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EDITORIAL

Periprosthetic joint infection


THE LAST FRONTIER

J. Parvizi,
F. S. Haddad
From The British
Editorial Society of
Bone and Joint
Surgery, London,
United Kingdom

J. Parvizi, MD, FRCS,


Orthopaedic Surgeon
The Rothman Institute, 925
Chestnut St, Philadelphia,
PA 19107, USA.
F.S. Haddad, BSc MD (Res),
FRCS (Tr&Orth), Professor of
Orthopaedic Surgery,
Editor-in-Chief
The Bone & Joint Journal,
22 Buckingham Street, London,
WC2N 6ET, UK.
Correspondence should be sent
to Professor F. S. Haddad:
editorbjj@boneandjoint.org.uk
2015 The British Editorial
Society of Bone & Joint
Surgery
doi:10.1302/0301-620X.97B9.
37018 $2.00
Bone Joint J
2015;97-B:11578.

The number of publications in the literature


related to periprosthetic joint infection (PJI)
has risen 100 fold during the last decade. This
confirms the fact that this is a dreaded complication in the minds of the medical community.
Infection also strikes fear in the hearts of
patients who contemplate joint replacement,
arguably one of the most successful surgical
procedures. The challenges that PJI pose are
many. Despite intense interest over the years,
we could argue that little has changed in the
management of PJI. The scientific community,
however, has intensified its efforts in dealing
with this issue and we foresee major accomplishments in the near future.
In this edition of The BJJ, a number of facets
of infection are addressed.We would like to
stress the increasing importance of the reporting of infections and of surveillance programmes. Andy Toms and his team attempt to
raise awareness of the importance of this. It
would be wise for all units to validate their
infection data on a regular basis in order to
understand the incidence and gravity of
periprosthetic sepsis in their practice.1
Tanner et al2 have recently published a
national survey of surgical site infection surveillance. They received data from 106 of the
156 Trusts in the United Kingdom, and found
considerable differences in both the methods of
collecting data, and the quality of reporting.
Inevitably those with high-quality surveillance
programmes had much higher infection rates
than those without them. Different definitions
were used by different Trusts, and some did
not submit their full data. The reality is we are
a long way from understanding the true prevalence of surgical site infection and how to deal
with it.
Shafafy et al3 have capitalised on the difficulties of diagnosis to share their experience
with leucocyte esterase strips. This is definitely
not the final solution to the diagnosis of
periprosthetic infection, but it is certainly a
step in the right direction, and heralds the
exciting prospect of using biomarkers as more

VOL. 97-B, No. 9, SEPTEMBER 2015

sophisticated, sensitive and specific tests. It is


likely that they will ultimately be used at the
bedside.4
John Herzenberg and his group5 highlight a
series of complex infections that are seen with
external fixators, including necrotising fasciitis
and toxic shock syndrome, both of which must
be recognised early by orthopaedic surgeons,
and both of which require early intervention.
Strategies to avoid such severe complications
would clearly be welcome.6
Many novel adjunctive strategies are
focused on improving the management of
infection. One of these is antibiotic eluding
absorbable calcium sulphate beads,7,8 We document a rare but nevertheless very worrying
complication that we have seen with an otherwise successful technique.9 There is a great
deal more to learn in this area.
Infection presents in a variety of forms
around the world, and we are reminded by
Mahale and Aga of the complexities of managing tuberculous infection around fractures and
implants.10
It is remarkable that in a non-themed issue,
we should have covered so much ground in
relation to infection. It is only by focusing a
great deal of resource in this area that we are
likely to move forward and resolve some of the
problems that face us.11-15
Looking to future developments, we would
like to highlight three main areas.
Firstly, and on the heels of developments in
cancer research, we have come to realise that
enhancing the immune system of the patients
to battle infection may be more efficacious
than the administration of systemic drugs with
toxicity. Thus, immunotherapy either by the
administration of vaccines (passive immunity)
or active immunotherapy by the administration of agents that target the infective microenvironment and bridge the innate and
adaptive immune response, is promising. Furthermore, and thanks to the human genome
project, genetic susceptibility to PJI is being
unraveled. Recent data suggest that the C allele
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J. PARVIZI, F. S. HADDAD

and genotype C/C for MBL-550 SNP, genotype A/A for


MBL-54 SNP and G allele for MBL-221 SNP increase the
risk of PJI, while G allele and genotype G/G for MBL-550
SNP decrease the risk of PJI in Caucasian populations.16
Thus, genetic or epigenetic manipulation in the future may
lend itself to combating a condition that has much to do
with genetic susceptibility.
Secondly, novel strategies are needed to prevent the adhesion of infecting organisms to the surface of foreign material implanted in humans. Despite a strict antiseptic
protocol in surgical suits, many bacteria gain access to the
surgical site. The immune threshold of the host and the
quantity of infecting organisms in the surgical site (the
bioburden) determine whether the contamination eventually translates to a clinically manifest infection. Although
much effort has been invested in developing self-protective
smart implants,17 the main hurdles in the way of introducing such technologies to orthopaedics are regulatory barriers. The regulatory agencies have traditionally insisted on
data that demonstrate reduction in PJI. The latter would
imply that an Investigational Device Exemption (IDE)
study be conducted to prove such efficacy, and that would
require thousands of patients and many years for patient
enrollment at an astronomical cost to the developers of
such technology. It is hoped that the policy of the regulatory
agencies will change so as to allow the conduct of scientifically valid, but less cumbersome studies, in the future.
Finally, another promise for the future lies in our ability to
eradicate biofilm.18 Many technologies to deal with this issue
are already in development or have been evaluated in preclinical models. Any ability to prevent the attachment of
organisms to the surface of the implant (by removing production of adhesion molecules, for example), preventing
their proliferation (by inducing an apoptotic agent, for
example), or preventing molecular communications between
the organisms (by disrupting quorum sensing, for example)
may have a promise in helping us circumvent PJI, a truly
endemic problem that has placed an immense burden on
society and the patients who are affected.
The future looks more promising as the medical community starts to focus its energy collectively on an issue that
has been overlooked for too long.

References
1. Patel A, Pavlou G, Ahmad RA, Toms AD. Do you have an infection problem?
Bone Joint J 2015;97-B:11701174.
2. Tanner J, Padley W, Kiernan M, et al. A benchmark too far: findings from a
national survey of surgical site infection surveillance. J Hosp Infect 2013;83:8791.
3. Shafafy R, Mcclatchie W, Chettiar K, et al. Utilisation of leucocyte esterase
reagent strips in the diagnosis or exclusion of prosthetic joint infection. Bone Joint
J 2015;97-B:12321236.
4. Deirmengian C, Kardos K, Kilmartin P, et al. Diagnosing periprosthetic joint
infection: has the era of the biomarker arrived? Clin Orthop Relat Res
2014;472:32543262.
5. Jauregui JJ, Bor N, Thakral R, et al. Life- and limb-threatening infections following the use of an external fixator. Bone Joint J 2015;97-B:12961300.
6. Uehara K, Yasunaga H, Morizaki Y, et al. Necrotising soft-tissue infections of
the upper limb: risk factors for amputation and death. Bone Joint J 2014;96B:15301534.
7. Roman CL, Logoluso N, Meani E, et al. A comparative study of the use of bioactive glass S53P4 and antibiotic-loaded calcium-based bone substitutes in the
treatment of chronic osteomyelitis: a retrospective comparative study. Bone Joint J
2014;96-B:845850.
8. Ferguson JY, Dudareva M, Riley ND, et al. The use of a biodegradable antibiotic-loaded calcium sulphate carrier containing tobramycin for the treatment of
chronic osteomyelitis: a series of 195 cases. Bone Joint J 2014;96-B:829836.
9. Kallala RF, Haddad FS. Hypercalcaemia following the use of antibiotic-eluting
absorbable calcium sulphate beads in revision arthroplasty for infection. Bone Joint
J 2015;97-B:12371241.
10. Mahale YJ, Aga N. Implant-associated mycobacterium tuberculosis infection following surgical management of fractures: a retrospective observational study.
Bone Joint J 2015;97-B:12791283.
11. Conway J, Mansour J, Kotze K, Specht S, Shabtai L. Antibiotic cement-coated
rods: an effective treatment for infected long bones and prosthetic joint nonunions.
Bone Joint J 2014;96-B:13491354.
12. Ibrahim MS, Raja S, Khan MA, Haddad FS. A multidisciplinary team approach
to two-stage revision for the infected hip replacement: a minimum five-year followup study. Bone Joint J 2014;96-B:13121318.
13. Chang YH, Tai CL, Hsu HY, et al. Liquid antibiotics in bone cement: an effective
way to improve the efficiency of antibiotic release in antibiotic loaded bone
cement. Bone Joint Res 2014;3:246251.
14. Fleiter N, Walter G, Bsebeck H, et al. Clinical use and safety of a novel gentamicin-releasing resorbable bone graft substitute in the treatment of osteomyelitis/osteitis. Bone Joint Res 2014;3:223229.
15. Chang Y, Tai CL, Hsieh PH, Ueng SW. Gentamicin in bone cement: A potentially
more effective prophylactic measure of infection in joint arthroplasty. Bone Joint
Res 2013;2:220226.
16. Zhou X, Yishake M, Li J, et al. Genetic susceptibility to prosthetic joint infection
following total joint arthroplasty: A systematic review. Gene 2015;563:7682.
17. Parvizi J, Antoci V Jr, Hickok NJ, Shapiro IM. Self-protective smart orthopedic
implants. Expert Rev Med Devices 2007;4:5564.
18. Chen M, Yu Q, Sun H. Novel strategies for the prevention and treatment of biofilm
related infections. Int J Mol Sci 2013;14:1848818501.

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