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282
Fig. 19.15 Coverage with gel mixed with rifampicin in one stage with sensitivity to rifampicin. (Reproduced with
permission of Sage from Ref. [119])
F. Da Rin de Lorenzo and J. Parvizi
Disadvantages:
• Delayed direct loading in waiting for
osseointegration
• The release time of the antibiotic is not
evident
Even today it is not known what the duration
of the DAC is even if the Authors report that the
greatest concentration must occur in the rst
48hours, i.e. the time necessary for the formation
of the biolm, and that in the following time, it
can be eliminated having nished its task.
19.6 Prostheses Already
Packaged by theCompanies
19.6.1 Covering withSilver (PorAg®
Surface) (Figs.19.16
and19.17) [124–132]
Silver has always been used as an antimicrobial. In
4000BC the Egyptians used silver-coated water
tanks and in 1200BC the Phoenicians used silvercoated amphorae to transport food. In 78AD Pliny
the Elder began treating wounds with silver, in
950BC Haian As Sus used honey and silver, in
powder form, to treat tonsillitis and in 1881AD
Dr. Cari Crede used silver nitrate eye drops for eye
infections. Thus the silver coating increases surface resistance to abrasion, a decreases the elimination of Co, Cr, Ti ions, and also has a
demonstrated antibacterial effect Together with
mercury it represents two effective natural elements for killing bacteria Henry Crookes (1910)
[125] demonstrated that B Coli communis was
killed in 2minutes using mercury and in 6 using
silver colloid. Another study from these early
years is that of Simpson and Hewlett [126] published in “The Lancet” in 1914. They used the suspension of colloidal silver to kill the typhoid
bacillus in 15minutes at 500ppm and in 2hours at
5ppm. This was the rst time in which low concentrations of colloidal silver proved effective. An
important consideration by Simpson and Hewlett
was to state that the great advantage of colloidal
elements, used in such low concentrations, is that
they are completely harmless to patients.
Research has conrmed that no organism
capable of causing disease (bacteria, viruses and
fungi) can live more than a few minutes in the
presence of a trace, albeit tiny, of metallic silver,
which appears to be one of the most powerful
natural antibacterials without side effects.
19 Periprosthetic Joint Infection: General Aspects
Fig. 19.16 This example shows a galvanic reaction between zinc and copper where zinc is eliminated (Zn anode) and
copper is added (Cu cathode)
283
RO Becker [133], from his research on the use
of silver in medicine, deduced that the deciency
of silver in the organism is responsible for the
improper functioning of the immune system and
that silver is not only a powerful antibacterial.
Colloidal silver is non-toxic to mammals, reptiles
and all life forms that are not single-celled. Silver,
however, like the most powerful chemical disinfectants, is toxic to primitive life forms such as
microorganisms. Single-celled life forms use different chemical processes. For oxygen metabolism. The presence of silver, especially in the
Fig. 19.17 A silver megaprosthesis. (Courtesy
R.Capanna)
form of colloid nanoparticles, interrupts the
enzymatic metabolic cycle and causes suffocation and death within six minutes; at that point,
Multiple tests, in different districts such as
urology, neurosurgery, cardiology, skin lesions,
have demonstrated the validity of silver as an
antiseptic:
the immune, lymphatic and purifying systems
will take care of their expulsion. The action of
colloidal silver is so fast that the pathogen does
not have time to mutate into a resistant strain. The
xation of silver to titanium occurs galvanically,
• Hsu. Biomaterials 2010
• Khalipour, J Biomed Mater Res B 2010
like all prosthesis coating formations.
There are four types of silver:
• Juan. Int J Nanomedicine 2010
• Song. J Biomed Mater Res A 2009
• Chen, J Biomed Mater Res A 2007
• Furno. J Antimictob Chemother 2004
• Sheehan. J Orthop Res 2004
• Blaker. Biomaterials 2004
1. Ionic silver
2. Ionic silver with the addition of proteins for
stabilizing purposes
3. True colloidal silver, made up almost exclusively of nanoparticles, industrially produced
284
Advantages
F. Da Rin de Lorenzo and J. Parvizi
4. Silver salts sold as drugs or medical aids
surgical.
The silver used is colloidal as it does not precipitate forming a salt and silver colloids are used
with particles of an average size of 10–15nm
practically free of ionic silver. It is added through
the industrial process of electrolysis In a work
review done on 23 studies, by Hua Li and other
authors [129] demonstrated some cases of
Argyria while no cases with gentamicin coating
and only one case of anaphylactic reaction to
iodine-coated prosthesis. For silver, the greatest
effort has been made in dressings, especially in
burns because it is antiseptic and stimulates granulation, while in the orthopedic eld, it has been
used in megaprostheses after the removal of a
bone tumor where both local and general conditions (just think of the antiblastic) are very at risk
of infection with an average of 7–23% Capanna
[127, 128] brought his work to 516 megaprostheses made from 2000 to 2015 (427 oncological
and 89 non-oncological) where he demonstrated
a lowering of the percentages of infection A work
by Handrik Hardes [132, 134] compared 74
megaprostheses made only of titanium with 51
megaprostheses made of titanium with a silver
covering and highlighted that in the rst case
there were 17.6% infections and 38% amputations In the second group there were 5–6% infections and no amputations.
A study comparing DAC and silver highlighted the longer duration of the antibacterial
effect of silver compared to DAC.Even today it
is not known what the duration of the DAC effect
is, even if the Authors report that the greatest
concentration must occur in the rst 48hours of
biolm formation time and which can be eliminated in the following time having nished its
task.
A study comparing titanium megaprostheses
(74 cases) and titanium Ag megaprostheses (51
cases) had the following result:
74 Cases
Megaprosthesis in
titanium
17.6% infection 5.9% infection
38.5% amputation No amputation
51 Cases Megaprosthesis
in titanium Silver
19.6.2 Prosthesis Cover withIodine
(Figs.19.18 and19.19)
[135–138]
Other studies involve the application of a coating
with Gentamicin or vancomycin [139–141].
Below the Figs.19.20 and 19.21, representing
the various elements currently used as prosthetic
coverings.
Fig. 19.18 Iodine-coated prosthesis. (Courtesy Hiroyuki
Tsuchiya)
Iodine vs Silver
no systemic toxicity
1
(Iodine is excreted from the kidney.)
2
essential trace element
(thyroid hormone)
osteoconductive
3
4
shelf-life: more than
10 years
reasonable cost
5
Fig. 19.19 A comparison between the silver-coated
prosthesis and the iodine-coated prosthesis [135–138]
1
(Metabolism is not clear)
2
3
4
(highest concentration on a few days)
5
SilverIodine
anxious for toxicity
foreign substance in the body
disturbed osteoconduction
no continuous release
expensive
obial peptides
s
StrategyFeatures Examples
19 Periprosthetic Joint Infection: General Aspects
Implants
Coatings
285
Antimicrobial
releasing based
coatings
MetalsAntisepticsAntibiotics Metal oxides Furanones
Fig. 19.20 Shows the various coatings. (Reproduced
with permission from [141] under the terms of the
Creative Commons Attribution-NonCommercial 4.0
License (
https://creativecommons.org/licenses/by-
nc/4.0/) which permits non-commercial use, reproduction
Fig. 19.21 Examples
of anti-infective
strategies proposed for
the antibacterial
treatment of implantable
Prevention in adhesion
and adsoiption
surfaces used in
orthopedic surgery.
(Reproduced from Gallo
etal. [142] under the
terms of Creative
Commons Attribution
(CC BY) license)
Methods to
kill bacteria
Multi-functional
and smart coating
Alternative approach
Antimicrobial
Coatings
Antifouling
coatings
Metal oxide
nanoparticles
Antimicrobial
non-releasing
based coatings
Superhydrophobic
Cationic
polymers
NaturalSynthetic
PolyzwitterionicPEG-based
and distribution of the work without further permission
provided the original work is attributed as specied on the
SAGE and Open Access pages (https://us.sagepub.com/
en- us/nam/open- access- at- sage))
Anti-adhesive polymers
Albumin
Super-hydrophobic surfaces
Nano-patterned surface
Hydrogels
Silver nanopruticles
Titanium dioxide
Inorganic
Selenium ion
Copper ion
Zinc ion
Coated or covalently linked antibiotics
Chitosan derivatives
Organic
Signaling, inhibiting and antimicr
Cytokines
Enzymes
Other
Non-antibiotic bactericidal substances
Multilayer coating
Combined
Synergy material intensification
Positively charged polymers
Passive
Active
Nanostructured “smart” material
Concept: sensors conjoined to nanocontainer
Lytic bacteriophages
Enzyme-based
At the conclusion of this chapter, it seems
important to underline another big problem,
the antibiotic resistance that we have in Italy
according to the European antibiotic resistance
surveillance report (2015) [143]. In Fig.19.22
the antibiotic resistance of K. pneumoniae to
carbapenems in Europe. In Fig.19.23 the resistance, again in Europe, of methicillin-resistant
Staphylococcus aureus. Finally, in Fig. 19.24
the evolution over time of various germs to
antibiotic resistance. Note the Italian
situation.
Tuberculosis should also be remembered
which in Italy, after the landings of immigrants,
is increasing with an extrapulmonary—bone
localization of 10% (Fig.19.25) [144, 145].
286
<1%
1% to <5%
5% to <10%
10% to <25%
25% to <50%
50%
No data reported or fewer than 10 isolates
Not included
Non-visible countries
Liechtenstein
Luxembourg
Malta
F. Da Rin de Lorenzo and J. Parvizi
Fig. 19.22 K. pneumoniae: percentage of isolates resistant to carbapenems by country and Italy, as you can see, has
among the highest resistances EU/EAA area—2015 data
<1%
1% to <5%
5% to <10%
10% to <25%
25% to <50%
50%
No data reported or fewer than 10 isolates
Not included
Non-visible countries
Liechtenstein
Luxembourg
Malta
Fig. 19.23 For the S. aureus, same situation of resistance in Italy. Here you see the percentage of isolated methicillin-
resistant strains (MRSA), by country, EU/EAA area—2015 data
%
19 Periprosthetic Joint Infection: General Aspects
287
Fig. 19.24 Evolution of the main bacterial resistance
over time. Courtesy of dell Ufcio Federale della Sanità
Pubblica (UFSP) in Italian - Bundesamt für Gesundheit
Fig. 19.25 Percentages of extra-pulmonary tuberculosis localizations
Therefore, based on the data reported, the prevention of these pathologies becomes fundamental and all scientic and industrial efforts must go
in this direction.
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