780 ASHP Therapeutic Guidelines
be responsible for 20–46% of SSIs and intraabdominal
infections.
894,933,935,937,938,940,943,945–947,951,952,955,964,965,969
S. aureus (frequently MRSA) and coagulase-negative
staphylococci are also common causes of postoperative
SSIs.
936–938,940,942,943,945–949,955,957–961,964,965,970,971
Candida
species commonly cause both early and late postoperative
infections.
933,936,937,940,942,943,945–947,949,951,969
Several studies have noted increasing concern about
antimicrobial resistance based on detection of resistant
organisms, including E. coli,
935,937
Enterococcus spe-
cies,
933,937,964,965
Enterobacter species,
964
Klebsiella spe-
cies,
933,937
coagulase-negative staphylococci,
937,964
and S.
aureus.
937,948,957–961,970
General information on antimicrobial
resistance is provided in the Common Principles section of
these guidelines. Of specific concern to the transplantation
community is the emergence of multidrug-resistant A. bau-
mannii,
972
carbapenem-resistant Enterobacteriaceae,
973,974
K. pneumoniae carbapenemase-producing organisms,
975
and
C. difficile.
976–978
Efficacy. Although there remains a high rate of infection
directly related to the liver transplantation procedure, there
are few well-controlled studies concerning optimal antimi-
crobial prophylaxis. In evaluating the efficacy of prophylac-
tic regimens, it is important to differentiate between early
infections (occurring within 14–30 days after surgery) and
late infections (occurring more than 30 days after surgery).
Infections occurring in the early postoperative period are
most commonly associated with biliary, vascular, and ab-
dominal surgeries involved in the transplantation procedure
itself and are thus most preventable with prophylactic anti-
microbial regimens.
939,940,943,945
The frequency of these in-
fections varies from 10% to 55% despite antimicrobial pro-
phylaxis
.939,940,943,945,979
It is difficult to assess the efficacy
of prophylactic regimens in reducing the rate of infection,
because prophylaxis has been routinely used in light of the
complexity of the surgical procedure; therefore, reliable
rates of infection in the absence of prophylaxis are not avail-
able. No controlled studies have compared prophylaxis with
no prophylaxis.
Choice of agent. Antimicrobial prophylaxis should be
directed against the pathogens most commonly isolated from
early infections (i.e., gram-negative aerobic bacilli, staphy-
lococci, and enterococci). Traditional prophylactic regimens
have therefore consisted of a third-generation cephalosporin
(usually cefotaxime, because of its antistaphylococcal activ-
ity) plus ampicillin.
936,937,943,944,946–948,951,952,954,962,965,967,979
The use of cefoxitin and ampicillin–sulbactam, cefotaxime
and ampicillin–sulbactam and gentamicin,
957–959
cefurox-
ime and metronidazole,
971
ceftriaxone and metronidazole,
980
cefotaxime and metronidazole,
953
ceftriaxone and ampicil-
lin,
949
ceftizoxime alone,
955
cefotaxime and tobramycin,
956
cefoxitin alone,
960,961
cefazolin alone,
951
amoxicillin–clavu-
lanate and gentamicin,
970
amoxicillin–clavulanate alone,
951
glycopeptides and antipseudomonal penicillin,
951
quinolone
and amoxicillin–clavulanate or glycopeptide,
951
vancomy-
cin and aztreonam,
951,981
and piperacillin–tazobactam
964,970
has also been reported. Alternative prophylaxis regimens
for
b-lactam-allergic patients have included cefuroxime
and metronidazole,
970
clindamycin and gentamicin or az-
treonam,
948,960–962
ciprofloxacin and metronidazole,
970
and
vancomycin or ciprofloxacin.
936
Imipenem alone was used
in one study for patients with renal failure.
956
The efficacy
of these regimens compared with cefotaxime plus ampi-
cillin is difficult to assess due to different definitions of
infection used in the available studies and variability of
study design (many single-center cohort studies) in differ-
ent countries. One prospective nonrandomized study found
no difference in the frequency of SSIs in orthotopic liver
transplant recipients with cefazolin alone and amoxicil-
lin–clavulanate alone, both given one hour before surgical
incision, with a second dose given in cases of significant
bleeding or surgery lasting over six hours, as antimicrobial
prophylaxis.
935
The study did find a significantly higher rate
of A. baumannii in the cefazolin group than the amoxicillin–
clavulanate group. The routine use of vancomy-
cin as antimicrobial prophylaxis is not recommended
because of the risk of developing vancomycin-
resistant organisms,
8,950
but vancomycin may be reserved for
centers with an MRSA or MRSE cluster.
8,950,957–959
No ran-
domized controlled studies have been conducted to compare
the efficacy of other antimicrobial prophylactic regimens in
the prevention of early postoperative infections. For patients
known to be colonized with MRSA, VRE, or resistant gram-
negative pathogens, it is reasonable to consider prophylaxis
specifically targeted at these organisms. See the Common
Principles section for further discussion.
Postoperative infections with Candida species after
liver transplantation are common, particularly in the abdo-
men, and are frequently considered organ/space SSIs. For
this reason, the use of antifungal prophylaxis in the periop-
erative period has become common. Efficacy has been dem-
onstrated for fluconazole,
964–984
lipid complex amphoteri-
cin B,
985–987
and caspofungin.
988
Finally, one meta-analysis
found a decreased risk of fungal infection and death asso-
ciated with fungal infection, though not overall mortality,
among patients given antifungal prophylaxis.
989
Universal
antifungal prophylaxis is probably not necessary, since the
risk of invasive candidiasis is low in uncomplicated cases.
Instead, prophylaxis is generally reserved for patients with
two or more of the following risk factors: need for reop-
eration, retransplantation, renal failure, choledochojejunos-
tomy, and known colonization with Candida species.
15
Risk
is also increased with prolonged initial procedure or transfu-
sion of >40 units of cellular blood products, but this cannot
be predicted before the procedure.
Selective bowel decontamination to eliminate aerobic
gram-negative bacilli and yeast from the bowel before the
transplantation procedure has been evaluated in several stud-
ies and a meta-analysis.
936,943,949,955,956,967,968,980,990,991
These
studies used combinations of nonabsorbable antibacterials
(aminoglycosides, polymyxin B or E), antifungals (nystatin,
amphotericin B), and other antimicrobials (cefuroxime in
suspension) administered orally and applied to the oropha-
ryngeal cavity in combination with systemically adminis-
tered antimicrobials. Results are conflicting, with no differ-
ences in patient outcomes (e.g., infection rates, mortality)
or cost and concerns of increasing gram-positive infections
with potential resistance in several studies
939,955,956,980,991
and others with positive results.
936,949
Two randomized
controlled studies found significantly fewer bacterial infec-
tions with early enteral nutrition plus lactobacillus and fi-
bers.
971,980
Based on currently available data, the routine use
of selective bowel decontamination or lactic acid bacteria
and fibers in patients undergoing liver transplantation is not
recommended.