Antibiotic prophylaxis

Charlotte Hall
Joanna Allen
Gavin Barlow
Abstract
Surgical site infection (SSI) is a common postoperative complication
which leads to signicant morbidity and mortality. The aim of antibiotic
prophylaxis is to reduce the incidence of SSI by preventing the develop-
ment of infection due to colonizing or contaminating organisms at the
operative site. It is used as an adjunct to, rather than a replacement
for, other evidence-based interventions to prevent wound infection,
such as the use of skin antiseptics. The choice of antimicrobial agent(s)
used is dependent on how clean the operation is, the operative site
(which determines the likely organisms), and a variety of patient factors
including the presence of allergies and colonization with resistant organ-
isms such as meticillin-resistant Staphylococcus aureus (MRSA). The prac-
ticalities of antibiotic prophylaxis administration are discussed. Not all
operations require antibiotic prophylaxis; use of antibiotics in any
context, including as prophylaxis, can be associated with adverse effects,
specically an increased risk of Clostridium difcile-associated diarrhoea
(CDAD) and resistance development; prophylaxis should therefore be
used responsibly. This article will address some of the common miscon-
ceptions about its use and special patient circumstances requiring devia-
tion from the usual guidance.
Keywords antibiotics; infection control; prophylaxis; surgical prophy-
laxis; surgical site infection
Surgical site infection
Surgical site infection (SSI) is infection arising in a wound
created by a surgical procedure or postoperative infection of any
cavity, bone, joint or tissue that was involved in the surgery. It
includes infection of prostheses inserted during an operation.
1
SSI is diagnosed if infection occurs within 30 days of surgery
(or within 1 year when an implant is affected), and is classied
according to the tissues involved:
2
Supercial incisional e infection involving only skin or
subcutaneous tissue at the incision site.
Deep incisional e infection involving deep soft tissues
(e.g. fascial and muscle layers) of the incision.
Organ space e infection involving any part of the anatomy
other than the incision that was opened or manipulated
during the operation.
SSI is a common postoperative complication, affecting nearly 5%
of patients overall and accounting for 14% of healthcare-
associated infections.
3
The true incidence of SSI may in fact be
higher given the increasing proportion of surgery done on a day-
case basis; many cases are now identied and treated in the
community. Table 1 shows the variation in incidence of SSI with
the type of surgery.
SSI can lead to increased length of stay and additional costs in
the order of hundreds to thousands of pounds depending on the
severity and site of infection. Consequences for patients include
the need for further surgery, additional antibiotic therapy and
adverse effects associated with this, scarring, long-term discom-
fort, and impact on emotional wellbeing. SSI affecting anasto-
motic or graft sites can be life or limb threatening; SSI contributes
to at least a third of all postoperative deaths.
5
Risk of SSI occurs when there is bacterial contamination of the
wound; the development of infection is then mediated by the
virulence of the contaminating organism and the hosts natural
immunological defences. The organisms that cause SSI are
usually endogenous to the patient and come from their skin or
any viscus that is opened. Exogenous infection develops when
the wound is contaminated preoperatively (e.g. a traumatic
wound), perioperatively from instruments or the theatre envi-
ronment, or postoperatively before the wound has healed.
Surgery can also involve transient bacteraemia, which is an
important mechanism in the development of infection at implant
sites distant to the infection. Antimicrobial prophylaxis targets
the perioperative risk of infection.
The rationale behind antibiotic prophylaxis
The aim of antibiotic prophylaxis in surgery is to prevent SSI
whilst minimizing the collateral damage that occurs with all
antibiotic use. This entails: (1) using antibiotics for which there
is evidence of effectiveness (i.e. a biologically appropriate agent
which has, ideally, been shown in a high-quality trial to reduce
infection rates); (2) minimizing the effect of antibiotics on
patients normal ora and host defences; and (3) minimizing
other adverse effects.
The predominant target for prophylactic antibiotics is the
wound; antibiotics are given to reduce the contaminating bacte-
rial load so that it does not overwhelm natural host defences
leading to infection. The targets of antibiotics therefore are skin/
mucosal colonizing and contaminating organisms at the opera-
tive site. Generally, for operations above the waist this involves
targeting Gram-positive bacteria (staphylococci and strepto-
cocci), and for operations below the waist Gram-positive and
Gram-negative bacteria (e.g. Escherichia coli). For trauma with
open wounds and in oral or abdominal operations, anaerobic
cover must be considered.
Antibiotic prophylaxis should not be used to prevent
postoperative complications which are unrelated to the wound or
surgical site, e.g. catheter-related urinary tract infections
following non-urological procedures, healthcare-associated
Charlotte Hall MBBS BSc MRCP DTM&H is a Specialty Registrar in Infectious
Diseases at Castle Hill Hospital, Hull, UK. Conicts of interest: none
declared.
Joanna Allen MBChB BSc MRCP DTM&H is a Specialty Registrar in Infectious
Diseases at Castle Hill Hospital, Hull, UK. Conicts of interest: none
declared.
Gavin Barlow MBChB MD FRCP DTM&H is a Consultant in Infectious Diseases
at Castle Hill Hospital, Hull, UK. Conicts of interest: none declared.
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pneumonia, and intravenous access device infections. Antibiotic
prophylaxis should cover the most likely infecting organisms, not
all potential pathogens, and should not be used to treat devel-
oping wound infection; a treatment course of antibiotics, the
choice of agent for which may be different to prophylaxis, should
be prescribed. Use of prophylactic antibiotics is not a replace-
ment for optimal patient preparation, good surgical technique
and theatre environment. These factors will not be explored here,
but are at least as or more important than antibiotic prophylaxis;
the 2008 SSI NICE guidance
6
provides further information.
The decision to administer prophylaxis should take into
account national guidelines (e.g. Scottish Intercollegiate Guide-
lines Network (SIGN)/NICE), British National Formulary (BNF)
advice, local patterns of drug resistance, local epidemiology of
Clostridium difcile-associated diarrhoea (CDAD), and local
consensus guidelines developed by anaesthetists, antibiotic
pharmacists, infection specialists and surgeons. The decisionmust
balance the individuals risk of SSI, potential severity of conse-
quences of SSI, effectiveness of prophylaxis in that operation, and
the potential adverse consequences such as colitis. The need for
prophylaxis is not always as black or white as sometimes appears
in local or national guidance. In our own trust a patient recently
died of recrudescent C. difcile infection (CDI) triggered by, as
recommended in local guidance, a single dose of co-amoxiclav
prior to percutaneous endoscopic gastrostomy insertion. The
fact the patient had recently had CDI was not considered when an
alternative lower risk agent or no prophylaxis would have been
more appropriate. Decisions about challenging patients must
therefore be multidisciplinary with discussions between surgeons
and infection experts occurring preoperatively.
Who is at risk of SSI and who needs prophylaxis?
Multiple factors determine the patients risk of developing SSI,
but predominantly risk is determined by the following:
Wound environment e low haemoglobin, presence of
necrotic tissue or foreign bodies, dead space, and patient
colonization by MRSA (meticillin-resistant Staphylococcus
aureus), Lanceeld group A/C/G streptococci or other
resistant organisms.
Patient characteristics including host defence e extremes of
age, presence of shock/hypoxia/hypothermia, glycaemic
control, chronic illness, immunosuppressive agents,
nutritional state, obesity, coexisting infection, American
Association of Anesthesiologists (ASA) score (see below),
previous SSI.
Pathogen exposure e virulence of organisms, size of
inoculum.
Operation factors e length of scrub, skin asepsis,
preoperative shaving and skin preparation, length of
operation, theatre ventilation, equipment sterilization,
foreign material at surgical site, surgical drains, surgical
technique (haemostasis, trauma, closure).
The US Centre for Disease Control NNIS (National Nosocomial
Infections Surveillance) risk index
7
is an internationally used
scoring system based on:
ASA score; this is calculated preoperatively by the anaes-
thetist and a score of more than 2 (3 a patient with
a severe systemic disease that limits activity but is not
incapacitating) is associated with increased risk of SSI.
Wound class.
Duration of operation, reecting technical aspects of the
operation.
With an increasing score the risk of SSI increases.
In the UK, the principal determinant in guidelines of whether
to give antibiotic prophylaxis or not is how clean the operation
is. Four classes of operation exist, with an increasing rate of
bacterial contamination and subsequent risk of SSI:
2,7
Clean e an operation in which no inammation is encoun-
tered. The respiratory, alimentary and genitourinary tracts are
not entered. There is no break in aseptic operating theatre
technique. Primary wound closure is undertaken (e.g. sebaceous
cyst excision).
Clean-contaminated e an operation in which the respiratory,
alimentary or genitourinary tract is entered but there is no
signicant spillage (e.g. appendicectomy).
Contaminated e an operation in which acute inammation
(without pus) is encountered or where there is visible contami-
nation of the wound. For example, gross spillage from a hollow
viscus during the operation or open/compound operations
operated on within 4 hours. Operations in which there is a major
break in aseptic technique also fall into this category (e.g. colo-
rectal surgery).
Surgical site infection incidence by type of surgery
(adapted from national surveillance data
4
)
Type of surgery Incidence
of SSI (%)
Median time to infection
(days) and interquartile
range
Orthopaedic
Hip prosthesis 0.8 13 (7e20)
Knee prosthesis 0.6 14 (6e26)
Repair neck of femur 1.6 14 (8e20)
Repair long bone fracture 1.4 14 (10e24.5)
Vascular
Limb amputation 5.0 9 (5e15)
General vascular 2.8 12 (9e17)
Neurosurgery
Cranial 0.9 12 (11e19)
Spinal 1.0 12 (8e18)
Gastrointestinal
Large bowel 10.1 8 (5e12)
Small bowel 6.8 8 (5.5e12)
Cholecystectomy 1.8 8 (5e20)
Gastric 4.4 9 (5.5e11)
Bile duct/liver/pancreatic 8.1 8 (5e12)
Others
Abdominal hysterectomy 1.5 8 (5e12)
Breast 1.2 10 (6e13)
Cardiac (non-CABG) 1.0 6 (4e8)
Cardiac (CABG) 4.4 11 (7e16)
CABG, coronary artery bypass graft; SSI, surgical site infection.
Table 1
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Dirty e operations in the presence of pus or devitalized tissue,
a previously perforated hollow viscus, or open/compound
injuries more than 4 hours old.
Antibiotic prophylaxis should be administered to patients who
are undergoing the following types of operation:
1,6
clean surgery involving prosthesis or implant placement
(e.g. joint replacement)
clean-contaminated surgery
contaminated surgery.
It should not be used routinely for clean, uncontaminated surgery
that does not involve prosthesis or implant placement unless
high-quality evidence suggests considerable benet over no
prophylaxis. Prophylaxis should not be used for dirty surgery as
in this circumstance a treatment course of antibiotics should be
prescribed.
Specic guidance by individual operation is not covered in
this article, but is available from SIGN.
1
Guidelines generally
cover elective operations, and emergency operations in the clean
(e.g. open reduction internal xation (ORIF) of closed fracture)
or clean-contaminated (e.g. C-section) setting only.
If a surgeon believes prophylaxis is required for a procedure
for which it is not routinely recommended, for example if
a patient is at particularly high risk of SSI, then the case should
be discussed with an infection expert with the decision clearly
documented in the case-notes.
Factors determining what antibiotics to use
Spectrum of cover
The antibiotic chosen for prophylaxis must cover the spectrum of
pathogens that are likely to cause SSI at that site (Table 2). The
local antibiotic protocol (where one exists) should be used as this
will have been developed taking into account factors such as the
local epidemiology of antibiotic resistance and CDI.
Penicillin allergy
True penicillin allergy is relatively rare, but important to detect.
This is because patients allergic to penicillin are more likely to be
allergic to other b-lactam agents (e.g. cephalosporins), which are
commonly used for surgical prophylaxis. Many patients consider
themselves to be allergic to penicillin when in fact they have
suffered non-immunological adverse reactions, in particular,
diarrhoea or vomiting. This can be claried by accurate history
taking at the preoperative assessment and is important as the
alternative non-b-lactam agents recommended for patients with
true penicillin allergy are likely to be less effective.
Allergy means the development of a rash or anaphylactic or
anaphylactoid reaction that is temporally associated with anti-
biotic administration. For patients who state they are allergic to
penicillin (or another antibiotic), the history should include
symptoms and signs, severity of the reaction, time course,
temporal proximity to other drugs, and whether they have since
had a penicillin (or b-lactam) without adverse effect. The
patients GP may need to be contacted if clarication is required.
Patients who report anaphylaxis, laryngeal oedema, bron-
chospasm, hypotension, urticaria, local swelling or pruritic rash
whilst taking penicillin should not receive b-lactam antibiotic
prophylaxis.
1
b-lactam antibiotics include penicillins, b-lactam/
b-lactamase inhibitor combinations, cephalosporins and
carbapenems. Although a history of a simple rash occurring more
than 24 hours after starting penicillin (or other b-lactam) is not
an absolute contraindication to b-lactam therapy in patients with
severe or life-threatening infection, the risk of an adverse reac-
tion, which might be difcult to diagnose in the perioperative
period, is generally considered to outweigh the benet for
patients with such a history. Local policies should recommend at
least one alternative regimen to be used in such circumstances.
MRSA carriage
MRSA carriage is a predictor for MRSA-associated SSI, although
the absolute risk of SSI is not increased. All NHS organizations
should have MRSA screening policies for patients undergoing
surgery. Almost all elective (including day case) and emergency
admissions are now screened for MRSA using swabs from the
nose, axilla and groin (as well as other open wounds the patient
has). The few exceptions to this, for example day case ophthal-
mology/endoscopy, are detailed in Department of Health guid-
ance.
8
Ideally, screening for elective patients should take place
during preoperative assessment to allow time for decolonization
if the screen is positive.
If an elective patient is found to be MRSA colonized they
should receive decolonization treatment preoperatively accord-
ing to local guidance (usually mupirocin nasal cream topically
every 8 hours plus triclosan (Aquasept)/octenidine (Octenisan)
washes daily for 5 days). There is some debate about the need to
demonstrate clearance preoperatively. On the one hand, this
provides reassurance to the patient and surgeon, although
a notable proportion of patients will not be cleared due to, for
example, resistance or poor application, but on the other hand
any delay between decolonization and surgery increases the risk
of a higher skin bacterial load at the time of surgery or re-
colonization from the environment. Decolonization therapy
(and re-screening) should occur as close to the time of operation
as possible.
If the patient cannot be screened preoperatively (e.g. emer-
gency surgery) and they are at high risk of being or known to be
colonized with MRSA (nursing or residential home resident,
previous colonization, recent hospitalization, extensive recent
antibiotic exposure), the prophylactic regimen should include
MRSA cover (usually a glycopeptide) and decolonization should
be commenced as early as possible in the perioperative period.
Practicalities: dose, timing, route of administration and duration
To prevent SSI, the tissue concentration of any prophylactic
agent used must be at an effective concentration (above the
minimum inhibitory concentration (MIC) of any contaminating
bacteria) at the time of initial skin incision. Antibiotics must
therefore be administered at the correct dose and right time, and
by the correct route, taking into account the pharmacokinetic
prole of the antibiotics used.
Dose
In general, the dose used for prophylaxis should be the same as
that used for treatment (e.g. ucloxacillin 1 g is the usual dose for
the in-patient treatment of skin/soft tissue infection and for
surgical prophylaxis).
1
For many of the commonly used prophy-
lactic agents, the rst dose does not require adjustment in renal
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Guide to likely organisms/antibiotic choices
Surgical site Common organisms Potential antibiotics (intravenous unless stated)
All surgery
Skin organisms Staphylococcus aureus,
-haemolytic streptococci
1. Flucloxacillin or
2. Glycopeptide
Gastrointestinal
Oesophagectomy
Pancreatic surgery
Colectomy
Skin organisms, Gram-negative bacilli,
anaerobes
1. Co-amoxiclav or
2. Flucloxacillin or glycopeptide plus gentamicin or
3. Cefuroxime
plus metronidazole (with all of above)
Genito-urinary
Transrectal biopsy
Transurethral resection prostate
*If antibiotic prophylaxis is given
for transurethral procedures,
recent (within 6 months)
MSU results should be reviewed
Gram-negative bacilli 1. Co-amoxiclav or
2. Gentamicin or
3. Cefuroxime or
4. Ciprooxacin (can be given orally)
Obstetric/gynaecological
Caesarean section
Vaginal/abdominal hysterectomy
*Not in C-section when antibiotics
given before skin incision (NICE)
Gram-negative bacilli, group B streptococci,
anaerobes
1. Co-amoxiclav* or
2. Cefuroxime plus metronidazole or
3. Clindamycin plus gentamicin (the latter should
only be given after the cord is clamped in C-section)
Vascular
Arterial reconstruction Skin organisms 1. Co-amoxiclav or
2. Flucloxacillin or glycopeptide plus gentamicin or
3. Cefuroxime
Lower limb amputation Skin organisms, anaerobes As above plus metronidazole (with all of above)
Orthopaedic
Major closed fractures
and implant surgery
Skin organisms 1. Flucloxacillin or
2. Glycopeptide
Gram-negative bacilli (if surgery below waist) plus Gentamicin (if below the waist) or monotherapy with:
1. Co-amoxiclav or
2. Cefuroxime
Open fracture Skin organisms, Gram-negative bacilli,
anaerobes
1. Co-amoxiclav or
2. Glycopeptide plus gentamicin or cefuroxime
plus metronidazole (with all of the above
suggestions for open fracture)
Head and neck
Oropharyngeal streptococci and anaerobes 1. Co-amoxiclav or
2. Glycopeptide plus metronidazole* or
3. Clindamycin*
*Consider addition of gentamicin to the second
and third regimens above if Gram-negatives are of concern
Thoracic
Coronary artery bypass grafts
Pneumonectomy
Skin organisms, Streptococcus pneumoniae,
Gram-negative bacilli
1. Co-amoxiclav or
2. Flucloxacillin or glycopeptide plus gentamicin or
3. Cefuroxime
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impairment, but the timing and/or dose of subsequent doses
(when recommended) may need adjustment. When adjusting
dosing in patients with renal impairment, the estimated creatinine
clearance using the CockrofteGault formula, rather than the
estimated glomerular ltration rate (eGFR), should be used;
advice can be sought from microbiology, infectious diseases or
pharmacy. If the patient is on renal-replacement therapy, discus-
sion with a renal physician/pharmacist is prudent.
Timing
Prophylaxis should be started in almost all circumstances at or
less than 30 minutes prior to the rst skin incision. To ensure
sufcient tissue concentrations are reached at the time of skin
incision, however, it may need to be administered earlier for
operations in which a tourniquet is used,
5
if the antibiotic
regimen includes an agent with a prolonged infusion time (e.g.
vancomycin, ciprooxacin) or if oral prophylaxis is used.
Route of administration
Generally, the intravenous (IV) route should be used, although
some antibiotics do reach equivalent tissue concentration when
given orally (e.g. uoroquinolones). Very little data exist on the
efcacy or timing of oral prophylaxis, although it is often adopted
for common day-case urological procedures, such as transrectal
prostate biopsy.
In some types of surgery alternative routes are used either
alone or combined with IV prophylaxis:
topical administration for grommet insertion
impregnated cement for cemented joint replacements in
addition to IV prophylaxis
1
intracameral prophylaxis in cataract surgery
intraventricular antibiotics during ventriculoperitoneal
shunt neurosurgery in addition to IV antibiotics
some surgeons use gentamicin-impregnated collagen ee-
ces or implants in, for example, abdominoperineal resec-
tion and cardiac surgery.
9,10
Duration
For many types of surgery, a single dose of antibiotic is adequate
providing the half-life of the antibiotic covers the operation
period. Additional doses are generally only needed for longer
operations or when using agents with a short half-life.
An additional dose of prophylactic antibiotic is needed if:
The operation lasts more than 4 hours and the antibiotic
used has a pharmacokinetic prole similar to cefazolin
1
; in
the UK, this includes ucloxacillin, co-amoxiclav and
cefuroxime.
There is intraoperative blood loss greater then 1500 ml (25
ml/kg in children).
1
This is because serum antibiotic
concentrations are reduced by blood loss and uid
replacement, especially early in the operation when the
serum levels are high, leading to levels falling below the
MIC of target bacteria. Any extra doses of antibiotic should
be given after uid resuscitation.
The operation is prolonged beyond the half-life of the
antibiotic used.
For arthroplasty, and other operations inserting foreign material,
24 hours of prophylaxis is generally recommended, albeit
controversial.
1
This is partly because the dose of bacteria needed
to cause SSI in surgery involving insertion of foreign material is
very low, and the consequences of infection devastating.
Documentation of the administration of prophylactic antibi-
otics is often poor, but should be as for therapeutic prescriptions;
minimal documentation such as prophylactic antibiotics given
in the anaesthetic or surgical record alone is unacceptable as it
promotes clinical errors and does not facilitate audit. Prophy-
lactic antibiotics should be prescribed either on a dedicated
proforma that is then led in the case-notes or on the once only
(STAT) section of the drug chart.
Special groups
A variety of patient factors inuence prophylaxis options. Some
antibiotics, for example aminoglycosides, should be avoided
during pregnancy. Co-morbidities that may impact on antibiotic
choice include: long QT syndrome (macrolides and quinolones
can cause further QT prolongation); epilepsy (quinolones lower
the seizure threshold); glucose-6-phosphate dehydrogenase
deciency (nitrofurantoin, quinolones and sulphonamides can
precipitate haemolytic crises); myasthenia gravis (many antibi-
otics can worsen symptoms); and acute intermittent porphyria
(multiple antibiotics can precipitate crises). Likewise, the BNF
and/or pharmacy, microbiology or infectious diseases should be
consulted regarding potential drug interactions.
Other special groups of patients are as follows.
Meticillin-sensitive S. aureus (MSSA)-colonized patients
MSSA is not systematically screened for in the majority of NHS
trusts in the same way as for MRSA. There is some evidence that
decolonizing patients who are nasal carriers of MSSA reduces the
risk of developing infection,
11
although a Cochrane review found
the protective effect disappeared if only SSI was included in the
subgroup analysis (possibly due to a lack of statistical power).
12
Patients known to be nasal or skin carriers of MSSA who are
Table 2 (continued)
Surgical site Common organisms Potential antibiotics (intravenous unless stated)
Neurosurgery
Craniotomy Skin organisms 1. Flucloxacillin or
2. Glycopeptide
Note: Glycopeptide vancomycin or teicoplanin; the latter can be given as a bolus whereas vancomycin must be given as a prolonged infusion. MSU, mid-stream urine
test; NICE, National Institute for Health and Clinical Excellence.
Table 2
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undergoing surgery with a high risk of major morbidity should
receive pre- or perioperative decolonization therapy as for MRSA.
1
Patients undergoing splenectomy
Individuals with an absent or dysfunctional spleen are at lifelong
risk of overwhelming infection, particularly from encapsulated
organisms (most commonly Streptococcus pneumoniae). Patients
should receive pneumococcal, meningococcal, Haemophilus
inuenzae type b (Hib) and inuenza vaccinations. In elective
surgery this should occur at least 2 weeks prior to surgery. In
emergency cases, immunizations should ideally be given 2 weeks
after surgery when physiological recovery has occurred (they
should be given prior to discharge or a clear plan made with the
patients GP for immunization at 2 weeks). For patients under-
going chemotherapy, immunizations should, ideally, be given at
least 2 weeks before chemotherapy commences.
All high-risk patients (<16 or >50 years old or those with an
inadequate serological response to pneumococcal vaccination,
history of invasive pneumococcal disease, underlying haemato-
logical malignancy) should be offered lifelong prophylactic
antibiotics (e.g. penicillin V 500 mg/12 hours oral or erythro-
mycin 500 mg/12 hours oral). Lower risk patients are still at
increased risk in the immediate postoperative period and should
be given antibiotics, but counselled as to the risks and benets of
continuing lifelong e some may choose to stop.
13
Written advice about infection and the risks of overseas travel
(in particular the risk of malaria) should be given to patients
prior to discharge with a supply of appropriate antibiotics for
emergency use. Patients should carry a card to alert health
professionals to their asplenic status. Communication with
primary care providers to ensure plans for completion of vacci-
nation schedules, boosters, and ongoing antibiotic supply is vital.
Other immunocompromised patients
This includes those with human immunodeciency virus (HIV)
infection, undergoing chemotherapy, on immunosuppressive
drugs, or with functional immunosuppression (e.g. due to
leukaemia). These patients should receive the same prophylaxis
as immunocompetent patients, but extra vigilance for the
development of SSI is needed.
Patients at risk of infective endocarditis
Infective endocarditis (IE) can occur following bacteraemia in
patients with predisposing cardiac lesions.
a
Historically, this
led to all such patients receiving prophylactic antibiotics for
dental and surgical procedures. However, 2008 NICE guid-
ance
14
recommended a change in this practice, and antibiotic
prophylaxis to prevent IE is no longer routinely recommended
for these patients.
a
The basis for this is that there is no
consistent data showing a relationship between having such
procedures and development of IE, the clinical effectiveness of
antibiotic prophylaxis to prevent IE is unproven and
prophylaxis may have severe negative consequences (e.g.
anaphylaxis).
All at-risk patients should receive information on IE preven-
tion, including the risks and benets of antibiotic prophylaxis
and an explanation of why it is no longer routinely recom-
mended, the importance of maintaining good oral health, and the
symptoms that may indicate IE. However, prophylactic antibi-
otics for the sole purpose of preventing IE should not be
administered except in the circumstance of gastrointestinal (GI)
or genito-urinary surgery at a site where there is suspected
infection, when prophylaxis with an antibiotic that covers IE
causing organisms (mainly Gram-positive bacteria) should be
given.
Paediatrics
The principles of prophylaxis are the same with paediatric
practice generally being extrapolated from adult prophylaxis
guidance with appropriate choice and dose adjustment depend-
ing on the age and weight of the child; see SIGN guidance and
local antibiotic policy for more information. The Paediatric BNF
provides antibiotic dosing information.
Obese patients
Physiological changes in obesity affect the distribution, protein
binding, metabolism and clearance of antimicrobials. Tissue
distribution, in particular, is affected for hydrophilic antibiotics
(b-lactams, aminoglycosides, glycopeptides) because approxi-
mately one-third of adipose tissue is water, leading to a greater
volume of distribution (Vd) and lowered tissue concentrations.
For lipophilic drugs (uoroquinolones, macrolides, lincosa-
mides, tetracyclines, tigecycline), the Vd also generally increases
(to what extent is unpredictable). Antibiotic clearance is also
altered by obesity.
15
Antimicrobial agents with a narrow therapeutic window (e.g.
aminoglycosides) are often dosed according to weight, but it has
not yet been established what index of weight is optimal (e.g.
total, ideal, lean mass), given the complex pharmacokinetics and
pharmacodynamics in obese patients. Other antibiotics are set at
a standard dose, which may lead to sub-optimal tissue concen-
trations in obese patients, leading to an increased risk of SSI and
resistance evolving. Some data support giving a higher induction
dose of b-lactams and vancomycin in obese patients to optimize
tissue concentrations, for example ucloxacillin 1.5 g instead of 1
g, but more research is needed.
16
Local antibiotic guidance and/
or infection experts should be consulted about the high-risk
obese patient.
Patients with intercurrent infection
Those with pre-existing infection that is being treated should
still receive antibiotic prophylaxis and then return to the
preoperative regimen. One special circumstance is those
undergoing urological surgery with a proven urinary tract
infection (UTI), where the prophylaxis should be tailored to
cover the sensitivities of the organism identied. If a patient is
deemed at operation to need antibiotics, the prophylactic
regimen may not necessarily be appropriate; relevant operative
samples for microbiological testing should be ascertained and
local antibiotic guidance consulted regarding the optimal
postoperative regimen.
a
At-risk patients are those with acquired regurgitant or stenotic
valvular disease, valve replacement, structural congenital heart disease
(excluding isolated atrial septal defect and repaired patent ductus
arteriosus), previous infective endocarditis, and hypertrophic
cardiomyopathy.
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Potential negative implications of prophylaxis
All antibiotic use, whether for prophylaxis or therapy or appro-
priate or not, carries a risk of harm through adverse reactions
(e.g. rash, anaphylaxis), risk of colonization and subsequent
infection with C. difcile, and the emergence of antibiotic resis-
tance. It is these risks that drive the antibiotic stewardship
agenda and advice to use the narrowest spectrum antibiotic
possible for the shortest time and only when anticipated clinical
benet outweighs potential risks.
All antibiotics will suppress to some extent the normal,
protective mucosal bacterial ora and facilitate the development of
colonization with C. difcile and antibiotic resistant pathogens
(e.g. MRSA). In general, these issues are greater with broader
spectrum agents (e.g. third-generation cephalosporins, uo-
roquinolones and b-lactam/b-lactamase inhibitors such as co-
amoxiclav). Even a single dose of a cephalosporin (and very
likely other antibiotics too) appears to increase the carriage of
C. difcile
17
and the incidence of CDAD
18
; the latter is not a benign
condition and contributes notably to morbidity, length of hospital
stay and mortality. Patients who have other risk factors for
C. difcile colonization are particularly vulnerable, the exact
prophylaxis to be used requiring careful preoperative assessment.
Risk factors include age over 65, previous CDAD, nursing or
residential home residents, recent or prolonged hospital stay,
extensive co-morbidities, GI surgery, severe intercurrent illness,
poor nutritional state, use of proton pump inhibitors or histamine-
2 antagonists, and the presence of a CDAD outbreak on the ward.
Other important issues
Patient information: Informationabout the riskof healthcare-
associated infection and SSI should be provided to patients
preoperatively with additional specic information to MRSA
carriers (see links toinformationsheets below). The risks and
benets of antibiotic prophylaxis should be discussed and
patients informed if they will receive it.
Audit: This must be undertaken on a regular basis to assess
compliance with local antibiotic prophylaxis guidelines and
act as a driver for change when practice is sub-optimal. The
SIGN guidelines provide criteria for standards and
minimum record keeping for audit purposes.
Sources of advice: Whilst local guidelines will help you
with most cases, they will not cover all eventualities.
Choice of antibiotic and dosing can be difcult in some
cases, particularly when multiple allergies, polypharmacy
and co-morbidities are present. It is also important to
consider any history of previous surgical site infection.
Complex cases should be discussed with your local anti-
biotic/infection pharmacist or microbiologist or infectious
diseases physician. Some additional sources of information
are suggested below.
FURTHER READING AND RESOURCES
Information leaets for patients:
SSI: http://www.hpa.org.uk/webc/HPAwebFile/HPA
web_C/1194947348455
MRSA: http://www.hpa.org.uk/web/HPAwebFile/HPA
web_C/1194947417699
C. difcile: http://www.hpa.org.uk/webc/HPAwebFile/
HPAweb_C/1194947349379
SIGN guideline and quick-reference guides: www.sign.ac.uk
Cochrane reviews database: www.cochrane.org/cochrane-
reviews
BNF: www.bnf.org (adult), http://bnfc.org/bnfc/index.
htm (paediatric)
NICE guidelines: www.nice.org.uk
Other articles related to SSI in Surgery:
OGrady H, Baker E. Prevention of surgical site infec-
tions. Surgery 2011; 29: 513e7.
Thompson S, Ridgway EJ. Rational antibiotic use in
surgery. Surgery 2009; 27: 435e40. A
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