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ASHP RePoRt Antimicrobial prophylaxis
195Am J Health-Syst PharmVol 70 Feb 1, 2013
A S H P r e P o r t
Clinical practice guidelines for antimicrobial prophylaxis in surgery
Dale W. Bratzler, e. Patchen Dellinger, Keith M. Olsen, trish M. Perl, Paul g. auWaerter, Maureen K. BOlOn, DOuglas n. Fish, lena M. naPOlitanO, rOBert g. saWyer, DOuglas slain,
JaMes P. steinBerg, anD rOBert a. Weinstein
Am J Health-Syst Pharm. 2013; 70:195-283
These guidelines were developed jointly by the American Society of Health-System Pharmacists (ASHP), the Infectious Diseases So-ciety of America (IDSA), the Surgi-cal Infection Society (SIS), and the Society for Healthcare Epidemiology of America (SHEA). This work rep-resents an update to the previously published ASHP Therapeutic Guide-lines on Antimicrobial Prophylaxis in Surgery,1 as well as guidelines from IDSA and SIS.2,3 The guidelines are intended to provide practitioners with a standardized approach to the rational, safe, and effective use of antimicrobial agents for the preven-tion of surgical-site infections (SSIs) based on currently available clinical evidence and emerging issues.
Dale W. Bratzler, D.O., M.P.H., is Professor and Associate Dean, College of Public Health, and Professor, College of Medicine, Okla-homa University Health Sciences Center, Oklahoma City. e. Patchen Dellinger, M.D., is Professor and Vice Chairman, Department of Surgery, and Chief, Division of General Surgery, University of Washington, Seattle. Keith M. Olsen, PharM.D., FCCP, FCCM, is Professor of Pharmacy Practice, Nebraska Medical Center, Omaha. trish M. Perl, M.D., M.sc., is Professor of Medicine, Pathology, and Epidemiology, Johns Hopkins University (JHU), and Senior Epidemiologist, The Johns Hopkins Health System, Baltimore, MD. Paul g. auWaerter, M.D., is Clinical Director and Associate Professor, Division of Infectious Diseases, School of Medicine, JHU. Maureen K. BOlOn, M.D., M.S., is Associate Professor of Medi-cine, Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, IL. DOuglas n. Fish, PharM.D., FCCM, FCCP, BCPS, is Professor and Chair, Department of Clinical Pharmacy, University of Colorado, Anschultz Medical Campus, and
Clinical Specialist, Critical Care/Infectious Diseases, Department of Pharmacy Services, University of Colorado Hospital, Aurora. lena M. naPOlitanO, M.D., FACS, FCCP, FCCM, is Professor of Surgery and Division Chief, Acute Care Surgery, Trauma, Burn, Critical Care, Emergency Surgery, and Associate Chair of Surgery, Critical Care, Department of Surgery, and Director, Surgical Critical Care, Uni-versity of Michigan Health System, Ann Arbor. rOBert g. saWyer, M.D., FACS, FIDSA, FCCM, is Professor of Surgery, Public Health Sciences, and Chief, Division of Acute Care, Surgery and Outcomes Research, University of Virginia Health System, Charlottesville, VA. DOuglas slain, PharM.D., BCPS, FCCP, FASHP, is Associate Professor of Pharmacy and Medicine, West Virginia University, Mor-gantown. JaMes P. steinBerg, M.D., is Professor of Medicine, Divi-sion of Infectious Diseases, Emory University, Atlanta, GA. rOBert a. Weinstein, M.D., is C. Anderson Hedberg MD Professor of Internal Medicine, Rush Medical College, Chicago, and Chairman, Department of Medicine, Cook County Health and Hospital System, Chicago.
Prophylaxis refers to the preven-tion of an infection and can be char-acterized as primary prophylaxis, secondary prophylaxis, or eradica-tion. Primary prophylaxis refers to the prevention of an initial infection. Secondary prophylaxis refers to the prevention of recurrence or reactiva-tion of a preexisting infection. Eradi-cation refers to the elimination of a colonized organism to prevent the development of an infection. These guidelines focus on primary periop-erative prophylaxis.
Guidelines development and use Members of ASHP, IDSA, SIS, and
SHEA were appointed to serve on an expert panel established to ensure the validity, reliability, and utility
of the revised guidelines. The work of the panel was facilitated by fac-ulty of the University of Pittsburgh School of Pharmacy and University of Pittsburgh Medical Center Drug Use and Disease State Management Program who served as contract re-searchers and writers for the project. Panel members and contractors were required to disclose any possible con-flicts of interest before their appoint-ment and throughout the guideline development process. Drafted docu-ments for each surgical procedural section were reviewed by the expert panel and, once revised, were avail-able for public comment on the ASHP website. After additional revi-sions were made to address reviewer comments, the final document was
ASHP RePoRt Antimicrobial prophylaxis
196 Am J Health-Syst PharmVol 70 Feb 1, 2013
approved by the expert panel and the boards of directors of the above-named organizations.
Strength of evidence and grading of recommendations. The primary literature from the previous ASHP Therapeutic Guidelines on Antimi-crobial Prophylaxis in Surgery1 was reviewed together with the primary literature published between the date of the previous guidelines, 1999, and June 2010, identified by searches of MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews. Particular attention was paid to study design, with greatest credence given to randomized, con-trolled, double-blind studies. There is a limited number of adequately powered randomized controlled trials evaluating the efficacy of an-timicrobial prophylaxis in surgical procedures. Guidelines develop-ment included consideration of the following characteristics: validity, reliability, clinical applicability, flex-ibility, clarity, and a multidisciplinary nature as consistent with ASHPs philosophy on therapeutic guide-lines.4 The limitations of the evidence base are noted within each individual procedure section of the guidelines. Published guidelines with recommen-dations by experts in a procedure area (e.g., American College of Obstetri-cians and Gynecologists [ACOG]) and noted general guidelines (e.g., Centers for Disease Control and Prevention [CDC], Scottish Intercol-
legiate Guidelines Network, Medical Letter, SIS, SHEA/IDSA) were also considered.2,3,5-11
Recommendations for the use of antimicrobial prophylaxis are graded according to the strength of evidence available. The strength of evidence represents only support for or against prophylaxis and does not apply to the antimicrobial agent, dose, or dosage regimen. Studies supporting the recommendations for the use of antimicrobial therapy were classified as follows:
Level I (evidence from large, well-conducted, randomized, controlled clinical trials or a meta-analysis),
Level II (evidence from small, well-conducted, randomized, controlled clinical trials),
Level III (evidence from well- conducted cohort studies),
Level IV (evidence from well- conducted casecontrol studies),
LevelV(evidence fromuncontrolledstudies that were not well conducted),
Level VI (conflicting evidence that tends to favor the recommendation), or
LevelVII (expert opinion or data ex-trapolated from evidence for general principles and other procedures).
This system has been used by the Agency for Healthcare Research and Quality, and ASHP, IDSA, SIS, and SHEA support it as an acceptable method for organizing strength of
evidence for a variety of therapeutic or diagnostic recommendations.4 Each recommendation was cat-egorized according to the strength of evidence that supports the use or nonuse of antimicrobial prophylaxis as category A (levels IIII), category B (levels IVVI), or category C (level VII).
When higher-level data are not available, a category C recommen-dation represents a consensus of expert panel members based on their clinical experience, extrapolation from other procedures with similar microbial or other clinical features, and available published literature. In these cases, the expert panel also extrapolated general principles and evidence from other procedures. Some recommendations include al-ternative approaches in situations in which panel member opinions were divided.
A major limitation of the available literature on antimicrobial prophy-laxis is the difficulty in establishing significant differences in efficacy between prophylactic antimicrobial agents and controls (including place-bo, no treatment, or other antimicro-bial agents) due to study design and low SSI rates for most procedures. A small sample size increases the likeli-hood of a Type II error; therefore, there may be no apparent difference between the antimicrobial agent and placebo when in fact the antimicro-bial has a beneficial effect.12 A valid
The following individuals are acknowledged for their significant contributions to this manuscript: Sandra I. Berros-Torres, M.D.; Rachel Bongiorno-Karcher, Pharm.D.; Colleen M. Culley, Pharm.D., BCPS; Susan R. Dombrowski, M.S., B.S.Pharm.; and Susan J. Skledar, B.S.Pharm., M.P.H., FASHP.
Financial support provided by Emory University, Johns Hopkins University, Northwestern University, Rush University, University of Colorado, University of Michigan, University of Oklahoma, Univer-sity of Nebraska, University of Virginia, University of Washington, and West Virginia University.
Dr. Bratzler is a consultant for Telligen; Dr. Dellinger has received honoraria for participation on advisory boards and consultation for Merck, Baxter, Ortho-McNeil, Targanta, Schering-Plough, WebEx, Astellas, Durata, Pfizer, Applied Medical, Rib-X, 3M, the American Hospital Association, Premier Inc., Oklahoma Foundation for Medi-cal Quality, and the Hospital Association of New York State; Dr. Perl serves on the advisory boards of Hospira and Pfizer and has received
a grant from Merck; Dr. Auwaerter serves on the advisory panel of Genentech; Dr. Fish serves on the advisory board and speakers bu-reau of Merck; and Dr. Sawyer serves as a consultant for Pfizer, Merck, Wyeth, 3M, and Ethicon and has received an R01 grant from the National Institute of General Medical Sciences and a T32 grant from the National Institute of Allergy and Infectious Diseases. Drs. Bolon, Napolitano, Olsen, Steinberg, Slain, and Weinstein have declared no potential conflicts of interest.
The bibliographic citation for this article is as follows: Bratzler DW, Dellinger EP, Olsen KM et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health-Syst Pharm. 2013; 70:195-283.
Copyright 2013, American Society of Health-System Pharma-cists, Inc. All rights reserved. 1079-2082/13/0201-0195$06.00.
DOI 10.2146/ajhp120568
ASHP RePoRt Antimicrobial prophylaxis
197Am J Health-Syst PharmVol 70 Feb 1, 2013
study is placebo controlled and ran-domized with a sufficient sample in each group to avoid a Type II error. Of note, prophylaxis is recommend-ed in some cases due to the severity of complications of postoperative in-fection (e.g., an infected device that is not easily removable) necessitating precautionary measures despite the lack of statistical support.
Summary of key updates. These guidelines reflect substantial changes from the guidelines published in 1999.1 Highlights of those changes are outlined here.
Preoperative-dose timing. The optimal time for administration of preoperative doses is within 60 min-utes before surgical incision. This is a more-specific time frame than the previously recommended time, which was at induction of anesthe-sia. Some agents, such as fluoro-quinolones and vancomycin, require administration over one to two hours; therefore, the administration of these agents should begin within 120 minutes before surgical incision.
Selection and dosing. Information is included regarding the approach to weight-based dosing in obese pa-tients and the need for repeat doses during prolonged procedures.13-18 Obesity has been linked to an in-creased risk for SSI. The pharma-cokinetics of drugs may be altered in obese patients, so dosage adjust-ments based on body weight may be warranted in these patients. For all patients, intraoperative redosing is needed to ensure adequate serum and tissue concentrations of the antimicrobial if the duration of the procedure exceeds two half-lives of the drug or there is excessive blood loss during the procedure (Table 1). Recommendations for selection of antimicrobial agents for specific surgical procedures and alternative agents (e.g., for patients with aller-gies to b-lactam antimicrobials) are provided in Table 2.
Duration of prophylaxis. New rec-ommendations for a shortened post-
Cont
inue
d on
nex
t pag
e
Reco
mm
ende
d D
ose
Ant
imic
robi
alA
dults
aPe
diat
rics
b
Hal
f-lif
e in
Adu
lts
With
Nor
mal
Ren
al
Func
tion,
hr1
9
Am
pic
illin
sul
bac
tam
Am
pic
illin
Azt
reon
amC
efaz
olin
Cef
urox
ime
Cef
otax
ime
Cef
oxiti
nC
efot
etan
Cef
tria
xone
Cip
roflo
xaci
nf
Clin
dam
ycin
Erta
pen
emFl
ucon
azol
eG
enta
mic
ing
Levo
floxa
cinf
Met
roni
dazo
le
Tab
le 1
. R
eco
mm
end
ed D
ose
s an
d R
edo
sin
g In
terv
als
for
Co
mm
on
ly U
sed
An
tim
icro
bia
ls fo
r Su
rgic
al P
rop
hyl
axis
Reco
mm
ende
d Re
dosi
ng
Inte
rval
(Fro
m In
itiat
ion
of
Preo
pera
tive
Dos
e), h
rc
3 g
(am
pic
illin
2 g
/sul
bac
tam
1 g
)2
g2
g2
g, 3
g fo
r pts
wei
ghin
g 1
20 k
g1.
5 g
1 gd 2 g
2 g
2 ge
400
mg
900
mg
1 g
400
mg
5 m
g/kg
bas
ed o
n do
sing
wei
ght
(sin
gle
dose
)50
0 m
g50
0 m
g
0.8
1.3
11.
91.
32.
41.
22.
21
20.
91.
70.
71.
12.
84.
65.
410
.93
72
43
5 30 2
3
68
68
2 2 4 4 4 3 2 6 NA
NA 6 NA
NA
NA
NA
NA
50 m
g/kg
of t
he a
mp
icill
in
com
pon
ent
50 m
g/kg
30 m
g/kg
30 m
g/kg
50 m
g/kg
50 m
g/kg
40 m
g/kg
40 m
g/kg
507
5 m
g/kg
10 m
g/kg
10 m
g/kg
15 m
g/kg
6 m
g/kg
2.5
mg/
kg b
ased
on
dosi
ng w
eigh
t
10 m
g/kg
15 m
g/kg
N
eona
tes
wei
ghin
g 9
mo
and 4
0 kg
: 10
0 m
g/kg
of t
he p
iper
acill
in
com
pon
ent
15 m
g/kg
20 m
g/kg
15 m
g/kg
15 m
g/kg
815
0.7
1.2
48
0.8
36
10
23
(3%
ab
sorb
ed u
nder
nor
mal
ga
stro
inte
stin
al c
ondi
tions
)
NA 2 NA
NA
NA
NA
a Adu
lt d
oses
are
ob
tain
ed fr
om th
e st
udie
s ci
ted
in e
ach
sect
ion.
Whe
n do
ses
diff
ered
bet
wee
n st
udie
s, e
xper
t op
inio
n us
ed th
e m
ost-
ofte
n re
com
men
ded
dose
.bTh
e m
axim
um p
edia
tric
dos
e sh
ould
not
exc
eed
the
usua
l adu
lt d
ose.
c For
ant
imic
rob
ials
with
a s
hort
hal
f-lif
e (e
.g.,
cefa
zolin
, cef
oxiti
n) u
sed
bef
ore
long
pro
cedu
res,
redo
sing
in th
e op
erat
ing
room
is re
com
men
ded
at a
n in
terv
al o
f ap
pro
xim
atel
y tw
o tim
es th
e ha
lf-lif
e of
the
agen
t in
pat
ient
s w
ith n
orm
al re
nal f
unct
ion.
Rec
omm
ende
d re
dosi
ng in
terv
als
mar
ked
as n
ot a
pp
licab
le (
NA
) are
bas
ed o
n ty
pic
al c
ase
leng
th; f
or u
nusu
ally
long
pro
cedu
res,
redo
sing
may
be
need
ed.
d Alt
houg
h FD
A-a
pp
rove
d p
acka
ge in
sert
lab
elin
g in
dica
tes
1 g,
14 e
xper
ts re
com
men
d 2
g fo
r ob
ese
pat
ient
s.e W
hen
used
as
a si
ngle
dos
e in
com
bin
atio
n w
ith m
etro
nida
zole
for c
olor
ecta
l pro
cedu
res.
f Whi
le fl
uoro
quin
olon
es h
ave
bee
n as
soci
ated
with
an
incr
ease
d ris
k of
tend
initi
s/te
ndon
rup
ture
in a
ll ag
es, u
se o
f the
se a
gent
s fo
r sin
gle-
dose
pro
phy
laxi
s is
gen
eral
ly s
afe.
g In
gene
ral,
gent
amic
in fo
r su
rgic
al a
ntib
iotic
pro
phy
laxi
s sh
ould
be
limite
d to
a s
ingl
e do
se g
iven
pre
oper
ativ
ely.
Dos
ing
is b
ased
on
the
pat
ient
s ac
tual
bod
y w
eigh
t. If
the
pat
ient
s ac
tual
wei
ght
is m
ore
than
20%
ab
ove
idea
l bod
y w
eigh
t (IB
W),
the
dosi
ng w
eigh
t (D
W) c
an b
e de
term
ined
as
follo
ws:
DW
= IB
W +
0.4
(act
ual w
eigh
t IB
W).
ASHP RePoRt Antimicrobial prophylaxis
199Am J Health-Syst PharmVol 70 Feb 1, 2013
Cont
inue
d on
nex
t pag
e
Type
of P
roce
dure
Reco
mm
ende
d A
gent
sa,b
Tab
le 2
. R
eco
mm
end
atio
ns
for
Surg
ical
An
tim
icro
bia
l Pro
ph
ylax
is
Stre
ngth
of
Evid
ence
c
Car
diac
C
oron
ary
arte
ry b
ypas
s
Car
diac
dev
ice
inse
rtio
n p
roce
dure
s (e
.g.,
pac
emak
er
imp
lant
atio
n)
Ve
ntric
ular
ass
ist d
evic
esTh
orac
ic
N
onca
rdia
c p
roce
dure
s, in
clud
ing
lob
ecto
my,
p
neum
onec
tom
y, lu
ng re
sect
ion,
and
thor
acot
omy
Vi
deo-
assi
sted
thor
acos
cop
ic s
urge
ryG
astr
oduo
dena
le
Pr
oced
ures
invo
lvin
g en
try
into
lum
en o
f gas
troi
ntes
tinal
tr
act (
bar
iatr
ic, p
ancr
eatic
oduo
dene
ctom
yf)
Pr
oced
ures
with
out e
ntry
into
gas
troi
ntes
tinal
trac
t
(a
ntire
flux,
hig
hly
sele
ctiv
e va
goto
my)
for h
igh-
risk
pat
ient
s Bi
liary
trac
t
Op
en p
roce
dure
La
par
osco
pic
pro
cedu
re
E
lect
ive,
low
-ris
kl
Ele
ctiv
e, h
igh-
riskl
Ap
pen
dect
omy
for u
ncom
plic
ated
ap
pen
dici
tis
Smal
l int
estin
e
Non
obst
ruct
ed
Cef
azol
in, c
efur
oxim
eC
efaz
olin
, cef
urox
ime
Cef
azol
in, c
efur
oxim
e
Cef
azol
in, a
mp
icill
ins
ulb
acta
m
Cef
azol
in, a
mp
icill
ins
ulb
acta
m
Cef
azol
in
Cef
azol
in
Cef
azol
in, c
efox
itin,
cef
otet
an, c
eftr
iaxo
ne,k
amp
icill
ins
ulb
acta
mh
Non
eC
efaz
olin
, cef
oxiti
n, c
efot
etan
, cef
tria
xone
,k
amp
icill
ins
ulb
acta
mh
Cef
oxiti
n, c
efot
etan
, cef
azol
in +
met
roni
dazo
le
Cef
azol
in
Clin
dam
ycin
,d va
ncom
ycin
d
Clin
dam
ycin
, van
com
ycin
Clin
dam
ycin
, van
com
ycin
Clin
dam
ycin
,d va
ncom
ycin
d
Clin
dam
ycin
,d va
ncom
ycin
d
Clin
dam
ycin
or v
anco
myc
in +
am
inog
lyco
side
g or a
ztre
onam
or
fluor
oqui
nolo
neh-
j
Clin
dam
ycin
or v
anco
myc
in +
am
inog
lyco
side
g or a
ztre
onam
or
fluor
oqui
nolo
neh-
j
Clin
dam
ycin
or v
anco
myc
in +
am
inog
lyco
side
g or a
ztre
onam
or
fluor
oqui
nolo
neh-
j
Met
roni
dazo
le +
am
inog
lyco
side
g or
fluor
oqui
nolo
neh-
j
Non
eC
linda
myc
in o
r van
com
ycin
+
amin
ogly
cosi
deg o
r azt
reon
am o
r flu
oroq
uino
lone
h-j
Met
roni
dazo
le +
am
inog
lyco
side
g or
fluor
oqui
nolo
neh-
j
Clin
dam
ycin
+ a
min
ogly
cosi
deg o
r az
treo
nam
or fl
uoro
quin
olon
eh-j
Met
roni
dazo
le +
am
inog
lyco
side
g or
fluor
oqui
nolo
neh-
j
Clin
dam
ycin
+ a
min
ogly
cosi
deg o
r az
treo
nam
or fl
uoro
quin
olon
eh-j
A A C A C A A A A A A C
Alte
rnat
ive
Age
nts
in P
ts W
ith
b-Lac
tam
Alle
rgy
ASHP RePoRt Antimicrobial prophylaxis
200 Am J Health-Syst PharmVol 70 Feb 1, 2013
Type
of P
roce
dure
Reco
mm
ende
d A
gent
sa,b
Tab
le 2
(con
tinue
d)
Stre
ngth
of
Evid
ence
c
O
bst
ruct
ed
Her
nia
rep
air (
hern
iop
last
y an
d he
rnio
rrha
phy
)C
olor
ecta
lm
Hea
d an
d ne
ck
Cle
an
Cle
an w
ith p
lace
men
t of p
rost
hesi
s (e
xclu
des
tym
pan
osto
my
tub
es)
C
lean
-con
tam
inat
ed c
ance
r sur
gery
O
ther
cle
an-c
onta
min
ated
pro
cedu
res
with
the
exce
ptio
n of
to
nsill
ecto
my
and
func
tiona
l end
osco
pic
sin
us p
roce
dure
sN
euro
surg
ery
El
ectiv
e cr
anio
tom
y an
d ce
reb
rosp
inal
flui
d-sh
untin
g
p
roce
dure
s
Imp
lant
atio
n of
intr
athe
cal p
ump
s C
esar
ean
deliv
ery
Hys
tere
ctom
y (v
agin
al o
r ab
dom
inal
)
Op
htha
lmic
Ort
hop
edic
Cle
an o
per
atio
ns in
volv
ing
hand
, kne
e, o
r foo
t and
not
in
volv
ing
imp
lant
atio
n of
fore
ign
mat
eria
ls
Spin
al p
roce
dure
s w
ith a
nd w
ithou
t ins
trum
enta
tion
Cef
azol
in +
met
roni
dazo
le, c
efox
itin,
cef
otet
an
Cef
azol
inC
efaz
olin
+ m
etro
nida
zole
, cef
oxiti
n, c
efot
etan
, am
pic
illin
sul
bac
tam
,h ce
ftria
xone
+
met
roni
dazo
le,n
erta
pen
em
Non
eC
efaz
olin
, cef
urox
ime
Cef
azol
in +
met
roni
dazo
le, c
efur
oxim
e +
m
etro
nida
zole
, am
pic
illin
sul
bac
tam
Cef
azol
in +
met
roni
dazo
le, c
efur
oxim
e +
m
etro
nida
zole
, am
pic
illin
sul
bac
tam
Cef
azol
in
Cef
azol
inC
efaz
olin
Cef
azol
in, c
efot
etan
, cef
oxiti
n, a
mp
icill
in
sulb
acta
mh
Top
ical
neo
myc
inp
olym
yxin
Bg
ram
icid
in o
r fo
urth
-gen
erat
ion
top
ical
fluo
roqu
inol
ones
(g
atifl
oxac
in o
r mox
iflox
acin
) giv
en a
s 1
drop
ev
ery
515
min
for 5
dos
eso
Add
ition
of c
efaz
olin
100
mg
by s
ubco
njun
ctiv
al
inje
ctio
n or
intr
acam
eral
cef
azol
in 1
2.5
mg
or c
efur
oxim
e 1
mg
at th
e en
d of
pro
cedu
re is
op
tiona
l
Non
e
Cef
azol
in
Met
roni
dazo
le +
am
inog
lyco
side
g or
fluor
oqui
nolo
neh-
j
Clin
dam
ycin
, van
com
ycin
Clin
dam
ycin
+ a
min
ogly
cosi
deg o
r az
treo
nam
or fl
uoro
quin
olon
eh-j ,
met
roni
dazo
le +
am
inog
lyco
side
g or
fluor
oqui
nolo
neh-
j
Non
eC
linda
myc
ind
Clin
dam
ycin
d
Clin
dam
ycin
d
Clin
dam
ycin
,d va
ncom
ycin
d
Clin
dam
ycin
,d va
ncom
ycin
d
Clin
dam
ycin
+ a
min
ogly
cosi
deg
Clin
dam
ycin
or v
anco
myc
in +
am
inog
lyco
side
g or a
ztre
onam
or
fluor
oqui
nolo
neh-
j
Met
roni
dazo
le +
am
inog
lyco
side
g or
fluor
oqui
nolo
neh-
j
Non
e
Non
e
Clin
dam
ycin
,d va
ncom
ycin
d
C A A B C A B A C A A B C A
Cont
inue
d on
nex
t pag
e
Alte
rnat
ive
Age
nts
in P
ts W
ith
b-Lac
tam
Alle
rgy
ASHP RePoRt Antimicrobial prophylaxis
201Am J Health-Syst PharmVol 70 Feb 1, 2013
Type
of P
roce
dure
Reco
mm
ende
d A
gent
sa,b
Tab
le 2
(con
tinue
d)
Stre
ngth
of
Evid
ence
c
Cont
inue
d on
nex
t pag
e
H
ip fr
actu
re re
pai
r
Imp
lant
atio
n of
inte
rnal
fixa
tion
devi
ces (
e.g.
, nai
ls, s
crew
s,
pla
tes,
wire
s)
Tota
l joi
nt re
pla
cem
ent
Uro
logi
c
Low
er tr
act i
nstr
umen
tatio
n w
ith ri
sk fa
ctor
s fo
r inf
ectio
n
(in
clud
es tr
ansr
ecta
l pro
stat
e b
iop
sy)
C
lean
with
out e
ntry
into
urin
ary
trac
t
Invo
lvin
g im
pla
nted
pro
sthe
sis
C
lean
with
ent
ry in
to u
rinar
y tr
act
C
lean
-con
tam
inat
ed
Vasc
ular
p
Hea
rt, l
ung,
hea
rtl
ung
tran
spla
ntat
ionq
H
eart
tran
spla
ntat
ionr
Lu
ng a
nd h
eart
lun
g tr
ansp
lant
atio
nr,s
Live
r tra
nsp
lant
atio
nq,t
Panc
reas
and
pan
crea
ski
dney
tran
spla
ntat
ionr
Cef
azol
inC
efaz
olin
Cef
azol
in
Fluo
roqu
inol
one,
h-j t
rimet
hop
rim
sulfa
met
hoxa
zole
, cef
azol
inC
efaz
olin
(the
add
ition
of a
sin
gle
dose
of a
n am
inog
lyco
side
may
be
reco
mm
ende
d fo
r p
lace
men
t of p
rost
hetic
mat
eria
l [e.
g., p
enile
p
rost
hesi
s])
Cef
azol
in a
min
ogly
cosi
de, c
efaz
olin
a
ztre
onam
, am
pic
illin
sul
bac
tam
Cef
azol
in (t
he a
dditi
on o
f a s
ingl
e do
se o
f an
amin
ogly
cosi
de m
ay b
e re
com
men
ded
for
pla
cem
ent o
f pro
sthe
tic m
ater
ial [
e.g.
, pen
ile
pro
sthe
sis]
)C
efaz
olin
+ m
etro
nida
zole
, cef
oxiti
n
Cef
azol
in
Cef
azol
in
Cef
azol
in
Pip
erac
illin
taz
obac
tam
, cef
otax
ime
+ a
mp
icill
in
Cef
azol
in, fl
ucon
azol
e (fo
r pat
ient
s at
hig
h ris
k of
fung
al in
fect
ion
[e.g
., th
ose
with
ent
eric
dr
aina
ge o
f the
pan
crea
s])
Cef
azol
in
Clin
dam
ycin
,d va
ncom
ycin
d
Clin
dam
ycin
,d va
ncom
ycin
d
Clin
dam
ycin
,d va
ncom
ycin
d
Am
inog
lyco
side
g with
or w
ithou
t cl
inda
myc
inC
linda
myc
in,d
vanc
omyc
ind
Clin
dam
ycin
a
min
ogly
cosi
de
or a
ztre
onam
, van
com
ycin
amin
ogly
cosi
de o
r azt
reon
amFl
uoro
quin
olon
e,h-
j am
inog
lyco
side
g w
ith o
r with
out c
linda
myc
in
Fluo
roqu
inol
one,
h-j a
min
ogly
cosi
deg +
m
etro
nida
zole
or c
linda
myc
inC
linda
myc
in,d
vanc
omyc
ind
Clin
dam
ycin
,d va
ncom
ycin
d
Clin
dam
ycin
,d va
ncom
ycin
d
Clin
dam
ycin
or v
anco
myc
in +
am
inog
lyco
side
g or
azt
reon
am o
r flu
oroq
uino
lone
h-j
Clin
dam
ycin
or v
anco
myc
in +
am
inog
lyco
side
g or a
ztre
onam
or
fluor
oqui
nolo
neh-
j
Clin
dam
ycin
or v
anco
myc
in +
am
inog
lyco
side
g or a
ztre
onam
or
fluor
oqui
nolo
neh-
j
A C A A A A A A A
A (b
ased
on
card
iac
pro
cedu
res)
A (b
ased
on
card
iac
pro
cedu
res)
B A A
Alte
rnat
ive
Age
nts
in P
ts W
ith
b-Lac
tam
Alle
rgy
ASHP RePoRt Antimicrobial prophylaxis
202 Am J Health-Syst PharmVol 70 Feb 1, 2013
Type
of P
roce
dure
Reco
mm
ende
d A
gent
sa,b
Tab
le 2
(con
tinue
d)
Stre
ngth
of
Evid
ence
c
Plas
tic s
urge
ry
Cle
an w
ith ri
sk fa
ctor
s or
cle
an-c
onta
min
ated
Cef
azol
in, a
mp
icill
ins
ulb
acta
mC
linda
myc
in,d
vanc
omyc
ind
C
a The
ant
imic
rob
ial a
gent
sho
uld
be
star
ted
with
in 6
0 m
inut
es b
efor
e su
rgic
al in
cisi
on (1
20 m
inut
es fo
r va
ncom
ycin
or
fluor
oqui
nolo
nes)
. Whi
le s
ingl
e-do
se p
rop
hyla
xis
is u
sual
ly s
uffici
ent,
the
dura
tion
of p
rop
hyla
xis
for
all p
roce
dure
s sh
ould
be
less
tha
n 24
hou
rs. I
f an
agen
t w
ith a
sho
rt h
alf-
life
is u
sed
(e.g
., ce
fazo
lin, c
efox
itin)
, it
shou
ld b
e re
adm
inis
tere
d if
the
pro
cedu
re d
urat
ion
exce
eds
the
reco
mm
ende
d re
dosi
ng in
terv
al (f
rom
the
tim
e of
initi
atio
n of
the
pre
oper
ativ
e do
se [s
ee T
able
1])
. Rea
dmin
istr
atio
n m
ay a
lso
be
war
rant
ed if
pro
long
ed o
r ex
cess
ive
ble
edin
g oc
curs
or
if th
ere
are
othe
r fa
ctor
s th
at m
ay s
hort
en t
he h
alf-
life
of t
he p
rop
hyla
ctic
age
nt (e
.g.,
exte
nsiv
e b
urns
). Re
adm
inis
trat
ion
may
not
be
war
rant
ed in
pat
ient
s in
who
m th
e ha
lf-lif
e of
the
agen
t may
be
pro
long
ed (e
.g.,
pat
ient
s w
ith re
nal i
nsuffi
cien
cy o
r fai
lure
).bFo
r pat
ient
s kn
own
to b
e co
loni
zed
with
met
hici
llin-
resi
stan
t Sta
phyl
ococ
cus a
ureu
s, it
is re
ason
able
to a
dd a
sin
gle
pre
oper
ativ
e do
se o
f van
com
ycin
to th
e re
com
men
ded
agen
t(s)
. cSt
reng
th o
f evi
denc
e th
at s
upp
orts
the
use
or
nonu
se o
f pro
phy
laxi
s is
cla
ssifi
ed a
s A
(lev
els
IIII
), B
(leve
ls IV
VI),
or
C (l
evel
VII)
. Lev
el I
evid
ence
is fr
om la
rge,
wel
l-con
duct
ed, r
ando
miz
ed c
ontr
olle
d cl
inic
al t
rials
. Lev
el II
ev
iden
ce is
from
sm
all,
wel
l-con
duct
ed, r
ando
miz
ed c
ontr
olle
d cl
inic
al t
rials
. Lev
el II
I evi
denc
e is
from
wel
l-con
duct
ed c
ohor
t st
udie
s. L
evel
IV e
vide
nce
is fr
om w
ell-c
ondu
cted
cas
eco
ntro
l stu
dies
. Lev
el V
evi
denc
e is
from
un
cont
rolle
d st
udie
s th
at w
ere
not w
ell c
ondu
cted
. Lev
el V
I evi
denc
e is
con
flict
ing
evid
ence
that
tend
s to
favo
r the
reco
mm
enda
tion.
Lev
el V
II ev
iden
ce is
exp
ert o
pin
ion.
d For
pro
cedu
res
in w
hich
pat
hoge
ns o
ther
tha
n st
aphy
loco
cci a
nd s
trep
toco
cci a
re li
kely
, an
addi
tiona
l age
nt w
ith a
ctiv
ity
agai
nst
thos
e p
atho
gens
cou
ld b
e co
nsid
ered
. For
exa
mp
le, i
f the
re a
re s
urve
illan
ce d
ata
show
ing
that
gra
m-n
egat
ive
orga
nism
s ar
e a
caus
e of
sur
gica
l-site
infe
ctio
ns (S
SIs)
for t
he p
roce
dure
, pra
ctiti
oner
s m
ay c
onsi
der c
omb
inin
g cl
inda
myc
in o
r van
com
ycin
with
ano
ther
age
nt (c
efaz
olin
if th
e p
atie
nt is
not
b-la
ctam
alle
rgic
; az
treo
nam
, gen
tam
icin
, or s
ingl
e-do
se fl
uoro
quin
olon
e if
the
pat
ient
is b-
lact
am a
llerg
ic).
e Pro
phy
laxi
s sh
ould
be
cons
ider
ed fo
r p
atie
nts
at h
ighe
st r
isk
for
pos
top
erat
ive
gast
rodu
oden
al in
fect
ions
, suc
h as
tho
se w
ith in
crea
sed
gast
ric p
H (e
.g.,
thos
e re
ceiv
ing
hist
amin
e H
2-re
cep
tor
anta
goni
sts
or p
roto
n-p
ump
in
hib
itors
), ga
stro
duod
enal
per
fora
tion,
dec
reas
ed g
astr
ic m
otili
ty, g
astr
ic o
utle
t ob
stru
ctio
n, g
astr
ic b
leed
ing,
mor
bid
ob
esit
y, o
r can
cer.
Ant
imic
rob
ial p
rop
hyla
xis
may
not
be
need
ed w
hen
the
lum
en o
f the
inte
stin
al tr
act i
s no
t ent
ered
. f C
onsi
der a
dditi
onal
ant
imic
rob
ial c
over
age
with
infe
cted
bili
ary
trac
t. Se
e th
e b
iliar
y tr
act p
roce
dure
s se
ctio
n of
this
art
icle
.g G
enta
mic
in o
r tob
ram
ycin
.h D
ue to
incr
easi
ng re
sist
ance
of E
sche
richi
a co
li to
fluo
roqu
inol
ones
and
am
pic
illin
sul
bac
tam
, loc
al p
opul
atio
n su
scep
tibili
ty p
rofil
es s
houl
d b
e re
view
ed p
rior t
o us
e.i C
ipro
floxa
cin
or le
voflo
xaci
n.j F
luor
oqui
nolo
nes
are
asso
ciat
ed w
ith a
n in
crea
sed
risk
of t
endo
nitis
and
ten
don
rup
ture
in a
ll ag
es. H
owev
er, t
his
risk
wou
ld b
e ex
pec
ted
to b
e qu
ite s
mal
l with
sin
gle-
dose
ant
ibio
tic p
rop
hyla
xis.
Alt
houg
h th
e us
e of
flu
oroq
uino
lone
s m
ay b
e ne
cess
ary
for s
urgi
cal a
ntib
iotic
pro
phy
laxi
s in
som
e ch
ildre
n, th
ey a
re n
ot d
rugs
of fi
rst c
hoic
e in
the
ped
iatr
ic p
opul
atio
n du
e to
an
incr
ease
d in
cide
nce
of a
dver
se e
vent
s as
com
par
ed w
ith c
ontr
ols
in s
ome
clin
ical
tria
ls.
k Cef
tria
xone
use
sho
uld
be
limite
d to
pat
ient
s re
quiri
ng a
ntim
icro
bia
l tre
atm
ent f
or a
cute
cho
lecy
stiti
s or
acu
te b
iliar
y tr
act i
nfec
tions
whi
ch m
ay n
ot b
e de
term
ined
prio
r to
inci
sion
, not
pat
ient
s un
derg
oing
cho
lecy
stec
tom
y fo
r non
infe
cted
bili
ary
cond
ition
s, in
clud
ing
bili
ary
colic
or d
yski
nesi
a w
ithou
t inf
ectio
n. lFa
ctor
s th
at i
ndic
ate
a hi
gh r
isk
of i
nfec
tious
com
plic
atio
ns i
n la
par
osco
pic
cho
lecy
stec
tom
y in
clud
e em
erge
ncy
pro
cedu
res,
dia
bet
es, l
ong
pro
cedu
re d
urat
ion,
int
raop
erat
ive
gallb
ladd
er r
uptu
re, a
ge o
f >
70 y
ears
, co
nver
sion
fro
m la
par
osco
pic
to
open
cho
lecy
stec
tom
y, A
mer
ican
Soc
iety
of
Ane
sthe
siol
ogis
ts c
lass
ifica
tion
of 3
or
grea
ter,
epis
ode
of c
olic
with
in 3
0 da
ys b
efor
e th
e p
roce
dure
, rei
nter
vent
ion
in le
ss t
han
one
mon
th f
or
noni
nfec
tious
com
plic
atio
n, a
cute
cho
lecy
stiti
s, b
ile s
pill
age,
jaun
dice
, pre
gnan
cy, n
onfu
nctio
ning
gal
lbla
dder
, im
mun
osup
pre
ssio
n, a
nd in
sert
ion
of p
rost
hetic
dev
ice.
Bec
ause
a n
umb
er o
f the
se ri
sk fa
ctor
s ar
e no
t pos
sib
le to
de
term
ine
bef
ore
surg
ical
inte
rven
tion,
it m
ay b
e re
ason
able
to g
ive
a si
ngle
dos
e of
ant
imic
rob
ial p
rop
hyla
xis
to a
ll p
atie
nts
unde
rgoi
ng la
par
osco
pic
cho
lecy
stec
tom
y.m
For m
ost p
atie
nts,
a m
echa
nica
l bow
el p
rep
arat
ion
com
bin
ed w
ith o
ral n
eom
ycin
sul
fate
plu
s or
al e
ryth
rom
ycin
bas
e or
with
ora
l neo
myc
in s
ulfa
te p
lus
oral
met
roni
dazo
le s
houl
d b
e gi
ven
in a
dditi
on to
i.v.
pro
phy
laxi
s.n W
here
ther
e is
incr
easi
ng re
sist
ance
to fi
rst-
and
sec
ond-
gene
ratio
n ce
phal
ospo
rins
amon
g gr
am-n
egat
ive
isol
ates
from
SSI
s, a
sing
le d
ose
of c
eftr
iaxo
ne p
lus
met
roni
dazo
le m
ay b
e pr
efer
red
over
the
rout
ine
use
of c
arba
pene
ms.
o The
nec
essi
ty o
f con
tinui
ng to
pic
al a
ntim
icro
bia
ls p
osto
per
ativ
ely
has
not b
een
esta
blis
hed.
pPr
ophy
laxi
s is
not
rout
inel
y in
dica
ted
for b
rach
ioce
pha
lic p
roce
dure
s. A
ltho
ugh
ther
e ar
e no
dat
a in
sup
por
t, p
atie
nts
unde
rgoi
ng b
rach
ioce
pha
lic p
roce
dure
s in
volv
ing
vasc
ular
pro
sthe
ses
or p
atch
imp
lant
atio
n (e
.g.,
caro
tid
enda
rter
ecto
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pediatric-specific prophylaxis data are sparse, available data have been evaluated and are presented in some of the procedure-specific sections of these guidelines. Selection of antimicrobial prophylactic agents mirrors that in adult guidelines, with the agents of choice being first- and second-generation cephalosporins, reserving the use of vancomycin for patients with documented b-lactam allergies.19,20 While the use of a pen-icillin with a b-lactamase inhibitor in combination with cefazolin or vancomycin and gentamicin has also been studied in pediatric patients, the number of patients included in these evaluations remains small.20-23 As with adults, there is little evidence supporting the use of vancomycin, alone or in combination with other antimicrobials, for routine perioper-ative antimicrobial prophylaxis in in-stitutions that have a high prevalence of methicillin-resistant Staphylococ-cus aureus (MRSA). Vancomycin may be considered in children known to be colonized with MRSA and, in one retrospective historical cohort study, was shown to decrease MRSA infections.21 Mupirocin use has been studied in and is efficacious in chil-dren colonized with MRSA, but there are limited data supporting its use perioperatively.24-30 However, there is little reason to think that the impact and effect would be any different in children, so its use may be justified. Additional studies in this setting are needed to establish firm guidelines.
Unless noted in specific sections, all recommendations for adults are the same for pediatric patients, except for dosing. In most cases, the data in pediatric patients are limited and have been extrapolated from adult data; therefore, nearly all pediatric recommendations are based on expert opinion. In some sections, pediatric efficacy data do not exist and thus are not addressed in these guidelines. Fluoroquino-lones should not be routinely used for surgical prophylaxis in pediatric
patients because of the potential for toxicity in this population. The same principle of preoperative dosing within 60 minutes before incision has been applied to pediatric patients.20-23 Additional intraoperative dosing may be needed if the duration of the procedure exceeds two half-lives of the antimicrobial agent or there is excessive blood loss during the procedure.19,21 As with adult patients, single-dose prophylaxis is usually sufficient. If antimicrobial prophy-laxis is continued postoperatively, the duration should be less than 24 hours, regardless of the presence of intravascular catheters or indwelling drains.19,22,23,31,32 There are sufficient pharmacokinetic studies of most agents to recommend pediatric dos-ages that provide adequate systemic exposure and, presumably, efficacy comparable to that demonstrated in adults. Therefore, the pediatric dos-ages provided in these guidelines are based largely on pharmacokinetic data and the extrapolation of adult efficacy data to pediatric patients. Because few clinical trials have been conducted in pediatric surgical pa-tients, strength of evidence criteria have not been applied to these rec-ommendations. With few exceptions (e.g., aminoglycoside dosages), pe-diatric dosages should not exceed the maximum adult recommended dos-ages. Generally, if dosages are calculat-ed on a milligram-per-kilogram basis for children weighing more than 40 kg, the calculated dosage will exceed the maximum recommended dosage for adults; adult dosages should there-fore be used.
Patients with prosthetic implants. For patients with existing prosthetic implants who undergo an invasive procedure, there is no evidence that antimicrobial prophylaxis prevents infections of the implant. However, updated guidelines from the Ameri-can Heart Association (AHA) suggest that prophylaxis may be justified in a limited subset of patients for the prevention of endocarditis.11
Common principles and procedure-specific guidelines. The Common Principles section has been devel-oped to provide information com-mon to many surgical procedures. These principles are general recom-mendations based on currently avail-able data at the time of publication that may change over time; therefore, these principles need to be applied with careful attention to each clinical situation. Detailed information per-tinent to specific surgical procedures is included in the procedure-specific sections of these guidelines.
In addition to patient- and procedure-specific considerations, several institution-specific factors must be considered by practitioners before instituting these guidelines. The availability of antimicrobial agents at the institution may be re-stricted by local antimicrobial-use policy or lack of approval for use by regulatory authorities. Medications that are no longer available or not ap-proved for use by the Food and Drug Administration (FDA) are so noted. Local resistance patterns should also be considered in selecting antimicro-bial agents and are discussed in the colonization and resistance patterns section of the Common Principles section.
Requirements for effective surgical prophylaxis
Appendix A lists the wound clas-sification criteria currently used by the CDC National Healthcare Safety Network (NHSN) and Healthcare Infection Control Practices Advisory Committee (HICPAC).33-35
Criteria for defining an SSI have also been established by NHSN (Ap-pendix B).8,36 These definitions as-sist in evaluating the importance of providing antimicrobial prophylaxis and the potential consequences of infection, including the need for treatment. Some criteria vary slightly by procedure.
Although antimicrobial prophy-laxis plays an important role in reduc-
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ing the rate of SSIs, other factors such as attention to basic infection-control strategies,37 the surgeons experience and technique, the duration of the procedure, hospital and operating-room environments, instrument-sterilization issues, preoperative prep-aration (e.g., surgical scrub, skin antisepsis, appropriate hair removal), perioperative management (tempera-ture and glycemic control), and the underlying medical condition of the patient may have a strong impact on SSI rates.5,8 These guidelines recognize the importance of these other factors but do not include a discussion of or any recommendations regarding these issues beyond the optimal use of prophylactic antimicrobial agents. Patient-related factors associated with an increased risk of SSI include extremes of age, nutritional status, obesity, diabetes mellitus, tobacco use, coexistent remote body-site infec-tions, altered immune response, cor-ticosteroid therapy, recent surgical procedure, length of preoperative hospitalization, and colonization with microorganisms. Antimicro-bial prophylaxis may be justified for any procedure if the patient has an underlying medical condition as-sociated with a high risk of SSI or if the patient is immunocompromised (e.g., malnourished, neutrope-nic, receiving immunosuppressive agents).
Antimicrobial prophylaxis may be beneficial in surgical procedures associated with a high rate of infec-tion (i.e., clean-contaminated or contaminated procedures) and in certain clean procedures where there are severe consequences of infection (e.g., prosthetic implants), even if in-fection is unlikely. While prophylac-tic antimicrobials are not indicated for some clean surgical procedures,8 available data suggest that the rela-tive risk reduction of SSI from the use of antimicrobial prophylaxis is the same in clean and in higher-risk procedures.38 The decision to use prophylaxis depends on the cost of
treating and the morbidity associ-ated with infection compared with the cost and morbidity associated with using prophylaxis. Antimicrobial prophylaxis is justified for most clean-contaminated procedures. The use of antimicrobial agents for dirty pro-cedures (Appendix A) or established infections is classified as treatment of presumed infection, not prophylaxis. See the procedure-specific sections for detailed recommendations.
Quality-improvement efforts. National, state, local, and institu-tional groups have developed and implemented collaborative efforts to improve the appropriateness of sur-gical antimicrobial prophylaxis. Vari-ous process and outcomes measures are employed, and results are dis-seminated. Institutional epidemiol-ogy and infection-control programs, state-based quality-improvement campaigns (e.g., the Michigan Sur-gical Quality Collaborative, the Washington State Surgical Clinical Outcomes Assessment Program39,40), CDC, NHSN, the National Surgical Quality Improvement Program, the Joint Commission, and the National Quality Forum have been instru-mental in developing programs to prevent SSIs.
Over the past decade or more, several organizations, payers, and government agencies, including the Centers for Medicare and Medicaid Services (CMS), have established national quality-improvement initia-tives to further improve the safety and outcomes of health care, includ-ing surgery.41-47 One area of focus in these initiatives for patients un-dergoing surgical procedures is the prevention of SSIs. The performance measures used, data collection and reporting requirements, and finan-cial implications vary among the ini-tiatives. The Surgical Care Improve-ment Project (SCIP) began in 2002 as the Surgical Infection Prevention (SIP) project, focusing on the tim-ing, selection, and duration of pro-phylactic antimicrobial agents.41,42
The SIP project was expanded to SCIP to include additional process measures surrounding patient safety and care during surgical procedures, including glucose control, venous thromboembolism prophylaxis, hair removal, and temperature control. Similar measures have been adopted by the Joint Commission.43 The Phy-sicians Quality Reporting System was established in 2006 to provide finan-cial incentives to physicians meeting performance standards for quality measures, including surgery-related measures similar to those reported for SCIP and the Joint Commis-sion.44 Data are required to be col-lected by institutions and reported to payers.42,44,46 Data for CMS and the Physicians Quality Reporting System measures are displayed on public websites to allow consumers to com-pare performance among hospitals. Institutional data collection and reporting are required, with financial incentives tied to performance to varying degrees, including payment for reporting, payment increases for meeting or exceeding minimum levels of performance, payment re-duction for poor performance, and lack of payment for the development of surgical complications, such as mediastinitis.
Quality-improvement initiatives and mandated performance report-ing are subject to change, so readers of these guidelines are advised to consult their local or institutional quality-improvement departments for new developments in require-ments for measures and data report-ing that apply to their practice.
Cost containment. Few pharma-coeconomic studies have addresed surgical antimicrobial prophylaxis; therefore, a cost-minimization ap-proach was employed in developing these guidelines. The antimicrobial agent recommendations are based primarily on efficacy and safety. In-dividual institutions must consider their acquisition costs when imple-menting these guidelines.
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Additional cost savings may be realized through collaborative man-agement by pharmacists and sur-geons to select the most cost-effective agent and minimize or eliminate postoperative dosing.48-50 The use of standardized antimicrobial order sets, automatic stop-order programs, and educational initiatives has been shown to facilitate the adoption of guidelines for surgical antimicrobial prophylaxis.51-58
Common principlesIdeally, an antimicrobial agent
for surgical prophylaxis should (1) prevent SSI, (2) prevent SSI-related morbidity and mortality, (3) reduce the duration and cost of health care (when the costs associated with the management of SSI are considered, the cost-effectiveness of prophylaxis becomes evident),51,52 (4) produce no adverse effects, and (5) have no adverse consequences for the mi-crobial flora of the patient or the hospital.53 To achieve these goals, an antimicrobial agent should be (1) ac-tive against the pathogens most likely to contaminate the surgical site, (2) given in an appropriate dosage and at a time that ensures adequate serum and tissue concentrations during the period of potential contamination, (3) safe, and (4) administered for the shortest effective period to minimize adverse effects, the development of resistance, and costs.8,59,60
The selection of an appropriate antimicrobial agent for a specific patient should take into account the characteristics of the ideal agent, the comparative efficacy of the antimicro-bial agent for the procedure, the safety profile, and the patients medication allergies. A full discussion of the safety profile, including adverse events, drug interactions, contraindications, and warnings, for each antimicrobial agent is beyond the scope of these guidelines. Readers of these guidelines should review the FDA-approved prescribing information and published data for specific antimicrobial agents before
use. For most procedures, cefazolin is the drug of choice for prophylaxis because it is the most widely studied antimicrobial agent, with proven ef-ficacy. It has a desirable duration of action, spectrum of activity against organisms commonly encountered in surgery, reasonable safety, and low cost. There is little evidence to suggest that broad-spectrum antimicrobial agents (i.e., agents with broad in vitro antibacterial activity) result in lower rates of postoperative SSI compared with older antimicrobial agents with a narrower spectrum of activity. How-ever, comparative studies are limited by small sample sizes, resulting in dif-ficulty detecting a significant differ-ence between antimicrobial agents; therefore, antimicrobial selection is based on cost, safety profile, ease of ad-ministration, pharmacokinetic profile, and bactericidal activity.
Common surgical pathogensThe agent chosen should have
activity against the most common surgical-site pathogens. The pre-dominant organisms causing SSIs after clean procedures are skin flora, includ-ing S. aureus and coagulase-negative staphylococci (e.g., Staphylococcus epidermidis).61 In clean-contaminated procedures, including abdominal pro-cedures and heart, kidney, and liver transplantations, the predominant organisms include gram-negative rods and enterococci in addition to skin flora. Additional details on common organisms can be found in procedure-specific sections of these guidelines.
Recommendations for the selec-tion of prophylactic antimicrobials for various surgical procedures are provided in Table 2. Adult and pe-diatric dosages are included in Table 1. Agents that are FDA-approved for use in surgical antimicrobial prophy-laxis include cefazolin, cefuroxime, cefoxitin, cefotetan, ertapenem, and vancomycin.62-67
Trends in microbiology. The causative pathogens associated with SSIs in U.S. hospitals have changed
over the past two decades. Analysis of National Nosocomial Infections Sur-veillance (NNIS) System data found that the percentage of SSIs caused by gram-negative bacilli decreased from 56.5% in 1986 to 33.8% in 2003.68 S. aureus was the most common pathogen, causing 22.5% of SSIs during this time period. NHSN data from 2006 to 2007 revealed that the proportion of SSIs caused by S. au-reus increased to 30%, with MRSA comprising 49.2% of these isolates.61 In a study of patients readmitted to U.S. hospitals between 2003 and 2007 with a culture-confirmed SSI, the proportion of infections caused by MRSA increased significantly from 16.1% to 20.6% (p < 0.0001).69
MRSA infections were associated with higher mortality rates, longer hospital stays, and higher hospital costs compared with other infections.
Spectrum of activity. Antimi-crobial agents with the narrowest spectrum of activity required for efficacy in preventing infection are recommended in these guidelines. Alternative antimicrobial agents with documented efficacy are also listed herein. Individual health sys-tems must consider local resistance patterns of organisms and overall SSI rates at their site when adopting these recommendations. Resistance patterns from organisms causing SSIsin some cases procedure-specific resistance patternsshould take precedence over hospitalwide antibiograms.
Vancomycin. In 1999, HICPAC, an advisory committee to CDC and the Secretary of the Department of Health and Human Services, col-laborated with other major organiza-tions to develop recommendations for preventing and controlling van-comycin resistance.70 The recom-mendations are echoed by these and other guidelines.6,7,41,71 Routine use of vancomycin prophylaxis is not recommended for any procedure.8 Vancomycin may be included in the regimen of choice when a cluster of
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MRSA cases (e.g., mediastinitis after cardiac procedures) or methicillin-resistant coagulase-negative staphy-lococci SSIs have been detected at an institution. Vancomycin prophylaxis should be considered for patients with known MRSA colonization or at high risk for MRSA colonization in the absence of surveillance data (e.g., patients with recent hospitalization, nursing-home residents, hemodi-alysis patients).5,41,72 In institutions with SSIs attributable to community- associated MRSA, antimicrobial agents with known in vitro activity against this pathogen may be consid-ered as an alternative to vancomycin.
Each institution is encouraged to develop guidelines for the proper use of vancomycin. Although van-comycin is commonly used when the risk for MRSA is high, data sug-gest that vancomycin is less effective than cefazolin for preventing SSIs caused by methicillin-susceptible S. aureus (MSSA).73,74 For this reason, vancomycin is used in combination with cefazolin at some institutions with both MSSA and MRSA SSIs. For procedures in which pathogens other than staphylococci and strep-tococci are likely, an additional agent with activity against those pathogens should be considered. For example, if there are surveillance data showing that gram-negative organisms are a cause of SSIs for the procedure, prac-titioners may consider combining vancomycin with another agent (cef-azolin if the patient does not have a b-lactam allergy; an aminoglycoside [gentamicin or tobramycin], aztreo-nam, or single-dose fluoroquinolone if the patient has a b-lactam allergy). The use of vancomycin for MRSA prophylaxis does not supplant the need for routine surgical prophylaxis appropriate for the type of proce-dure. When vancomycin is used, it can almost always be used as a single dose due to its long half-life.
Colonization and resistance. A national survey determined that S. aureus nasal colonization in the
general population decreased from 32.4% in 200102 to 28.6% in 200304 (p < 0.01), whereas the prevalence of colonization with MRSA increased from 0.8% to 1.5% (p < 0.05) during the same time periods.75 Coloniza-tion with MRSA was independently associated with health care exposure among men, having been born in the United States, age of >60 years, diabetes, and poverty among women. Similarly, children are colonized with S. aureus and MRSA, but coloniza-tion varies by age. Children under 5 years of age have the highest rates, mirroring rates seen in patients over age 60 years.76 The rates drop in children between 5 and 14 years of age and gradually increase to rates seen in the adult population. Lo et al.77 reported that in a large cohort of children, 28.1% were colonized with S. aureus between 2004 and 2006. Between 2007 and 2009, 23.3% of children were colonized with S. au-reus, but the proportion of children colonized with MRSA had increased from 8.1% in 2004 to 15.1% in 2009.
Surgical antimicrobial prophylaxis can alter individual and institutional bacterial flora, leading to changes in colonization rates and increased bacterial resistance.78-84 Surgical pro-phylaxis can also predispose patients to Clostridium difficile-associated colitis.81 Risk factors for development of C. difficile-associated colitis include longer duration of prophylaxis or therapy and use of multiple antimicro-bial agents.85 Limiting the duration of antimicrobial prophylaxis to a single preoperative dose can reduce the risk of C. difficile disease.
The question of what antimicro-bial surgical prophylaxis to use for patients known to be colonized or recently infected with multidrug-resistant pathogens cannot be an-swered easily or in a manner that can be applied uniformly to all patient scenarios. Whether prophy-laxis should be expanded to provide coverage for these pathogens de-pends on many factors, including the
pathogen, its antimicrobial suscepti-bility profile, the host, the procedure to be performed, and the proximity of the likely reservoir of the pathogen to the incision and operative sites. While there is no evidence on the management of surgical antimicro-bial prophylaxis in a patient with past infection or colonization with a resistant gram-negative pathogen, it is logical to provide prophylaxis with an agent active against MRSA for any patient known to be colonized with this gram-positive pathogen who will have a skin incision; specific prophy-laxis for a resistant gram-negative pathogen in a patient with past in-fection or colonization with such a pathogen may not be necessary for a purely cutaneous procedure. Similarly, a patient colonized with vancomycin-resistant enterococci (VRE) should receive prophylaxis ef-fective against VRE when undergoing liver transplantation but probably not when undergoing an umbilical hernia repair without mesh place-ment. Thus, patients must be treated on a case-by-case basis, taking into account multiple considerations.
Patients receiving therapeutic antimicrobials for a remote infection before surgery should also be given antimicrobial prophylaxis before surgery to ensure adequate serum and tissue levels of antimicrobials with activity against likely pathogens for the duration of the operation. If the agents used therapeutically are appropriate for surgical prophylaxis, administering an extra dose within 60 minutes before surgical incision is sufficient. Otherwise, the antimi-crobial prophylaxis recommended for the planned procedure should be used. For patients with indwelling tubes or drains, consideration may be given to using prophylactic agents active against pathogens found in these devices before the procedure, even though therapeutic treatment for pathogens in drains is not in-dicated at other times. For patients with chronic renal failure receiving
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vancomycin, a preoperative dose of cefazolin should be considered in-stead of an extra dose of vancomycin, particularly if the probable patho-gens associated with the procedure are gram-negative. In most circum-stances, elective surgery should be postponed when the patient has an infection at a remote site.
Allergy to b-lactam antimicrobi-als. Allergy to b-lactam antimicro-bials may be a consideration in the selection of surgical prophylaxis. The b-lactam antimicrobials, including cephalosporins, are the mainstay of surgical antimicrobial prophylaxis and are also the most commonly im-plicated drugs when allergic reac-tions occur. Because the predominant organisms in SSIs after clean proce-dures are gram-positive, the inclusion of vancomycin may be appropriate for a patient with a life-threatening allergy to b-lactam antimicrobials.
Although true Type 1 (immuno-globulin E [IgE]-mediated) cross-allergic reactions between penicillins, cephalosporins, and carbapenems are uncommon, cephalosporins and carbapenems should not be used for surgical prophylaxis in patients with documented or presumed IgE- mediated penicillin allergy. Confu-sion about the definition of true allergy among patients and practi-tioners leads to recommendations for alternative antimicrobial therapy with the potential for a lack of ef-ficacy, increased costs, and adverse events.86,87 Type 1 anaphylactic reac-tions to antimicrobials usually occur 3060 minutes after administration. In patients receiving penicillins, this reaction is a life-threatening emer-gency that precludes subsequent use of penicillins.88 Cephalosporins and carbapenems can safely be used in patients with an allergic reaction to penicillins that is not an IgE-mediated reaction (e.g., anaphylaxis, urticaria, bronchospasm) or exfo-liative dermatitis (Stevens-Johnson syndrome, toxic epidermal necroly-sis), a life-threatening hypersensitiv-
ity reaction that can be caused by b-lactam antimicrobials and other medications.88,89 Patients should be carefully questioned about their history of antimicrobial allergies to determine whether a true allergy exists before selection of agents for prophylaxis. Patients with allergies to cephalosporins, penicillins, or both have been excluded from many clini-cal trials. Alternatives to b-lactam antimicrobials are provided in Table 2 based mainly on the antimicrobial activity profiles against predominant procedure-specific organisms and available clinical data.
Drug administrationThe preferred route of admin-
istration varies with the type of procedure, but for a majority of pro-cedures, i.v. administration is ideal because it produces rapid, reliable, and predictable serum and tissue concentrations.
Timing of initial dose. Successful prophylaxis requires the delivery of the antimicrobial to the operative site before contamination occurs. Thus, the antimicrobial agent should be administered at such a time to pro-vide serum and tissue concentrations exceeding the minimum inhibitory concentration (MIC) for the prob-able organisms associated with the procedure, at the time of incision, and for the duration of the procedure.41,90 In 1985, DiPiro et al.91 demonstrated that higher serum and tissue cepha-losporin concentrations at the time of surgical incision and at the end of the procedure were achieved when the drugs were given intravenously at the time of anesthesia induction compared with administration in the operating room. The average interval between antimicrobial administra-tion and incision was 1722 minutes91 (Dellinger EP, personal communica-tion, 2011 May).
A prospective evaluation of 1708 surgical patients receiving antimicro-bial prophylaxis found that preop-erative administration of antimicro-
bials within 2 hours before surgical incision decreased the risk of SSI to 0.59%, compared with 3.8% for early administration (224 hours before surgical incision) and 3.3% for any postoperative administration (any time after incision).92 In a study of 2048 patients undergoing coronary bypass graft or valve replacement surgery receiving vancomycin pro-phylaxis, the rate of SSI was lowest in those patients in whom an infusion was started 1660 minutes before surgical incision.93 This time interval (1660 minutes before incision) was compared with four others, and the rates of SSIs were significantly lower when compared with infusions given 015 minutes before surgical inci-sion (p < 0.01) and 121180 minutes before incision (p = 0.037). The risk of infection was higher in patients receiving infusions 61120 minutes before incision (odds ratio [OR], 2.3; 95% confidence interval [CI], 0.985.61) and for patients whose infusions were started more than 180 minutes before surgical incision (OR, 2.1; 95% CI, 0.825.62).93
In a large, prospective, multi-center study from the Trial to Reduce Antimicrobial Prophylaxis Errors (TRAPE) study group, the timing, duration, and intraoperative redosing of antimicrobial prophylaxis and risk of SSI were evaluated in 4472 patients undergoing cardiac surgery, hyster-ectomy, or hip or knee arthroplasty.94 The majority of patients (90%) re-ceived antimicrobial prophylaxis per the SCIP guidelines.41 Patients were assigned to one of four groups for analysis. Group 1 (n = 1844) received a cephalosporin (or other antimicro-bial with a short infusion time) ad-ministered within 30 minutes before incision or vancomycin or a fluoro-quinolone within one hour before incision. Group 2 (n = 1796) received a cephalosporin 3160 minutes be-fore incision or vancomycin 61120 minutes before incision. Group 3 (n = 644) was given antimicrobials earlier than recommended, and group
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4 (n = 188) received their initial an-timicrobial doses after incision. The infection risk was lowest in group 1 (2.1%), followed by group 2 (2.4%) and group 3 (2.8%). The risk of infec-tion was highest in group 4 (5.3%, p = 0.02 compared with group 1). When cephalosporins and other an-timicrobials with short infusion times were analyzed separately (n = 3656), the infection rate with antimicrobi-als administered within 30 minutes before incision was 1.6% compared with 2.4% when antimicrobials were administered 3160 minutes before incision (p = 0.13).
In a multicenter Dutch study of 1922 patients undergoing total hip arthroplasty, the lowest SSI rate was seen in patients who received the antimicrobial during the 30 minutes before incision.95 The highest risk for infection was found in patients who received prophylaxis after the incision.
It seems intuitive that the entire antimicrobial dose should be infused before a tourniquet is inflated or before any other procedure that re-stricts blood flow to the surgical site is initiated; however, a study of total knee arthroplasties compared cefu-roxime given 1030 minutes before tourniquet inflation with cefuroxime given 10 minutes before tourniquet deflation and found no significant difference in SSI rates between the two groups.96
Overall, administration of the first dose of antimicrobial beginning within 60 minutes before surgical in-cision is recommended.41,94,97 Admin-istration of vancomycin and fluoro-quinolones should begin within 120 minutes before surgical incision be-cause of the prolonged infusion times required for these drugs. Because these drugs have long half-lives, this early administration should not com-promise serum levels of these agents during most surgical procedures. Although the recent data summarized above suggest lower infection risk with antimicrobial administration
beginning within 30 minutes before surgical incision, these data are not sufficiently robust to recommend narrowing the optimal window to begin infusion to 130 minutes before surgical incision. However, these data do suggest that antimicrobials can be administered too close to the time of incision. Although a few articles have suggested increased infection risk with administration too close to the time of incision,93,96,97 the data presented are not convincing. In fact, all of these articles confirm the in-creased rate of SSI for antimicrobials given earlier than 60 minutes before incision. In one article, the infection rate for patients given an antimicro-bial within 15 minutes of incision was lower than when antimicrobials were given 1530 minutes before incision.97 In another article, small numbers of patients were reported, and an asser-tion of high infection rates for infu-sion within 15 minutes of incision was made, but no numeric data or p values were provided.98 In a third article, only 15 of over 2000 patients received antimicrobials within 15 minutes be-fore incision.93 Earlier studies found that giving antimicrobials within 20 minutes of incision and as close as 7 minutes before incision resulted in therapeutic levels in tissue at the time of incision.41,90,91,94,97,98
Dosing. To ensure that adequate serum and tissue concentrations of antimicrobial agents for prophylaxis of SSIs are achieved, antimicrobial-specific pharmacokinetic and phar-macodynamic properties and patient factors must be considered when selecting a dose. One of the earliest controlled studies of antimicrobial prophylaxis in cardiac surgery found a lower rate of infection in patients with detectable concentrations of the drug in serum at the end of surgery compared with patients in whom the drug was undetectable.99 In another study, higher levels of antimicrobial in atrial tissue at the time of starting the pump for open-heart surgery were associated with fewer infections
than were lower antimicrobial con-centrations.100 In patients undergo-ing colectomy, infection levels were inversely related to the serum gen-tamicin concentration at the time of surgical closure.17 In general, it seems advisable to administer prophylactic agents in a manner that will ensure adequate levels of drug in serum and tissue for the interval during which the surgical