Diabetic foot osteomyelitis: a progress report on diagnosis and a systematic review of treatment
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DIABETES/METABOLISM RESEARCH AND REVIEWS REVIEW ARTICLE
Diabetes Metab Res Rev 2008; 24(Suppl 1): S145–S161.
Published online in Wiley InterScience (www.interscience.wiley.com) DOI: 10.1002/dmrr.836
Diabetic foot osteomyelitis: a progress report on
diagnosis and a systematic review of treatment†
A. R. Berendt1 *, E. J. G. Summary
Peters2 , K. Bakker3 , J. M. The International Working Group on the Diabetic Foot appointed an
Embil4 , M. Eneroth5 , R. J. expert panel to provide evidence-based guidance on the management of
Hinchliffe6 , W. J. Jeffcoate7 , osteomyelitis in the diabetic foot. Initially, the panel formulated a consensus
B. A. Lipsky8 , E. Senneville9 , scheme for the diagnosis of diabetic foot osteomyelitis (DFO) for research
J. Teh10 , G. D. Valk11 purposes, and undertook a systematic review of the evidence relating to
treatment. The consensus diagnostic scheme was based on expert opinion;
1
Bone Infection Unit, Nuffield the systematic review was based on a search for reports of the effectiveness
Orthopaedic Centre NHS Trust, of treatment for DFO published prior to December 2006.
Headington, Oxford, UK; 2 Department The panel reached consensus on a proposed scheme that assesses the
of Infectious Diseases, University
probability of DFO, based on clinical findings and the results of imaging and
Medical Center Utrecht, Utrecht, The
Netherlands; 3 International Working laboratory investigations.
Group on the Diabetic Foot (IWGDF), The literature review identified 1168 papers, 19 of which fulfilled criteria
Heemstede, The Netherlands; 4 Section for detailed data extraction. No significant differences in outcome were
of Infectious Diseases, Department of associated with any particular treatment strategy. There was no evidence
Medicine, University of Manitoba,
that surgical debridement of the infected bone is routinely necessary. Culture
Winnipeg, Canada; 5 Department of
Orthopedics, Malmö University and sensitivity of isolates from bone biopsy may assist in selecting properly
Hospital, Malmö, Sweden; 6 Department targeted antibiotic regimens, but empirical regimens should include agents
of Vascular Surgery, St. Georges active against staphylococci, administered either intravenously or orally (with
Hospital Medical School, University of a highly bioavailable agent). There are no data to support the superiority
London, UK; 7 Department of Diabetes
of any particular route of delivery of systemic antibiotics or to inform the
and Endocrinology, Nottingham
University Hospitals Trust, Nottingham, optimal duration of antibiotic therapy. No available evidence supports the use
UK; 8 Veterans Administration Puget of any adjunctive therapies, such as hyperbaric oxygen, granulocyte-colony
Sound Heath Care System & University stimulating factor or larvae.
of Washington, Seattle, Washington, We have proposed a scheme for diagnosing DFO for research purposes.
USA; 9 Department of Infectious
Data to inform treatment choices in DFO are limited, and further research is
Diseases, Hôpital Dron-Tourcoing,
France; 10 Department of Radiology, urgently needed. Copyright 2008 John Wiley & Sons, Ltd.
Nuffield Orthopaedic Centre NHS Trust,
Oxford, UK; 11 Department of Internal Keywords diabetes; diabetic foot; osteomyelitis; antibiotics; surgery; diagnosis;
Medicine, University Medical Center systematic review
Utrecht, Utrecht, The Netherlands
*Correspondence to: A. R. Berendt, Introduction
Bone Infection Unit, Nuffield
Orthopaedic Centre NHS Trust, Osteomyelitis (infection of bone) is present in approximately 20% of cases
Windmill Road, Headington, Oxford of foot infection in persons with diabetes [1,2] and greatly increases the
OX3 7LD, UK. E-mail: likelihood that the patient will require a lower-extremity amputation [3,4].
tony.berendt@noc.anglox.nhs.uk Unfortunately, there are no widely agreed guidelines for either the diagnosis
† Published of diabetic foot osteomyelitis (DFO) or its treatment, and the management
on behalf of the
of this problem is among the most controversial and challenging problems
International Working Group on the
in the field. The International Working Group on the Diabetic Foot (IWGDF)
Diabetic Foot.
recognized that DFO was an area in which guidelines for diagnosis and treat-
ment (that could be modified according to the availability of local services
and resources in different centres and communities) were needed [5,6]. To
Received: 11 October 2007
that end, they appointed an expert advisory group to suggest criteria for
Revised: 24 December 2007
Accepted: 2 January 2008
the diagnosis of DFO which could be used in future research, as well as to
undertake a systematic review of the evidence pertaining to its treatment.
Copyright 2008 John Wiley & Sons, Ltd.S146 A. R. Berendt et al.
Diabetic foot osteomyelitis is also hampered by issues relating to the definition of
outcome. In common with expert opinion in other areas
Unlike most childhood osteomyelitis, DFO rarely occurs by of bone infection, the term cure should not be used, given
haematogenous seeding, and almost all cases result from that very late relapse of apparently successfully treated
contiguous spread of infection from adjacent soft tissue. osteomyelitis is not uncommon. The term arrest is used
The soft-tissue infection usually starts as a complication of instead, to describe the situation in which there is no
a neuropathic ulcer, but can result from penetrating injury clinical evidence of ongoing infection in the bone. Expe-
[7] or ischaemic soft-tissue loss. Arterial insufficiency may rience suggests that the conclusion that there is arrest of
be present but tends to play a less important role than infection should not be reached earlier than one year after
neuropathy. Osteomyelitis therefore most often affects the cessation of treatment.
bones underlying sites where ulcers are most common: The term healing also needs to be used with care
the toes, metatarsal heads and calcaneum. The midfoot to its meaning. In practice, it may be applied either to
bones are less commonly involved unless foot deformity epithelialization of an overlying ulcer (wound healing),
(from neuropathic osteoarthropathy, for example) has or to X-ray appearances that suggest that the infection
caused ulceration. is no longer active (radiological healing). Criteria
While puncture wounds may directly inoculate for radiological healing include consolidation of ill-
pathogens into bone or joint [7], the usual trigger to defined (‘fluffy’) periosteal reaction into a well-organized
bone involvement is the damage of overlying and vas- involucrum with discrete boundaries, no progression of
cularizing periosteal tissue by ulceration or soft-tissue bone lucency, union of pathological fractures associated
infection. The loss of this anatomical and physiological with infection and sometimes substantial reformation of
barrier allows microorganisms to gain access, with subse- mineralized bone in areas of previous bone loss.
quent devitalization of the superficial cortex. Extension of
infection via the Haversian system leads to involvement of
medullary bone and marrow, where infection may spread
rapidly. Tracking of infection beneath the periosteum
A scheme for the diagnosis of DFO for
leads to periosteal stripping, underlying bone necrosis research purposes
(forming the sequestrum) and overlying periosteal reac-
tion with formation of new bone (the involucrum). Since Accurate diagnosis of DFO is necessary to ensure
osteomyelitis generally occurs by contiguous spread, the appropriate treatment. But it is also an essential pre-
causative microorganisms are similar to those isolated requisite for research and for the comparison of outcomes
from complicated soft-tissue infections [8–11]. While in different studies or medical centres. These comparisons
staphylococci (especially Staphylococcus aureus) predomi- are needed to advance understanding of the best practice
nate, many cases are polymicrobial, especially when DFO and to inform health care planning. Nevertheless, there
complicates chronically infected wounds or the foot is are no agreed criteria for the diagnosis, or exclusion, of
ischaemic [12]. DFO. There are two particular problems in establishing
Persistence of infection in bone has multiple underly- such criteria. The first is that it may take several weeks
ing causes, including impaired immune and inflammatory for bone infection to produce defects on plain X-rays, so
responses (especially in necrotic bone) and reduced leuco- early infection may be missed. The second is that diabetic
cyte number and activity, especially when microorganisms patients with peripheral neuropathy are also at risk of
are adherent to the sequestrum [13,14]. Such adherent developing neuro-osteoarthropathy, which may closely
bacteria, in mono- or poly-microbial communities (called resemble – and, indeed, co-exist with – DFO.
biofilms) [15], contain highly persistent phenotypes that Osteomyelitis is considered proven if one or more
resist host responses and most antibiotic agents [16]. The pathogens are cultured from a reliably obtained bone
host response contains infection within a discrete area specimen that shows bone death, acute or chronic
of the bone, leading to detachment of the sequestrum; it inflammation and reparative responses on histological
can then be extruded from the ulcer base, or fragments examination. Unfortunately, this criterion standard is
can pass through one or more sinuses to the skin sur- infrequently achieved because bone biopsy is not widely
face. If the remaining bone is uninfected and covered in used. The results of bone biopsy may also occasionally
healthy granulation tissue, the process is arrested and be misleading, and are particularly dependent on the
wound healing is possible. If bone infection persists, how- sampling technique and specimen processing. Cultures
ever, there is further bone death, with possible spreading may be falsely negative because of sampling error,
of soft-tissue infection. The clinical presentation of DFO prior antibiotic therapy or inability to culture fastidious
can vary, depending on the site involved, the extent of organisms; likewise, they may be falsely positive because
infected and dead bone, any associated abscess and soft- of contamination by wound-colonizing flora or skin
tissue involvement, the causative organism(s) and the commensals. Similarly, histological examination may be
presence of limb ischaemia. falsely positive in the face of other causes of inflammation,
Apart from problems arising from differing presenta- or falsely negative because of sampling error. In most
tions and resultant lack of consensus about how to make cases, clinicians rely not on bone biopsy but on clinical
the diagnosis of DFO, scientific evaluation of treatments presentation, combined with imaging and a variety of
Copyright 2008 John Wiley & Sons, Ltd. Diabetes Metab Res Rev 2008; 24(Suppl 1): S145–S161.
DOI: 10.1002/dmrrReview of the Management of Diabetic Foot Osteomyelitis S147
laboratory investigations. Few of these have, however, Bone biopsy
been subjected to rigorous assessment. In order to create
an acceptable scheme for diagnosis, the following factors Obtaining a culture and histological examination of bone
were considered. will both confirm the diagnosis and potentially identify
the responsible pathogen(s) and their in vitro antibiotic
sensitivities. A bone specimen may be obtained either
History percutaneously (through uninfected skin) or as part of
Underlying osteomyelitis should be considered when an an operative procedure. If bone cannot be obtained, it
ulcer fails to heal with no other obvious reason, or if the is important to understand that cultures of adjacent soft
patient reports discharge of bony fragments. tissue may give different results [32], and swabs will
often overstate the number of pathogens involved. Where
possible, antibiotics should be discontinued (for at least
Physical examination 48 h and preferably longer) before the biopsy to maximize
A probe to bone test may help if properly performed the yield from cultures [33,34].
after debridement of any callus or necrotic material in the
wound [17–19]. A negative test substantially reduces the
probability of osteomyelitis, while a positive one makes it Formulation of the proposed scheme
more likely. DFO is also likely if there is visible bone or for the diagnosis of diabetic foot
discharging bone fragments. osteomyelitis
Plain radiographs The highest quality evidence for diagnostic criteria would
come from prospective studies assessing the proposed
X-rays of the foot should be obtained if osteomyelitis criteria against a criterion standard, such as bone culture
is a possibility, but it may take several weeks for bony and histology. Because of the problems with bone
changes to become radiologically apparent. Additionally, specimens described above, it is inevitable that future
abnormalities of a bone may be caused by Charcot neuro- studies will need to encompass broader criteria. This
osteoarthropathy [20,21] makes a compelling case for reaching consensus on the
relative value of integrating the results of a range of
Radionuclide bone scans clinical, laboratory and imaging findings in the diagnosis
of DFO. Schemes of this sort are common in situations
Technetium-99 bone scanning is more sensitive than plain
where no single criterion is sufficiently reliable to make
X-rays, but is not recommended because the results are
absolute decisions about the diagnosis, such as the Duke
non-specific and positive scans can be caused by non-
criteria for diagnosing infective endocarditis [35], and
infectious processes [22].
the American College of Rheumatology’s criteria for
certain rheumatological conditions [36–38]. Consensus
Radionuclide white blood cell scans diagnostic schemes will usually be used initially for
Leucocyte scans may be may be slightly less sensitive than research purposes, which require a greater degree of
bone scanning, are technically more difficult and are more specificity, rather than in clinical practice, which requires
costly, but their specificity is typically considerably higher. a greater level of sensitivity. Our proposed scheme for
Newer methods of labelling white cells are promising research purposes provides a potential means to compare
[23,24], as are scans using labelled anti-neutrophil data from different studies, provided the diagnostic
antibodies [25,26]. In most instances, leucocyte scans are methodology has been specified in sufficient detail.
currently used only when magnetic resonance imaging Nevertheless, the clinical usefulness of the scheme will
scans (MRI) are unavailable. remain uncertain until it has been validated.
The levels of diagnostic certainty in our proposed
scheme have been stratified into four categories (Table 1).
Positron emission tomography (PET) The use of post-test probabilities to define broad levels
Positron emission tomography may be helpful in the of diagnostic certainty is deliberate, and reflects the
diagnosis of DFO, but its role is not yet established [27]. desirability in clinical practice of using diagnostic tests
with defined performance characteristics (sensitivity,
specificity and likelihood ratio) to convert probability
MRI of disease into a post-test probability for each case.
There is general agreement that this is the most useful This will require serial mathematical calculations, as
imaging study for diagnosing DFO, as well as for evalu- the results of each test are considered in sequence. The
ating the extent of both bone and soft-tissue involvement scheme simplifies the process by using combinations of
and for planning surgery [28–31]. MRI will not always different diagnostic criteria, the weightings of which have
reliably distinguish between infection and acute Char- been derived by a consensus based on collective clinical
cot neuro-osteoarthropathy; an accurate reading largely experience. This scheme also recognizes that the diagnosis
depends on the experience of the reporting radiologist. becomes increasingly or decreasingly likely as the clinical
Copyright 2008 John Wiley & Sons, Ltd. Diabetes Metab Res Rev 2008; 24(Suppl 1): S145–S161.
DOI: 10.1002/dmrrS148
Table 1. Proposed consensus criteria for diagnosing osteomyelitis in the diabetic foot
Post-test
probability of Management
Category osteomyelitis advice Criteria Comments
Definite (‘beyond >90% Treat for osteomyelitis Bone sample with positive culture AND positive histology OR Sample must be obtained at surgery or
reasonable doubt’) through uninvolved skin
Purulence in bone found at surgery OR Definite purulence identified by experienced
Copyright 2008 John Wiley & Sons, Ltd.
surgeon
Atraumatically detached bone fragment removed from ulcer by Definite bone fragment identified by
podiatrist/surgeon OR experienced surgeon/podiatrist
Intraosseous abscess found on MRI OR
Any two probable criteria OR one probable and two possible criteria OR,
any four possible criteria below
Probable (‘more 51–90% Consider treating, but Visible cancellous bone in ulcer OR
likely than not’); further investigation may
be needed MRI showing bone oedema with other signs of osteomyelitis OR Sinus tract; sequestrum, heel or metatarsal
head involved; cloaca
Bone sample with positive culture but negative or absent histology OR
Bone sample with positive histology but negative or absent culture OR
Any two possible criteria below
Possible (but on 10–50% Treatment may be Plain X-rays show cortical destruction OR
balance, less rather justifiable, but further
than more likely) investigation usually MRI shows bone oedema OR cloaca, OR
advised
Probe to bone positive OR, Visible cortical bone OR
ESR >70 mm/h with no other plausible explanation OR
Non-healing wound despite adequate offloading and perfusion for
>6 weeks OR ulcer of >2 weeks duration with clinical evidence of
infection
UnlikelyReview of the Management of Diabetic Foot Osteomyelitis S149
course evolves, changing the diagnostic certainty over every study design. The methodological quality score was
time. In many situations, however, the diagnosis will be translated into a level of evidence according to the Scottish
either immediately evident or can be excluded with a high Intercollegiate Guidelines Network (SIGN) instrument as
degree of confidence. follows: (1) randomized controlled trials and (2) studies
with case–control, cohort, controlled before-and-after
design or interrupted time series design. Studies were
A systematic review of the also rated as: ++ (high quality with low risk of bias), +
(well conducted with low risk of bias) and – (low quality
effectiveness of treatments for with higher risk of bias), according to the methodological
diabetic foot osteomyelitis quality score.
Co-reviewers discussed the findings from the data
Because guidance is urgently needed to resolve uncertain- extraction and the evaluation of methodological quality
ties concerning the management of this limb-threatening of each paper and reached a final decision by consensus.
condition [39], a systematic search was undertaken for Extracted data were summarized in Evidence tables (see
evidence of the effectiveness of treatments for DFO. The Appendix B) and described on a study-by-study narrative
review was particularly aimed at answering the following basis. Because of the heterogeneity of study designs,
questions. interventions, follow-up and outcomes, no attempt was
• What are the absolute and relative indications for made to pool the results. These Evidence tables were
surgery? compiled following collective discussions (by electronic
• Which surgical interventions are of value? and in-person conferences) by all members of the working
• Can osteomyelitis be treated with antibiotics alone? party, who then formulated consensus recommendations.
• What empirical choices of antibiotic are sound?
• What is the appropriate duration of antibiotic therapy?
• What is the preferred route of administration of antibiotic Results
therapy?
• Is there evidence for efficacy of any adjunctive treatments? Of 1168 papers identified in the initial search (3 of which
were found by cross-referencing), 284 were selected
for full paper review. Of these, 19 met the criteria
Materials and methods for inclusion, all of which were in English. Three were
controlled clinical trials, while the remainder were mainly
We searched the literature for all prospective and of uncontrolled (retrospective) case series. Patients with
retrospective studies in any language that evaluated DFO frequently formed a sub-group within a larger group
interventions for the treatment of DFO in people aged of patients with infected diabetic foot ulcers and soft-
18 years or older with diabetes mellitus. The search tissue infections, or patients with osteomyelitis in general
strategy employed is described in Appendix A. Eligible or ulceration from various causes. Significant selection
studies included randomized controlled trials (RCTs), bias was a potential problem in the majority of studies.
case–control studies, prospective and retrospective cohort
studies, interrupted time series (ITS) design, controlled
before-and-after design (CBA) and uncontrolled case Absolute and relative indications for
series, but not single-case reports. Publications were surgery
eligible for inclusion if they reported outcome of
management of DFO following a specified intervention in The available data, with necessary caveats on population
an identifiable group with diabetes. One reviewer assessed selection and reporting bias, suggest that there is little
all identified references by title and abstract to assess evidence to help choose between primarily medical
eligibility. We retrieved full copies of possibly eligible and primarily surgical therapy in the management of
publications and two independent expert reviewers DFO. Reported success rates were generally within
agreed on whether or not the publications were eligible the range 60–90%, but no controlled studies, whether
to be included. Each included paper was then further randomized or not, directly compared outcomes with the
assessed by the two reviewers, working independently, two approaches. One observational study reported that
using custom-prepared data extraction sheets. amputation and death were less common in patients
The reviewers noted the study design, patient pop- receiving early surgical intervention compared with
ulations, interventions, outcomes and duration of (and medical therapy alone [40], perhaps because of a high
loss to) follow-up of included patients. Studies were proportion of cases of severe deep infection in the
also scored for methodological quality using different study group. Others reported improved outcomes (higher
scoring lists developed by the Dutch Cochrane Center healing rate and less antibiotic use) when limited surgery
(www.cochrane.nl/index.html). Quality items were rated was combined with antibiotics, compared to antibiotic
as ‘done’, ‘not done’, or ‘not reported’ and only those rated therapy alone [41]. Yet others have demonstrated
as ‘done’ contributed to methodological quality score. comparable levels of success by reserving surgery only
Equal weighting was applied to each validity criterion for for failures of medical therapy [42].
Copyright 2008 John Wiley & Sons, Ltd. Diabetes Metab Res Rev 2008; 24(Suppl 1): S145–S161.
DOI: 10.1002/dmrrS150 A. R. Berendt et al.
Choice of surgical intervention by different routes, or have assessed the efficacy of locally
administered antibiotics, such as antibiotic-impregnated
A range of foot-salvaging surgical interventions have polymethylmethacrylate or calcium sulfate beads.
been described, including debridement to bleeding bone
marrow with epidermal sheet grafting [43], two-stage
debridement with secondary closure [44] and limb Effectiveness of adjunctive therapies
amputation [45,46]. We did not include other surgical
techniques described in methodologically inferior studies. Successful revascularization may enable debridement
and minor surgery [56], but no evidence was found
to indicate that revascularization was associated with
The effectiveness of non-surgical improved outcome in DFO. Similarly, no conclusive
management evidence demonstrates that hyperbaric oxygen therapy
[57,58] improves outcome, and further well-designed and
Studies of non-surgical management reported rates of controlled studies are needed to assess its effectiveness.
arrest and healing comparable to those following surgery There is no evidence to suggest that the use of maggots
[47–50]. Two of these studies were sufficiently large to (larvae), growth factors (including granulocyte-colony
identify the following as factors associated with the failure stimulating factor, G-CSF) or topical negative pressure
of non-surgical treatment: more severe signs of infection therapy (e.g. vacuum-assisted closure, VAC) [59] is
with necrosis and gangrene; lower transcutaneous oxygen beneficial in the management of DFO.
tension; a high serum creatinine level; and pyrexia
(>38.5 ◦ C) [42,51]. It was not possible to establish
whether the outcome of surgery was worse in those Prognosis
who had previously failed to respond to non-surgical
management. The available evidence indicates that infection can be
arrested in over 60% of cases, whether the patient is
treated with surgical resection or antibiotic therapy alone.
Empirical choice of antibiotic Amputation rates of 5–10% can be anticipated in cases
selected for medical management, and may be higher in
None of the selected studies demonstrated the superiority unselected cohorts because those requiring early surgery
of any one antibiotic agent over another. Antibiotics with were not excluded.
activity predominantly against Gram positive organisms
(staphylococci and streptococci) [52] and broad-spectrum
antibiotics with increased activity against Gram negative Aftercare
organisms and obligate anaerobes [53] appear equally
effective. These findings confirm the results of a recent Osteomyelitis commonly leads to changes in the structure
review of the antibiotic management of all types of and load-bearing properties of the foot, either through its
osteomyelitis [54]. Nevertheless, it is still not known direct effects on bone, or because of surgical intervention.
if antibiotic therapy should be selected on the basis of Observational studies suggest that transfer ulcers may
the sensitivities of all isolated organisms or simply against be more common when DFO is managed surgically as
those judged most likely to be pathogenic. opposed to medically [60,61]. No studies specifically
addressed aftercare issues in patients with osteomyelitis,
as against all forms of diabetic foot ulceration.
Duration of antibiotic treatment
Selected studies reported responses to treatment dura-
tions ranging from 2 weeks (following aggressive surgi-
Discussion
cal debridement) [4] to a mean of 42 weeks (without
surgery) [50]. Results in all were comparable, and there While there is no evidence of differences in the
are no reports of studies comparing treatment with antibi- effectiveness of various treatment strategies, this does
otics for different durations. not mean that such differences do not exist. Important
differences in both effectiveness and cost effectiveness
may yet emerge from adequately powered studies that
Route of administration use appropriate definitions and outcome measures. The
quality of published work is poor, with few controlled
Published studies variously reported treatment with studies, unclear reporting and small or heterogeneous
intravenous [4] or oral antimicrobials [48,50], or short- populations. The lack of standardization of diagnostic
duration intravenous followed by oral therapy [55]. A criteria and of consensus on the choice of outcome
single randomized study compared results with oral and measures pose particular difficulties. The weakness of the
intravenous antibiotics [52]. No studies in DFO have available evidence necessarily weakened the conclusions
compared the outcome of administering the same agents that we could draw in this review and we urge caution
Copyright 2008 John Wiley & Sons, Ltd. Diabetes Metab Res Rev 2008; 24(Suppl 1): S145–S161.
DOI: 10.1002/dmrrReview of the Management of Diabetic Foot Osteomyelitis S151
before they are extrapolated into practice. Decisions stud∗ ) OR (cohort stud∗ ) OR (Comparative stud∗ ))
concerning clinical care should be based on individual AND ((‘‘Infection’’[MeSH]) OR osteomyelitis OR osteitis
circumstances, taking into account the needs and desires OR (‘‘Bone Diseases, Infectious’’[MeSH]) OR (‘‘Diabetic
of each patient, local resources, expertise and trends in Foot’’[MeSH]))) AND ((‘‘Anti-Bacterial Agents’’[MeSH])
antimicrobial resistance. OR (‘‘Anti-Infective Agents’’[MeSH]) OR (‘‘administration
Available evidence suggests that if those who need and dosage [Subheading]’’[MeSH]) OR (‘‘Drug Admin-
urgent surgery for life- or limb-threatening infection are istration Routes’’[MeSH]) OR parenteral OR oral OR
excluded, surgical debridement of infected bone may not topical OR duration OR cement OR (‘‘Methylmethacry-
be routinely necessary and arrest of infection may be late’’[MeSH]) OR (‘‘Calcium Sulfate’’[MeSH]) OR implant
achieved with antibiotics alone in the majority of cases. OR collagen OR ceramic OR (‘‘Aminoglycosides’’[MeSH])
Despite the lack of evidence, however, many experts feel OR gentamicin OR amikacin OR tobramycin OR (‘‘Gly-
that arrest of bone infection is facilitated by appropriate copeptides’’[MeSH]) OR vancomycin OR teicoplanin OR
debridement of necrotic bone. The choice of antibiotic (‘‘Metronidazole’’[MeSH]) OR (‘‘Linezolid’’[MeSH]) OR
regimen may be optimized by obtaining culture and (‘‘Fusidic Acid’’[MeSH]) OR (‘‘Daptomycin’’[MeSH]) OR
sensitivity results of a bone specimen, but empirical (‘‘Monobactam’’[MeSH]) OR (‘‘Carbapenem’’[MeSH]) OR
regimens should include anti-staphylococcal coverage. imipenem OR meropenem OR (‘‘beta-Lactams’’[MeSH])
There are no data to establish the superiority of any OR (‘‘Cephalosporins’’[MeSH]) OR cefuroxime OR cef-
particular route of delivery of systemic antibiotics for tazidime OR cephalexin OR ceftriaxone OR cefpirome
treating DFO. There are also no data to inform decisions (‘‘Clavulanic Acids’’[MeSH]) Clavulanic Acid∗ OR (‘‘Mox-
on the optimal duration of antibiotic therapy, and no alactam’’[MeSH]) OR (‘‘Penicillins’’[MeSH]) OR penicillin
evidence to support the use of adjunctive therapies, such OR flucloxacillin OR oxacillin OR Methicillin OR naf-
as hyperbaric oxygen, granulocyte-colony stimulating cillin OR ampicillin OR penicillin OR piperacillin OR
factor or larvae. Further research is urgently needed, (‘‘Tetracyclines’’[MeSH]) OR tetracycline OR minocy-
and until more data are available from robust trials, there cline OR doxycycline OR (‘‘Macrolides’’[MeSH]) OR ery-
is limited justification for didactic recommendations of thromycin OR azithromycin OR clarithromycin OR (‘‘Lin-
any particular treatment strategy. comycin ‘‘[MeSH]) OR clindamycin OR (‘‘Trimethoprim-
Sulfamethoxazole Combination’’[MeSH]) OR cotrimoxa-
zole OR co-trimoxazole OR (‘‘Quinolones’’[MeSH]) OR
Appendix A ciprofloxacin OR ofloxacin OR moxifloxacin OR lev-
ofloxacin OR (‘‘Anti-Infective Agents, Local’’[MeSH]) OR
Literature search string for each (Silver OR Silver Sulfadiazine OR iodine)).
database
Search EMBASE
Search PubMed
Database: EMBASE
Search Strategy:
Limits: human
Surgery (hits 638) 1. exp ∗ Diabetes Mellitus/
(((‘‘Diabetes Mellitus’’[MeSH]) OR (Diabetes Melli- 2. Clinical Trial/
tus) OR (Diabetes) OR (diabetic)) AND ((‘‘Clinical 3. Clinical Trial/
Trials’’[MeSH]) or (‘‘comparative study’’[Mesh]) OR 4. exp ∗ Comparative Study/
(‘‘epidemiologic study characteristics’’[Mesh]) OR (Clin- 5. exp ∗ Epidemiology/
ical Trial∗ ) OR (case-control stud∗ ) OR (case control 6. exp ∗ INFECTION/
stud∗ ) OR (cohort stud∗ ) OR (Comparative stud∗ )) 7. exp ∗ Bone Infection/
AND ((‘‘Infection’’[MeSH]) OR osteomyelitis OR osteitis 8. exp ∗ Diabetic Foot/
OR (‘‘Bone Diseases, Infectious’’[MeSH]) OR (‘‘Diabetic 9. (diabetes mellitus or diabetes or diabetic).mp. [mp =
Foot’’[MeSH]))) AND ((‘‘Surgery’’[MeSH]) OR (‘‘Amputa- title, abstract, subject headings, heading word, drug
tion’’[MeSH]) OR (‘‘Surgery, Plastic’’[MeSH]) OR (‘‘Pre- trade name, original title, device manufacturer, drug
operative Care’’[MeSH]) OR dead space OR drain OR manufacturer name]
hardware OR bone samples OR (‘‘Vascular Surgical Pro- 10. (Clinical Trial or case-control stud$ or case control
cedures’’[MeSH]) OR (‘‘Thrombolytic Therapy’’[MeSH]) stud$ or cohort stud$ or Comparative stud$).mp.
OR (‘‘Costs and Cost Analysis’’[MeSH]) OR (‘‘Wound [mp = title, abstract, subject headings, heading word,
Healing’’[MeSH])) drug trade name, original title, device manufacturer,
Antibiotics (hits: 265 (27 duplicates with surgery drug manufacturer name]
search, total 611)) 11. exp ∗ SURGERY/
(((‘‘Diabetes Mellitus’’[MeSH]) OR (Diabetes Melli- 12. exp ∗ AMPUTATION/
tus) OR (Diabetes) OR (diabetic)) AND ((‘‘Clinical 13. exp ∗ Plastic Surgery/
Trials’’[MeSH]) or (‘‘comparative study’’[Mesh]) OR 14. exp ∗ Preoperative Care/
(‘‘epidemiologic study characteristics’’[Mesh]) OR (Clin- 15. (dead space or drain or hardware or bone sam-
ical Trial∗ ) OR (case-control stud∗ ) OR (case control ples).mp. [mp = title, abstract, subject headings,
Copyright 2008 John Wiley & Sons, Ltd. Diabetes Metab Res Rev 2008; 24(Suppl 1): S145–S161.
DOI: 10.1002/dmrrS152 A. R. Berendt et al.
heading word, drug trade name, original title, device title, device manufacturer, drug manufacturer name]
manufacturer, drug manufacturer name] 43. exp ∗ Latamoxef/
16. exp ∗ Vascular Surgery/ 44. exp ∗ Penicillin Derivative/
17. exp ∗ Fibrinolytic Therapy/ 45. (penicillin or flucloxacillin or oxacillin or Methi-
18. (Costs and Cost Analysis).mp. [mp = title, abstract, cillin or nafcillin or ampicillin or penicillin or
subject headings, heading word, drug trade name, piperacillin).mp. [mp = title, abstract, subject head-
original title, device manufacturer, drug manufac- ings, heading word, drug trade name, original title,
turer name] device manufacturer, drug manufacturer name]
19. exp ∗ Wound Healing/ 46. exp ∗ Tetracycline Derivative/
20. exp ∗ Antiinfective Agent/ 47. (tetracycline or minocycline or doxycycline).mp.
21. (administration and dosage).mp. [mp = title, [mp = title, abstract, subject headings, heading word,
abstract, subject headings, heading word, drug trade drug trade name, original title, device manufacturer,
name, original title, device manufacturer, drug man- drug manufacturer name]
ufacturer name] 48. exp ∗ Macrolide/
22. exp ∗ Drug Administration Route/ 49. (erythromycin or azithromycin or clarithromycin)
23. (parenteral or oral or topical or duration or .mp. [mp = title, abstract, subject headings, heading
cement).mp. [mp = title, abstract, subject headings, word, drug trade name, original title, device
heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
manufacturer, drug manufacturer name] 50. exp ∗ LINCOMYCIN/
24. exp ∗ Methacrylic Acid Methyl Ester/ 51. clindamycin.mp. [mp = title, abstract, subject head-
25. exp ∗ Calcium Sulfate/ ings, heading word, drug trade name, original title,
26. (implant or collagen or ceramic).mp. [mp = title, device manufacturer, drug manufacturer name]
abstract, subject headings, heading word, drug trade 52. exp ∗ Cotrimoxazole/
name, original title, device manufacturer, drug 53. (cotrimoxazole or co-trimoxazole).mp. [mp = title,
manufacturer name] abstract, subject headings, heading word, drug trade
27. exp ∗ Aminoglycoside/ name, original title, device manufacturer, drug
28. (gentamicin or amikacin or tobramycin).mp. [mp = manufacturer name]
title, abstract, subject headings, heading word, drug 54. exp ∗ Quinolone Derivative/
trade name, original title, device manufacturer, drug 55. (ciprofloxacin or ofloxacin or moxifloxacin or lev-
manufacturer name] ofloxacin).mp. [mp = title, abstract, subject head-
29. exp ∗ Glycopeptide/ ings, heading word, drug trade name, original title,
30. (vancomycin or teicoplanin).mp. [mp = title, device manufacturer, drug manufacturer name]
abstract, subject headings, heading word, drug trade 56. exp ∗ Topical Antiinfective Agent/
name, original title, device manufacturer, drug man- 57. (Silver or Silver Sulfadiazine or iodine).mp. [mp =
ufacturer name] title, abstract, subject headings, heading word, drug
31. exp ∗ METRONIDAZOLE/ trade name, original title, device manufacturer, drug
32. exp ∗ LINEZOLID/ manufacturer name]
33. exp ∗ Fusidic Acid/ 58. 1 or 9
34. exp ∗ DAPTOMYCIN/ 59. 3 or 4 or 5 or 10
35. exp ∗ MONOBACTAM/ 60. 6 or 7 or 8
36. exp ∗ CARBAPENEM/ 61. 58 and 59 and 60
37. (imipenem or meropenem).mp. [mp = title, abstract, 62. 11 or 12 or 13 or 14 or 15 or 16 or 17 or 18 or 19
subject headings, heading word, drug trade name, 63. 61 and 62
original title, device manufacturer, drug manufac- 64. 20 or 21 or 22 or 23 or 24 or 25 or 26 or 27 or 28 or
turer name] 29 or 30 or 31 or 32 or 33 or 34 or 35 or 36 or 37 or
38. exp ∗ Beta Lactam/ 38 or 39 or 40 or 41 or 42 or 43 or 44 or 45 or 46 or
39. exp ∗ Cephalosporin Derivative/ 47 or 48 or 49 or 50 or 51 or 52 or 53 or 54 or 55 or
40. (cefuroxime or ceftazidime or cephalexin or ceftriax- 56 or 57
one or cefpirome).mp. [mp = title, abstract, subject 65. 61 and 64
headings, heading word, drug trade name, original 66. 63 or 65
title, device manufacturer, drug manufacturer name] 67. 66
41. exp ∗ Clavulanic Acid/ 68. limit 67 to human
42. Clavulanic Acid$.mp. [mp = title, abstract, subject
headings, heading word, drug trade name, original
Copyright 2008 John Wiley & Sons, Ltd. Diabetes Metab Res Rev 2008; 24(Suppl 1): S145–S161.
DOI: 10.1002/dmrrAppendix B
Evidence tables
Results of primary/
Study design Study population Diagnosis Intervention and secondary outcomes Evidence Comments/
Reference + quality and characteristics osteomyelitis control conditions Outcome category + statistic SIGN weaknesses
Akova 1996 [62] Case series 74 patients with 21 of 49 with Duration of therapy for Clinical cure and Clinical cure rate 86% 3 ‘Severe infection’ not
Copyright 2008 John Wiley & Sons, Ltd.
Study quality: 3/4 severe diabetic foot osteomyelitis, osteomyelitis group, microbiological (42/49) 25/32 (78%) defined in this study
infection including microbiologically 41 ± 5 days Follow-up: eradication microbiological
49 with documented. 16 weeks (range 8–26) eradication Duration of
osteomyelitis No Osteomyelitis defined by treatment 41 ± 5 days.
specific data for infected exposed bone, 14 amputations (10/14
osteomyelitis and/or related findings sterile bone cultures)
population Age: were discovered with
mean 57 ± 10 plain X-ray, triphasic Te
Gender: unknown scan, CT scan
Review of the Management of Diabetic Foot Osteomyelitis
Bamberger 1987 Case series 51 patients with All three of the following IV antibiotics for Good outcome: 27 of 51 (52.9%) had 3 No statistical analysis
[49] diabetes and criteria: characteristic 4 weeks, or, IV and oral resolution of clinical good outcome. 15 between the patients
osteomyelitis radiographic changes antibiotics for 10 weeks evidence of received a below knee within the different
Mean age 62 ± 1 (cortical bone erosion at inflammation at the time amputation, 9 a toe intervention groups
year (range 48–85) the site of soft tissue of the last follow up amputation
inflammation); clinical examination without the
signs of inflammation need for ablative surgery
(erythema, drainage, Follow up period of
swelling, or warmth) or 19 months
necrosis; and a wound,
bone, or blood culture
yielding pathologic
bacteria
Cohen 1991 [46] Case series 53 patients with Not stated Partial ray resections, Definition of success: Success rate: 13/35 3 Unknown cases of
Study quality: 3/4 peripheral transmetatarsal cessation of infection partial ray resections, osteomyelitis although
neuropathy (52 with amputations, without transfer lesions 14/15 transmetatarsal osteomyelitis was an
diabetes) with panmetatarsal head or long-term follow-up amp, 6/7 panmetatarsal indication for partial ray
gangrene or resections. needed head resections amputation and
uncontrollable transmetatarsal
osteomyelitis amputation
All male This was a study of
Mean follow up outcome of different
22.3 months surgical procedures data
for osteomyelitis not
given
(continued overleaf)
S153
DOI: 10.1002/dmrr
Diabetes Metab Res Rev 2008; 24(Suppl 1): S145–S161.S154
Copyright 2008 John Wiley & Sons, Ltd.
Results on primary
Study design Study population Diagnosis Intervention and /secondary outcomes Evidence Comments
Reference + quality and characteristics osteomyelitis control conditions Outcome category + Statistic SIGN /weaknesses
Diamantopoulos Case series 84 patients with Soft tissue infection Parenteral Clindamycin Cure = resolution of all Cure in 33/49 (76.3%) 3 Of the total population,
1998 [63] Study quality: 3/4 limb threatening accompanied by bone (600 mg tid) + signs and symptoms of Of the cured, bone 16 of the 18 patients
infections including erosion was classified as ciprofloxacin (300 mg infection incision and drainage who failed had
49 patients with osteomyelitis, confirmed bid), followed by oral Assessment 3 weeks took place in 11 patients osteomyelitis
osteomyelitis (30 by histology if possible At discharge, patients after the initiation of Mean follow-up (p = 0.007)
with peripheral or radionuclide scan received ciprofloxacin treatment 16 months (range 2–28) The follow-up period is
arterial disease) 1.5–2 g daily if Recurrent infection in 8 short compared to the
Mean anaerobes were of 33 long duration of
age = 62.4 years undetected Overall success rate at treatment
51 male, 33 female Duration of the end of follow up
No specific data for therapy = 6 –24 months 25/49 (51%)
osteomyelitis (outpatient setting)
patients
Embil 2006 [50] Case series n = 325 consecutive At least one of the Mean duration of Osteomyelitis in Remission: 75/93 3 Retrospective review
Study quality: 4/4 patients with following: therapy 40 ± 30 weeks, remission = resolution (80.5%)
diabetes receiving - Plain radiographs oral route ± short initial of both clinical findings oral alone = 53/64
care at a specialized - bone scan IV route: 2 to 4 agents, and destructive bone (82.8%)
wound clinic, of - bone seen, probed or culture directed changes on plain oral + IV = 22/29
which 79 of 93 palpated (metronidazole, radiographs or bone (75.8%)
episodes of foot ciprofloxacin, scans Patients with or without
osteomyelitis (all co-trimoxazole, bone debridement had
grade 3 Wagner) amoxicillin/clavulate no significant difference
Patients with foot acid, clindamycin) in clinical response to
abscess or acute 26 cases (28%) had bone therapy (23/26 (88%)
osteomyelitis that debridement and 9 versus 52/67 (78%),
necessitated (10%) had toe respectively; p > .05)
debridement were amputation
excluded Mean relapse free
follow-up
duration = 50 ± 50
weeks
A. R. Berendt et al.
DOI: 10.1002/dmrr
Diabetes Metab Res Rev 2008; 24(Suppl 1): S145–S161.Grayson 1994 RCT Overall Histopathological, Agressive surgical Assessed at day 5 of Success rate of soft 1+ Comparison of
[2] Study quality: 8/9 population = 93 radiological and clinical debridement combined therapy and at the end tissue infection and ampicillin/sulbactam and
diabetic patients criteria with either of intravenous therapy. osteomyelitis groups imipenem/cilastin for
with 96 episodes of imipenem/cilastin Cure was defined as combined: 48/59 diabetic foot infection,
foot infections (N = 27) or eradication of clinical (81.3%). 57 of 93 total combined with surgical
including 59 cases of ampicillin/sulbactam signs of soft tissue cases had a minor debridement, including a
osteomyelitis (N = 32). infection amputation, 4 had a sub-group of cases with
No specific Duration of intravenous below knee amputation. osteomyelitis. No specific
demographic data treatment: 12.5 days Cure was achieved in data for the cases with
for patients with (amp/sulb), 16.5 (imi/cil) 22/27 (81.4% imi/cil) and osteomyelitis were given
osteomyelitis 26/32 (81.2% amp/sulb) except for some follow
Copyright 2008 John Wiley & Sons, Ltd.
Mean age: in the group of soft up data
ampicillin/sulbactam tissue infection and
59 years; osteomyelitis combined.
Imipenem/cilastin In the selected group of
61 years patients with
osteomyelitis, cure was
maintained for
approximately a year in
17 (65%) of the imi/cil
Review of the Management of Diabetic Foot Osteomyelitis
group and 16 (73%) of
the amp/sulb treated
group
Ha Van 1996 Case series 32 patients with Probe to bone and X-ray Conservative surgery Primary outcome: 25 (78%) healed in 3 Outcomes of cases
[41] Study quality: 3/4 diabetic foot ulcers confirmation (ulcerectomy with healing. 181 days. Duration of compared with 35
and osteomyelitis limited resection of the Secondary outcomes: antibiotic therapy historical controls
but without critical infected part of the time to healing, duration 111 days. treated with antibiotics
ischaemia phalanx or metatarsal) of antibiotic therapy, Secondary surgical alone to suggest benefit
Mean age plus medical treatment secondary surgical procedures in 3 patients of conservative surgery
59.4 years. procedures
29/32 male.
None lost to
follow-up
Kerstein 1974 Case series, 14 male patients Plain radiographs and Transmetatarsal Healing of wound All healed at All patients initially
[45] retrospective mean age 64.4 bone cultures amputation in 4, digit 6–18 months follow up offered major limb
range 55–78 with amputation in 4, with amputation but refused
osteomyelitis, 8 intravenous antibiotics
diabetic, age range while hospitalized
55–78
Kumagi 1998 Case series, 33 patient with 37 Histological appearance Resection to bleeding Wound healing (days to 1 failed (unhealed), one
[44] retrospective wounds, 29 diabetic of bone biopsy healthy bone and six healing presented) recurrence in
with 33 wounds, 17 weeks intravenous osteomyelitis group; 2
with osteomyelitis, antibiotics failed (BKA) in
18 episodes non-osteomyelitis group,
2 lost to follow up
(continued overleaf)
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Diabetes Metab Res Rev 2008; 24(Suppl 1): S145–S161.S156
Results on primary
Study design Study population Diagnosis Intervention and /secondary outcomes Evidence Comments
Reference + quality and characteristics osteomyelitis control conditions Outcome category + Statistic SIGN /weaknesses
Lipsky 1997 [55] Randomized 108 patients with Clinical, laboratory, and Intervention: ofloxacin. Cure = Disappearance of After bone debridement: 1− No specific characteristic
Copyright 2008 John Wiley & Sons, Ltd.
controlled trial diabetes with foot plain radiographs controls: all signs and symptoms 9/12 cured and improved data for patients with
Study quality: 3/9 infection. Age: ampicillin/sulbactam associated with active in the Ofloxacin group osteomyelitis. Only 1/5
61.5 years, 84% infection. versus 2/3 in the patients had
male, 54% Duration of therapy Improved = incomplete Aminopenicillin. osteomyelitis
Caucasian Type of IV = 9.2 days, abatement of the signs Without bone Comparison of Ofloxacin
diabetes unknown oral = 11.5 days for or symptoms. debridement: 3/4 cured and Ampicillin/
21 (19%) patients intervention and control Failed = no and improved in the Sulbactam for diabetic
with osteomyelitis groups with improvement Ofloxacin group versus foot infection including
Of these, 16 received osteomyelitis combined 1/2 in the osteomyelitis
ofloxacin and 5 Aminopenicillin group Unclear why bone was
ampicillin/sulbactam not debrided in 6
12 patients in the patients when protocol
ofloxacin group and indicated it should be
3 in the amp/sulb Too few patients to draw
with osteomyelitis conclusions based on
had the infected these data
bone debrided soon
after enrolment
Lipsky 2004 [52] Randomized Overall population Actual, and presumed Intervention: Linezolid Cured and improved Intervention: 27/44 1− No specific data for
open-label study 371. Age: osteomyelitis according Controls: (61%), Controls: 11/16 characteristics of
Study quality: 3/9 62.5 years. Gender: to individual clinicians’ ampicillin/sulbactam. (69%) (95% CI −34.3 to patients with
71% male, type 2 criteria According to the 19.5) cured and osteomyelitis. Only 1/5
diabetes: 52–61% bacterial profile, improved patients had
77 (21%) diabetic vancomycin or osteomyelitis
foot osteomyelitis aztreonam could be For the entire population Comparison of IV, then
added. Duration of studied, the number of oral ampi/sulb and
therapy 19 ± 9 days. adverse events was linezolid (2 LZD FOR 1
Evaluation in an superior for linezolid A/S) for all types of
intention to treat at the than for diabetic foot infections
test of cure visit (+5 days ampicillin/sulbactam including some cases of
after the end of trial) (26.6% versus 10.0%; osteomyelitis
p < .001) Duration of antimicrobial
therapy was significantly
shorter in this study than
in others
Antimicrobial therapy
mainly administered in
an outpatient setting
even for patients with
non-critical foot ischemia
A. R. Berendt et al.
DOI: 10.1002/dmrr
Diabetes Metab Res Rev 2008; 24(Suppl 1): S145–S161.Nehler 1999 [64] Case series, 92 patients with 97 Plain radiography Empirical broad Recurrence (measured by 48% recurrence in 3 Observational study. A
retrospective forefoot infections. spectrum intravenous need for osteomyelitis group, futher 23 had
55 extremities (56%) antibiotics and re-hospitalization 20% in osteomyelitis, 7
had osteomyelitis. debridement surgery and because of infection). non-osteomyelitis group diagnosed on MRI, 16 on
All had ‘clinically primary digit amputation Eventual foot Same eventual bone scan but results are
salvageable’forefoot amputation proportion of foot not extractable from 40
infection. 32 were amputation (22%) and others without
diagnosed on plain no difference in time to osteomyelitis
radiographs and amputation
have extractable
results
Copyright 2008 John Wiley & Sons, Ltd.
Pittet 1999 [42] Case series, 120 pts hospitalized Only 58 (55%) of the pts 14 (13%) had an Success = healing or no Clinical failure in 15 of 3 It was classified in the
retrospective for foot lesions. had osteomyelitis, immediate amputation. infection. Failure = need 34 (44%), success in article as a cohort study.
Investigated factors defined by 2 blinded Conservative treatment for amputation or a new 35/57 (61%) Without a defined
predictive of failure radiologists; clinical + successful for 57 (63%) contiguous lesion during Elsewhere it is stated control group it is in fact
(fever, azotemia, X-ray + bone scan of remaining 91 follow-up that 35/50 (70%) was a case series
prior hospitalization successful and 15 (30%) The set-up is
for DFI, gangrenous failure. retrospective. There are
lesions). 50 patients some concerns about
Review of the Management of Diabetic Foot Osteomyelitis
had ‘osteo & deep confounders, selection
tissue infection’. 52 bias and lack of blinding.
female, 53 male
Seidel 1991 [65] Case series, 40 patients with Not defined Patients chose ‘Cured’ 4/5 RVP group cured, 0/7 3 Patients allowed to
retrospective diabetic neuropathic retrograde venous control group. Follow up chose treatment; no
acrodystrophy of perfusion (RVP) once duration not given blinding, definitions and
whom 12 stated to daily or no perfusion. All outcomes of
have superadded patients received osteomyelitis not stated,
osteomyelitis Piperacillin 4G q8h. and all patients had
Control group also abnormal radiographs
received Gentamycin
60 mg q8h, Buflomdedil
50 mg q8h, Dextran 40
500 mL q8h and Heparin
5000 IU q8h. RVP group
received Gentamycin
120 mg, Buflomedil
50 mg, Dexamethoasone
4 mg, Lignocaine 4 mg
and Heparin 2500 IU in
120 mL normal saline
intravenously once daily
into the extravasated
limb under tourniquet
control. RVP group also
received additional daily
Gentamycin 60 mg i.m.
daily and a retard tablet
of Buflomedil.
(continued overleaf)
S157
DOI: 10.1002/dmrr
Diabetes Metab Res Rev 2008; 24(Suppl 1): S145–S161.S158
Copyright 2008 John Wiley & Sons, Ltd.
Results on primary
Study design Study population Diagnosis Intervention and /secondary outcomes Evidence Comments
Reference + quality and characteristics osteomyelitis control conditions Outcome category + Statistic SIGN /weaknesses
Senneville 2001 Case series, 17 pts with 20 Bone biopsy in all Rifampicin and ofloxacin Cure = disappearance of Cure in 15 (88%) at end 3
[48] prospective osteomyelitic bones therapy all signs and symptoms of treatment (15/17 after
treated with and no relapse. Failure = 3 months; 12/14 after
rifampicin and anything else 6 months) and
ofloxacin maintained in 13 (77%)
combination therapy at end of average period
for median of of treatment follow-up
6 months of 22 months
Venkatesan Case series, 22 patients, 15 male, Interruption of cortex Antibiotic therapy at Cure = ‘‘freedom from 4 patients did not 3 No routine follow-up
1997 [47] retrospective 7 female, median and clinical features. least 3 months clinical signs of respond and had x-rays. Outcome
age 66, treated with inflammation or x-ray amputations. measures not clearly
antibiotics and no evidence.’’ Osteomyelitis recurred in defined.
surgery if possible one at same site.
Resolution of infection in
all remaining inferred
from ‘freedom from
clinical signs of inflame
or x-ray evidence’. In all
other cases medical
therapy was successful in
resolving osteomyelitis
and there was absence
of recurrence.
Wilson 1985 Case series 2 patients Clinical findings and Nafcillin intravenous Clinical and radiological Follow-up 11 months 3 First report of oral
[66] 57 and 73 years, plain radiographs (inpatient), followed by after the end of antimicrobial therapy for
males with clindamycin and treatment cured (clinical diabetic foot
insulin-dependent cephalexin duration of and radiological). osteomyelitis
diabetes therapy = 7 months. 4 months after the end
Clindamycin and of treatment:
metronidazole oral stabilisation of the
(outpatient). radiological
Duration of therapy abnormalities
3 months.
A. R. Berendt et al.
DOI: 10.1002/dmrr
Diabetes Metab Res Rev 2008; 24(Suppl 1): S145–S161.Yadlapalli 2002 Case series 58 patients with Clinical (grossly infected 47 patients with empiric Healing, failure 12 failed 3 Authors did not give
[60] Chart review diabetes and or exposed bone, probe intravenous antibiotic 46 healed (79.3%) details about
osteomyelitis to bone) or radiograph therapy 4 to 6 weeks 9 persistence of culture-based antibiotic
48 male, 10 female and radionuclide scan using miscellaneous ulceration. therapy
Mean age 60 years agents (ceftizoxime, Follow up 12 months 24 of 58 patients had
ampicillin/sulbactam, after the end of operative procedures
cefoxitine, vancomycin). treatment. (41.3%)
11 patients received
culture-based antibiotic
therapy for a mean
duration 40.3 days
Copyright 2008 John Wiley & Sons, Ltd.
(range 19–90)
Debridement: 34,
excision of bone: 13,
amputation toe or ray: 8,
major amputation: 3
Yamaguchi 2004 Cohort study 11 patients with Visible necrotic and Epidermal sheets grafted Wound healing, 11 pts with experimental 2 Patients chose their
[43] Study quality: 5/7 intervention, 38 infected bone with onto foot ulcers w/o amputation treatment had fewer treatment options.
patients in study, 20 positive cultures exposed bone (n = 11). amputations (0 vs 8) and Strong possibility of
Review of the Management of Diabetic Foot Osteomyelitis
patients with In patients with exposed similar time to healing. selection bias
osteomyelitis bone compared standard No recurrence of
Age range 36–84; treatment (n = 9) with osteomyelitis
mean age experimental procedure (p < 0.0001)
58.1 years. (n = 11) – bone
Experimental, 64.8 debrided, partly excised,
controls for exposed covered with occlusive
bone patients. dressing, then epidermal
Gender: 25/38 were skin graft
male; 7/2 Standard,
8/3 Experimental
S159
DOI: 10.1002/dmrr
Diabetes Metab Res Rev 2008; 24(Suppl 1): S145–S161.You can also read
