can combine with gentamicin or netilmicin. The phar- macokinetics of this combination are attractive. ; all the contained antibiotic becomes available for use and.
EDITORIALS
Antibiotic The
depots
concept
of
the
antibiotic
depot
is one
that
has
immediate sharp edge
appeal to orthopaedic surgeons. As with the of the scalpel, it makes sense to concentrate
effort where now ample
it is most likely scientific evidence
method
in a variety
be delivered
the
routes.
there is of the
conditions.
use of a depot
directly
allows
antibiotics
to the site of an infection
concentrations
tional
to be effective and for the usefulness
ofclinical
In principle,
higher
349
than can be achieved many times greater than
Levels
to
at much
secondary removed. merisation
bacterial The high inactivate
and
is some
there
well
understood,
with
(Chang
and
unpublished improved
when
the
structural
have
acquired
organisms
are
resistance
in
inherently vivo
resistant
by
developing
protective cocoon of slime or glycocalyx. Ideally, it should be possible to control release and
and the
recent
thereby
period
years
to the
The plaster
added 1982).
methacrylate employed treatment
acrylic
the form (Walenkamp in
antiseptics
(ALAC)
management
Most
the
material
acrylic
of
and
rapidly soon
of
Vancouver British
pellets,
antibiotic
is not
available
Orthopaedics,
Hospital, Canada
should
V5Z
J Bone Joint Surg [Br]
be sent
75-B, No. 3, MAY
1993
1993
was first and its Antibiotic-
;
and
1987 ; has some for
poorly
of
910
10th
use.
the
Avenue,
4E3. to Dr C. P. Duncan.
and Joint
75-B :349-50.
Surgery
Merritt
1992
work 1992). or at least for in
Vancouver,
; Kendall,
(Grisslime-
when are
Duncan
which
do
and
not
it is
sensitive Smith,
for an could
require
carrier
would
release
all the
the
contained
be compatible with the surrounding degradable so that it would not need If it were to react with the surrounding
tissues to be tissues
to promote healing by osseoinduction orosseoconduction, so much the better. The vehicle needs to be safe, costeffective, and easy to use. A biodegradable cement was investigated by Ocrhart was
et al in concern
substances
1988. about
It had obvious the potential
released
during
work by Ascherl of a bovine type with gentamicin
macokinetics
of this
contained material Careful
et al (1986) has led to the I collagen carrier which or netilmicin. The phar-
combination
antibiotic becomes is fully biodegradable control
advantages but there cytotoxic effects of the
its degradation.
Extensive development can combine
are
attractive
available for (Stemberger
in its manufacture
; all the use and the et al 1991).
is important
to avoid
an immune response (Dc Lustro et al 1986). Preliminary results ofclinical trials suggest that it is safe and effective,
with
and
even they
not to
of PMMA.
locked
and
are prone
organisms laboratory these
to PMMA
circumstances
soft-tissue healing, osseoconductive.
rate
that
There is therefore room an alternative depot that
characteristics
ideal
needs to be during polythermolabile
for reasons be uniquely
to which
promote tive nor
against
Columbia
adhere antibiotic
serious The
of Orthopaedics British
The antibiotic, and be removed.
an
not necessarily and Joka
implanted
protected
may
although Rosenthal
spacers Duncan et
remains
University
ofBone
widely
infections
so that
West
had
more
blocks
relatively
65
and Debeauand his co-
soon became
the
©l993 British Editorial Society 030l-620X/93/360l $2.00
VOL.
implanted
depot. This of infection arthroplasty.
diminishes
becomes
General
Columbia,
Correspondence
at least
who
1970; Buchholz et al expansion in joint use of polymethyl-
C. P. Duncan, MSc, FRCS C, Professor (PT) Head, Division of Reconstructive Orthopaedics B. Masri, MD, Resident and Research Assistant Department
back
or antibiotics
and Gearen however, ALAC
As a carrier,
elution
of the
of musculoskeletal
of beads, 1983 ; Borden
disadvantages.
of
date
and Engelbrecht with the rapid popularised the
cement
in the
the
characteristics
field
a
In
from
of elution.
in Leningrad,
(PMMA) as for the prophylaxis by direct-exchange
al 1992).
the rate
in this
to which
(Buchholz coincided replacement and
within
the
of
tissues.
of interest
(Peltier 1961 ; Mackey, Varlet The seminal work of Buchholz
1981)
applied
since
of Petrova
workers
loaded
a shift
rate
antibiotic
infected
used
a
the
of the
in the
been
efforts
work
of Paris
been mont
has carrier
earliest
to the
concentration
activity
determine
largely
years
its
there
antibiotic vehicle
the
of
be
or
that,
PMMA
bacteria
loaded
inhibitory concentration required to kill organisms are easily achieved, with little risk to the patient since systemic absorption is so low. This may be very important infecting
concern
and reached that are
colonisation by glycocalyx-producing tina and Costerton 1985). In the producing
by conventhe minimal
contamination, temperatures antibiotics
the addition
better 1991).
ofbone
than The
other depots (Letsch, collagen may itself
but it is neither Perhaps it might morphogenic
osseoinducbecome
protein
so
or marrow
aspirate. Ceramics have been extensively investigated as potential carriers for many therapeutic agents including antibiotics (Bajpai and Benghuzzi 1988). Hydroxyapatite granules containing been used in the
flucloxacillin canine model
or fosfomycin and in man
have with
encouraging early results (EitenmUller et al 1985), and Shinto et al (1992) have shown that hydroxyapatite blocks containing gentamicin have many ofthe desirable features of an ideal depot. latter group has compared loaded ceramic, ALAC, antibiotics in an animal
In its most recent report this the effectiveness of antibiotic-
and debridement modelofosteomyelitis
with
systemic (Korkusuz
EDITORIALS
350
et al 1993). The ceramic depot proved to be the best method of eradicating infection and it has the additional advantage that it is known to be osseoconductive (Uchida et al 1990). for prosthetic
It is not difficult to imagine components coated with
hydroxyapatite
or some
Many
other
including
naturally
bone),
depots
similar
potential
have
materials
from
been
(blood,
natural
materials
of the
current
recent
research
work
is as yet
and development
fibrin
De
Lustro
F, Condell
study
from
and
dermal
adherence
surfaces.
RA, Nguyen
of the biologic
derived
infected
and
(cellulose,
are aimed
Microbial
MA,
immunologic
collagen.
J Biomed
McPherson
on
Mater
Res
J. A comparative
response to medical devices J Biomed Mater Res 1986; 20:
Duncan CP, Beauchamp CP, Masn B, et al. The antibiotic loaded joint replacement system : a novel approach to the management of the
studied
unpublished.
K.
109- 120.
gelatin, protein polymers and monoclonal antibodies), and synthetic polymers (polylactic acid, polyglycolic acid and others). Silicone elastomer has also been studied for possible use in treating infected smalljoint replacements and in tendon reconstruction surgery (Lawson et al 1992). Much
Merritt
poly(methylmethacrylate)(PMMA) 1992; 26:197-207.
role
ceramic. carriers
occurring
derived
a potential antibiotic-loaded
CC,
Chang
knee
Suppl
replacement.
J Bone
Surg
[Br]
1992;
74-B
EitenmBller J, Schmidt KH, Peters G, et al. Experimental and preliminary clinical experience with absorbable calcium phosphate granules containing an antibiotic or antiseptic for the local treatment ofosteomyelitis. J Hosp Infect 1985 ; 6 Suppl A :177-84.
Gerhart TN, Roux RD, Horowitz experimental biodegradable
G, et al Antibiotic release from an bone cement. J Orthop Res 1988;
6:585-92.
Gristina
AG, Costerton JW. Bacterial tissue ; the significance of its role Surg[Am] 1985; 67-A :264-73.
While
Joint
III :296.
at improv-
adherence in clinical
to biomaterials sepsis. J Bone
and Joint
ing the deficiencies of PMMA, and it is likely that we will have better carriers in the near future, it is also likely
Korkusuz F, Uchida A, Shinto Y, et a]. Experimental implant-related osteomyelitis treated by antibiotic-calcium hydroxyapatite ceramic composites. J Bone Joint Surg [Br] 1993 ; 75-B :1 1 1-4.
that PMMA will continue to be used in circumstances which its mechanical qualities are also required.
Lawson
in
C. P. DUNCAN B. MASRI
I, Duncan ofTobramycin R acrylic
Letsch
CP, Beauchamp CP, et al. The elution characteristics from Silastic as compared to Simplex P and Palacos
cement.
Orthop
R, Rosenthal
Trans
E, Joka
1992 ; 16:102-3.
T. A comparative
study
of two
local
antibiotic carriers in the treatment of osteomyelitis of long bones. In : Stemberger A, Ascherl R, Lechner F, Bl#{252}melG, eds. Collagen as
a drug
carrier
Scientific
Ascherl R, Stemberger A, Lechner F, et al. Behandlung der chronischen osteomyelitis mit einem kollagen-antibiotika-verbund-vorlaufige mitteilung. Unfallchirurgie 1986; 12:125-7. PK, Benghuzzi chemicals Borden
and
Gearen
IS,
management.
Buchholz HW, Antibiotica 1970
;
.‘
some
1991
applications
London
in surgery.
: Franklin
:109-13.
Mackey D, Varlet A, Debeaumont D. Antibiotic loaded plaster of Paris pellets : an in vitro study of a possible method of local antibiotic
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THE JOURNAL
OF BONE
AND
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