Injury, Int. J.

Care Injured (2006) 37, S87—S94

www.elsevier.com/locate/injury

Principles of systemic antimicrobial therapy in

foreign material associated infection in bone tissue,
with special focus on periprosthetic infection
Lars Frommelt

Institut für Infektiologie, klinische Mikrobiologie und Krankenhaushygiene, ENDO-Klinik Hamburg GmbH,
Hamburg, Germany

KEYWORDS:
Foreign body
associated infec-
tion; osteomyelitis;
anti-infective chemo-
therapy; 1-staged
revision; 2-staged
revision; therapy for
suppression.
Summary1 Foreign material associated infection in bone tissue is mostly char-
acterized by the features of sessile pathogens acting from the foreign material
surface. These bacteria protected by biofilm attached to the surface are highly
resistant for antimicrobial agents and host’s own defense as well.
Therapy is based on surgical revision, with removal of the foreign material and
supplementary antimicrobial therapy. Empirical antimicrobial therapy cannot be
recommended unless life threatening septicemia occurs.
Infected bone tissue is lower compartment with respect to antimicrobial chem-
otherapy. Therefore, antibiotics must be administered in high dosage for an
extended period of time. It is almost impossible to eradicate these pathogens by
antibiotics alone even though the clinical symptoms may be influenced.
The options of antimicrobial therapy are:
1. Antibiotics alone: Only suppression of clincal symptoms. 2. Amputation or resec-
tion arthroplasty in combination with antibiotics: The results are fair but poor in
function. 3. Surgical revision with retention of the foreign material and long-term
antibiotic therapy including rifampicin: This procedure is possible in early, not yet
established foreign material infections. 4. Treatment of the periprosthetic infec-
tion: Surgical revision with exchange of the prosthesis combined with systemic
(and optional local) therapy, regardless whether the revision is performed in 1- or
multiple-stages. Treatment of these infections should be carried out in special-
ized centers in cooperation with an experienced infectious disease specialist.
Since most available data are empirical, further prospective studies are needed
for evaluation of these therapeutic concepts.

Introduction that of other infections in humans, which should

Infection of artificial joint replacement or other
foreign material incorporated into bone tissue is a
rare complication in orthopedic surgery. The formal
pathogenesis of this type of infection differs from
1 Abstracts in German, French, Italian, Spanish, Japanese,
and Russian are printed at the end of this supplement.
be taken into account when selecting antimicrobial
agents for treatment.
Foreign body infection results from colonization of
the artificial surface by specialized bacteria that
are able to form a biofilm [1]. Bacteria living in a
biofilm are highly resistant to antimicrobial agents
and the biofilm protects them from the influence of
the host’s defense [2]. Sessile bacteria in the biofilm

0020–1383/$ — see front matter # 2006 Published by Elsevier Ltd.

doi:10.1016/j.injury.2006.04.014
S88
only make a small contribution to the inflammatory
reaction in the surrounding bone tissue [3]. This
reaction results grossly from bacteria that switched
back to the planktonic form, which is well recognized
in most infectious lesions in humans. If antibiotics
are used in foreign body associated infection, they
act almost exclusively on the planktonic bacteria.
Defeating these bacteria means gaining control the
symptoms of the infection but not the infectious
disease, resulting in a condition that makes it con-
venient for the physician to prescribe antimicrobial
agents, with the patients being released from their
complaints as long as the antimicrobial agents are
being administered. If antibiotics are discontinued,
the infectious disease restarts, caused by pathogens
released from the biofilm on the surface of the
colonized foreign body. A further problem is that
pathogens in the biofilm are able to obtain resist-
ance to antimicrobial agents by selection of resistant
subpopulations or developing resistance by mutation
of the bacterial genome [4].
Apart from some rare conditions, surgical removal
of the foreign material is necessary for the treatment
of periprosthetic infection and other foreign mate-
rial associated infections [5]. Antimicrobial therapy
is able to support the surgical therapy and ensure
the success of the measures taken [6, 7].
The following sections describe the options for
systemic use of antimicrobial agents as reported
empirically.
Antimicrobial agents and foreign
material associated infection in bone
tissue
Osteomyelitis alone is a difficult disease to treat
because bone tissue is functionally in a lower
compartment with respect to pharmacokinetics of
drugs acting on bone tissue. Inflammation results in
hyperemia in tissue in general, which in turn causes
hyperthermia and swelling. Since bone tissue can-
not expand, due to its mineral “skeleton”, swelling
leads to a reduction in the blood supply and conse-
quently reduces the supply of drugs transported in
the bloodstream [8]. It may even lead to necrosis of
bone tissue, so-called sequestra.
Mader and coworkers showed that most systemi-
cally applied antimicrobial agents are only available
in low concentration under these circumstances at
the site of infection [8].
Another point for consideration is the time re-
quired for revascularization after osteotomy, which
takes about three weeks in animal experiments.
The consequence for bone infection therapy is that
L Frommelt
antimicrobial agents have to be administered at
high doses for at least three weeks. The choice of
antibiotics also has to account for the susceptibility
pattern of the causative pathogen [9].
Apart from some rare exceptions, osteomyeli-
tis cannot be controlled by antimicrobial therapy
alone. Although surgical debridement and removal
of necrotic bone tissue are mandatory, additional an-
tibiotic therapy is a further benefit for the patient.
Antibiotics can prevent bacteria left in the wound
from perpetuating bone infection.
If foreign material is involved in bone-tissue infec-
tion, the situation is worse because the surface of
foreign material covered by sessile bacteria acts as
reservoir for relapsing infection. It is almost impossi-
ble to eradicate these bacteria protected by biofilm
without removing the foreign material [4, 10].
General rules for the use of
antimicrobial agents in bone infection
Since there is a very wide range of causative bacte-
rial agents with varying susceptibility patterns, the
pathogen causing the infection must be isolated and
identified to select an appropriate antimicrobial
therapy. An empirical therapy cannot be recom-
mended for treating these chronic infections. Life-
threatening septicemia and other dramatic symp-
toms in patients are exceptional conditions in which
empirical antimicrobial therapy is necessary.
The choice of antibiotic agents follows the po-
tential susceptibility pattern and availability of the
antibiotics in infected bone tissue. Before this life-
saving therapy is initiated, specimens must be taken
for microbiological investigation. Specimens from
the site of infection are preferable, such as aspi-
rates of joint fluid, biopsies of infected tissue, and,
if septicemia is suspected, blood cultures. Therapy
can then be adjusted to the microbial records, if
necessary.
Antimicrobial therapy of bone tissue infections has
to account for the reduced availability of drugs in
bone inflammation. This therapy needs to provide a
high dosage of the agents over an extended period
of time. If possible, treatment should be sequential,
starting with intravenous administration, followed
by a period of oral application of the antibiotics.
A minimum antibiotic therapy of 4−6 weeks is
widely accepted as suitable [10, 11], based on
empirical findings and supported by animal experi-
ments by Mader and coworkers, who showed that
the period of reconstruction of blood vessels after
osteotomy takes 3−4 weeks [8]. If local antibiotics
are used, eg, in antibiotic-loaded bone cement, the
Principles of systemic antimicrobial therapy in foreign material associated infection
period of systemic therapy can be shorter because
of long-term elution of antimicrobial agents at the
site of infection [7, 12].
In long-term antibiotic therapy, physicians must
be aware of unwanted side-effects and interactions
with other drugs. Liver and renal function should
be included in the monitoring program for tailoring
the dosage to avoid the patient being harmed by
the drugs.
Table 1 shows some antibiotics that may be used
for therapy of bone-tissue infection.
The following section describes the options for
correct use of antibiotics in the presence of foreign
material.
Option 1: Antibiotics alone (suppression
of infection not control)
In rare situations such as hematogenous osteomyeli-
tis in childhood, systemically administered antibiot-
ics alone may succeed in controlling a bone infec-
tion. However, in the presence of foreign material,
this is almost impossible. This option is reserved for
patients who cannot be operated on and who will
perhaps need life-long therapy.
There is some data available on the success of an-
timicrobial therapy alone in artificial joint replace-
ment. Bengtson reported a success rate of 11% for
the treatment of artificial knee replacement, with
a follow-up of five months [13]. Tattevin reported a
success rate of about 20%, depending on the early
onset of therapy after the appearance of the first
symptoms of infection, and in some of these cases
surgical revision was performed [14]. Brause and
co-workers stated that a suppressive therapy of
periprosthetic infection is possible and delineated
the following prerequisites [15]:
1. Removal of the prosthesis is impossible.
2. Presence of a less virulent pathogen.
3. High susceptibility of the pathogen to antibiotics
that can be administered orally.
4. Compliance of the patient for the antibiotics
chosen.
5. The function of the artificial joint is not impaired
(no loosening).
This (life-long) suppression of periprosthetic in-
fection worked successfully in 63% of these excep-
tional patients, as reported by Goulet [16].
This kind of therapy is the last resort in difficult
cases and should be performed in consultation with
an infectious disease specialist. It needs to be dis-
tinguished from the emergency use of antibiotics to
S89
control a life-threatening condition, which is carried
out with the intention of restoring the patient to a
condition that allows surgical treatment.
Option 2: Systemic antibiotics and
removal of foreign material alone
This option is the most radical approach to a for-
eign-material infection and leads to amputation or
other functional deficiencies such as Girdlestone’s
arthroplasty. The success of these measures is fair,
but they result in loss of function for the patient.
Antibiotic therapy has to be defined for the in-
dividual case and it depends on whether resection
into an area free of infection is possible. Systemic
antimicrobial therapy should be administered at a
high dosage for at least 4−6 weeks. The choice of
antibiotic should follow the susceptibility pattern
of the pathogen identified beforehand and may be
adjusted by findings obtained from specimens taken
during surgery.
Option 3: Surgery, retention of foreign
material, and antibiotics
Most antimicrobial agents are unable to influence
bacteria that are sessile in a biofilm on artificial
surfaces. The only agent with a proven effect on
sessile staphylococci is rifampicin [5]. The success
of rifampicin has been reported for several combi-
nations, especially with chinolones [17]. However,
therapy with rifampicin alone is not possible because
it induces resistance in staphylococci within 24 hours
if administered alone. This effect can be avoided if
rifampicin is combined with another antimicrobial
agent that also affects the pathogen.
Option 3.1: Artificial joint replacement
Tattevin and coworkers reported a success rate of
about 20% after systemic antimicrobial therapy and
retention of the artificial joint replacement [14].
Success depended on the early onset of therapy, and
the probability of success was improved in cases with
surgical revision. Zimmerli and Ochsner’s group in
Switzerland developed a protocol for these cases,
with strict rules for the eligibility of patients for
this therapy [5]. Eligible cases include patients with
an artificial joint replacement that was integrated
into the function of the joint and whose symptoms
of periprosthetic infection had not been present for
S90 L Frommelt

Pathogen Therapy of first choice Alternative therapy

Antimicrobial Dosage (the dosage rec-

agent ommended applies to
adults)

Staphylococci

Methicillin-susceptible Flucloxacillin 4 x 2 g / iv /day Cephalosporin (1st /2nd generation)

Vancomycin (2 x 1 g / iv /day)

Methicillin-resistant Vancomycin 2 x 1 g / iv /day Teicoplanin

(2 x 400 mg / iv/ 1st day, then
1 x 400 mg / iv /day)

Levofloxacin (2 x 500 mg/ p. os / day) +

Rifampicin (10 mg/ kg BW in 2 portions)

Fosfomycin (3 x 5 g / iv /day)

Linezolid (2 x 600 mg / iv or p. os / day)

Streptococci Penicillin G 4 x 5 Mio. IE / iv/ day Ceftriaxon (1 x 2 g / iv /day)

S. pneumoniae

Enterococci Ampicillin + 4 x 3 g /iv/day Vancomycin (2 x 1g / iv /day)

Sulbactam
Gentamicin 3 x 1 mg /kg BW*/iv/day Linezolid (2 x 600 mg / iv or p. os / day)

Enterobacteriaceae Ciprofloxacin 2 x 750 mg / p. os / day Cephalosporin (2nd / 3rd generation) i.v.

Haemophilus influenzae
Levofloxacin 2 x 500 mg / p. os /day

Pseudomonas aeruginosa Ceftazidim or 3 x 2 g / iv / day Imipenem / Cilastatin (4 x 500 mg / iv /

Cefipime day) + Aminoglycoside

Gentamicin 3 x 1 − 1.5 mg/ kg BW* / Piperacillin / Tazobactam + Aminogly-

iv /day coside
Piperacillin / Tazobactam ( 3 x 4, 5 g / iv
/ day) +
Ciprofloxacin (2 x 750 mg / p. os / day)

Anaerobes Clindamycin 3 x 600 mg / iv / day Ampicillin + ß-Lactamase-Inhibitor (eg,

ampicillin + sulbactam 4 x 3 g / iv /
day)

Imipenem / Cilastatin (4 x 500 mg / iv /

day)

Metronidazole (3 – 4 x 500 mg / iv/ day)

Explanations: iv = intravenous; p. os = oral; BW = body weight; * = relevant body weight for dosage of
aminoglycoside antibiotics = ideal body weight (height [cm]- 100) + 40 % of the overweight.

Table 1: Antimicrobial agents suitable for treatment of osteomyelitis and foreign body associated infection in bone
tissue (modified after Koch and Masche [9]).
Principles of systemic antimicrobial therapy in foreign material associated infection
longer than two weeks. In these cases, surgical revi-
sion was performed with meticulous debridement
of infected tissue and retention of the prosthesis.
Suction-irrigation drainage using polxyhexanide was
performed for three days and systemic antimicrobial
chemotherapy with chinolones such as ciprofloxacin
and rifampicin was carried out for 3−6 months. Suc -
cess was reported in up to 85 % of patients in whom
the protocol was strictly followed [5].
Another similar approach for infections that oc-
cur early after implantation of an artificial joint
replacement was developed in the ENDO-Klinik in
Germany. If infection occurs within 3−4 weeks of im -
plantation, suction-irrigation drainage is performed
immediately after the first symptoms of infection
arise. This measure is accompanied by systemic
antimicrobial therapy for 3−4 weeks. The success
rate of this procedure is about 50 % if Staphylococ-
cus aureus or ß-hemolytic streptococci are causing
the infection [18].
Option 3.2: Other foreign material as devices for
osteosynthesis
Osteomyelitis and septic nonunion of fractures af-
ter osteosynthesis are special problems that cannot
be solved by systemic antimicrobial chemotherapy
alone. Repeated surgical revision is needed to
bring infection under control in these cases. The
problem is that the foreign material often cannot
be removed. Under these circumstances, systemic
antibiotic therapy is useful to suppress the infec-
tion, allowing bone healing in some cases. In most
cases, surgical revision with radical sequestrotomy
and fragment fixation, preferably with an exter-
nal fixator, is standard therapy. In the literature,
attention is focused on the local application of
antimicrobial agents, eg, antibiotic-loaded bone
cement [19, 20]. For infection with staphyloco-
cci, Pavoni and co-workers reported on complete
control of infection in 20 patients. In most cases,
they started with teicoplanin in combination with
rifampicin, preferably followed by ciprofloxacin
and rifampicin for a mean treatment period of
27.7 weeks [21].
Option 4: Surgical revision with
exchange of the artificial joint
replacement
In most cases, total artificial joint replacement is
practiced. The philosophy of this approach is the
complete removal of all foreign material, including
S91
bone cement if available, radical debridement of
bone and soft tissue, systemic antibiotic therapy,
and re-implantation of the prosthesis. The com-
bination of this approach with local application
of antibiotic-loaded bone cement, whether for
fixation of the prosthetic device or as temporary
spacer, was shown to be beneficial by Robbins and
coworkers [22].
Because of the emerging world-wide resistance
pattern of the different pathogens, it is necessary to
undertake targeted antimicrobial therapy according
to the pathogen’s susceptibility pattern [23]. For
these infections, empirical therapy is only for in-
tervention in life-threatening disease or in 2-staged
revision, which should be revised according the
microbiological findings from specimens obtained
intraoperatively [7].
Option 4.1: 1-staged revision with primary
exchange of the prosthesis
The 1-stage exchange of infected artificial joint
replacement was introduced by Buchholz in the
1970s [24]. This therapy is based on identifying the
pathogen before revision and using local antibiot-
ics incorporated in PMMA bone cement as the main
principle for preventing recurrence of infection [12].
Supplementary antimicrobial agents are adminis-
tered intravenously on a short-term basis.
The elements of this protocol are:
1. Reliable identification of the pathogen before
revision.
2. Removal of the artificial joint replacement,
including all foreign material (eg, bone cement)
together with radical debridement of bone and
soft tissue.
3. Local antimicrobial therapy with antibiotic-load-
ed bone cement for fixation of the new prosthesis
implanted during the same session.
4. Intravenous antimicrobial therapy administered
for 10−14 days, provided there are no postopera -
tive complications.
In the literature, success rates ranging from
38−100% have been reported by ten different work -
ing groups. Of these, seven publications report a
success rate of between 80 % and 90 % [25].
Option 4.2: 2- or multiple-stage revision with
secondary exchange of the prosthesis
Two- or multiple-stage exchange is a widespread
procedure to control periprosthetic infection and
S92
several methods are used [10, 26]. The main ele-
ments of this procedure are:
1. Removal of the artificial joint replacement, in-
cluding all foreign material (eg, bone cement),
together with radical debridement of bone and
soft tissue.
2. Optional: interposition of a spacer system with
or without antibiotic-loaded bone cement.
3. Systemic long-term antimicrobial chemotherapy
at high dosage (for about six weeks) in the ab-
sence of the prosthesis.
4. Re-implantation of a new prosthesis after the
infection has been brought under control (in most
cases after 6−8 weeks) using antibiotic-loaded
bone cement (if un-cemented fixation of the
artificial joint replacement is intended, tests
must prove that the infection has definitely been
brought under control).
5. Systemic long-term antimicrobial chemotherapy
at high dosage (for about six weeks).
The success rate of the 2-stage revision is reported
as between 86 % and 93 % following a meta-analysis
by Langlais and coworkers [25].
Discussion
In foreign material associated infection in bone tis-
sue, antimicrobial agents alone are insufficient to
control the bacterial disease. If bacteria are sessile
on artificial surfaces, they cannot be eradicated by
antibiotics alone. Surgery is necessary. However,
systemically administered antibiotic agents are
able to suppress the symptoms of infection to the
extent that this effect is often mistaken for control
of infection.
In special situations, suppression is the aim of ther-
apy, either on a temporary or life-long basis. It may be
intended in cases where surgery is impossible because
of the patient’s general condition. If the prerequisites
are respected, it is possible to carry out this therapy
in about 60 % of cases [16]. However, life-threaten-
ing septicemia has to be distinguished from these
cases. Here, intervention by antibiotic agents serves
to prevent a severe septic syndrome and prepare the
patient for surgical therapy at a later date.
In early infections that are not yet firmly estab-
lished, retention of the foreign material is possible
if surgical debridement is accompanied by long-term
antimicrobial therapy (including rifampicin when
staphylococci are the causative agents) [5]. This
treatment is only appropriate in a few special cases
and the indication has to be very strict. If adverse
L Frommelt
side effects occur, this therapy cannot be contin-
ued. However, if the prerequisites are respected,
the success rate is good. A special situation is deep
surgical infection immediately after implantation
of an artificial joint replacement. In these cases,
surgical revision together with suction-irrigation and
prolonged antibiotic therapy is of benefit in about 50
% of cases if Staphylococcus aureus or ß-hemolytic
streptococci are responsible for the infection [18].
In most cases, exchange revision is necessary to
bring periprosthetic infection under control. Al-
though the 2- or multiple-stage procedure is widely
used, the 1-stage revision is also an appropriate
method. Comparison of these two methods is dif-
ficult because the published studies are mostly
empirical and the methods used differ too greatly. A
direct comparison of these two methods performed
in the same institution shows that the results are
similar (Langlais) [25].
The use of local antibiotics is an advantage in
these infections because it is possible to achieve an
extremely high concentration of antibiotics at the
site of infection. Antibiotic-loaded bone cement is
widely used as a carrier for the antibiotics if PMMA-
bone cement is used as temporary spacer in 2-stage
revisions or for final fixation of a new artificial
joint replacement. PMMA bone cement is a mate-
rial used for delivery of antimicrobial agents over
a long period of time, but this biomaterial has the
disadvantage that a foreign body is left in the bone
tissue and its surface may serve as a platform for
bacteria to become sessile as the drug concentration
diminishes over time.
These exchange procedures must be performed by
an experienced surgical team. Meticulous removal
of the foreign material and radical debridement is
crucial for a successful outcome. Antibiotic therapy
can ensure the success of surgery, but only if an-
tibiotics are used prudently and rationally. Having
an infectious disease specialist or a microbiologist
experienced in these infections as a member of the
surgical team is advisable.
Both 1- and 2-stage revisions produce good re-
sults, but unfortunately there are very few studies
that allow direct comparison of these methods
because the exact procedure differs depending on
the institution that performs the revision. What is
needed is a strategy that determines which method
is most beneficial for each patient and under which
circumstances.
Amputation, exarticulation, and permanent
resection arthroplasty should be the last resort,
reserved for infections that cannot be controlled in
any other way. Arthrodesis is also a procedure that
should be reserved for situations in which restoration
of function is not possible.
Principles of systemic antimicrobial therapy in foreign material associated infection
Foreign body associated infection in bone tissue
is a very special condition. To treat it successfully,
physicians need to have a great deal of experience.
Treatment of these infections should be performed
in specialist centers where this experience is avail-
able. Such institutions are able to carry out con-
trolled follow-up studies, which lead to a rational
approach to the question of which method is most
suitable for which condition.
Conclusion
Much empirical data is available on the treatment
of foreign body associated infection in bone tissue.
The concepts reported are based on credos that
are then developed to the extent that the different
approaches result in at least comparable outcomes,
but there is little exact knowledge of which meas-
ures lead to success in individual cases.
It is clear that these infections need surgical re-
vision. Systemic antibiotics alone do not eradicate
these infections. However, antimicrobial therapy is a
powerful element that serves to ensure the success
of surgical revision after the removal of the infected
foreign material. Antibiotics must be chosen accord-
ing to the susceptibility pattern of the individual
pathogens and the pharmacological properties of the
drugs with respect to their availability in infected
bone tissue. This necessitates antibiotics being ad-
ministered in high doses over a sufficient period of
time to act on bacteria at the site of infection.
Under very special conditions, as described
above, retention of the foreign material is possible
if staphylococci are the cause of infection and an
extended antimicrobial therapy involving rifampicin
is administered.
S93
Bibliography
1. Costerton JW, Stewart PS, Greenberg EP (1999) Bacterial
biofilm: a common cause of persistent infections. Science;
284(5418):1318−1322.
2. Zimmerli W, Lew PD, Waldvogel FA (1984) Pathogenesis
of foreign body infection. Evidence for a local granulocyte
defect. J Clin Invest; 73(4):1191−1200.
3. Frommelt L (2000) Periprosthetic Infection – bacteria and the
interface between prosthesis and bone. Learmonth ID (ed)
Interfaces in total hip arthroplasty. London: Springer Verlag,
153−161.
4. Stewart PS, Costerton JW (2001) Antibiotic resistance of
bacteria in biofilms. Lancet; 358(9276):135−138.
5. Zimmerli W, Trampuz A, Ochsner PE (2004) Prosthetic-joint
infections. N Engl J Med; 351(16):1645−1654.
6. Bernard L, Hoffmeyer P, Assal M, et al (2004) Trends in the
treatment of orthopaedic prosthetic infections. J Antimicrob
Chemotherap; 53(2):127−129.
7. Frommelt L (2004) [Guidelines on antimicrobial therapy
in situations of periprosthetic THR infection]. Orthopäde;
33(7):822−826.
8. Mader JT, Adams KR (1988) Experimental osteomyelitis.
Schlossberg D (ed) Orthopedic Infection. New York: Springer
Verlag, 39−48.
9. Koch T, Masche UP (1999) Gelenk- und Knocheninfektionen.
pharma-kritik; 21(11):1−4.
10. Salvati EA, Gonzalez Della Valle A, Masri BA, et al (2003) The
infected total hip arthroplasty. Instr Course Lect; 52:223−45.
11. Houshian S, Zawadski AS, Riegels-Nielsen P (2000) Dura-
tion of postoperative antibiotic therapy following revision
for infected knee and hip arthroplasties. Scand J Infect Dis;
32(6):685−688.
12. Steinbrink K, Frommelt L (1995) [Treatment of peripros-
thetic infection of the hip using one-stage exchange surgery].
Orthopäde; 24(4): 335−343.
13. Bengtson S, Knutson K (1991) The infected knee arthro-
plasty. A 6-year follow-up of 357 cases. Acta Orthop Scand;
62(4):30111.
14. Tattevin P, Cremieux AC, Pottier P, et al (1999) Prosthetic
joint infection: When can prosthesis salvage be considered?
Clin Infect Dis; 29(2):292−295.
15. Brause BD (2000) Infection with prostheses in bone and joint.
Mandell GL, Bennet JE, Dolin R (eds) Principles and practice
of infectious Diseases. 5th ed. Philadelphia: Churchhill Liv-
ingstone, 1196−1200.
16. Goulet JA, Pellicci PM, Brause BD, et al (1988) Prolonged sup-
pression of infection in total hip arthroplasty. J Arthroplasty;
3(2):109−116.
17. Drancourt M, Stein A, Argenson JN, et al (1993) Oral
rifampin plus ofloxacin for treatment of Staphylococcus-in-
fected orthopedic implants. Antimicrob Agents Chemother;
37(6):1214−1218.
18. Mella-Schmidt C, Steinbrink K (1989) [Value of irrigation-
suction drainage in the treatment of early infection of joint
implants]. Chirurg; 60(11):791−794.
19. Ekkernkamp A, Muhr G, Josten C (1996) [Infected pseudar-
throsis]. Unfallchirurg; 99(12):914−924.
S94 L Frommelt

20. Norden C (1999) Acute and chronic osteomyelitis. Armstrong

D, Cohen J (eds), Infectious Diseases. London Philadelphia:
Mosby, 43:1−10.
21. Pavoni GL, Falcone M, Baiocchi P, et al (2002) Conservative
medical therapy of infections following osteosynthesis: a
retrospective analysis of a six-year experience. J Chemother;
14(4):378−383.
22. Robbins GM, Masri BA, Garbuz DS, et al (2001)
Primary Total hip arthroplasty after infection.
J Bone Joint Surg Am; 83(4):601−614.
23. Kresken M, Hafner D, Witte W, et al (1999) Resistenzentwick-
lung bei Staphylokokken und anderen grampositiven Erregern
gegenüber Chemotherapeutika im mitteleuropäischen Raum.
Chemother; J 8(4):136−145
24. Buchholz HW, Engelbrecht H (1970) [Depot effects of
various antibiotics mixed with Palacos resins]. Chirurg;
41(11):511−515.
25. Langlais F, Lambotte JC, Thomazeau H (2003) Treatment of
infected hip replacement. Lemaire R, Herom F, Scott J, (eds),
European Instructional Course Lectures Vol 6. London: The
British Society of Bone and Joint Surgery, 158−167.
26. Fitzgerald RH Jr, Jones D (1985) Hip implant infection.
Treatment with resection arthroplasty and late total hip
arthroplasty. JAMA; 78(6B):225−228.

Correspondence address:

Lars Frommelt, MD
Institut für Infektiologie, klinische Mikrobiologie
und Krankenhaushygiene
ENDO-Klinik Hamburg GmbH
Hostenstrasse 2
21767 Hamburg, Germany
Phone: +49 40 3197 2170
Fax: +49 40 890 5355
E-mail: lars.frommelt@t-online.de