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 eInfections Review: VOLUME
2, NUMBER 9
Osteomyelitis/Diabetic Foot
Infections
In
this Issue...
Diabetic foot infections and the ensuing osteomyelitis are
common occurrences among persons with diabetes, and many
patients eventually require amputation. Health care costs
associated with managing diabetic foot ulcers are quite
high. Additionally, the indirect costs, in terms of
disability and overall economic impact, overshadow the
direct medical costs.
Because of the polymicrobial nature of many of the wounds
and their association with osteomyelitis, antibiotic
selection is challenging. It is often unclear which
organisms are commensal and which are pathogenic. In this
issue, we review the microbiology of diabetic wound
infections and osteomyelitis, the importance of
appropriate bone sampling, the radiographic modalities for
diagnosis, and current controversies in treatment. |
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At
the conclusion of this activity, participants should be
able to:
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Review the
microbiology of chronic diabetic wound infections and
osteomyelitis. |
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Review the
diagnostic modalities used to define osteomyelitis and
diabetic wounds, including the role radiology and
nuclear medicine. |
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Develop an
evidence-based approach to treating and managing
osteomyelitis and chronic wounds. |
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| IMPORTANT CME INFORMATION |
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Course
Directors
Paul
G. Auwaerter, MD
Associate Professor
of Medicine
Clinical Director,
Division of Infectious
Diseases and General Internal Medicine
The Johns Hopkins
University
School of Medicine
Baltimore, MD
John
G. Bartlett, MD
Professor of Medicine
Department of Medicine
The Johns Hopkins
University
School of Medicine
Baltimore, MD
Sara
E. Cosgrove, MD, MS
Associate Professor
of Medicine
Division of Infectious
Diseases
Director,
Antibiotic Management
Program
Associate Hospital
Epidemiologist
The Johns Hopkins
University
School of Medicine
Baltimore, MD |
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GUEST
AUTHOR OF THE MONTH |
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Commentary
& Reviews: |
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Kristine E. Johnson,
MD
Assistant Professor of Medicine
Division of Infectious Diseases
Johns Hopkins University School of Medicine
Baltimore, Maryland
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Guest
Faculty Disclosures
Kristine E.
Johnson, MD, has disclosed she has received
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It has been estimated that approximately 15% to 25% of patients with diabetes will
develop a diabetic foot ulcer at some point.1 Among these individuals, 14% to 24%
will experience soft tissue infection, undergo an amputation for osteomyelitis, or
both.1 Health care costs associated with diabetic foot ulcers are enormous, with
treatment of these wounds accounting for 20% to 25% of all hospitalizations among
persons who have diabetes.2
The combination of diabetic peripheral neuropathy and small-vessel arterial disease
places persons with diabetes at high risk for foot ulcers and osteomyelitis,
affecting in particular the phalangeal, metatarsal, and tarsal bones. Primary
prevention and foot care should be integrated into all aspects of diabetes care.
Aggressive management of wounds and recognition of signs of osteomyelitis through
careful physical examination and radiographic studies3 may lead to earlier
intervention (surgical or nonsurgical) that might prevent progression and limb
loss.4,5 Such wounds are often polymicrobial on tissue or swab culture, and
identifying pathogen(s) vs. commensal colonizers is difficult. Greater numbers of
bacterial isolates correlate with an increased risk for local infection.6 Bacteria
cultured from superficial samples vary from deep tissue or bone culture results, and
the relative "bioburden"7 of the wound may
be associated with clinical outcomes, although this has not been well defined. The
microbiome of diabetic foot wounds is more diverse, including prominent populations
of anaerobes, and does not appear to be influenced by flora on the normal host
skin.8,9
Selecting antibiotics for treating diabetic osteomyelitis
is a daunting task because of the difficulties associated
with determining the causative organism(s). Bone biopsy is
considered the gold standard for identifying pathogen(s).
Biopsy with the incision away from the ulcer site is
ideal, as little correlation has been demonstrated between
bone biopsy and superficial swab cultures.5 In the absence
of reliable biopsy data, the Infectious Diseases Society
of America's guidelines suggest
broad-spectrum coverage for gram-negative (including
Pseudomonas aeruginosa), anaerobic, and gram-positive
organisms (including methicillin-resistant Staphylococcus
aureus [MRSA]).10 Anaerobes are particularly prevalent in
diabetic osteomyelitis and are often difficult to culture
under routine circumstances. For high tissue
concentration, intravenous (IV) rather than oral
antibiotics are recommended for osteomyelitis, although
orally administered agents have been used
successfully.5,11 Prolonged courses of 6 to 8 weeks are
suggested. Unfortunately, no tests or radiologic studies
define cure, but reimaging is reassuring if bony
abnormalities resolve.
Physical examination findings and radiographic studies are
key to appropriate diagnosis. The bedside probe-to-bone
test is specific for osteomyelitis (pooled
specificity=0.91; 95% confidence interval [CI], 0.86 to
0.94) 3. If the probe-to-bone test is positive, additional
studies are probably unnecessary; however, radiography
helps to define the extent of infection. The presence of
acute soft tissue infection, ischemia, and necrosis is of
concern. Although magnetic resonance imaging (MRI) is the
most sensitive and specific modality,3 nuclear medicine
scans (triple-phase and leukocyte scans) can be useful as
well. It is reasonable to begin with plain x-rays.
However, as these films are neither sensitive nor
specific, workup should advance to more sophisticated
studies (MRI or nuclear medicine scans) if suspicion is
high.
Erythrocyte sedimentation rate (ESR) and C-reactive
protein (CRP) are useful inflammatory markers to follow
with respect to therapeutic response. Treatment beyond 8
weeks to achieve normal inflammatory markers is reasonable
in some settings. However, in patients with poorly
controlled diabetes, the ESR and CRP may be elevated in
the absence of osteomyelitis, and autoimmune disease or
occult infection (i.e., central line infection) should be
considered in those receiving long-term IV antibiotic
therapy when these inflammatory markers remain elevated
despite targeted treatment for osteomyelitis. Although not
common practice, it can be useful to reimage a patient
before discontinuing antibiotics and evaluate the
patient's response.
The greatest debate in the approach to treating
osteomyelitis of the distal lower extremity is whether to
treat conservatively with antibiotics or to pursue prompt
surgical debridement accompanied by antibiotics (with
possible amputation). Data are inconsistent and suggest
similar success rates (approximately 50%),4,5 with either
approach. The lack of randomized, controlled trials that
address this issue provides little compelling evidence for
selecting one approach over another. However, in the
absence of toxicity, active gangrene, or frankly necrotic
tissue, initial treatment with antibiotics provides a
chance for limb salvage. If MRSA or multidrug-resistant
gram-negative organisms are present, long-term IV therapy
may be necessary, but that has its own inherent risks.
In summary, the diagnostic and treatment approach to osteomyelitis must be tailored
to the individual patient. Since osteomyelitis can be elusive on plain film,
negative initial studies should prompt additional workup. Moreover, new laboratory
techniques have shown that the bacterial flora of chronic wounds is far more complex
than previously thought, suggesting that anaerobes as well as S. aureus may play a
significant role in soft tissue infection and osteomyelitis. Where at all possible,
bone biopsy should be obtained to guide antibiotic selection. Although osteomyelitis
is a common condition, evidence is lacking about superior antibiotic combinations,
timing of debridement, and the utility of cultures. Additional prospective studies
of new technologies to speed prompt diagnosis and targeted antibiotic and surgical
treatment are warranted.
Take–Home Points
- Diabetic foot wounds are frequently associated with osteomyelitis and delayed
healing.
- Diagnostic approach: Physical examination, revealing a positive probe-to-bone
test, is highly suggestive of osteomyelitis; MRI is the preferred imaging
modality.
- Microbiology: Wound cultures are frequently polymicrobial in nature but do not
correlate well with bone cultures. In the absence of a bone culture, gram-negatives,
anaerobes, and resistant gram-positives (MRSA in particular) should be considered
with antibiotic selection.
- Treatment approach: Early surgical vs. conservative antibiotic therapy first for
diabetic wound osteomyelitis is controversial. In the absence of necrotic soft
tissue infection that warrants debridement, it is reasonable to attempt a course of
antibiotic therapy initially.
- Oral antibiotics appear to be equally effective for treating staphylococcal
osteomyelitis compared with IV regimens.
- Staphylococcal osteomyelitis is most often methicillin-sensitive S. aureus
(MSSA), rather than MRSA. This should help to guide antibiotic selection when
reliable culture data are available.
Commentary References
| 1. |
American
Diabetes Association. Consensus development conference on
diabetic foot wound care. Diabetes Care 22,
1354-1360. 1999. |
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| 2. |
Reiber GE,
Smith DG, Carter J et al. A
comparison of diabetic foot ulcer patients managed in
VHA and non-VHA settings. J Rehabil Res
Dev. 2001;38(3):309-317. |
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| 3. |
Dinh MT, Abad
CL, Safdar N. Diagnostic accuracy of the physical examination and
imaging tests for osteomyelitis underlying diabetic
foot ulcers. Clin Infect Dis. 2008;47(4):519-527. |
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| 4. |
Aragón-Sánchez FJ, Cabrera-Galván JJ, Quintana-Marrero Y et al. Outcomes of surgical treatment of diabetic foot
osteomyelitis: a series of 185 patients with
histopathological confirmation of bone
involvement. Diabetologia. 2008;51(11):1962-1970. |
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| 5. |
Senneville E,
Lombart A, Beltrand E et al. Outcome of diabetic foot osteomyelitis treated
nonsurgically: a retrospective cohort study. Diabetes Care. 2008;31(4):637-642. |
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| 6. |
Louie TJ,
Bartlett JG, Tally FP, Gorbach SL. Aerobic and anaerobic bacteria in diabetic foot
ulcers. Ann Intern Med. 1976;85(4):461-463. |
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| 7. |
Gardner SE,
Frantz RA. Wound bioburden and infection-related complications in
diabetic foot ulcers. Biol Res Nurs. 2008;10(1):44-53. |
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| 8. |
Price LB, Liu
CM, Melendez JH et al. Community analysis of chronic wound bacteria using 16S
rRNA gene-based pyrosequencing: impact of diabetes and
antibiotics on chronic wound microbiota. PLoS
One. 2009;4(7):e6462. |
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| 9. |
Gontcharova V,
Youn E, Sun Y, Wolcott RD, Dowd SE. A
comparison of bacterial composition in diabetic ulcers
and contralateral intact skin. Open Microbiol
J. 2010;4:8-19. |
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| 10. |
Lipsky BA,
Berendt AR, Deery HG et al. Diagnosis and treatment of diabetic foot
infections. J Clin Infect Dis. 2004;39(7):885-910. |
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| 11. |
Euba G, Murillo
O, Fernandez-Sabe N et al. Long-term follow-up trial of oral
rifampin-cotrimoxazole combination versus intravenous
cloxacillin in treatment of chronic staphylococcal
osteomyelitis. J Antimicrob Agents Chemother. 2009;53(6):2672-2676. |
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DEFINING THE MICROBIOME OF CHRONIC
WOUNDS |
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Gontcharova V, Youn E,
Sun Y, Wolcott RD, Dowd SE. A
comparison of bacterial composition in diabetic
ulcers and contralateral intact skin. Open Microbiol J. 2010;4:8-19.
(For non-subscribers to this journal, an
additional fee may apply to obtain full-text
articles.) |
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According to the study by Gontcharova and coworkers, conventional cultures do not
adequately describe the microbial populations of chronic wounds. The goal of this
study was to identify the microbial community (microbiome) that may be shared across
chronic wounds compared with intact skin using 16s ribosomal DNA techniques. Many
anaerobic bacteria are not isolated even when routine anaerobic collection
techniques are used. As a culture-independent technique, the use of 16s ribosomal
DNA (highly conserved across bacterial species and absent from animal cells) allows
genus- and species-level identification of cultivable and noncultivable
bacteria.
The authors collected wound debridement and skin
swab samples from diabetic patients who had chronic
wounds and were receiving treatment at a regional
wound care center. DNA extracted from the samples
underwent bacterial amplicon pyrosequencing. More
than 93,000 sequences across all wounds were
studied. Comparing wound and intact skin samples,
the data were analyzed using a receiver-operating
characteristic curve to determine the bacteria that
most and least discriminated between healthy skin
and wounds. Similarity and variability among
bacterial populations in wounds and intact skin were
evaluated using Pearson's
correlation and Principal Component Analysis.
The bacterial genus that differed the most between
healthy skin and wounds was Segetibacter. Using area
under the curve analysis, all bacteria shown to have
discriminating capacity were found in low frequency
in both healthy skin and wound tissue. The most
prevalent bacterial genera in intact skin were
Pseudomonas, Corynebacterium, and Staphylococcus. In
wounds, Corynebacterium, Pseudomonas, and
Streptococcus were the most prevalent. Escherichia,
Serratia, and Shigella were also more common in
wounds than in intact skin. Intra-individual
populations had approximately the same clustering as
did inter-individual comparisons, suggesting that
intact and wounded skin microbiota do not influence
each other in the same host. Corynebacterium genera
were found at considerably higher levels within
wounds compared with intact skin samples. Finally,
Finegoldia and Peptoniphilus were among the most
populous anaerobes identified in wounds.
The microbiome of intact skin differs significantly
from that of wounds, but surprisingly, host factors
do not appear to play a role in the microbial
composition of intact vs wounded skin in a
particular individual. Corynebacterium and
Pseudomonas are prevalent in both intact and wounded
skin, whereas Streptococcus is more common in
wounds. Consistent with the findings of other
studies, anaerobes previously not recognized are
also frequently present in wounds.
Defining the role of the microbiome in the context
of chronic wounds is in the early stages of
development with the availability of 16s DNA
amplification and pyrosequencing. This study
provides a foundation for further description of the
wound microenvironment and future study of protein
expression. Ultimately, a key research question will
be what is the role of the microbiome in inhibition
of the normal healing cascade?
Although the study approach and results of the
investigation are intriguing, they are compromised
by a poor study design, inconsistent selection
criteria, and absence of outcomes measurement.
Nevertheless, despite these methodological
shortcomings, the study is valuable because it
outlines a new approach to defining the microbiology
of chronic wounds.
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THE VALUE OF TISSUE
CULTURE IN DIAGNOSIS OF OSTEOMYELITIS |
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Senneville E, Morant H,
Descamps D, et al. Needle puncture and
transcutaneous bone biopsy cultures are inconsistent
in patients with diabetes and suspected osteomyelitis
of the foot. Clin Infect Dis. 2009;48(7):888-893.
(For non-subscribers to this journal, an
additional fee may apply to obtain full-text
articles.) |
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The primary goal of this prospective study was to determine the intra-individual
agreement in bacterial culture results among multiple tissue samples from patients
with diabetic wounds and suspected osteomyelitis. Samples were collected via (1)
needle puncture (away from the ulcer site); (2) transcutaneous bone biopsy (away
from the ulcer site); and (3) superficial swabs of ulcers.
Of the 451 patients with diabetes who presented with foot
ulcers, 31 met the study inclusion criteria. The mean
number of bacterial species per positive sample was 1.32
for needle puncture specimens, 1.35 for bone biopsy
specimens, and 2.51 for swab samples. The most common
organisms grown from bone biopsy, in descending order,
were Staphylococcus aureus, Proteus mirabilis, and
Morganella morganii. The correlation between bone biopsy
and needle puncture cultures was 23.9%, whereas the
correlation between bone biopsy and swab culture results
was higher, at 41.7%. When present, S. aureus was common
across all collection methods, with a correlation of
82.3%. Coagulase-negative staphylococci did not correlate
across the sample types. Other gram-positive cocci were
found in low concordance among the sampling techniques, at
30.7%. Gram-negative bacilli and anaerobes were poorly
correlated across intra-individual samples, at 50% and
37.5%, respectively. When comparing needle puncture and
biopsy alone, S. aureus was poorly correlated at 46.7%,
whereas gram-negative bacilli and anaerobes were even less
concordant at 24% and 25%, respectively. Across all 3
sampling techniques, bacterial isolates did not correlate
significantly. Of 14 patients with histopathology
available, bone biopsy specimens yielded positive cultures
in 6 (42.9%). Among the differences in culture results
across sampling techniques, gram-negative rods
(Pseudomonas and Proteus in particular) were responsible
for most (76%) of the variation.
The results of this study suggest that currently available
techniques for identifying the bacterial etiology of
diabetic osteomyelitis are suboptimal at best. In most
settings, bone biopsy is recommended as the diagnostic
procedure most likely to define etiology. The authors
point out that if needle puncture by itself had been used
as the single sampling method, 5 patients without
osteomyelitis (negative bone cultures) would have been
treated unnecessarily, and 8 patients with osteomyelitis
(positive bone cultures) would not have been treated. In
the setting of an open wound, the finding of greater
numbers of bacterial species from superficial swab samples
compared with the other 2 modalities is not unexpected.
Although a needle puncture would be a simpler method
available to more physicians in the outpatient setting,
the poor correlation of this technique with bone biopsy
does not support its broader clinical application.
Surgical bone biopsy away from the wound site remains the
gold standard for identification of the causative organism
in patients with osteomyelitis. When bone biopsy is not an
option, deep tissue curettage culture, rather than swab
culture, may be beneficial if it reveals drug-resistant
organisms that may be pathogens, particularly MRSA and
Pseudomonas aeruginosa. In these cases, treatment with
broad-spectrum antibiotics (oral or IV, depending in part
on organism sensitivities) is indicated. Finally, the
ability to generalize these results is somewhat limited
because of the small sample size.
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DIAGNOSTIC TESTING
FOR OSTEOMYELITIS |
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Dinh, MT, Abad
CL, Safdar N. Diagnostic accuracy of the
physical examination and imaging tests for
osteomyelitis underlying diabetic foot
ulcers. Clin Infect Dis. 2008:47(4);519-527.
(For non-subscribers to this journal, an
additional fee may apply to obtain full-text
articles.) |
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The goal of this study was to
conduct a systematic review of the literature to determine
the predictive value of physical examination and
radiography in diagnosing osteomyelitis in patients with
diabetic foot ulcers. Using the gold standard of
histopathologic examination and/or bone culture, this
meta-analysis synthesized results from 59 studies. Studies
describing examination of the wound, ulcer size,
appearance, and radiographic evaluation were included in
the meta-analysis. Radiology included plain films, MRI,
triple-phase bone scan, and leukocyte scan. The authors
calculated the sensitivity and specificity for examination
components and imaging then pooled the results into a
statistical model. They calculated inter-study
heterogeneity, provided a summary of study accuracy, and
addressed potential bias among the studies.
The literature search yielded 917 articles, with 9 meeting
review criteria. An additional 59 studies were included
following a review of article references. Only 2 studies
evaluated diagnostic characteristics of the physical
examination, and 1 study examined ulcer characteristics
predictive of osteomyelitis. From 288 pooled cases, the
sensitivity of exposed bone or probe-to-bone test was 0.60
(95% CI, 0.46 to 0.73; P < .001), and the specificity
was 0.91 (95% CI, 0.86 to 0.94; P =.11). The pooled odds
ratio (OR) for osteomyelitis with palpable or visible bone
was 49.45 (no CI or accuracy value reported). In addition,
4 studies of plain film radiographs yielded a sensitivity
of 0.54 (95% CI, 0.44 to 0.63; P =.006) and a specificity
of 0.68 (95% CI, 0.53 to 0.80; P = .01), with a diagnostic
OR of 2.84 and low to intermediate accuracy. Evaluators
were not blinded or blinding was not reported. A total of
4 prospective studies of MRI provided a sensitivity of
0.90 (95% CI, 0.82 to 0.95; P < .001) and a specificity
0.79 (95% CI, 0.62 to 0.91; P = .41), with a diagnostic OR
of 24.36 and high accuracy. Evaluators were blinded or
were given minimal clinical information.
For the triple-phase bone scan, 6 studies provided a
sensitivity of 0.81 (95% CI, 0.73 to 0.87;
P <.001) and a specificity of 0.28 (95% CI, 0.14 to
0.42; P =.01), with a diagnostic OR of 2.10 and moderate
accuracy. Evaluators had minimal clinical data or blinding
was not reported.
Finally, from 6 studies of leukocyte scans, the
sensitivity was 0.74 (95% CI, 0.67 to 0.80;
P <.001), the specificity was 0.28 (95% CI, 0.17 to
0.42; P =.01), the diagnostic OR was 10.07, and there was
low to moderate accuracy. Blinding was not mentioned, or
evaluators were not blinded or were given minimal clinical
data.
This thorough meta-analysis provides a useful overview of
the discriminatory capacity of the probe-to-bone test and
available imaging modalities. The results reflect a
reasonable specificity of the probe-to-bone test. The poor
sensitivity reported is counterbalanced by a high
discriminatory value. MRI was the best predictive
modality, but the specificity of this technique is
moderate, due in part to enhancement from Charcot
arthropathy. An expected finding is the poor
discriminatory value of x-rays. Nuclear medicine studies
have improved but limited value as screening and
confirmatory tests. In summary, the detection of palpable
or exposed bone on examination is concerning for
osteomyelitis, but the absence does not exclude the
diagnosis. MRI is the best screening and confirmatory
modality, with nuclear medicine studies reasonable
second-choice options if MRI is not possible. Given
similar prices, the use of MRI first, rather than nuclear
scans, could lead to cost savings. Negative plain films do
not rule out osteomyelitis, and if clinical suspicion of
infection exists, additional studies should be pursued.
A correlate of this review is the finding that despite the
high incidence of osteomyelitis, few well-performed
studies have carefully evaluated the diagnosis, treatment,
and prognosis of patients with this infection.
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TREATMENT OF
OSTEOMYELITIS: ORAL VS. IV? |
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Euba G, Murillo
O, Fernandez-Sabe N, et al. Long-term
follow-up trial of oral rifampin-cotrimoxazole
combination versus intravenous cloxacillin in
treatment of chronic staphylococcal
osteomyelitis. Antimicrob Agents
Chemother. 2009;53(6):2672-2676.
(For non-subscribers to this journal, an
additional fee may apply to obtain full-text
articles.) |
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The goal of this noninferiority
study was to determine whether treatment with orally
administered trimethoprim/sulfamethoxazole (TMP/SMX) for 8
weeks could achieve similar rates of success in patients
with nonaxial osteomyelitis due to MSSA compared with the
use of IV cloxacillin for 6 weeks, followed by oral
cloxacillin for 2 weeks. Diagnostic criteria included
inflammatory signs and/or sinus drainage for
≥10 days, x-ray results consistent with
osteomyelitis, and the presence of necrotic bone. Patients
with prosthetic joint infections, polymicrobial culture
results, or MRSA were excluded from the study. Follow-up
occurred at a minimum of 1 year after completion of
therapy. The primary outcome of the study was cure rate,
which was defined as symptom cessation and no relapse,
such as local inflammation or sinus tract drainage.
Patients with orthopedic implants at the time of diagnosis
were included in the study. Blinding was not
discussed.
Plachouras and colleagues aimed to characterize the PK
parameters of colistin in a population of critically ill
patients with MDR gram-negative infections. The
investigators administered the intravenous form of
colistin methanesulfonate (CMS) at a dose of 3 million
units every 8 hours, measured plasma CMS and colistin
concentrations, and performed population PK analysis. In
the second study, Roberts and colleagues aimed
to compare plasma and subcutaneous tissue levels of meropenem when administered by
intermittent bolus versus extended or continuous infusion methods in order to
recommend ways to optimize dosing regimens against resistant gram-negative
infections.
A total of 50 patients were randomized to TMP/SMX plus
rifampin or cloxacillin alone, and all underwent surgical
debridement. After 6 patients were excluded for
noncompliance, the median follow-up was 10 years. Taking
into account losses to follow-up, the overall cure rate
was 89.6% (43 of 48 patients), with no significant
differences reported between the treatment groups. The
cure rate difference between the groups was 1.6% (95% CI,
-15.7% to 33.3%). In all, 5 relapses occurred (10%), and 2
of 5 patients (40%) had orthopedic implants. The findings
across treatment groups did not vary after controlling for
gender, age, osteomyelitis-associated comorbidities (not
defined), previous osteomyelitis, fever, number of
surgical debridements, closed suction irrigation, and
duration of hospital stay.
This randomized, controlled study demonstrates that oral combination therapy with
TMP/SMX plus rifampin is equivalent to IV therapy with cloxacillin for the treatment
of MSSA osteomyelitis. In the United States, IV agents that are comparable to
cloxacillin in treating MSSA are nafcillin and oxacillin (or, as oral options,
amoxicillin and cephalexin). Although the study was not blinded, the criteria for
failure were clearly defined. This investigation challenges the commonly accepted
approach that IV therapy is the best modality for treating chronic osteomyelitis.
Combination regimens of oral antibiotics offer considerable cost savings if
compelling evidence of noninferiority exists. The use of orally administered
antibiotics negates the need for prolonged-use indwelling IV lines, which are
associated with bloodstream infections and substantial costs and are not practical
in some clinical settings. Additional randomized, controlled studies are warranted
to strengthen the evidence supporting the use of oral vs. IV antibiotics for the
treatment of diabetic osteomyelitis.
As discussed previously in Review 1, wounds can be a highly complex
microenvironment, with polymicrobial infection vs. colonization. Therefore,
identification of causative organisms in osteomyelitis should be pursued
aggressively beyond simple wound culture. Isolation of S. aureus alone is highly
suggestive, but the absence of other organisms (particularly anaerobes) may be due
to culture or sampling methods. If the response to treatment of S. aureus is poor,
expanding the therapeutic spectrum is worthy of consideration.
Finally, as an additional note, biofilm-a layer of
extracellular matrix proteins with slowly replicating
planktonic bacteria-has been implicated in
osteomyelitis, mainly in the setting of orthopedic
implants. The use of rifampin, in particular, can be
helpful in targeting staphylococcal biofilms and may be a
critical component of the oral combination regimen
evaluated by Zimmerli and associates.1
References
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SURGICAL VS.
NON-SURGICAL TREATMENT OF OSTEOMYELITIS |
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Aragon-Sanchez
FJ Cabrera-Galvan JJ, Quintana-Marrero Y, et al.
Outcomes of surgical treatment of diabetic foot
osteomyelitis: a series of 185 patients with
histopathological confirmation of bone involvement.
Diabetologia. 2008;51(11):1962-1970.
(For non-subscribers to this journal, an
additional fee may apply to obtain full-text
articles.) |
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Senneville E,
Lombart A, Beltrand E, et al. Outcome of
diabetic foot osteomyelitis treated nonsurgically: a
retrospective cohort study. Diabetes
Care. 2008;31(4):637-642.
(For non-subscribers to this journal, an
additional fee may apply to obtain full-text
articles.) |
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Aragón-Sánchez and colleagues assessed outcomes of a conservative
surgical approach for the management of osteomyelitis. The authors studied 185
patients with infected and osteomyelitic diabetic foot ulcers. Patients underwent
early surgical treatment within 12 hours of hospital admission. Early conservative
management included debridement, minor amputations (limb
salvage-e.g., phalanx, sesamoidectomy, or partial calcanectomy, and
other foot-level procedures) and major amputations (below the knee or above the
knee). Infection included purulence plus ≥2 of the following:
induration, erythema, pain, calor, lymphangitis, odor, or gas. Osteomyelitis, which
was defined by probe-to-bone tests and x-rays, was confirmed via histopathology as
acute, chronic, or acute-on-chronic. Primary outcomes were failure of conservative
surgery because of immediate major amputation or any amputation after initial
surgery. Other outcomes included 30-day mortality and healing time. Lower limb
ischemia was defined as an ankle/arm index <0.9 or transcutaneous oxygen pressure
<30 mm Hg.
The average ulcer duration was 113 days (±264
days). Nearly half of the study population had a history
of ulcer (49.7%) and more than one-third had undergone
amputation (34.5%). The bone was visible in 31.3% of the
patients, and probing to bone was positive in nearly all
subjects (94.6% [175 of 185]). Of these, plain x-ray
revealed osteomyelitis in most individuals (84.8%).
Ischemia was present in 19.4% of patients, and only 1.6%
(3 of 185) of patients required initial major amputation.
Soft tissue infection correlated highly with any
amputation (P =.0005). A minority of patients (17.1% [19
of 111]) ultimately required minor amputations. However,
among the latter, 31.6% (6 of 19) of patients went on to
undergo a major amputation.
Most patients undergoing initial minor amputations
required follow-up minor amputations (93% [66 of 71]),
whereas far fewer (7% [6 of 71]) went on to undergo major
amputations. By study end, only a minority of patients
(8.1% [15 of 185]) had undergone major amputation at any
point. Subjects with acute osteomyelitis required minor
amputation nearly twice as often as did those with chronic
osteomyelitis (52.1% vs. 23.2%, respectively; P =.004).
Rates of major amputation did not differ based on duration
of osteomyelitis. Additionally, exposed bone occurred more
frequently in patients with acute osteomyelitis than in
those with chronic osteomyelitis, and probe-to-bone tests
were positive more often in patients with acute
osteomyelitis than those with acute-on-chronic
osteomyelitis (97.8% vs 88.8%, respectively; P < .05).
S. aureus was the organism most frequently isolated as the cause of osteomyelitis,
reported in 46.5% of cultures (95 of 176). It was present alone in 64.2% of cases
with positive cultures. MRSA was less frequent (36.8% of cultures).
Amputation was more likely to occur in the presence of exposed bone, lower limb
ischemia, and necrotizing soft tissue infection.
In patients without immediate major amputation, median
healing time was 90 days. Wound healing following
conservative debridement was 80 days (range, 12 to 365
days), vs 120 days (range, 21 to 365 days) with minor
amputations. Soft tissue infection and limb ischemia were
associated with prolonged wound healing.
Does early debridement of diabetic foot infections allow
limb salvage and prevent the occurrence of major
amputation? Because of the lack of randomization and a
control arm in this study, no clear answer to this
question exists. The majority of subjects with initial
minor amputations required subsequent minor amputations,
but the overall frequency of major amputations was low
(8.1%). This may be a reflection of the degree of disease
at the time of presentation, rather than an outcome
related to the intervention. The low prevalence of limb
ischemia (19.4%) and neuropathy (25.9%) supports this
finding. High rates of S. aureus are not surprising and
are consistent with those in the current literature. An
interesting finding of the study is the more frequent bone
exposure reported with acute vs. chronic osteomyelitis.
This is consistent with accelerated tissue ischemia and
necrosis in patients with acute osteomyelitis and the
greater need for amputation in such patients compared with
those with chronic osteomyelitis. Finally, prolonged
healing following minor amputation or with soft tissue
infection or ischemia likely reflects the severity of
underlying disease at the time of presentation.
In their retrospective medical record review, Senneville
and coworkers evaluated use of swab and
bone-culture-guided, nonsurgical therapy on outcomes in
patients with diabetic foot osteomyelitis. Nonsurgical
therapy was defined as no intervention on bone during the
10 days following antibiotic initiation. Diabetic adults
with suspected or confirmed osteomyelitis of a nonischemic
foot were eligible to participate. Suspected osteomyelitis
was defined as a foot wound lasting ≥2
weeks over a bony prominence, with an ulcer surface >2
cm2 or a depth >3 mm, associated
with positive probing to bone and/or radiographic findings
consistent with a diagnosis of osteomyelitis. Subjects
with confirmed osteomyelitis also had positive bone
cultures. Bone cultures were performed in the operating
room using a biopsy needle, with the incision at least 20
mm from the ulcer's edge. When bone
cultures were unavailable or negative, swab cultures
guided antibiotic selection. When bone biopsy results were
positive, selection of antibiotic regimens was based on
coverage of microorganisms isolated from bone, with no
reference to swab culture results. IV antibiotics were
administered for <7 days, followed by a long course of
oral antimicrobial therapy (duration not specified by the
authors). The use of topical antimicrobial agents was
prohibited. Remission was defined as no evidence of
infection at the primary wound location or a proximal site
for ≥12 months following treatment.
The authors evaluated 50 subjects. More than half (54% [27
of 50]) of the patients had already been followed in a
diabetic foot clinic prior to enrollment, and 32% (16 of
50) of the patients had experienced a prior episode of
osteomyelitis. S. aureus was the most common organism
isolated on both swab and bone cultures, and MRSA was
detected in 11.1% (4 of 22) and 10% (3 of 28) of bone and
swab cultures, respectively. Gram-negative bacilli were
the next most frequently isolated organisms, detected in
27.8% (10 of 22) of bone biopsy and 33.3% of swab cultures
(10 of 28). Mean duration of antibiotic therapy was 11.5
± 4.21 weeks. Treatment was guided by bone
culture results in 44% (22 of 50) of patients and by swab
culture results in the remaining individuals. A minority
of subjects (32%) received IV therapy for the first week.
The most commonly used antibiotics were
fluoroquinolone/rifampin and
fluoroquinolone/pristinamycin, followed by other
combinations.
At follow-up, 64% (32 of 50) of subjects were in
remission. Bone-culture-guided therapy was associated with
higher rates of remission (81.8% [18 of 22 patients] vs.
50% [14 of 28 patients] without the use of
bone-culture-based antibiotic therapy; P =.02). After
controlling for demographic and clinical parameters, the
only factor predictive of remission was
bone-culture-guided therapy (adjusted OR, 4.78; 95% CI 1.0
to 22.7; P =.04).
A comparison of this study with the work on early
conservative surgical management by
Aragón-Sánchez and collaborators suggests
that the patient populations were similar in both studies,
with approximately half of each population having received
previous care for diabetic foot wounds and approximately
one-third having a history of prior osteomyelitis.
Treatment failure in the studies ranged from 46% to 51%.
In the study by Aragón-Sánchez and
colleagues, however, subjects undergoing amputation at the
initial procedure did not receive a trial of antibiotics
alone. The lack of a control group in each study is
problematic. Although the investigation by Senneville and
associates suggests that reasonable success may be
achieved with a nonsurgical approach to the treatment of
osteomyelitis, the work by Aragón-Sánchez
and coworkers suggests that in patients with acute
osteomyelitis, a surgical approach may help prevent
disease progression and the need for additional
amputation. In summary, rates of success in the prevention
of future amputations or local infection were similarly
poor in both studies.
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MRSA OSTEOMYELITIS IS NOT ASSOCIATED WITH WORSE OUTCOMES |
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Aragón-Sánchez J,
Lazaro-Martinez JL, Quintana-Marrero Y, et al. Are diabetic foot ulcers complicated by MRSA
osteomyelitis associated with worse prognosis?
Outcomes of a surgical series. Diabet
Med. 2009;26(5):552-555.
(For non-subscribers to this journal, an
additional fee may apply to obtain full-text
articles.) |
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The objective of this study was to
assess whether MRSA osteomyelitis is associated with worse
outcomes than is MSSA osteomyelitis. The authors of the
study used data from a series of 185 patients undergoing
surgery for conservative management of diabetic ulcers
within the first 12 hours after hospital admission.
Surgical bone samples were assessed histologically and
were cultured for the presence of osteomyelitis. Surgical
outcomes of minor amputation, major amputation, number of
surgeries, duration of hospital stay, postoperative death
(within 30 days of procedure), and time to full healing
were examined.
S. aureus was identified in 95 subjects (47.5% of all bone
cultures) and was the only organism isolated in 64.2% of
positive cultures. MRSA was present in 36.8% (35 of 95) of
patients with any detectable S. aureus. There were no
differences between the MRSA and MSSA groups in terms of
prior antibiotic treatment or hospitalization. Overall,
MRSA bone infections were associated with higher body
temperatures (36.8° C vs. 36.5° C with
MSSA; P =.02) and increased leukocyte counts (P =.01). In
addition, MRSA osteomyelitis was associated with necrosis
(P <.001) and foul odor (P =.01) compared with MSSA
osteomyelitis. Moreover, subjects with MRSA osteomyelitis
required a greater number of procedures (P =.04). However,
there were no differences in healing times or rates of
limb salvage between the groups.
MRSA diabetic infections and osteomyelitis are associated
with increased acuity in clinical presentation. However,
this study indicates that MRSA does not necessarily
influence the outcomes of early conservative management of
patients with diabetic osteomyelitis and the subsequent
need for amputation. The findings of this study also
suggest that other factors (including noncultivable
anaerobes, particularly given the report of foul odor,
which is considered diagnostic for anaerobic infection)
may influence clinical outcomes in patients with diabetic
osteomyelitis. Further investigation is warranted in
order to examine these factors in greater detail.
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COMPLETE
THE
POST-TEST
Step
1.
Click on link to download instructions for the posttest and
evaluation
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©
2010 JHUSOM and eInfections Review
Presented by JHUSOM in collaboration with DKBmed. |
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