c
e
r
ib
L
e
r
tu
y
r
a
L
Surgical Antimicrobiale
Prophylaxis in SOT:
n organisms?
which antibiotic forliwhich
n
O
Nicola Petrosillo,
D M.D.or
I
M
h
t
C
u
S
a
E
y
b
©
National Institute for Infectious Diseases
“Lazzaro Spallanzani”, Rome, Italy
Disclosures
y
r
a
L
e
r
ib
Has received fees for advisory board membership e/o
honary as speaker for:
c
e
r
tu
-Astellas, Astra Zeneca, CareFusion, Johnson &
Johnson, MSD, Novartis, Pfizer
L
e
n
i
l
n
O
D SanofiorAventis, Italian Ministry of
-Astra Zeneca,
I
Health M
h
t
C
u
S
a
E
y
b
©
Is participating in research projects supported by:
Outline
r
ib
L
e
r
tu
y
r
a
-Burden of SSI (epidemiology, microrganisms,
risk factors) ONLY liver and kidney
c
e
-Current practices of perioperative
L
prophylaxis
e
n
i
l
-Recommendednpractices
O
-Colonization and perioperative prophylaxis: a
D or
I
conundrum?
M
h
t
C
u
S
a
E
y
b
©
SSI in different organ transplantsry
Number
patients
included
Year
Heart
51
282
2002-3
Liver
1222
113
315
L
e
SSI incidence
n
i
l
n
r
tu
c
e
L
e
O
D or
I
M
h
t
C
u
S
a
E
y
b
©
a
r
ib
10%
5%
10%
37%
21%
KidneyPankreas
51
2005
45%
Lung
Heart-Lung
21
73
117
20
1993
1993
2002-3
2002-3
28%
4%
11%
35%
Kidney
1400
4%
Kettelhut VV et al. Progress in Transplantation 2010;20:320-328
y
r
a
r
ib
Kidney transplantation and SSI
L
e
•The frequency of SSIs in kidney transplant recipients
has ranged from zero to 11% with antimicrobial
prophylaxis to 2% to 7.5% without systemic prophylaxis.
L
e
c
e
r
tu
•The majority of these infections were superficial in
nature and were detected within 30 days after
transplantation
n
i
l
n
O
D or
I
M
h
t
C
u
S
a
E
y
b
©
SSI after Kidney Transplantation
y
r
a
Wszola M et al. Transplantation 2013;95: 878-882
L
e
n
i
l
n
O
D or
I
M
h
t
C
u
S
a
E
y
b
©
L
e
r
tu
c
e
r
ib
SAP: ceftriaxone for 48h
SSI after Kidney Transplantation
y
r
a
Wszola M et al. Transplantation 2013;95: 878-882
L
e
r
ib
Independent risk factors for SSI are kidney from ECD,
CIT of more than 30 hr, time of surgical procedure longer
than 200 min, recipients having diabetes, recipients having a
BMI higher than 27 kg/m2, and occurrence of DGF.
L
e
c
e
n
i
l
n
O
D or
I
M
h
t
C
u
S
a
E
y
b
©
r
tu
Liver transplantation and SSI
r
ib
y
r
a
L
•SSIs within 30 days after transplantation
e ranged from 4%
r
u
to 48% with antimicrobial prophylaxis
in several cohort
t
c
and controlled studies
e
L
e
most often within the first two to
•Superficial SSIs are seen
n
i
l
three weeks postoperatively,
whereas organ/space
n
infections and deep
infections are seen after three to four
O
weeks
D or
I
M
h
t
C
u
S
a
E
y
b
©
Liver transplantation and SSI
-microrganisms-
y
r
a
L
e
r
ib
•Early SSIs and intraabdominal infections are those derived from the
normal flora of the intestinal lumen and the skin.
r
tu
•Aerobic gram-negative bacilli, including E. coli, Klebsiella species,
Enterobacter species, A. baumannii and Citrobacter species are
common causes of SSIs and intraabdominal infections and account
for
up to 65% of all
bacterial pathogens.
increasing
concern
about antimicrobial
L
e
c
e
n
i
l
n
resistance based on detection of resistant
organisms
•Infections due to P. aeruginosa may also occur but are much less
common in the early postoperative period.
O
D or
I
M
h
t
C
u
S
a
E
y
b
©
•Enterococci are particularly common pathogens and may be
responsible for 20–46% of SSIs and intraabdominal infections.
•Staphylococcus aureus (frequently MRSA) and coagulase-negative
staphylococci are also common causes of postoperative SSIs
Bratzel DW et al. Am J Health-Syst Pharm 2013;70:195-283
Of the 113 LDLT
recipients, 42 (37%)
developed 57 episodes
of SSIs
-21 intraabdominal
abscess,
- 20 peritonitis,
-8 cholangitis,
-and 9 wound.
L
e
n
i
l
n
O
D or
I
M
h
t
C
u
S
a
E
y
b
©
SAP: flomoxef, an oxacefem
antibiotic, for 72 h
c
e
r
ib
L
e
r
tu
y
r
a
Iinuma Y et al. Transplantation 2004;78: 704–709
y
r
a
r
ib
Retrospective analysis of 370 patients who
underwent first liver transplantation in 2003 and 2004
c
e
r
tu
SSIs were identified in 66 pts (18%)
-43 organ or space,
-18 superficial,
- 5 deep.
n
i
l
n
L
e
O
D or
I
M
h
t
C
u
S
a
E
y
b
©
L
e
More than one bacterial or fungal pathogen was recovered in
22 (33%) infections.
Hellinger WC et al. Transplantation 2009;87: 1387–1393
Antibiotic Prophylaxis
- the principles -
y
r
a
L
e
r
ib
•When administering prophylactic antibiotics, the goal is to
give the appropriate antibiotic at the right time, for the
appropriate indication/surgery type.
c
e
r
tu
L
•Achieving the optimal tissue
concentration of the
e
n is the main aim.
antibiotic at the time ofliincision
n
O
•SCIP outlinesD
recommended protocols for administering
I
r
antibiotic prophylaxis
for
infection prevention, including
o
M
h
t
administration
of the
antibiotic within one hour prior to
C
u
S
the
surgery and
discontinuation within 24 hours after
a
E
y
surgery end
b time (48 hours for cardiac patients).
©
SAP
L
e
c
e
r
ib
L
e
r
tu
y
r
a
•95% of respondents indicated that they use routine
antibiotic coverage in the peri-operative transplant
period;
n
i
l
n
O
D
I
r
•For thoseM
centers using
antibiotics, 100% indicated that
o
h
t
it is used
in all patients.
C
u
S
a
E
y
b
©
•5% indicated that they do not use antibiotic prophylaxis.
Batiuk TD et al. Clin Transplant 2002: 16: 1-8
r
ib
L
e
Surgical prophylaxis.
r
tu
y
r
a
•A cephalosporin is used exclusively or as part of a regimen
in 92% of centers.
c
e
L
•In 50% of centers, antibiotice
coverage is limited to the first
na single dose.
i
24 h, and is often limited lto
n
O
•At the remainder of the centers, antibiotic coverage
D h (35%),
I
r
continued for 24-48
2-5 days (10%) or until
o
M
lines/Foley catheter was
removed (5%).
h
t
C
u
S
a
E
•Two centers indicated
that the antibiotic coverage is
y
b results of intraoperative cultures are
continued until
©
available.
Batiuk TD et al. Clin Transplant 2002: 16: 1-8
L
e
c
e
n
i
l
n
O
D or
I
M
h
t
C
u
S
a
E
y
b
©
r
ib
L
e
r
tu
y
r
a
Vandecasteele E et al. Transpl Int 2010;23:182-90
r
ib
y
r
a
Vandecasteele E et al.
L
e
c
e
n
i
l
n
O
D or
I
M
h
t
C
u
S
a
E
y
b
©
r
tu
L
e
Transpl Int 2010;23:182-90
r
ib
y
r
a
Vandecasteele E et al.
Transpl Int 2010;23:182-90
L
e
c
e
n
i
l
n
O
D or
I
M
h
t
C
u
S
a
E
y
b
©
r
tu
L
e
y
r
a
Latium Region practice on perioperative
antimicrobial prophylaxis (LIVER)
2007-2008
c
e
r
tu
L
e
r
ib
L
-Center A (# 54)  Amoxicillin/Clav
+ Amikacin
e
n
i
l
-Center B (# 47) nAmpicillin/Sulbact +
Metronidazole O
D
I
r
-Center M
C (# 52)  o
Piperacillin/Taz
h
t
C
u
S
a
E
y
b
©
Personal data
y
r
a
r
ib
Intravenous ceftriaxone (1 g) was administrated after induction and 30 minutes before
the surgical inscision as well as postreperfusion for intraoperative antibiotic prophylaxis.
It was continued (1g every 12 hours) for 1–3 days after liver transplantation.
L
e
c
e
n
i
l
n
O
D or
I
M
h
t
C
u
S
a
E
y
b
©
r
tu
L
e
367 pts
74 SSI (20%)
Transplantation Proceedings 2013; 45: 993–997
y
r
a
r
b
i
Routine perioperative bacterial prophylaxis
L
includes
e
r
intravenous ampicillin plus
sulbactam
u
t
c
e
L
e
n
i
l
n
O
D or
I
M
h
t
C
u
S
a
E
y
b
©
Vagopian PG et al. Ann Surg 2013;258:409–421
c
e
r
ib
L
e
r
tu
y
r
a
Liver transplantation
L
e
n
i
l
n
•Antimicrobial prophylaxis should be directed against the
pathogens most commonly isolated from early infections (i.e.,
gram-negative aerobic bacilli, staphylococci, and enterococci).
O
•Traditional prophylactic regimens have therefore consisted of
D
I
r
a third-generation cephalosporin
(usually cefotaxime, because
o
M
of its antistaphylococcal
activity) plus ampicillin.
h
t
C
u
S
a
•However,
almost
all type of antimicrobials have been used in
E
y
SAP.
b
©
ASHP, IDSA, SHEA
y
r
a
r
ib
• Prospective study of SSI in a cohort of 167 OLT.
•Two different schedules of antibiotic SSI prophylaxis were compared
(Cefazolin 1 g-Amo/Clav 2g).
•Fifty-six episodes of SSI were included (0.34 episodes/patient).
L
e
c
e
n
i
l
n
O
D or
I
M
h
t
C
u
S
a
E
y
b
©
r
tu
L
e
Garcia Prado ME et al. Transplantation 2008; 85: 1849-54
L
e
c
e
n
i
l
n
O
D or
I
M
h
t
C
u
S
a
E
y
b
©
r
ib
L
e
r
tu
y
r
a
Garcia Prado ME et al. Transplantation 2008; 85: 1849-54
and the duration?
y
r
•No studies have assessed the optimal duration ofa
r
antimicrobial prophylaxis in liver transplantation.
b
i
L
e
•Although antimicrobials have been administered
in
r
u
studies for five days and seven days,
the majority of
t
c
recent studies have limited the duration
of prophylaxis
e
to 72 h, 36 h, 24 h, and a singleLdose, with no apparent
e
differences in early infection
rates.
n
i
l
n
O
D or
I
M
h
t
C
u
S
a are in favour of a duration less than
E ofyexperts
Opinion
b
three days
©
(Soave R. Clin Infect Dis 2001; 33(suppl 1):S26–S31; Villacian JS et al.
Transpl Infect Dis 1999; 1:50–64).
and for MRSA, VRE colonized?....
• MRSA mupirocin, chlorexidine baths (?)
y
r
a
L
e
r
ib
•A patient colonized with vancomycin-resistant
enterococci (VRE) should receive prophylaxis effective
against VRE when undergoing liver transplantation.
L
e
c
e
r
tu
•Thus, patients must be treated on a case-by-case basis,
taking into account multiple considerations.
n
i
l
n
O
D or
I
M
h
t
C
u
S
a
E
y
b
©
Bratzel DW et al. Am J Health-Syst Pharm 2013;70:195-283
and Candida prophylaxis?
y
r
a
r
ib
•Postoperative infections with Candida species after
liver transplantation are common, particularly in the
abdomen, and are frequently considered organ/space
SSIs.
c
e
r
tu
L
e
L
e
•For this reason, the use of antifungal prophylaxis in
the perioperative period has become common.
n
i
l
n
O
D or
I
M th found a decreased risk of
•Finally,C
one meta-analysis
u
S
fungal
infection
and
death associated with fungal
a
E though
infection,
not overall mortality, among patients
y
b prophylaxis
given antifungal
©
•Efficacy has been demonstrated for fluconazole, lipid
complex amphotericin B, and caspofungin.
2006; 12:850–858.989).
(Cruciani M et al. Liver Transpl
y
r
• Universal antifungal prophylaxis is probablyra
not
b
i
necessary in liver transplant, since the risk
of
L
invasive candidiasis is low in uncomplicated
e
r
cases.
u
t
c
e
• Instead, prophylaxis is generally
reserved for
L
patients with two or more
of the following risk
e
n
i
factors:
l
n
O
1. need for reoperation,
D or
I
2. retransplantation,
3. renal M
failure, th
C
u
4. choledochojejunostomy,
S
a
E
5. and known
colonization with Candida species.
y
b it applies not only to Candida SSI
however,
©
and Candida prophylaxis?
Pappas PG et al. Am J Transplant 2009; 9(suppl 4):S173–179.
y
r
a
L
e
r
ib
• Lung Tx: most donor organs are contaminated, most
contaminations do not lead to post-Tx-infection under the
condition of wide peri-operative prophylaxis
• Donor liver, lung and heart-lung contamination with candida
species may be a risk for post-Tx SSI
L
e
c
e
n
i
l
n
O
D or
I
M
h
t
C
u
S
a
E
y
b
©
r
tu
Mattner F et al. Infection 2008;36:207-12
y
r
a
What to do in case of recipient’s MDR Gram neg
colonization?
L
e
c
e
n
i
l
n
O
D or
I
M
h
t
C
u
S
a
E
y
b
©
r
tu
L
e
r
ib
y
r
a
r
ib
L
e
•From mid-2010 to early 2013 the Leipzig University Hospital, a 1,300bed referral center, experienced the largest outbreak owing to KPC-2producing KP (KPC-2-KP) observed in Germany up to that time,
involving 103 patients.
r
tu
L
e
c
e
•A retrospective study cohort comprised nine patients who had
undergone orthotopic liver transplantation.
n
i
l
n
•Of these nine cases, eight (89 %) progressed to infection due to KPC2-KP, and five (56 %) were confirmed to have bloodstream infection
with KPC-2-KP.
O
D or
I
M
h
t
C
u
S
a
E
y
b
©
•2/8 had a SSI
•Risk of 7.0 (95 % CI 1.8–27.1) for fatal Infection.
Lubbert C et al. Infection 2014; 42:309–316
L
e
n
i
l
n
O
D or
I
M
h
t
C
u
S
a
E
y
b
©
r
tu
c
e
r
ib
L
e
matched case-control study
y
r
a
Giannella M et al. Liver Transpl 2014; 20:631-3
L
e
c
e
n
i
l
n
O
D or
I
M
h
t
C
u
S
a
E
y
b
©
r
ib
L
e
r
tu
y
r
a
ASHP, IDSA, SHEA
Kidney transplantation and SSI
-microrganisms-
r
ib
L
e
r
tu
y
r
a
Postoperative SSIs in kidney transplant recipients are
caused by gram-positive organisms, particularly:
c
e
L
-Staphylococcus species (including
S. aureus and S.
e
n species,
i
epidermidis) and Enterococcus
l
n
-gram-negative organisms,
E. coli, Enterobacter species,
O
Klebsiella species, P. aeruginosa,
D
I
r
- and yeast with Candida
species.
o
M
h
t
C
u
S
a
E
y
b
©
Bratzel DW et al. Am J Health-Syst Pharm 2013;70:195-283
Kidney transplantation and SSI
-perioperative prophylaxis-
y
r
a
r
ib
L
e
A prospective randomized controlled trial of perioperative
antibiotic prophylaxis in renal transplantation.
r
tu
Cohen J et al. J Hosp Infect 1988; 11:357–363.
L
e
c
e
•Perioperative prophylaxis with cefuroxime and piperacillin in 53
recipients of renal allografts.
n
i
l
n
27: three doses of cefuroxime 750 mg and piperacillin 4 g,
O
D or
I
M
h
t
C
u
S
a
E
y
b
©
26: no prophylaxis.
•In the first 5 days, patients receiving antibiotics had fewer
infections (3 vs. 11, P = 0.04) but by 14 days this difference was no
longer apparent (21 vs. 30, P = NS).
•They conclude that perioperative antibiotic prophylaxis results in a
modest but worthwhile reduction in the incidence of wound
infections after renal transplantation.
L
e
c
e
n
i
l
n
O
D or
I
M
h
t
C
u
S
a
E
y
b
©
r
ib
L
e
r
tu
y
r
a
ASHP, IDSA, SHEA
y
r
a
r
ib
Laftavi MR et al. Transplant Proc 2011;43:533.-35
L
e
Question: can SAP be avoided in kidney transplant?
r
tu
•There are no current randomized prospective studies of patients post–renal
transplantation that help guide the use of SAP.
c
e
•In this retrospective study, they evaluate the clinical course of 349
recipients of kidney transplants without the use of routine SAP in their
center.
L
e
n
i
l
n
O
D or
I
M
h
t
C
u
S
a
E
y
b
©
y
r
a
L
e
r
ib
•Their immunosuppression protocol was based on very
low doses of steroids (525 mg of steroids during the
first posttransplant week), and low-dose thymoglobulin.
L
e
c
e
r
tu
•Their center avoided using drains or stents during
kidney transplant surgery.
n
i
l
n
O
D or
I
M
h
t
C
u
S
a
E
y
b
©
•Only 13% of our kidney recipients were stented for
complicated transplant surgery such as small scarred
bladder due to prolonged anuria, questionable
vascularization of the ureter, or large diabetic
neurogenic bladder.
Laftavi MR et al. Transplant Proc 2011;43:533.-35
y
r
a
L
e
r
ib
•There was a higher UTI rate in the stented group
compared to nonstented patients when SAP was not
used (11.4% vs 0.3%, P .001).
L
e
c
e
r
tu
•They suggest that SAP may be considered in
complicated kidney transplants requiring ureteral
stents.
n
i
l
n
O
D or
I
M
h
t
C
u
S
a
E
y
b
©
Laftavi MR et al. Transplant Proc 2011;43:533.-35
y
r
a
L
e
r
ib
•This retrospective observational study of 174 renal
allograft recipients who underwent transplantation
from January 2006 to July 2010 included 97 grafts
procured from living donors and 77 from deceased
donors.
L
e
c
e
n
i
l
n
r
tu
•The recipients were divided into two groups; SAP
versus no SAP.
O
D
I
r
•SAP recipients wereoprescribed
a first-generation
M
h
cephalosporin
(Cefazolin,
1 g) intravenously just before
t
C
u
S
commencing
surgery.
a
E
y
b
©
Choi SU et al. Transplantation Proceedings 2013; 45: 1392–1395
L
e
c
e
n
i
l
n
O
D or
I
M
h
t
C
u
S
a
E
y
b
©
r
ib
L
e
r
tu
y
r
a
No difference
Choi SU et al. Transplantation Proceedings 2013; 45: 1392–1395
Take home messages
r
ib
y
r
a
L
e
1. Know your infection rates
2. Intensify all well-known infection prevention measures; best using
checklists and education
3. Look for donor and recipients colonisations and adapt SAP when
appropriate
4. Give adequate dosing and timing of SAP
L
e
c
e
r
tu
However, there is a need for sound studies on
n
i
l
n
O
D
I
r
• colonization, decontamination
and SAP
o
M
h
t
C
• duration of SAP
u
S
E… and onytheainfection rates…
b
©
• antibiotic choice (by organ and organism)
y
r
a
Sometimes Tx physicians are reluctant to publish data on infections
L
e
c
e
n
i
l
n
O
D or
I
M
h
t
C
u
S
a
E
y
b
©
r
tu
L
e
r
ib