Is prolonged systemic antibiotic treatment
essential in two-stage revision hip
replacement for chronic Gram-positive
infection?
J. P. Whittaker,
R. E. Warren,
R. S. Jones,
P. A. Gregson
From the Robert
Jones and Agnes
Hunt Orthopaedic
Hospital NHS Trust,
Oswestry, England
„ J. P. Whittaker, FRCS(Trauma
& Orth), Adult Reconstruction
Fellow
„ R. S. Jones, FRCS(Trauma &
Orth), Consultant Orthopaedic
Surgeon
„ P. A. Gregson, FRCS(Trauma
& Orth), Consultant
Orthopaedic Surgeon
Robert Jones and Agnes Hunt
Orthopaedic Hospital NHS
Trust, Oswestry SY10 7AG, UK.
„ R. E. Warren, FRCSPath,
Consultant Microbiologist
Royal Shrewsbury Hospital,
Mytton Oak Road, Shrewsbury,
Shropshire SY3 8XQ, UK.
Correspondence should be sent
to Mr J. P. Whittaker; e-mail:
[email protected]
©2009 British Editorial Society
of Bone and Joint Surgery
doi:10.1302/0301-620X.91B1.
20930 $2.00
J Bone Joint Surg [Br]
2009;91-B:44-51.
Received 18 February 2008;
Accepted after revision 12
September 2008
44
When using a staged approach to eradicate chronic infection after total hip replacement,
systemic delivery of antibiotics after the first stage is often employed for an extended period of
typically six weeks together with the use of an in situ antibiotic-eluting
polymethylmethacrylate interval spacer. We report our multi-surgeon experience of 43
consecutive patients (44 hips) who received systemic vancomycin for two weeks in
combination with a vancomycin- and gentamicin-eluting spacer system in the course of a twostage revision procedure for deep infection with a median follow-up of 49 months (25 to 83).
The antibiotic-eluting articulating spacers fractured in six hips (13.9%) and dislocated in
five patients (11.6%). Successful elimination of the infecting organisms occurred in 38
(92.7%) of 41 hips with three patients developing superinfection with a new organism.
We conclude that prolonged systemic antibiotic therapy may not be essential in the twostage treatment of a total hip replacement for Gram-positive infection, provided that a high
concentration of antibiotics is delivered locally using an antibiotic-eluting system.
Infection is a catastrophic complication of
total hip replacement (THR). It occurs following 1% or more of primary procedures.1-3 Several methods have been described for the
evaluation of chronic peri-prosthetic infection4
with surgical techniques following a common objective of thorough debridement and
removal of all foreign material. This
approach is based on the ability of some
micro-organisms to adhere to foreign material under a covering of glycocalyx and
thereby to evade both the host immune
response and antibiotic therapies.5
Methods of antibiotic delivery to a debrided tissue bed include systemic therapy
alone, the use of a locally eluting antibiotic
polymethylmethacrylate (PMMA) carrier or
a combination of both. The local delivery of
antibiotics in combination with systemic
therapy has been shown to be superior to
systemic therapy alone in two-stage procedures.6 This approach has been reported as
the method of choice for peri-prosthetic
infection with reports usually describing an
extended period of systemic antibiotic
treatment6-11 after the first-stage debridement, although the optimum length of antibiotic treatment has not been definitively
established.12 There have been few reports of
the outcome after long periods of systemic
antibiotic treatment. Some have reported a
higher rate of infection with treatment for
less than four weeks,13 in the absence of a
local antibiotic eluting system. Others have
reported good results with treatment for less
than six weeks14,15 and also poor results with
no systemic treatment in combination with
an antibiotic eluting system.16-19
Staged surgical approaches using antibiotic-impregnated PMMA in various forms
have been reported including prefabricated
beads, custom beads and articulating spacers,9,19-21 with the reported success of the last
being comparable with that of other twostage procedures.8,20,21 Articulating spacers
maintain the length of soft tissues, minimise
limb shortening, avoid periarticular scarring
and muscle contracture, preserve bone
quality and reduce the energy requirements
for gait.8,21
We report our experience of treating
patients with a proven infection of the hip by
a two-stage revision technique using an antibiotic-eluting spacer and interim systemic
treatment with vancomycin for two weeks.
Our objective was to demonstrate that successful eradication of Gram-positive infection can be achieved by a shortened period of
systemic antibiotic treatment between
stages, while delivering high local concentrations of antibiotics by means of an antibiotic-eluting spacer.
THE JOURNAL OF BONE AND JOINT SURGERY
IS PROLONGED SYSTEMIC ANTIBIOTIC TREATMENT ESSENTIAL IN TWO-STAGE REVISION HIP REPLACEMENT?
Table I. Clinical details of the 43 patients
Mean (range) age in years
Male:female ratio
69 (33 to 90)
21:22
Diagnosis of infection
Positive first-stage microbiology 44
Positive first-stage histology
39
Previous surgery
Primary THR*
41
Single-revision THR
10
Multiple-revision THR
2
Hemi-arthroplasty
3
Proximal femoral osteotomy
2
Multiple debridement for infection 2
Removal of trochanteric wires
1
Charnley categories25
A
B
BB
C
16
2
10
15
* THR, total hip replacement
Patients and Methods
Between 1998 and 2003 we treated 43 consecutive patients
(44 hips) with chronic peri-prosthetic infection of the hip
using a two-stage revision procedure with a vancomycinand gentamicin-impregnated articulating acrylic cement
spacer. The diagnosis of infection was confirmed by either
positive microbiological or histological results. Data were
collected prospectively and reviewed retrospectively.
Patients in whom a diagnosis of infection could not be confirmed on microbiological or histological results were
excluded from the study.
Criteria used to confirm infection at the first stage of surgical debridement include either a neutrophil infiltrate on
histological analysis22 in the absence of an inflammatory
arthropathy or the presence of the same organism in two or
more samples on microbiological culture.23 Inflammatory
markers were considered to be raised when the erythocyte
sedimentation rate (ESR) was more than 30 mm/hr (normal
range 0 to 15 mm/hr) or the C-reactive protein level (CRP)
was greater than 10 mg/l (normal range 0 mg/l to 5 mg/l).24
The patients had a mean age of 69 years (33 to 90). The
Charnley categories25 are shown in Table I. The primary
diagnosis for THR included primary osteoarthritis in
28 patients, inflammatory arthropathy in eight and posttraumatic osteoarthritis in seven.
Most patients (33) were taking antibiotics at the time of
their referral. Treatment with antibiotic suppression was
undertaken only when the patient’s comorbidity precluded
surgery. Prior to revision antibiotics were withheld for a
minimum of two weeks. Surgery was performed in a
laminar air-flow environment with disposable drapes and
impervious gowns. At the first-stage a transtrochanteric
approach was used for radical debridement which was
VOL. 91-B, No. 1, JANUARY 2009
45
performed using revision instruments and a high-speed
burr to allow removal of the infected components and
avascular soft tissue and bone.
Before the administration of antibiotics and avoiding
disturbance of bone cement when feasible,26 five tissue specimens including capsular tissue and acetabular and femoral
membrane were taken for histological analysis22 and microbiological culture23 using individual sterile instrument sets to
avoid cross-contamination. Antibiotic treatment was by vancomycin and gentamicin articulating cement spacer (Fig. 1)
and systemic vancomycin for two weeks. Serum levels were
monitored and dose titration was performed to maintain a
pre-dose serum concentration in excess of 5 mg/l. Vancomycin was chosen because of its effectiveness against Grampositive infection, including gentamicin-resistant staphylococci which can be selected out by the use of gentamicin in
the bone cement for primary surgery.
The spacer was made using three 40 g batches of Palacos
R cement27 containing 0.25 g of gentamicin per batch
(Schering-Plough Ltd, Welwyn Garden City, United Kingdom), with 2.0 g of vancomycin added per 40 g batch of
cement, before addition of the liquid monomer. The cement
was then injected into a silicone mould system (Biomet
Merck UK Ltd, Bridgend, United Kingdom) to form an
articulating spacer in the shape of a unipolar hemiarthroplasty. These single-use mould systems came in three sizes,
with femoral head diameters of 51 mm, 57 mm and 64 mm.
The smallest of these was the most frequently used because
of the stem size. The press-fit cement spacer was allowed to
cure sufficiently before it was inserted in order to decrease
interdigitation into bone, thereby allowing removal with
minimal difficulty and bone loss at the second stage. In the
presence of deficient femoral bone when the proximal third
of the spacer was unsupported or when there were bone
defects near the tip of the spacer, the following modifications were made. A femoral nail was cut to the desired
length and inserted into the stem portion of the spacer
mould before the cement was polymerised with further
cement used to coat the distal aspect of the nail. This modified system was used to enhance stability and to bypass
stress risers in the femur. Patients were discharged when
their wound was dry and when they were able to achieve
protected weight-bearing.
At the start of the period, the process for microbiological
culture involved direct plate inoculation and liquid enrichment for two days with a secondary plate subculture as outlined in the United Kingdom national standard methods for
the investigation of tissues and biopsies.28 Aerobic plates
were only incubated for 48 hours. Microbiological culture
methods were modified to avoid manipulation of the samples which could result in laboratory contamination. By the
end of the study period the following methodology was in
use to increase the number of isolates of clear significance.
Pea-sized samples were collected in the clean-air theatre
and placed into pre-prepared universal glass bottles
containing 2 ml of special peptone (Oxoid, Basingstoke,
46
J. P. WHITTAKER, R. E. WARREN, R. S. JONES, P. A. GREGSON
Fig. 1a
Fig. 1b
Fig. 1c
Radiographs showing an a) infected Charnley cemented hip replacement with b) antibiotic eluting spacer inserted during the first-stage procedure
and c) uncemented second- stage reconstruction.
United Kingdom) with 20 pre-washed ballotini glass beads
for shaking and homogenisation in the laboratory. The peptone was immediately subcultured to blood agar incubated
in 10% CO2 and anaerobically with all culture plates incubated for seven days. Antibiotic susceptibility tests for gentamicin and methicillin were performed using the British
Society for Antimicrobial Chemotherapy disc method29
and the minimum inhibitory concentration for vancomycin
and teicoplanin determined by the E-test.
During the interval between the first- and second-stage
procedures, patients received vancomycin for two weeks
through a peripherally inserted central cannula and were
reviewed by serial clinical examination and radiological
and laboratory tests. The timing of the second-stage was
guided by the recovery of the inflammatory markers
towards normal levels at six weeks, with repeat debridement scheduled in three patients when this did not occur.
During the second-stage procedure a further debridement was performed with tissue samples sent for microbiological and histological analysis in a manner similar to
that of the first-stage procedure. Revision procedures with
cemented components used Palacos R cement (ScheringPlough Ltd) with 1 g of vancomycin added per 40 g batch,
with appropriate antibiotic modification in the presence of
Gram-negative infection at the first-stage surgery. Parenteral antibiotics were administered post-operatively until
the intra-operative tissue culture and histological results
were available. Post-operatively, the patients were assessed
clinically and radiologically at six weeks, at three, six and
12 months and annually thereafter, with none being lost to
follow-up. After the second stage the radiographs were
evaluated for the presence of radiolucent zones30,31 around
both the femoral32,33 and the acetabular34 components.
The success of the treatment was defined as the elimination of the infecting organisms found at the first stage
from all subsequent samples from the joint or the surgical
wound at follow-up at two years. An interval of two years
has been suggested as the assessment interval for new
forms of antibiotic treatment for deep prosthetic joint
infection by a working party of the Infection Disease Society of America and the Food and Drug Administration.35
Positive cultures with an organism indistinguishable on
speciation and antibiotic susceptibility tests from the
infecting organisms found at the first-stage operation was
defined as persistent infection, with superinfection being
defined as the isolation from a deep sample taken later in
the patient’s post-operative course of an organism not
encountered in the first-stage samples.
Results
A total of 14 patients had a history of alteration in their
immune status secondary to diabetes, malignancy, hypogammaglobulinaemia, use of steroids, psoriasis and rheumatoid disease, with three of these developing an infection
following the second-stage reconstruction. A total of 16 had
previously had multiple surgical procedures on the affected
hip (Table I) and nine presented with a sinus. There were 17
who presented with more than one joint replacement, with
THE JOURNAL OF BONE AND JOINT SURGERY
IS PROLONGED SYSTEMIC ANTIBIOTIC TREATMENT ESSENTIAL IN TWO-STAGE REVISION HIP REPLACEMENT?
Table II. Levels of inflammatory markers (CRP*, ESR†) and
complications relevant to the stage of the procedure
First stage
Mean CRP before first stage (mg/l)
Mean ESR before first stage (mm/hr)
Dislocation of spacer
Fracture of spacer
Deep-vein thrombosis
39.1 (5 to 139)
49.7 (8 to 182)
5
6
1
Second stage
Mean CRP before second stage (mg/l)
9.8 (5 to 25)
Mean ESR before second stage (mm/hr) 24.6 (11 to 50)
Persistent infection
3
Superinfection
3
Dislocation
0
Deep-vein thrombosis
1
Pulmonary embolus
1
Deaths within two years
3
* CRP, C-reactive protein
† ESR, erythrocyte sedimentation rate
two of these having multiple peri-prosthetic joint sepsis. The
mean number of surgical procedures undergone before presentation was 1.6 (1 to 8) with a median duration of
symptoms before diagnosis of 12 months (3 to 36).
Three patients had a repeat first-stage debridement.
Three patients received a modified articulated spacer with
an incorporated femoral nail. Six of 44 articulated spacers
fractured (13.6%) after a mean of 132 days (3 to 450). Dislocation occurred in five patients (11.6%) who had associated soft-tissue attenuation from chronic infection and
trochanteric nonunion. The changes in the ESR and CRP
levels between stages and the complications are shown in
Table II. The complications were treated conservatively
with the patient mobilising non-weight-bearing.
All 43 patients (44 hips) underwent a second-stage procedure after a median interval between stages of 21 weeks
(8 weeks to 23 months). In 13 patients this was delayed for
more than six months for reasons of medical comorbidity.
Three patients died within two years of their second-stage
procedure from unrelated causes. Two of these had no clinical or radiological evidence of recurrent infection, with the
remaining patient having a superinfection on subsequent
cultures. In the remaining 41 hips, the mean pre-operative
Merle D’Aubigné and Postel score36 was 7.2 (4 to 16),
which improved to 11.4 (8 to 16) at a median follow-up of
49 months (25 to 83), with the pain component improving
most consistently. From the surviving 41 patients (41 hips),
successful elimination of the infecting organisms occurred
in 38 hips (92.7%). Superinfections were seen in three of
the 44 hips (6.8%), two with rheumatoid disease culturing
Enterococcus and a mixed growth and the third a mixed
growth of coagulase-negative staphylococcus and Enterobacter cloacae. The time intervals between stages were
similar for patients with recurrent infection (mean 32.4
weeks) compared with those in whom treatment had been
successful (mean 27.3 weeks).
VOL. 91-B, No. 1, JANUARY 2009
47
Complications after the second-stage re-implantation
included one case of pulmonary embolus and one of deep-vein
thrombosis. A trochanteric osteotomy was performed for the
second-stage surgical approach in all but one when a posterolateral approach was used. The prostheses used included
11 uncemented and 33 cemented femoral components with
13 uncemented and 31 cemented acetabular reconstructions
(Table III). There were no cases of dislocation. Patients
remaining free from infection after the second-stage showed
no radiological signs of loosening32,34 of either the femoral or
the acetabular component at the latest follow-up.
The micro-organisms cultured from tissue samples taken
at both procedures are shown in Table IV. No strains of
Staphylococcus aureus were vancomycin- or gentamicinresistant, although gentamicin resistance was seen with
other organisms (Tables IV and V). Unfortunately, information was not available on whether gentamicin-impregnated
cement had been used at primary surgery. Although no permanent toxic effects were seen in our patients receiving a
two-week regimen of vancomycin, transient renal impairment did occur in two patients. Additional treatment with
ciprofloxacin was required in one patient with a Gramnegative infection.
Discussion
The shortened period of treatment with vancomycin in our
study minimises the exposure of patients to the potentially
serious side-effects while maintaining a successful eradication rate similar to that reported with regimes of longer
duration.6-11,20 The potential side-effects include venoirritation, nephrotoxicity and ototoxicity in addition to
generic side-effects of antibiotics such as the induction of
Clostridium difficile diarrhoea, which is related to prolonged use. The use of vancomycin also necessitates central
venous administration and repeated blood sampling to
monitor serum levels and renal function, with adjustment
of the dose to minimise the associated morbidity.
In practice, vancomycin is active against all Gram-positive
organisms without acquired resistance and in particular
against gentamicin-resistant staphylococcus which may be
increased by the use of gentamicin in the bone cement for primary surgery. Most infections are caused by Gram-positive
organisms7,37-44 which are covered by the post-operative use
of systemic vancomycin without the unnecessary selection
for resistance and Clostridium difficile of broad-spectrum
agents such as cephalosporins and fluoroquinolones. If a
Gram-negative infection is suspected from pre-operative
blood cultures, aspiration of the joint or previous surgery,
additional agents should be considered for use both within
the antibiotic-eluting spacer and systemically.
A potential disadvantage of our regime is the dose of gentamicin within the spacer in the uncommon and unexpected
occurrence of Gram-negative infection, when appropriate
doses of > 1 g per 40 g cement have been advised. We had one
such patient in our series, who received subsequent appropriate oral treatment with successful eradication of the infection
48
J. P. WHITTAKER, R. E. WARREN, R. S. JONES, P. A. GREGSON
Table III. Components used during the second-stage revision procedure
Femoral
Acetabular
Uncemented modular
Link MP (Newsplint, Hampshire, UK)
ZMR (Zimmer, Swindon, UK)
SROM (Depuy, Leeds, UK)
Total femoral replacement (Stanmore)
5
3
2
1
Cemented
C stem
Exeter (Stryker, Berkshire, UK)
Exeter (long)
24
5
4
Other
Trochanteric claw/cable system
2
Uncemented modular
Reflection (Smith &
Nephew, Warwick, UK)
Trilogy (Zimmer)
11
2
Cemented
Elite (Depuy)
31
Other
Contour ring
1
Table IV. Details of micro-organisms cultured during the first- and second-stage procedures
Pathogen
First stage
Gentamicin-resistant
Second stage
Staphylococcus aureus (including 2 MRSA*)
CNS†
Streptococcus agalactiae (Lancefield Group B)
Streptococcus intermedius (Lancefield Group F)
Streptococcus oralis
Streptococcus viridans (unspeciated)
Enterococcus faecalis
Enterococcus faecium
Enterococcus faecalis + faecium
Enterobacter cloacae
5
27
2
1
1
1
4
1
1
1
13
2
1
1
1
2
1
1
-
1
-
* methicillin-resistant Staph. aureus
† coagulase-negative staphylococcus
which was maintained at the latest follow-up of three years.
It is unlikely that the presence of gentamicin in the spacer
contributed greatly to the outcome in our study, given the
frequency of gentamicin resistance (Table IV), the wellrecorded emergence of small-colony forms of Staphylococcus on gentamicin monotherapy in joint infection and its
inactivity against enterococcal isolates which make it an
unsuitable choice alone. At the time of surgery the routine
use of a spacer loaded with antibiotics which, based on the
United Kingdom antibiotic susceptibility data, are active
against most Gram-negative organisms (gentamicin) and
most Gram-positive organisms (vancomycin) is suitably
broad spectrum without the necessity of further tailoring of
individualised antibiotic regimens based on the pre-operative
cultures provided that the occurrence of vancomycinresistant enterococci is rare in the orthopaedic unit.
The origin of peri-prosthetic infection is debatable and the
joint space, the prosthetic-bone interface or potentially both
may be implicated. Vancomycin reportedly elutes well from
Palacos R cement delivering high concentrations45-50 of antibiotic locally into the joint space. Although articulating
PMMA spacers have a lower surface area compared with
that of beads for antibiotic elution, they have been shown to
be safe and effective in studies comparing the two methods.20
Our preference of combination therapy with both systemic
and local delivery was used to address the potential for
metastatic joint infection in patients with multiple joint
replacements, which was seen in two of our 43 patients at
presentation. With low-virulence organisms such as
coagulase-negative staphylococcus in which metastatic
infection is rare, systemic antibiotics may not be necessary.
However, we consider that with Staph. aureus in which
metastatic infection is well described, systemic therapy is
certainly of relevance. A combined antibiotic approach is
therefore justified until the results of cultures are available,
particularly if the joint is removed during an acute episode
of infection.
Despite the intended regime of protected weight-bearing
during mobilisation, there were fractures of the articulating
spacers, none of which required an exchange procedure. The
durability of the spacers was variable, with early structural
failure seen in patients with poor weight-bearing compliance
and later failure in those with a prolonged interval between
stages. The full benefit of maintaining the length of soft
tissues after the first stage is compromised in this scenario,
although the spacers remain effective for eliminating dead
space and there remains the potential for further antibiotic
elution.26 To address this issue some authors have reported
THE JOURNAL OF BONE AND JOINT SURGERY
IS PROLONGED SYSTEMIC ANTIBIOTIC TREATMENT ESSENTIAL IN TWO-STAGE REVISION HIP REPLACEMENT?
49
Table V. Details of gentamicin and vancomycin susceptibility results in patients with persistent infection or
superinfection
Infection
Organisms cultured at
first-stage surgery
Gentamicin
Vancomycin
MIC*
(mg/l)
Outcome
Persistent
Persistent
Persistent
Superinfection
Superinfection
Superinfection
Enterococcus
CNS§
Streptococcus agalactiae
Staph. capitis
CNS
CNS and Enterococcus
R†
R
R
S
S
R
S‡
S
S
S
<4
2
<4
NA¶
NA
<4
Girdlestone procedure
Girdlestone procedure
Antibiotic suppression
Antibiotic suppression
Girdlestone procedure
Girdlestone procedure
* MIC, minimum inhibitory concentration
† R, resistant to antibiotics
‡ S, sensitive to antibiotics
§ CNS, coagulase negative staphylococcus
¶ NA, not available
using a cement spacer reinforced by metal pins, which would
seem to reduce but not fully eliminate the rate of fracture.9,10
Studies on the use of temporary spacers inserted through
anterolateral, direct lateral (transtrochanteric) and posterolateral approaches have described dislocation in both antibiotic-loaded prostheses of hemi-arthroplasty design9,11
and alternative functional spacer systems.8,10,11,46 This
reflects the difficulty in achieving stability in these patients
who may have poor general health in addition to compromised local tissues in response to chronic peri-prosthetic
infection. In particular, local soft-tissue factors associated
with dislocation of the first-stage prosthesis in our series
included trochanteric nonunion. In order to address these
complications, consideration is now given to reinforcement of the antibiotic-loaded spacers with incorporation
of a manually contoured metal rod and addressing the offset if required, by manipulating the silicone mould
system with the contained bone cement before complete
polymerisation.
Our patients received systemic vancomycin for a total of
two weeks after the first-stage debridement which is a
shorter duration than conventionally described.8-11 Twostage techniques for revision of infected THR have been
reported using a variety of methods to deliver local antibiotics at high concentrations19,21 with the rate of successful eradication of infection being quoted as around 90%
which is in keeping with our findings. Successful antibiotic
regimes of duration of less than six weeks for chronic
infection14-19 emphasise the use of aggressive surgical debridement in combination with the local delivery of a high
concentration of antibiotics from an antibiotic-eluting
cement spacer. The prolonged release of high concentrations of local antibiotics from the spacer is paramount
given that the remaining, apparently healthy bone, may
represent a source for infection with Staph. aureus reported
to incorporate within osteoblasts in vivo,37 obtaining sanctuary from antibiotic regimes and remaining active after
osteoblast senescence.51
A variable highlighted as important, although independent of local antibiotic delivery in the staged surgical
VOL. 91-B, No. 1, JANUARY 2009
treatment of prosthetic hip infection, involves the time
delay between the stages12 with longer intervals associated
with a greater chance of success. We were not able to associate failure of treatment with the number of previous operations, the chronicity of infection, the time interval between
stages or the organisms involved. Patients with comorbid
risk factors for infection52 appeared to have a higher rate of
infection, although the numbers were small.
In the United Kingdom, staphylococcal resistance to vancomycin is considered when the minimum inhibitory concentration is > 4 mg/l,29 although recent literature
recommends that resistance be considered at the lower level
of > 2 mg/l.53,54 In our series only one patient had a minimum inhibitory concentration of > 2 mg/l. This patient had
a successful eradication of the infecting organism although
subsequently developed a superinfection (Table V). The
optimum serum level of vancomycin is a potential issue for
debate during the treatment of prosthetic joint infection.
Failures in the treatment of bacteraemia with vancomycin
have been reported when the concentrations of antibiotic at
which visible bacterial growth ceases (minimum inhibitory
concentration) > 1 mg/l).55,56 It is possible that this new
mechanism of resistance may represent a problem in infection with Staph. aureus in orthopaedics. Reports of staphylococcal infection from North America relate to the
genetics of the bacterial strain and may not relate to United
Kingdom practice in which strains are of different lineages.57,58 Randomised studies reporting staphylococcal
bacteraemia in the intensive-care setting have shown no
improvement in outcome when trough levels of 20 mg/l
were obtained suggesting that there is not a simple relationship between dosage and outcome.59,60 Further studies have
shown that trough levels of 20 mg/l are associated with
nephrotoxicity even in the absence of other agents.
We conclude that the prolonged administration of systemic antibiotics may not be essential to achieve a high rate
of success in the eradication of Gram-positive chronic periprosthetic hip infection, provided that a thorough surgical
debridement is combined with a system delivering high
concentrations of antibiotics locally.
50
J. P. WHITTAKER, R. E. WARREN, R. S. JONES, P. A. GREGSON
We wish to thank Mr C. McGeogh (retired Consultant Orthopaedic Surgeon),
Dr C. Mangham (Consultant Histopathologist) from the Robert Jones and
Agnes Hunt Orthopaedic Hospital, Oswestry, UK and Dr R. B. Bourne (Professor of Orthopaedic Surgery) and Dr. J. P. McAuley (Associate Professor of
Orthopaedic Surgery) of the London Health Sciences Centre, London, Ontario,
Canada for their support in producing this article.
No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.
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