been reported. P. aeruginosa has been
reported infrequently.
Efficacy. Antibiotic prophylaxis is
generally recognized as effective in
the prevention of postoperative SSIs
in patients undergoing appendectomy
when compared with placebo.374
Choice of agent. Randomized controlled
trials have failed to identify
an agent that is clearly superior to
other agents in the prophylaxis of
postappendectomy infectious complications.
An appropriate choice for
SSI prophylaxis in uncomplicated
appendicitis would be any single
agent or combination of agents that
provides adequate gram-negative
and anaerobic coverage. The secondgeneration
cephalosporins with anASHP
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Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 221
aerobic activity and a first-generation
cephalosporin plus metronidazole
are the recommended agents on the
basis of cost and tolerability. Given
the relatively equivalent efficacy between
agents, a cost-minimization
approach is reasonable; the choice of
agents should be based on local drug
acquisition costs and antimicrobial
sensitivity patterns.
A wide range of antimicrobials
have been evaluated for prophylaxis
in uncomplicated appendicitis.
The most commonly used agents
were cephalosporins. In general, a
second-generation cephalosporin
with anaerobic activity (cefoxitin or
cefotetan) or third-generation cephalosporins
with partial anaerobic
activity (cefotaxime) were effective,
with postoperative SSI rates of <5%
in most studies.364,375-381
Piperacillin 2 g was comparable
to cefoxitin 2 g in a well-controlled
study.381 Metronidazole used alone
was less effective than cefotaxime,
with infection rates above 10%.376
However, when metronidazole was
combined with cefazolin, ampicillin,
382 or gentamicin,378,383 the postoperative
SSI rates were 3–6%.
A double-blind, randomized,
controlled trial was conducted at
two hospitals to evaluate the effect
of metronidazole, which is effective
against most anaerobes, and
cefazolin, which is effective against
many aerobic organisms, singly and
in combination, on the rate of sepsis
after appendectomy.384 Patients were
randomized into one of four groups:
metronidazole and placebo, cefazolin
and placebo, metronidazole and
cefazolin, or double placebo. Patients
with generalized peritonitis were excluded
for ethical reasons. Treatment
was started before the procedure and
continued every 8 hours for 24 hours.
All patients in the trial were followed
for about two weeks after discharge
from the hospital, and their surgical
sites were inspected. A total of 271
patients were assessed. Sepsis rates
at the two hospitals were similar.
Patients who received both cefazolin
and metronidazole had a significantly
lower infection rate compared
with the other groups.384 Consistent
with the antibacterial spectrum of the
agents, a prospective study of antimicrobial
prophylaxis for colorectal procedures
found that the combination
of metronidazole with aztreonam did
not show adequate coverage of grampositive
organisms.385 The Common
Principles section of these guidelines
provides additional considerations
for weight-based dosing.
Duration. In most of the studies of
second- or third-generation cephalosporins
or metronidazole combinations,
a single dose376-378,380,383 or two
or three doses364,379,382 were given.
Although direct comparisons were
not made, there was no discernible
difference in postoperative SSI rates
between single-dose and multidose
administration in most studies. A
randomized trial specifically comparing
different durations of regimens
found no statistical difference between
a single preoperative dose, three doses
(preoperative dose plus two additional
doses), or a five-day regimen.386 A large
cohort study found that single doses
of metronidazole and gentamicin in
patients undergoing open appendectomy
were effective and sufficient in
decreasing the SSI rate.387
Pediatric efficacy. In pediatric
patients, as with adults, preoperative
determination of complicated versus
uncomplicated appendicitis is difficult.
A comprehensive review is not
provided here, but this topic has been
addressed by SIS.388
Two pediatric studies demonstrated
no difference in SSI rates between
placebo and several antimicrobials.
The first study compared metronidazole,
penicillin plus tobramycin,
and piperacillin.389 The second study
compared single-dose metronidazole
and single-dose metronidazole plus
cefuroxime.390 A meta-analysis including
both adult and pediatric studies
found that for pediatric patients,
antimicrobial prophylaxis trended toward
being beneficial, but the results
were not statistically significant.374 A
retrospective chart review questioned
the routine need for antimicrobial
prophylaxis in children with simple
appendicitis, due to relatively low
infection rates in children not receiving
prophylaxis.365 However, these
and other study authors have suggested
antimicrobial prophylaxis may
be considered due to the morbidity
associated with infectious complications
(e.g., prolonged hospitalization,
readmission, reoperation) and due to
the inability to preoperatively identify
appendicitis.
As a single agent, metronidazole
was no more effective than placebo
in two double-blind studies that included
children 10 years of age or
older360 and 15 years of age or older.363
In a randomized study that included
pediatric patients, ceftizoxime and
cefamandole were associated with
significantly lower infection rates
and duration of hospitalization than
placebo.391 Both cefoxitin and a combination
of gentamicin and metronidazole
were associated with a lower
rate of postoperative infection in a
randomized study that included pediatric
patients younger than 16 years.378
Second-generation cephalosporins
with anaerobic activity (cefoxitin
or cefotetan) and third-generation
cephalosporins with anaerobic activity
(cefotaxime) were effective, with
postoperative infection rates of <5%
in two studies that included pediatric
patients younger than 12 years.364,378,379
A single dose of gentamicin with
clindamycin was found to be safe
and effective in children with simple
appendicitis.392
Recommendations. For uncomplicated
appendicitis, the recommended
regimen is a single dose of a
cephalosporin with anaerobic activity
(cefoxitin or cefotetan) or a single
dose of a first-generation cephalosporin
(cefazolin)plus metronidazole
(Table 2). For -lactam-allergic
patients, alternative regimens include
(1) clindamycin plus gentamicin,
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222 Am J Health-Syst Pharm—Vol 70 Feb 1, 2013
aztreonam, or a fluoroquinolone and
(2) metronidazole plus gentamicin or
a fluoroquinolone (ciprofloxacin or
levofloxacin). (Strength of evidence
for prophylaxis = A.)