 SPECIALTY UPDATE
Antibiotic prophylaxis in orthopaedic
D. J. Bryson,
D. L. J. Morris,
F. S. Shivji,
K. R. Rollins,
S. Snape,
B. J. Ollivere
From Queen’s
Medical Centre,
Nottingham, United
Kingdom
 D. J. Bryson, MBChB, MRCS,
Specialist Trainee, Department
of Trauma and Orthopaedics
 F. S. Shivji, BM, BS, BMedSci,
MRCS, Specialist Trainee
 K. R. Rollins, BM, BS,
BMedSci, MRCS, Specialist
Trainee, Department of Surgery
 B. J. Ollivere, MBBS,
MA(Oxon), MD FRCS (Tr&Orth),
Honorary Associate Clinical
Professor
Queen’s Medical Centre,
Nottingham NG7 2UH, UK.
 D. L. J. Morris, BMedSci
(Hons), BM BS (Hons), MRCS,
Specialist Trainee, Department
of Trauma and Orthopaedics
King’s Mill Hospital, Sutton-in-
Ashfield, Nottinghamshire,
NG17 4JL, UK.
 S. Snape, BM, BCh, PhD,
MRCP, MRCPath, Consultant
Microbiologist, Department of
Microbiology
Nottingham University
Hospitals NHS Trust,
Nottingham City Hospital,
Hucknall Rd, Nottingham NG5
1PB, UK.
Correspondence should be sent
to Mr B. J. Ollivere; e-mail:
ben.ollivere@nuh.nhs.uk
©2016 The British Editorial
Society of Bone & Joint
Surgery
doi:10.1302/0301-620X.98B8.
37359 $2.00
Bone Joint J
2015;98-B:1014–19.
1014
surgery
DIFFICULT DECISIONS IN AN ERA OF EVOLVING ANTIBIOTIC
RESISTANCE
Prophylactic antibiotics can decrease the risk of wound infection and have been routinely
employed in orthopaedic surgery for decades. Despite their widespread use, questions still
surround the selection of antibiotics for prophylaxis, timing and duration of administration.
The health economic costs associated with wound infections are significant, and the
judicious but appropriate use of antibiotics can reduce this risk.
This review examines the evidence behind commonly debated topics in antibiotic
prophylaxis and highlights the uses and advantages of some commonly used antibiotics.
Cite this article: Bone Joint J 2016;98-B:1014–19.
Antibiotics were once considered a medical representing deep infection.8 Other reports
panacea.1 Since Alexander Fleming’s fortui- suggest that the rate of deep infection may be
tous discovery of penicillin in 1928, over 100 as high as 3.6%.9 About half of all patients
derivative compounds have been discovered. who develop an SSI following surgery for frac-
Their use has become integral to orthopaedic ture of the hip will die within a year. The cost
practice for the prophylaxis and treatment of of treating one such patient has been calculated
infections. Prophylactic antibiotics can reduce to be £31 164, rising to £38 464 if the causa-
the rate of surgical site infection (SSI) follow- tive organism is methicillin resistant Staphylo-
ing arthroplasty from between 4% and 8% to coccus aureus (MRSA).10 In elective surgery,
between 1% and 3%.2 infection accounts for about 23% of revisions
Methods of controlling infection have been following total knee arthroplasty (TKA),11 and
widely published but guidance is frequently between 7% and 13% of revisions following
not followed.3 The World Health Organisation total hip arthroplasty (THA).12-15 The mortal-
(WHO) has warned that antibiotic resistance ity associated with prosthetic joint infection
poses a major global threat, and might herald a (PJI) has been reported to range between 2%
post-antibiotic era in which common infec- and 18%.16
tions and minor injuries once again threaten
life.4 This review examines the evidence for Prophylaxis
some of our current strategies for the use of Whilst animal studies demonstrated the effec-
antibiotics in orthopaedic surgery. tiveness of antibiotic prophylaxis as early as
1961,17 the effectiveness of prophylactic anti-
Surgical site infection biotics in orthopaedic surgery was confirmed
Most SSIs are acquired at the time of surgery, by the 1984 study of Lidwell et al18, funded by
with airborne organisms and those present on the Medical Research Council, which demon-
the patient’s skin being the cause in most strated a three-fold reduction in PJI using anti-
cases.2,3,5 Humans shed 10 000 bacteria every biotic prophylaxis following THA and TKA.18
minute6 and the interposition of staff between Later, the results of the Dutch Trauma Trial,
vertical laminar flow and the patient can where patients with closed fractures were given
increase the number of bacteria contaminating a single dose of either a third generation ceph-
a wound during surgery by a factor of 27.7 alosporin or a placebo, demonstrated a > 50%
Staphylococcus aureus and coagulase negative reduction in the incidence of superficial and
staphylococci such as Staphylococcus epider- deep infections from 8.3% in the placebo arm
midis, are the most common causative infective to 3.6% with antibiotics.19 In open fractures,
organisms (Table I).3 the provision of antibiotics effective against
The overall risk of SSI following surgery for both Gram-positive and Gram-negative organ-
fractures of the hip has been reported to isms is the most important factor in minimising
be 4.97%, with about a third of these cases the risk of infection;20 this has a greater
THE BONE & JOINT JOURNAL
 ANTIBIOTIC PROPHYLAXIS IN ORTHOPAEDIC SURGERY
Table I. Micro-organisms commonly encountered in orthopaedic practice
Name Type
Staphylococcus aureus (methicillin sensitive) Gram positive cocci
Staphylococcus aureus (methicillin resistant) Gram positive cocci
Staphylococcus epidermidis Gram positive cocci
Streptococcus ssp Gram positive cocci
Enterococcus Gram positive cocci
Enterobacter Gram negative bacilli
Escherichia coli Gram negative bacilli
Klebsiella Gram negative bacilli
influence on the rate of infection than the timing of surgical
debridement.21,22 In elective arthroplasty, prophylactic
antibiotics may reduce the absolute risk of wound infection
by 8% and the relative risk by 81%; for every 13 patients
treated, one wound infection is prevented.12 Patient-
specific factors such as colonisation with MRSA, and local
or departmental factors such as endemic bacterial flora and
emerging patterns of resistance may influence the decisions
to use specific antibiotic prophylaxis.
The timing of prophylaxis
In order to be effective, prophylaxis must deliver levels of
antibiotics above the minimum inhibitory concentration
(MIC) for bacterial growth, for the duration of the opera-
tion.23 In order to achieve this, the antibiotic should be
administered prior to the incision and before inflation of a
tourniquet; it should have a sufficiently long half-life to
maintain an MIC throughout the procedure, and it should
be effective against the most common causative organisms.
The first two hours following either incision or contam-
ination is the most important period for the concentration
of antibiotics to be maintained.5 It is best practice to admin-
ister antibiotics within an hour of the incision, although
some authors argue that administration within two hours is
acceptable.23-25 Failure to administer antibiotics within this
two-hour window is associated with a two- to six-fold
increase in the rate of SSI.26 When a tourniquet is used, a
ten minute interval between administration of the antibi-
otic and inflation of the tourniquet is the minimum
required.27
In patients with an open fracture, most recommenda-
tions suggest administration within three hours of injury,
but the results of a recent retrospective review of 137
Gustilo-Anderson Grade III open tibial fractures have
revealed a significantly lower rate of infection when antibi-
otics were administered within 66 minutes of injury.21 The
immediate administration of antibiotic prophylaxis and
VOL. 98-B, No. 8, AUGUST 2016
1015
Sensitivity
Flulcoxacillin, cephalosporins, carbapenems, clindamycin, fluroquinolo-
nes, gentamicin, vancomycin, teicoplanin, rifampicin.
Resistant to flucloxacillin, cephalosporins and carbapenems. Reliably sen-
sitive to vancomycin and teicoplanin. Usually sensitive to gentamicin and
rifampicin.
Reliably sensitive to vancomycin and teicoplanin.Usually sensitive to gen-
tamicin, and rifampicin. Only 10% are sensitive to flucloxacillin, cephalo-
sporins and carbapenems.
Penicillins, cephalosporins, vancomycin, teicoplanin
Sensitive to linezolid and daptomycin. Usually sensitive to vancomycin
and teicoplanin (unless vancomycin resistant enterococcus (VRE)) and
gentamicin. Enterococcus faecalis is sensitive to amoxicillin but Enterococ-
cus faecium is resistant. All enterococci are resistant to cephalosporins
and clindamycin.
Carbapenems, fluroquinolones, aminoglycosides.
Amoxicillin, fluroquinolones, aminoglycosides, cephalosporins, carbapen-
ems, trimethoprim.
Cepaholsporins, aminoglycosides, fluroquinolones, carbapenems.
achievement of soft-tissue cover within five days were inde-
pendently associated with a decreased rate of deep infec-
tion; the timing of early surgical debridement did not affect
subsequent rates of infection.21 Timing may also be influ-
enced by the antibiotic itself. Vancomycin, which may be
used in patients with an allergy to β-lactams, in those colo-
nised with MRSA or in departments experiencing recent
MRSA outbreaks,3 should be infused over a minimum of
60 minutes because of the risk of anaphylactic reactions.28
The duration of prophylaxis
There is little high quality evidence to support decisions
about the duration of prophylaxis. The American Academy
of Orthopaedic Surgeons (AAOS) advise that prophylaxis
should not exceed 24 hours, irrespective of the use of drains
or catheters.5 In a retrospective review of 1341 patients
undergoing THA and TKA, Williams and Gustilo29 found
no difference in the rate of infection in patients who received
prophylaxis for one day (0.67%) and those who received it
for three days (0.6%). Similarly, a randomised controlled
trial (RCT) found no difference in the rate of SSI between
patients who received prophylaxis for 24 hours and those
who received it for seven days following THA and TKA.30
In both elective and trauma surgery, there is reasonable
evidence that single dose antibiotic prophylaxis may suffice
(Table II),31-34 but two meta-analyses on the topic included
heterogeneous studies.32,33 In a more refined meta-analysis
reporting outcomes for 921 patients examining multiple
versus single dosing regimens of the same antibiotic, no sig-
nificant differences were reported, except a higher rate of
deep infection following single-dose prophylaxis (RR 0.13,
95% CI 0.02 to 0.99).35 However, this finding was based
on the results of a single study.
The evidence supporting single dose prophylaxis is not
reflected in current practice. Perhaps the reticence of sur-
geons to change regimes is based on a lack of knowledge of
current research, a general aversion to change, or the fear of
1016 D. J. BRYSON, D. L. J. MORRIS, F. S. SHIVJI, K. R. ROLLINS, S. SNAPE, B. J. OLLIVERE
Table II. Evidence comparing single dose and multiple dose antibiotic prophylaxis regimens31-35
Study Methodology
Tang et al31 1367 TKA/THA performed between
1991 to 1999;compared single dose
cefazolin (1g) with 3× 750 mg doses
of cefurxoime
Slobogean et al32 Meta-analysis
Southwell-Keely et al33 Meta-analysis
Gillespise and Walkenkamp34 Systematic review
Morrison et al35 Systematic review and meta-analysis Two randomised trials totaling 921
CI, confidence interval; SSI, surgical site infection; RR, risk ratio
infection. A definitive RCT would require a sample size of
14 000 per arm32 and so seems unlikely.
Prophylaxis: which antibiotic?
Whilst there is strong evidence for prophylaxis, there is lit-
tle evidence supporting the effectiveness of one antibiotic
over another.
Cephalosporins offer cover against most Staphylococcus
aureus and some Gram negative organisms but do not
cover 90% of coagulase-negative staphylococci (CoNS). As
with all β-lactam antibiotics, cephalosporins are ineffective
against MRSA. Cephalosporins have a good safety profile,
a long half-life and good penetration in bone, synovium
and muscle.36,37 In 2008, the AAOS recommended cefazo-
lin or cefuroxime for patients undergoing arthroplasty.24
In the United Kingdom, cephalosporins are no longer the
first line prophylactic agents in many centres, largely due to
concerns about Clostridium difficile infection. Third-gener-
ation cephalosporins have been strongly linked with the
development of Clostridium difficile38 with single dose
cephalosporin prophylaxis sufficient to promote colonisa-
tion with Clostridium difficile.39,40 A retrospective review
Intervention Result
1152 arthroplasties (1× cefazolin) Deep infection Hip: Cefazolin = 1.1%
215 arthroplasties (3× cefuroxime) (95% CI 0 to 3.3) Cefuroxime = 1.1%
(95% CI 0 to 2.2) Fisher’s exact, p = 1.0
Deep infection Knee: Cefazolin
= 1.0 (95% CI 0.3 to 1.7) Cefuroxime
= 1.6% (95% CI 0 to 3.8) Fisher’s exact,
p = 0.63
Seven trials and 3808 patients Single versus multiple dose prophy-
comparing single dose prophylaxis laxis has
versus multiple doses of same or RR of 1.24 (95% CI 0.60 to 2.60) Pooled
different antibiotics; results pooled risk difference = 0.005 (95% CI -0.011 to
using random effects model 0.021) which favours multiple dose
regimes but did not reach significance.
15 randomised controlled trials Antibiotic prophylaxis significantly
examining antibiotic prophylaxis in reduced wound infection compared
hip fracture patients; included trials with placebo and was equally effective
comparing antibiotic prophylaxis for superficial and deep infection
versus placebo, multiple dose Single dose prophylaxis seemed no
(> 24 hours) versus single dose less effective than multiple dose
and multiple dose versus 24 hours regimes
antibiotics
Randomised or quasi-randomised Single dose prophylaxis significantly
trials comparing parenteral antibiotic reduced deep SSI (RR 0.40, 95% CI 0.24
prophylaxis versus no prophylaxis, to 0.67) to multiple dose prophylaxis
placebo, or a regime of different has similar size effect on deep SSI (RR
duration in hip fracture patients 0.35, 95% CI 0.19 to 0.62)
(fixation or prosthetic replacement) or
internal fixation of closed long bone
fractures; included 23 studies and 8447
participants
No significant difference in overall
patients pooled using a random- surgical site infection rate between sin-
effects model. Patients received gle dose and multiple dose prophy-
single or multiple dose (of the same laxis (RR 0.3, 95% CI 0.07 to 1.25)
antibiotic) cephalosporin for prophy- Multiple dose prophylaxis marginally
laxis in hip fracture surgery or closed more effective in reducing deep
fracture fixation surgical infection (RR 0.13, 95% CI 0.02
to 0.99).
comparing 625 trauma and elective patients who received
prophylaxis with cefuroxime with 706 patients who were
treated with flucloxacillin or teicoplanin and gentamicin
showed a reduction in Clostridium difficile from 4% to 1%
(p = 0.004), with a greater effect in trauma patients (reduc-
tion from 8% to 3%; p = 0.02).41 Other studies have
reported an 80% reduction in the incidence of Clostridium
difficile when the agent of prophylaxis is changed from
cefuroxime to Co-amoxiclav.42
Flucloxacillin is a penicillinase-resistant penicillin offering
good cover against Staphylococcus aureus (again, it is inef-
fective against MRSA and 90% of CoNS), and is routinely
used as first-line treatment for Staphylococcus aureus infec-
tion in the United Kingdom.43 In a comparison of common
antibiotic prophylaxis agents, flucloxacillin demonstrated a
97% bacterial kill rate at concentrations equivalent to serum
levels at one hour after intravenous administration.44 In
2011, flucloxacillin and gentamicin was the most common
prophylactic regime for orthopaedic trauma in the United
Kingdom, used by 50% of NHS trusts.36
Co-amoxiclav, a mixture of amoxicillin and clavulanic
acid, a beta-lactamase inhibitor, is the recommended first-
THE BONE & JOINT JOURNAL
 ANTIBIOTIC PROPHYLAXIS IN ORTHOPAEDIC SURGERY
line antibiotic for open fractures according to the guidelines
of the British Orthopaedic Association (BOA) and the Brit-
ish Association of Plastic, Reconstructive and Aesthetic
Surgeons (BAPRAS). While there is no direct evidence to
support its use, it is recommended based on its broad spec-
trum of Gram-positive, Gram-negative and anaerobic
cover.45 The addition of a beta-lactamase inhibitor renders
amoxicillin effective against resistant strains of Staphylo-
coccus aureus, Escherichia coli, Haemophilus influenzae,
Bacteroides and Klebsiella spp.46 In experimental studies,
co-amoxiclav demonstrated bacterial kill rates of 99.4%,
equivalent to impienem (99.6%) and significantly better
than cefuroxime (95.9%, p = 0.001).44
Clindamycin provides Gram-positive and anaerobic
cover but has no activity against aerobic Gram-negative
bacteria. It is recommended by the AAOS for patients with
β-lactam allergy and by the BOA and BAPRAS guidelines
for the management of open fractures in patients who are
allergic to penicillin.24,45 Clindamycin offers excellent pen-
etration into bone where it can exceed the MIC for Staph-
ylococcus aureus.43 Clindamycin has been shown to be
effective as prophylaxis for Grade I and II open fractures
where rates of infection of 3.8% and 1.8% respectively,
have been reported; but in Grade III open fractures, where
43% of pathogens are Gram-negative, rates of infection can
be as high as 75% with clindamycin prophylaxis.47
Quinolones offer excellent oral bioavailability and pro-
vide broad spectrum cover against Gram-positive and
Gram-negative bacteria. Experiments in rats suggest that
ciprofloxacin may predispose to delayed or nonunion.48
Ciprofloxacin is not used as prophylaxis because resistance
may develop rapidly, because of the a risk of Clostridium
difficile and because there is evidence to support the use of
other agents for prophylaxis.49
Teicoplanin is a glycopeptide antibiotic that has excellent
penetration into bone, covers Gram-positive bacteria
including methicillin sensitive (MSSA) and resistant Staph-
ylococcus aureus, has a long half-life and low toxicity, and
can be administered as a bolus.50 The use of teicoplanin as
prophylaxis, either alone or in combination with gen-
tamicin, increased in the United Kingdom from 2.0% to
10.3% for elective surgery and from 1.3% to 6.7% in
trauma surgery between 2005 and 2011.36 It is frequently
used as first-line antibiotic in patients who are allergic to
penicillin.
Vancomycin is another glycopeptide antibiotic that
offers cover against Gram-positive bacteria including
MRSA and MSSA. It may be used in patients who are aller-
gic to β-lactams. It is commonly used in patients known to
be colonised with MRSA.23 The routine use of systemic
vancomycin is not indicated because of the possible devel-
opment of vancomycin resistance.51 Vancomycin may also
be added to polymethylmethacrylate (PMMA) bone cement
for prophylaxis in arthroplasty,52 or in antibiotic spacers or
beads for the prevention of infection in contaminated open
fractures.
VOL. 98-B, No. 8, AUGUST 2016
1017
Gentamicin is an aminoglycoside antibiotic that offers
activity against Gram-negative and Gram-positive bacteria
including Staphylococcus aureus. It is routinely used in
combination with flucloxacillin as prophylaxis in both elec-
tive and trauma surgery. The introduction of gentamicin as
a prophylactic agent was in response to the increasing prev-
alence of MRSA. Gentamicin used as a prophylactic agent
contributed to a statistically significant reduction in infec-
tions, including MRSA infections, in a study of patients
undergoing hemiarthroplasty for fractures of the hip.53
However, the susceptibility of MRSA to gentamicin is vari-
able. Gentamicin is the most common antibiotic additive to
PMMA bone cement54 and provides local elution at highly
effective antibacterial concentrations.55 Gentamicin-eluting
PMMA beads and sponges may be used in the treatment of
contaminated open fractures.
Antibiotics and urinary catheters
Asymptomatic urinary tract colonisation or bacteriuria is
significantly associated with, but not necessarily causally
related to, superficial and deep joint infections.56,57 Sousa et
al57 established in a series of 2479 patients that asympto-
matic bacteriuria (ASB) was an independent risk factor for
PJI. Urinary catheterisation has been linked to deep wound
infections in patients with a fracture of the hip, with a higher
incidence of deep sepsis in those who have a urinary catheter
inserted peri-operatively or within five days of surgery, those
who undergo more than two catheterisations or have a long-
term catheter (≥ 21 days). As a result, antibiotic cover is rec-
ommended by some for urinary catheterisation.58
Antibiotic treatment for ASB and prophylaxis for the
removal of urinary catheters is a contentious issue and
practice varies between and within centres. A multi-centre
prospective study found no benefit from pre-operative anti-
biotic treatment for ASB and it was concluded that ASB did
not result in direct seeding to the surgical site, but was an
independent risk factor for infection, especially those due to
gram-negative organisms. The authors theorised that ASB
might be a surrogate marker for a condition that increases
the risk of bacterial colonisation or infection.57 Evidence in
other branches of medicine and surgery suggests that anti-
biotic prophylaxis is not needed when a catheter is
removed,59 and we are not aware of any evidence to sup-
port antibiotic cover when catheters are removed in ortho-
paedic patients.
Guidance for immunocompromised patients
Immunosuppression predisposes to infection. The causes of
immunosuppression include, but are not limited to, malig-
nancy, diabetes, acquired immunodeficiency (HIV), and
drugs used in the treatment of such conditions as rheuma-
toid arthritis or following organ transplantation. The com-
bination of immunosuppression and the excessive use of
antibiotics may also predispose to fungal infection.60
Diabetic patients are at increased risk of orthopaedic
complications.61 The risk of infection in diabetic patients
1018 D. J. BRYSON, D. L. J. MORRIS, F. S. SHIVJI, K. R. ROLLINS, S. SNAPE, B. J. OLLIVERE
undergoing THA and TKA is about twice that of non-dia-
betic patients.62 The relative risk of post-operative compli-
cations following fixation of a fracture of the ankle is 2.76
times greater in diabetic than in non-diabetic patients, and
in this setting, mortality, post-operative complications and
length of stay are all higher in diabetic patients.63,64 In dia-
betic patients who have undergone internal fixation of a
fracture of the ankle, rates of infection of between 12% and
40% have been reported.63,65-68 In a retrospective review of
pilon fractures in a level 1 trauma centre, rates of infection
of 71% (43% deep infection) were seen in diabetic patients
compared with 19% (9% deep infection) for non-
diabetics.69 Despite this increased risk, there is no evidence
to support any deviation from standard antibiotic prophy-
laxis in diabetics. In elective surgery, measures should be
undertaken to optimise glycaemic control, promote weight
loss, smoking cessation and modification of activity in an
attempt to minimise the risk of complications.
There is no evidence that HIV-positive patients have a
higher rate of infection in either elective or trauma surgery
and there is no indication for extended antibiotics in
patients with HIV.70,71
Rheumatoid arthritis (RA) is an independent risk fac-
tor for PJI (hazard ratio 4.08; 95% confidence interval
(CI) 1.35 to 12.33).72 Whilst the use of drugs such as
tumour necrosis factor α (TNF-α) inhibitors have revolu-
tionised the treatment of RA they also increase the risk of
post-operative infection after orthopaedic surgery (odds
ratio (OR) 4.4, 95% CI 1.1 to 18.41)73,74 with the great-
est risk seen when given within a cycle (< 1 administra-
tion interval) of surgery.75 While there is guidance to
support peri-operative changes to anti-rheumatic drugs,
the literature does not appear to support changes to rou-
tine antibiotic prophylaxis pre- or post-operatively in
patients with RA.
In conclusion, antibiotics are an integral component of
orthopaedic practice as prophylactic agents. As surgical
practitioners we can be guilty of prescribing and using
antibiotics without having a full understanding of the
indications and uses for many of those agents that we rely
so heavily upon. The threat of antibiotic resistance is real;
at least two million illnesses and 23 000 deaths a year are
caused by antibiotic-resistant bacteria in the United States
alone.76 Tazocin is now ineffective against bacteria such
as Extended spectrum β-lactamase Enterobacteriaceae
(ESBL). Carbapenamase resistant Enterobacteriaceae
(CRE), which are resistant to meropenem, are being
spread through global travel. Only 70% of CRE are sen-
sitive to Colistin and only 50% are sensitive to Tigecy-
cline, with many resistant to all antibiotics. Greater
awareness and the judicious use and improved antibiotic
stewardship are required if we are to continue to derive
benefit from antibiotics for the prevention of SSIs and the
treatment of bone, joint and soft-tissue infections.
Take home message:
Orthopaedic surgeons must have an awareness of the efficacy
and indications for commonly used antibiotics to ensure good
clinical care and to promote stewardship in an era of evolving antibiotic
resistance.
Author contributions:
D. J. Bryson: Concept of the review, Literature review, Writing of the manu-
script.
D. L. J. Morris: Literature review, Writing of the manuscript.
F. S. Shivji: Literature review, Writing of the manuscript.
K. R. Rollins: Literature review, Writing of the manuscript.
S. Snape: Concept of the review, Writing and reviewing of the manuscript.
B. J. Ollivere: Concept of the review, Writing and reviewing of the manuscript.
No benefits in any form have been received or will be received from a commer-
cial party related directly or indirectly to the subject of this article.
This article was primary edited by A. D. Liddle and first proof edited by J. Scott.
References
1. Cooperman EM. Antibiotics: no panacea. Can Med Assoc J. 1977;116:229–232.
2. Uçkay I, Hoffmeyer P, Lew D, Pittet D. Prevention of surgical site infections in
orthopaedic surgery and bone trauma: state-of-the-art update. J Hosp Infect
2013;84:5–12.
3. Fletcher N, Sofianos D, Berkes MB, Obremskey WT. Prevention of perioperative
infection. J Bone Joint Surg [Am] 2007;89-A:1605–1618.
4. No authors listed. Antimicrobial resistance: global report on surveillance 2014.
http://www.who.int/drugresistance/documents/surveillancereport/en/ (date last
accessed 3 March 2016).
5. Meehan J, Jamali AA, Nguyen H. Prophylactic antibiotics in hip and knee arthro-
plasty. J Bone Joint Surg [Am] 2009;91-A:2480–2490.
6. Adeli B, Parvizi J. Strategies for the prevention of periprosthetic joint infection. J
Bone Joint Surg [Br] 2012;94-B:42–46.
7. Taylor GJS, Bannister GC. Infection and interposition between ultraclean air
source and wound. J Bone Joint Surg [Br] 1993;75-B:503–504.
8. Ridgeway S, Wilson J, Charlet A, et al. Infection of the surgical site after arthro-
plasty of the hip. J Bone Joint Surg [Br] 2005;87-B:844–850.
9. Mackay DC, Harrison WJ, Bates JH, Dickenson D. Audit of deep wound infec-
tion following hip fracture surgery. J R Coll Surg Edinb 2000;45:56–59.
10. Edwards C, Counsell A, Boulton C, Moran CG. Early infection after hip fracture
surgery: risk factors, costs and outcome. J Bone Joint Surg [Br] 2008;90-B:770–777.
11. Vanhegan IS, Morgan-Jones R, Barrett DS, Haddad FS. Developing a strategy to
treat established infection in total knee replacement: a review of the latest evidence
and clinical practice. J Bone Joint Surg [Br] 2012;94-B:875–881.
12. AlBuhairan B, Hind D, Hutchinson A. Antibiotic prophylaxis for wound infections
in total joint arthoplasty. J Bone Joint Surg [Br] 2008;90-B:915–919.
13. Puolakka TJ, Pajamäki KJ, Halonen PJ, et al. The Finnish Arthroplasty Register:
report of the hip register. Acta Orthop Scand 2001;72:433–441.
14. Lucht U. The Danish Hip Arthroplasty Register. Acta Orthop Scand 2000;71:433–439.
15. No authors listed. National Joint Registry 12th Annual Report. http://www.njrcen-
tre.org.uk/njrcentre/Portals/0/Documents/England/Reports/
12th%20annual%20report/NJR%20Online%20Annual%20Report%202015.pdf
(date last accessed 3 March 2016).
16. Matar WY, Jafari SM, Restrepo C, et al. Preventing infection in total joint arthro-
plasty. J Bone Joint Surg [Am] 2010;92-A:36–46.
17. Burke JF. The effective period of preventive antibiotic action in experimental inci-
sions and dermal lesions. Surgery 1961;50:161–168.
18. Lidwell OM, Lowbury EJ, Whyte W, et al. Infection and sepsis after operations
for total hip or knee-joint replacement: influence of ultraclean air, prophylactic antibi-
otics and other factors. J Hyg (Lond) 1984;93:505–529.
19. Boxma H, Broekhuizen T, Patka P, Oosting H. Randomised controlled trial of sin-
gle-dose antibiotic prophylaxis in surgical treatment of closed fractures: the Dutch
Trauma Trial. Lancet 1996;347:1133–1137.
20. Patzakis MJ, Wilkins J. Factors influencing infection rate in open fracture wounds.
Clin Orthop Relat Res 1989;243:36–40.
21. Lack WD, Karunakar MA, Angerame MR, et al. Type III open tibia fractures:
immediate antibiotic prophylaxis minimizes infection. J Orthop Trauma 2015;29:1–6.
22. Penn-Barwell JG, Murray CK, Wenke JC. Early antibiotics and debridement inde-
pendently reduce infection in an open fracture model. J Bone Joint Surg [Br] 2012;94-
B:107–112.
THE BONE & JOINT JOURNAL
 ANTIBIOTIC PROPHYLAXIS IN ORTHOPAEDIC SURGERY
23. Bratzler DW, Houck PM, Surgical Infection Prevention Guidelines Writers
Workgroup. Antimicrobial prophylaxis for surgery: an advisory statement from the
National Surgical Infection Prevention Project. Clin Infect Dis 2004;38:1706–1715.
24. Prokuski L. Prophylactic antibiotics in orthopaedic surgery. J Am Acad Orthop Surg
2008;16:283–293.
25. Classen DC, Evans RS, Pestotnik SL, et al. The timing of prophylactic administra-
tion of antibiotics and the risk of surgical-wound infection. N Engl J Med
1992;326:281–286.
26. Burke JP. Maximizing appropriate antibiotic prophylaxis for surgical patients: an
update from LDS Hospital, Salt Lake City. Clin Infect Dis 2001;33:S78–S83.
27. Johnson DP. Antibiotic prophylaxis with cefuroxime in arthroplasty of the knee. J
Bone Joint Surg [Br] 1987;69-B:787–789.
28. Bryson DJ, Gulihar A, Aujla RS, Taylor GJ. The hip fracture best practice tariff:
early surgery and the implications for MRSA screening and antibiotic prophylaxis. Eur
J Orthop Surg Traumatol 2015;25:123–127.
29. Williams DN, Gustilo RB. The use of preventive antibiotics in orthopaedic surgery.
Clin Orthop Relat Res 1984;190:83–88.
30. Nelson CL, Green TG, Porter RA, Warren RD. One day versus seven days of pre-
ventive antibiotic therapy in orthopedic surgery. Clin Orthop Relat Res 1983;176:258–
263.
31. Tang WM, Chiu KY, Ng TP, et al. Efficacy of a single dose of cefazolin as a prophy-
lactic antibiotic in primary arthroplasty. J Arthroplasty 2003;18:714–718.
32. Slobogean GP, Kennedy SA, Davidson D, O’Brien PJ. Single- versus multiple-
dose antibiotic prophylaxis in the surgical treatment of closed fractures: a meta-anal-
ysis. J Orthop Trauma 2008;22:264–269.
33. Southwell-Keely JP, Russo RR, March L, et al. Antibiotic prophylaxis in hip frac-
ture surgery: a metaanalysis. Clin Orthop Relat Res 2004;419:179–184.
34. Gillespie WJ, Walenkamp GH. Antibiotic prophylaxis for surgery for proximal fem-
oral and other closed long bone fractures. Cochrane Database Syst Rev
2010;17:CD000244.
35. Morrison S, White N, Asadollahi S, Lade J. Single versus multiple doses of anti-
biotic prophylaxis in limb fracture surgery. ANZ J Surg 2012;82:902–907.
36. Aujla RS, Bryson DJ, Gulihar A, Taylor GJ. Trends in orthopaedic antimicrobial
prophylaxis in the UK between 2005 and 2011. Ann R Coll Surg Engl 2013;95:495–
502.
37. Neu HC. Cephalosporin antibiotics as applied in surgery of bones and joints. Clin
Orthop Relat Res 1984;190:50–64.
38. No authors listed. Scottish Intercollegiate Guidelines Network: Antibiotic prophy-
laxis in surgery: a national clinical guideline. http://www.sign.ac.uk (date last
accessed 3 March 2016).
39. Privitera G, Scarpellini P, Ortisi G, et al. Prospective study of Clostridium difficile
intestinal colonization and disease following single-dose antibiotic prophylaxis in sur-
gery. Antimicrob Agents Chemother 1991;35:208–210.
40. Ambrose NS, Johnson M, Burdon DW, Keighley MR. The influence of single
dose intravenous antibiotics on faecal flora and emergence of Clostridium difficile. J
Antimicrob Chemother 1985;15:319–326.
41. Al-Obaydi W, Smith CD, Foguet P. Changing prophylactic antibiotic protocol for
reducing Clostridium difficile-associated diarrhoeal infections. J Orthop Surg (Hong
Kong) 2010;18:320–323.
42. Gulihar A, Nixon M, Jenkins D, Taylor GJ. Clostridium difficile in hip fracture
patients: prevention, treatment and associated mortality. Injury 2009;40:746–751.
43. Darley ESR, MacGowan AP. Antibiotic treatment of gram-positive bone and joint
infections. J Antimicrob Chemother 2004;53:928–935.
44. Brown AR, Vicca AF, Taylor GJ. A comparison of prophylactic antibiotic regimens
against airborne orthopaedic wound contamination. J Hosp Infect 2001;48:117–121.
45. Nanchahal J, Nayagam S, Khan U, et al. British Association of Plastic, Recon-
structive and Aesthetic Surgeons. Standards for the management of open fractures of
the lower limb. http://www.nvpc.nl/uploads/stand/100NVPC090000DOC-FN-Stand-
ards%20for%20Lower%20Limb.pdf (date last accessed 7 March 2016).
46. No authors listed. Medicines complete. https://www.medicinescomplete.com/mc/
bnflegacy/current/PHP3322-broad-spectrum-penicillins.htm (date last accessed 31
May 2016).
47. Vasenius J, Tulikoura I, Vainionpää S, Rokkanen P. Clindamycin versus cloxacil-
lin in the treatment of 240 open fractures. A prospective randomized study. Ann Chir
Gynaecol 1998;87:224–228.
48. Zimmerli W, Widmer AF, Blatter M, Frei R, Ochsner PE. Role of rifampin for
treatment of orthopedic implant-related staphylococcal infections: a randomized con-
trolled trial. Foreign-Body Infection (FBI) Study Group. JAMA 1998;279:1537–1541.
49. Zimmerli W. Antibiotic Prophylaxis. https://www2.aofoundation.org/wps/portal/
surgerymobile?contentUrl=/srg/popup/further_reading/PFxM2/
45_Antibio_prophyl.jsp&soloState=precomp&title=&Language=en (date last
accessed 7 March 2016).
VOL. 98-B, No. 8, AUGUST 2016
1019
50. Periti P, Mini E, Mosconi G. Antimicrobial prophylaxis in orthopaedic surgery: the
role of teicoplanin. J Antimicrob Chemother 1998;41:329–340.
51. Bratzler DW, Houck PM, Richards C, et al. Use of antimicrobial prophylaxis for
major surgery: baseline results from the National Surgical Infection Prevention Pro-
ject. Arch Surg 2005;140:174–182.
52. Jiranek WA, Hanssen AD, Greenwald AS. Antibiotic-loaded bone cement for
infection prophylaxis in total joint replacement. J Bone Joint Surg [Am] 2006;88-
A:2487–2500.
53. Johnson B, Starks I, Bancroft G, Roberts PJ. The effect of care bundle develop-
ment on surgical site infection after hemiarthroplasty: an 8-year review. J Trauma
Acute Care Surg 2012;72:1375–1379.
54. Webb JC, Spencer RF. The role of polymethylmethacrylate bone cement in modern
orthopaedic surgery. J Bone Joint Surg [Br] 2007;89-B:851–857.
55. Wahlig H, Dingeldein E, Buchholz HW, Buchholz M, Bachmann F. Pharmacoki-
netic study of gentamicin-loaded cement in total hip replacements. Comparative
effects of varying dosage. J Bone Joint Surg [Br] 1984;66-B:175–179.
56. Ollivere BJ, Ellahee N, Logan K, Miller-Jones JC, Allen PW. Asymptomatic uri-
nary tract colonisation predisposes to superficial wound infection in elective ortho-
paedic surgery. Int Orthop 2009;33:847–850.
57. Sousa R, Muñoz-Mahamud E, Quayle J, et al. Is asymptomatic bacteriuria a risk
factor for prosthetic joint infection? Clin Infect Dis 2014;59:41–47.
58. Cumming D, Parker MJ. Urinary catheterisation and deep wound infection after hip
fracture surgery. Int Orthop 2007;31:483–485.
59. Marschall J, Carpenter CR, Fowler S, Trautner BW; CDC Prevention Epicent-
ers Program. Antibiotic prophylaxis for urinary tract infections after removal of uri-
nary catheter: meta-analysis. BMJ 2013;346:3147.
60. Azzam K, Parvizi J, Jungkind D, et al. Microbiological, clinical, and surgical fea-
tures of fungal prosthetic joint infections: a multi-institutional experience. J Bone
Joint Surg [Am] 2009;91-A:142–149.
61. Aderinto J, Keating JF. Intramedullary nailing of fractures of the tibia in diabetics.
J Bone Joint Surg [Br] 2008;90-B:638–642.
62. Jämsen E, Nevalainen P, Eskelinen A, et al. Obesity, diabetes, and preoperative
hyperglycemia as predictors of periprosthetic joint infection: a single-center analysis
of 7181 primary hip and knee replacements for osteoarthritis. J Bone Joint Surg [Am]
2012;94-A:101.
63. Blotter RH, Connolly E, Wasan A, Chapman MW. Acute complications in the
operative treatment of isolated ankle fractures in patients with diabetes mellitus.
Foot Ankle Int 1999;20:687–694.
64. Ganesh SP, Pietrobon R, Cecílio WA, et al. The impact of diabetes on patient out-
comes after ankle fracture. J Bone Joint Surg [Am] 2005;87-A:1712–1718.
65. Flynn JM, Rodriguez-del Rio F, Pizá PA. Closed ankle fractures in the diabetic
patient. Foot Ankle Int 2000;21:311–319.
66. Costigan W, Thordarson DB, Debnath UK. Operative management of ankle frac-
tures in patients with diabetes mellitus. Foot Ankle Int 2007;28:32–37.
67. McCormack RG, Leith JM. Ankle fractures in diabetics. Complications of surgical
management. J Bone Joint Surg [Br] 1998;80-B:689–692.
68. Low CK, Tan SK. Infection in diabetic patients with ankle fractures. Ann Acad Med
Singapore 1995;24:353–355.
69. Kline AJ, Gruen GS, Pape HC, et al. Early complications following the operative
treatment of pilon fractures with and without diabetes. Foot Ankle Int 2009;30:1042–
1047.
70. Graham SM, Lubega N, Mkandawire N, Harrison WJ. Total hip replacement in
HIV-positive patients. Bone Joint J 2014;96-B:462–466.
71. Bates J, Mkandawire N, Harrison WJ. The incidence and consequences of early
wound infection after internal fixation for trauma in HIV-positive patients. J Bone
Joint Surg [Br] 2012;94-B:1265–1270.
72. Bongartz T, Halligan CS, Osmon DR, et al. Incidence and risk factors of prosthetic
joint infection after total hip or knee replacement in patients with rheumatoid arthri-
tis. Arthritis Rheum 2008;59:1713–1720.
73. Bongartz T, Sutton AJ, Sweeting MJ, et al. Anti-TNF antibody therapy in rheuma-
toid arthritis and the risk of serious infections and malignancies: systematic review
and meta-analysis of rare harmful effects in randomized controlled trials. JAMA
2006;295:2275–2285.
74. Giles JT, Bartlett SJ, Gelber AC, et al. Tumor necrosis factor inhibitor therapy and
risk of serious postoperative orthopedic infection in rheumatoid arthritis. Arthritis
Rheum 2006;55:333–337.
75. Scherrer CB, Mannion AF, Kyburz D, Vogt M, Kramers-de Quervain IA. Infec-
tion risk after orthopedic surgery in patients with inflammatory rheumatic diseases
treated with immunosuppressive drugs. Arthritis Care Res (Hoboken) 2013;65:2032–
2040.
76. No authors listed. Antibiotic/Antimicrobial Resistance. http://www.cdc.gov/dru-
gresistance/ (date last accessed 7 March 2016).