Chronic Osteomyelitis
Chronic Osteomyelitis
Chronic Osteomyelitis
Abstract:
OBJECTIVE: To conduct an observational study of the long-term outcome of people with
chronic osteomyelitis treated with combined surgical and oral antibiotic therapy. METHODS:
All patients included in the study were seen at the University of Connecticut Bone Infection
Clinic from January 1992 to July 1999, had documented chronic osteomyelitis by intraoperative
biopsy, and were treated with, but not limited to, combined surgical and oral antibiotic therapy.
The charts of these patients were retrospectively reviewed specifically for the duration of post-
operative parenteral antibiotic use. These patients were then sent a questionnaire concerning
views about their health. This questionnaire included: (1) questions pertaining to the patient’s
background and treatment history; (2) a standardized Short Form-36 (SF-36) survey; and (3) the
twelve “bother index” questions from the Short Musculoskeletal Function Assessment (SMFA).
RESULTS: Retrospective chart review showed that the median duration of postoperative
parenteral antibiotic use was 16 days. Outcome information was obtained from 44 of the 122
patients contacted after the first mailing. The data from these surveys reveal that patients
suffering from chronic osteomyelitis view their overall health as “good” and are “moderately
bothered” by functional problems associated with their disability. A majority of these patients
(68%) say that their expectations of treatment have been met. CONCLUSION: At the University
of Connecticut Bone Infection Clinic from 1992 to 1999, the median duration of postoperative
intravenous antibiotic administration was well below the traditional 4-to-6 week course. Without
a control group at this stage of the study, it is to be determined whether this shorter course of
parenteral treatment has adversely affected patient outcome. Regardless, this survey can serve as
a helpful point of reference for practitioners as they discuss quality of life issues with their
chronic osteomyelitis patients.
Introduction:
Osteomyelitis that occurs at the site of trauma is, by definition, chronic from the outset
because dead bone is already present. Therefore, therapy of any such infection must be focused
upon elimination of all devitalized bone and soft tissue. The orthopaedic community is in full
agreement that administering antibiotics without the complete excision of all necrotic tissue
(sequestra, scars) is futile. Where there has been some controversy, however, is regarding the
role of antibiotics in this group of patients. Traditionally, four to six weeks of postoperative
parenteral antibiotics has been the standard of care. Up until fairly recently, administering oral
antibiotics during this time period was rarely considered as a viable option. However, because of
the cost-effectiveness and non-invasiveness of substituting oral for intravenous medications, this
issue has been the subject of several studies over the past fifteen years.
The purpose of this study is to review a group of patients with chronic osteomyelitis who
have been treated with combined surgical debridement and a “substandard” duration of
addition to performing a chart review on this cohort, the ultimate goal will be to assess whether
these patients are doing just as well as those treated with the traditional 4-to-6 week regimen.
All 140 patients selected for this study were seen at the University of Connecticut Bone
Infection Clinic from January 1992 to July 1999, had documented chronic osteomyelitis by
intraoperative biopsy, and were treated with, but not limited to, combined surgical and oral
antibiotic therapy. The two aspects of this study consisted of a retrospective chart review and the
administration of a survey regarding patients’ views about their current state of health. The
questionnaire that was sent to the patients included: (1) questions pertaining to their background
and treatment history; (2) a standardized Short Form-36 (SF-36) survey; and (3) the twelve
“bother index” questions from the Short Musculoskeletal Function Assessment (SMFA). [The
The questions pertaining to the patient’s background and treatment history were designed
by the research team specifically for this study. They have no historical precedent. In contrast,
the two standardized questionnaires, the SF-36 and the SMFA, have been widely used and
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reported upon in the literature over the past several years. It should be noted that neither of these
surveys were created specifically for patients suffering from chronic osteomyelitis. In fact, no
such assessment tools exist. The SF-36, instead, is a generic questionnaire of 36 questions
designed for the assessment of functional outcomes in populations of patients with any type of
disease. It was utilized in this study because of its proven reliability as an indicator of patients’
perceptions about their health. The SMFA is a 46-item questionnaire abbreviated from the longer
referred to as the “bother index,” which are designed to assess how much patients are bothered
osteoarthritis patients, are broad enough to assess people with most musculoskeletal disabilities,
By using the SF-36 and the SMFA in concert, this observational study attempts to
elucidate both: (1) the views patients with chronic osteomyelitis have about their overall state of
health and (2) how much they are bothered by their disability in everyday life.
Results:
Of the 140 patients reviewed in this study, the vast majority suffer from chronic
osteomyelitis secondary to open fractures from automobile and motorcycle accidents. The tibia is
by far the most common site of involvement. They have all been treated with, but not limited to,
(25.4%) were found to be the most common pathogens in these patients by way of intraoperative
biopsy. [See Appendix 4 for a graphical distribution of bacterial isolates]. Retrospective chart
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review showed that the median duration of postoperative parenteral antibiotic use was 16 days.
Median duration is more reflective of the duration of postoperative parenteral antibiotics in this
cohort because there were a few outliers kept on intravenous antibiotics for as long as a year who
Of the 140 patients who fulfilled criteria to receive the outcome questionnaire, 122
actually received it (87%) and, of that number, 46 (37.7%) returned it after the first mailing. Two
people chose not to answer the questions, leaving 44 (36.0%) who were actual respondents to the
questionnaire. The data from these surveys were entered into an Access database for analysis.
[Mean results from the SF-36 and SMFA are depicted by shading in the closest corresponding
answer box on the questionnaire forms in Appendices 5 and 6. Numbers are rounded for ease of
viewing].
Of note from the SF-36 survey, an overwhelming majority of subjects (81%) say they are
“limited a lot” in performing vigorous activities (question #3). On average, however, the subjects
describe their current state of health as “good” (question #1). From the responses to the SMFA, it
is apparent that these people are “moderately bothered” by their disability during most everyday
activities, but rarely to the point of extreme pain and total dysfunction.
Infection Clinic, a majority of the respondents (54%) expected to have a “complete recovery”
from their post-traumatic infection. 68% of respondents say their expectations of treatment have
been met, 20% say they have not, and 12% say it is “too early to tell.”
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Discussion:
either acute or chronic. This division is not as elementary as it may seem. Stated simply, acute
and chronic osteomyelitis are distinguished by the development of dead bone in the latter. Note
that they are not defined by the duration of infection as their names might suggest. Acute
(usually S. aureus) infiltrate vascularized bone and produce a vigorous inflammatory response.
Since bone is a rigid tissue, this influx of phagocytes and other inflammatory cells into its canals
has the unintended effect of raising intraosseus pressure and occluding its own blood supply.
Without the intervention of antibiotics, bone death or osteonecrosis may result. What makes this
natural history particularly troublesome is that these fragments of devitalized bone, also called
sequestra, act like foreign bodies and perpetuate the problem by exposing sites to which
pathogenic bacteria can bind. At the point in which bone death actually occurs, the infection can
this is rarely the manner in which chronic osteomyelitis develops. In fact, acute hematagenous
By far the most common etiology of chronic osteomyelitis is trauma, in which bone is
devitalized from the outset. Because of its obvious association with motor vehicle accidents,
chronic osteomyelitis occurs primarily in adults. In contrast to the cascade of events in acute
hematogenous osteomyelitis whereby pathogenic bacteria seed previously alive bone, the role of
bacteria in chronic osteomyelitis is solely an opportunistic one. In this case, bacteria take
advantage of bone that is already injured and ischemic. Because necrotic bone is present from the
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outset, therapy must be first and foremost focused upon the surgical elimination of all devitalized
tissue. If not excised, this tissue would otherwise serve as a nidus for further infection by
providing a sanctuary for virulent micro-organisms which are essentially “hidden” from the
bloodstream. Once again, S. aureus is the most common culprit, but the possibility of co-
infection with gram-negatives and anaerobes needs to be entertained in these cases of post-
traumatic infection.
Because the injured bone in chronic osteomyelitis is, by definition, lacking adequate
blood supply, antibiotics (whether they be delivered parenterally or orally) are useless without
surgical debridement. The purpose of antibiotics then is not to heal the dead tissues per se, but
rather to kill any bacteria in the periphery that would otherwise prevent adequate blood supply to
the “transition zone” around the sequestrum. In this light, it is easy to understand why the route
of administration of the antibiotic should theoretically not affect patient outcome so long as it is
If both parenteral and oral antibiotics can attain such levels, oral delivery would naturally
be favored as it is clearly more comfortable for the patient, decreases the chance of line
infections, and is more cost-efficient. There are a few contraindications to oral delivery which
should be mentioned. These include: insensitivity of the microbe to oral treatments (i.e., MRSA),
a patient who cannot tolerate oral medication or is noncompliant, and lastly, a patient who is
Conclusion:
At the University of Connecticut Bone Infection Clinic from 1992 to 1999, the median
duration of postoperative intravenous antibiotic administration (=16 days) was well below the
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traditional 4-to-6 week course. Undoubtedly, this result stems from a belief that antibiotics are
soft tissue around the devascularized focus of infection, it is theorized, depends not on their route
of administration but rather on their bacteriocidal properties. While this makes sense, it has not
been proven in the literature that decreasing the duration of postoperative intravenous antibiotics
Has our study proven this? The answer is no, at least not yet. While we do have a cohort
of patients who have received less parenteral antibiotics than is standard and we do have
standardized ways to assess their outcomes (i.e., via the SF-36 and the “bother index” from the
SMFA), this observational study falls short on two accounts. Firstly, there are a number of
variables in the therapies of these patients. Some patients utilized electric stimulation devices to
facilitate bone growth at the site of injury. Others were tried on trials of hyperbaric oxygen. Still
others had antibiotic beads placed during surgery to fill dead space or required muscle flaps to
help revascularize areas of low perfusion. Indeed, while each of the 44 respondents were treated
with combined surgical debridement and oral antibiotics, these were far from their only
therapeutic interventions. Therefore, it is difficult to conclude that the outcome of these patients
is directly linked to the route of postoperative antibiotic administration and not, for instance,
some other treatment modality which happens to be more frequently employed at the University
of Connecticut Health Center than at other institutions. Second, without any control groups at
this stage of the study, it is difficult to say what “normal” SF-36 or SMFA answers may be for
people suffering from chronic osteomyelitis. It would be extremely informative in the future to
include patients treated at other centers with more traditional postoperative regimens and send
them the same outcome questionnaires by way of comparison. If incorporating another bone
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infection center proves to be problematic, perhaps a control group could be achieved by
randomizing patients at the University of Connecticut Health Center into two different treatment
groups.
At this stage of the study therefore, it is impossible to make any conclusions regarding
the efficacy of a combined surgical and oral antibiotic approach to patients with chronic
osteomyelitis. If, after a control group is added, outcomes are shown to be similar to those
achieved with more traditional regimens, the following treatment algorithm utilized by the
(1) Obtain the patient’s history and perform a physical exam in the office. If clinical suspicion of
chronic osteomyelitis is high, order appropriate radiologic tests, lab work, and cultures of
exposed sinus tracts, pus, and fistulae.
(2) If the patient is diagnosed with chronic osteomyelitis, surgery (i.e., complete excision of all
devitalized tissue) remains the cornerstone of treatment. If the patient is going to surgery
without any cultures and sensitivities, it is best to cover presumptively for the most
commonly involved pathogen, S. aureus (with parenteral cefazolin, a first-generation
cephalosporin). If the lower extremity is involved, as in a punctured foot wound, or the
patient has Diabetes Mellitus, also cover for Pseudomonas aeruginosa (with parenteral
ceftazadime, a third-generation cephalosporin).
(3) If the cultures and sensitivities are back prior to surgery, cover with the appropriate
parenteral antibiotic.
(4) Switch to oral antibiotics around post-operative day #2, guided by intraoperative cultures and
sensitivities. Do not switch to oral medication if the patient has one of the contraindications
described previously.
As the other treatment modalities of the subjects are controlled for, the sample size of the
study increases, and a control group is added, we will be better able to determine whether the
current standard of postoperative care in chronic osteomyelitis should be replaced with a less-
invasive and less-costly alternative. Nonetheless, even at this early stage, this observational study
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has important value. As there are currently no standardized outcome studies in the chronic
osteomyelitis literature, these data will prove to be helpful to orthopaedists and general
practitioners by providing them with some general prognostic information regarding the quality
of life patients suffering from this indolent disease can expect after surgery. Undoubtedly, it will
be of some comfort to the recently infected polytrauma patient to know that there is a study out
there which clearly demonstrates that most chronic osteomyelitis patients, even after all of their
debridements and hardship, view their overall health as “good” and are able to continue with
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References:
• Bhandari M, “High and low pressure pulsatile lavage of contaminated tibial fractures: an
in vitro study of bacterial adherence and bone damage.” Journal of Orthopaedic
Trauma, 13 (8): 526-533, November 1999.
• Black J, Hunt TL, Godley PJ, Matthew E, “Oral antimicrobial therapy for adults with
osteomyelitis or septic arthritis.” The Journal of Infectious Disease, 155 (5): 968-972,
May 1987.
• Cierny G, Mader JT, Penninck JJ, “A clinical staging system for adult osteomyelitis.”
Contemporary Orthopaedics, 10 (5): 17-37, May 1985.
• Fitzgerald RH, et. al., “Local muscle flaps in the treatment of chronic osteomyelitis.” The
Journal of Bone and Joint Surgery, 67-A (2): 175-185, February 1985.
• Lew DP, Waldvogel FA, “Osteomyelitis.” New England Journal of Medicine, 336 (14):
999-1007, April 1997.
• Martin DP, et. al., “Development of a musculoskeletal extremity health status instrument:
The Musculoskeletal Function Assessment Instrument.” Journal of Orthopaedic
Research, 14 (2): 173-181, November 1996.
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• Norden CW, Shinners E, Niederriter K, “Clindamycin treatment of experimental chronic
osteomyelitis due to Staphylococcus aureus.” The Journal of Infectious Disease, 153
(5): 956-959, May 1986.
• SF-36 Health Survey, Standard U.S. Version 1.0, Medical Outcomes Trust, Copyright
1992.
• Waldvogel FA, “Use of quinolones for the treatment of osteomyelitis and septic
arthritis.” Reviews of Infectious Disease, 11 (Suppl. 5): 1259-1263, July-August 1989.
• Waldvogel FA, Vasey H, “Osteomyelitis: the past decade.” New England Journal of
Medicine, 303 (7): 360-369, August 1980.
• Weiss SJ, “Tissue destruction by neutrophils.” New England Journal of Medicine, 320:
365-376, 1989.
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Craig Rodner MSIV
Selective Addendum
Dr. Bruce Browner preceptor
28 April 2000
This year my selective project turned out to be more of a chronic osteomyelitis tour-de-
force than working on just a specific study. Although my survey on the “Long-term outcome of
treatment of chronic osteomyelitis with combined surgical and oral antibiotic therapy” was a
major part of my year, I wanted to give you an outline of how my selective months were spent on
a few other projects.
JULY: The first thing I had to do was expand upon the database set-up by Lance Baldo
(Uconn School of Medicine 1998) and enter all the patients seen by Drs. Browner and Pesanti
over the past 7 years into it. I entered not just the patients’ postoperative antibiotic usage, but
also a plethora of other factors. This was a very time-consuming process, requiring extensive
chart review (looking for each patient’s trauma history, past medical history, social history,
intraoperative bacteriology, radiologic tests, surgical reports, etc.). In the end, I successfully
entered data on all 140 patients into an Access database.
During this time I also was helping Dr. Browner put together a lecture he was giving on
grand rounds concerning treatment of chronic osteomyelitis. Dr. Browner gave me a lot of
freedom with this task and, by the end of July, I had made about half of the power-point slides
for his lecture. In these slides, I incorporated the new data from my chart review (regarding
duration of parenteral antibiotics, bacteriology, and comorbidities of his clinic’s patients), as well
as revising his outdated slides on the role of nuclear medicine testing in diagnosis.
After completing this assignment, I then searched the literature for which questionnaires
would be most suitable to send out to the 140 patients in the database. Ms. Rose Maljanian at the
Hartford Hospital Institute for Outcomes Research and Evaluation was particularly helpful in
helping me decide which questionnaires to use.
MARCH: In the middle part of March, the questionnaires started to come back. Of the
140 people in my initial database, 122 were contacted, and 46 responded. I then scanned these
data into the database. While I was getting back surveys, Dr. Browner asked me if I would like to
be the lead-author of the new chapter on osteomyelitis in the 3rd edition of his textbook, Skeletal
Trauma. Naturally, this was an exciting opportunity and I am currently busy working on it with
Drs. Salvana, Browner, and Pesanti as my “senior editors.”
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APRIL AND BEYOND: As I am staying here at UConn for residency in orthopaedic
surgery, I plan on continuing all of the following projects over the next several months and into
the upcoming academic year:
(2) Continuing with my outcome analysis (hopefully adding a control group by making it a
multi-center study or by randomizing the postoperative treatment of our own patients).
(3) And, last but not least, writing my chapter. The date the latest edition of Skeletal
Trauma goes to press is December of 2000. Currently, I am focusing most of my time on
trying to get a rough draft to Dr. Browner.
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Finally, I’d like to say thanks because my selective project this year has truly been a great
opportunity for me to learn about orthopaedics, the topic of osteomyelitis, and to immerse myself
in several projects pertaining to it.
Sincerely,
Craig Rodner
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