As discussed below in Question 6, L.D. can complete most of her treatment with
oral antibiotics, but oral therapy should not be given until the effectiveness of IV
therapy can be assessed. Children with uncomplicated acute osteomyelitis are
candidates for oral therapy when clinically improved, and the CRP has normalized,
typically between 3 and 7 days.
14 Total duration of antibiotic therapy should be 3–
4 weeks; however, current IDSA guidelines recommend 4 to 6 weeks of therapy for
children with MRSA osteomyelitis.
13,14 Neonatal cases warrant 4 weeks of IV
Empiric Intravenous Antibiotics for Acute Osteomyelitis in Children
Host Likely Organisms Antibiotics
<3 years S. aureus Vancomycin or 40–60 4
Kingella kingae Cefazolin or 50–100 3–4
≥3 years S. aureus Vancomycin or 40–60 4
After puncture P. aeruginosa Ceftazidime 100–150 3
CASE 73-1, QUESTION 6: After 1 week of IV nafcillin, L.D. is afebrile and reports that the pain and
oral antibiotic regimen for L.D.? How often should she return to the clinic for evaluation?
Again, oral antibiotics are only appropriate if a clear clinical response has
occurred within the first week of IV therapy, the patient’s parents are aware of the
vital importance of compliance, and the patient can swallow and tolerate oral
Assuming her parents agree to supervise treatment outside of the hospital, L.D. is a
candidate for oral therapy. She has responded promptly to the IV therapy: her
symptoms have improved, and the ESR and CRP are trending downward. Oral
therapy will be effective only if L.D. consistently takes her medications; therefore,
assurances must be in place to facilitate compliance. L.D.’s parents have made
arrangements with her teacher to help her take her oral antibiotic during the day.
L.D. can complete her 4-week course of antibiotics with oral cephalexin capsules
or suspension, which is more palatable (and is usually better tolerated) than
dicloxacillin suspension. Cephalexin should begin at 37.5 mg/kg/dose every 6 hours.
Weekly follow-up is necessary to monitor compliance and clinical response to
therapy. Parenteral therapy should be reinitiated, and re-evaluation is warranted if
L.D.’s compliance is not optimal, symptoms recur, or ESR or CRP increases.
antibiotic doses for children with osteomyelitis are summarized in Table 73-3.
Osteomyelitis Secondary to a Contiguous Source of
Oral Antibiotic Doses for the Treatment of Osteomyelitis in Children
Drug Dose (mg/kg/day) Doses/day
Few of the systemic signs and symptoms usually associated with acute
osteomyelitis are seen in secondary osteomyelitis. The most common subjective
complaint in acute contiguous osteomyelitis is pain in the area of infection, localized
tenderness, swelling, erythema, and drainage. Considering several weeks might pass
before the patient becomes symptomatic, radiographic studies at the time of diagnosis
might reveal abnormalities consistent with bone deterioration.
M.K.’s case is consistent with osteomyelitis secondary to a contiguous focus of
infection. Infection likely is at the site of surgical repair of the left femur fracture.
M.K.’s localized symptoms, along with the absence of fever and leukocytosis, are
characteristic of secondary osteomyelitis. In these cases, bone becomes infected from
an exogenous source or through spread of an infection from adjacent tissue to bone.
Infection can result from any trauma with or without subsequent orthopedic procedure
to fix a bone fracture. The bones most commonly involved are the tibia, fibula, femur,
Unlike hematogenous osteomyelitis, which occurs mostly in children, acute
contiguous infection occurs more often in adults. This finding is explained by the
higher incidence of precipitating factors within this age-group, such as hip fractures,
orthopedic procedures, oral cancers, sternotomy incisions for cardiac surgery,
1 Other conditions potentially associated with secondary
osteomyelitis include gunshot wounds, punctures, or soft-tissue infections.
CASE 73-2, QUESTION 2: What organisms are most likely causing infection in M.K.?
Whereas hematogenous osteomyelitis usually involves a single pathogen,
polymicrobial infection is common in contiguous-spread osteomyelitis. Although S.
aureus is the most common pathogen, it is often part of a mixed infection. Other
common pathogens include Pseudomonas, Proteus, Streptococcus, and Klebsiella
species, E. coli, and S. epidermidis. Most cases of osteomyelitis involving the
mandible, pelvis, and small bones (e.g., those of the hands and feet) are caused by
gram-negative organisms. Pseudomonas often is isolated from infections after
1 Anaerobes also are associated with contiguous-spread
osteomyelitis, and most commonly isolated are Bacteroides species and anaerobic
cocci. Possible predisposing factors include previous fractures or injuries resulting
from human bites. Adjacent soft-tissue infections can also lead to anaerobic bone
infections, as in the case of sacral osteomyelitis secondary to severe decubitus
ulcers. To identify the true pathogen(s), M.K. should have surgical re-evaluation and
a biopsy of involved bone at the probable site of infection.
scan will help localize the possible infectious process to direct the surgical biopsy.
vancomycin, 1 g IV every 12 hours. Is this adequate antibiotic treatment for M.K.?
M.K. has had surgery to obtain bone material for culture because cultures of
adjacent wound or sinus tract material are not always predictive of the bacteria
1 Broad empiric antibiotic coverage is necessary because
S. aureus and polymicrobial gram-negative aerobic bacilli most likely are causing
M.K. has been started on vancomycin for possible MRSA infection while awaiting
results of bone tissue cultures. Many clinicians target goal trough concentrations
between 15 and 20 mcg/mL for osteomyelitis.
9 Given his normal renal function and
weight, M.K. will likely require at least 1.5 g IV every 12 hours of vancomycin (15
quinolone (ciprofloxacin, levofloxacin) could be added. The choice of agent should,
in part, be based on local susceptibility patterns. In locations in which quinolone
gram-negative resistance approaches 30%, these agents have limited utility.
Anaerobic coverage should be initiated if an anaerobe is cultured from bone or
anaerobes are suspected. Vancomycin has activity against gram-positive anaerobes,
but not against the gram-negative anaerobe, Bacteroides fragilis. If B. fragilis is
cultured from bone, additional therapy with metronidazole is indicated.
Alternatively, combined, broad-spectrum aerobic (including Pseudomonas) and
anaerobic gram-negative coverage could be provided by a β-lactam/β-lactamase
inhibitor combination therapy with piperacillin/tazobactam or a carbapenem.
Although cultures are pending, M.K.’s antibiotic regimen is changed to
vancomycin 1.5 g IV every 12 hours and cefepime 2 g IV every 8 hours.
CASE 73-2, QUESTION 4: The bone biopsy from M.K. grows MRSA that is sensitive to vancomycin,
afebrile. How should M.K. now be treated? Is he a candidate for oral therapy?
Because no gram-negative organisms grew on culture, cefepime may be
discontinued. Therapy should be directed against the MRSA. Thus, it is justified to
continue treating M.K. with vancomycin (1.5 g IV every 12 hours) as long as he is
monitored closely, following his symptoms, a vancomycin trough level between
15 and 20 mg/L, weekly ESR or CRP concentrations, complete blood count, and
metabolic panel. Vancomycin can be administered at home with the appropriate home
health care. Studies have shown that oral antibiotics can achieve adequate
concentrations in bone. Based on clinical improvement and provider preference,
combination with rifampin (600 mg once daily) for a minimum of 8 total weeks of
9 He should be followed closely for at least 2 years to detect recurrent
Osteomyelitis Associated with Vascular Insufficiency
mg/dL, serum creatinine 5.6 mg/dL, fasting blood glucose 240 mg/dL, hemoglobin A1c
M.S. has chronic lower extremity vascular insufficiency as a result of type 2
diabetes. Patients with impaired blood flow may develop osteomyelitis in the toes or
small bones of the feet. Infection often first presents as cellulitis, as in M.S.’s case,
progressing to deep ulcers and finally to the underlying bone.
Similar to contiguous-spread osteomyelitis, systemic signs of infection (e.g., fever
and leukocytosis) are often absent in patients who experience bone infection
secondary to vascular insufficiency. Local symptoms such as pain, swelling, and
erythema usually predominate, but there are no specific clinical findings.
M.S. may have a bone infection under the chronic, cutaneous ulcer on the bottom of
her left great toe. Because of peripheral neuropathy, the skin lesion may not be
painful, and poor blood supply to the site likely contributed to the development of a
chronic infection and possibly secondary osteomyelitis. The true depth of an ulcer is
not always clinically apparent so careful physical examination and evaluation of
patient risk factors are essential for diagnosis.
elevated ESR, fasting glucose (consistent with infection), and Hb A1c
uncontrolled diabetes). In addition, diabetic foot ulcers with an area larger than 2
cm2 or that penetrate to bone are often predictive for underlying osteomyelitis.
CASE 73-3, QUESTION 2: M.S. is admitted into the hospital for diagnostic workup, wound care, and
ciprofloxacin (750 mg every 12 hours). Is this appropriate initial, empiric therapy?
In many cases of osteomyelitis associated with vascular insufficiency, multiple
pathogens can be cultured from surgical specimens or the wound. The most
commonly isolated pathogen is S. aureus; however, gram-negative and anaerobic
bacteria are also often recovered. The bacteria isolated from a wound or soft-tissue
culture may not correlate with bacteria found in a concomitant bone biopsy.
Therefore, empiric antibiotic therapy for osteomyelitis associated with vascular
insufficiency should be active against both gram-positive and gram-negative aerobic
bacteria and possibly anaerobes. No specific regimens have demonstrated
superiority, so a broad-spectrum empiric regimen can be chosen based on local
1 An antipseudomonal β-lactam (ceftazidime, cefepime) or
quinolone (ciprofloxacin, levofloxacin) for gram-negative coverage is frequently
used as an empiric regimen. If anaerobic bacteria are believed to be clinically
involved (e.g., foul-smelling wound), metronidazole should be added to the regimen;
alternatively an antipseudomonal β-lactam/β-lactamase inhibitor combination, such
as piperacillin-tazobactam, can be used.
M.S. has risk factors for MRSA and resistant gram-negative bacilli because of her
diabetes, hemodialysis, and recent course of antibiotics. The initial regimen of
vancomycin and ciprofloxacin for M.S. is not optimal for several reasons. Because
of her recent, prolonged ciprofloxacin exposure, a quinolone-resistant organism may
be responsible for infection and a β-lactam-based antibiotic regimen would be more
appropriate. Secondly, IV antibiotics should be used during initial treatment. Lastly,
M.S. would be vancomycin intermittently dosed based on serum drug concentrations
and her dialysis regimen, and cefepime 1 g IV every 24 hours with the dose
administered after dialysis on dialysis days.
Further antibiotic refinement should occur after the results of the deep wound swab
culture are available. The optimal duration of IV therapy for diabetic foot
osteomyelitis is patient-dependent, and some patients may require longer-term, oral
suppressive therapy. The overall duration of antibiotic treatment can range from 6
weeks to many months depending on the degree of surgical debridement and the
15 Oral linezolid (600 mg every 12 hours) has been used to
treat MRSA osteomyelitis in diabetic patients, although long-term therapy can be
associated with hematologic and neuropathic adverse effects.
M.S. should be made aware that osteomyelitis associated with diabetic foot ulcers
is difficult to treat. Despite adequate surgical debridement of the infection followed
by appropriate treatment with long-term IV and oral antibiotic therapy, cure rates are
low. Even minor amputations (one or two toes) are unsuccessful in eradicating
infection. Radical surgical approaches, such as transmetatarsal, below-the-knee, or
above-the-knee amputations, often are necessary to cure these infections.
ago. Two weeks ago he noted increased sinus drainage, pain, swelling, and
J.F.’s case are characteristic of chronic osteomyelitis?
Inadequate treatment of an acute episode of osteomyelitis can lead to formation of
necrotic, infected bone and recurrent symptoms consistent with chronic disease.
Despite appropriate initial therapy, osteomyelitis can reactivate, even with
organisms different from the initial episode. Some propose that previously infected
bone might be a risk for reinfection. Persistent symptoms or signs lasting longer than
10 days are consistent with chronic osteomyelitis and the development of necrotic
bone. Draining sinus tracts often develop from the bone to the skin with chronic
J.F. probably experienced a chronic bone infection after the farming accident. The
reappearance of sinus tract drainage in his left upper arm indicates an indolent
infection of bone that was periodically suppressed, but not completely treated by oral
antibiotics. Cultures of sinus drainage now reveal multiple organisms including
normal skin flora. These sinus tract cultures usually do not correlate with the
organisms actually causing bone infection. J.F.’s recurrent course of bone
involvement with drainage and local symptoms, and lack of any remarkable systemic
symptoms, suggests chronic osteomyelitis.
J.F.’s poor response should have been expected for at least two reasons:
Antibiotic therapy was started before surgical debridement of avascular tissue, and
he was given an antibiotic that was inactive against the cultured bone organisms.
Surgery plays an important role in the treatment of chronic osteomyelitis. Bone
necrosis will continue to progress if decompression and drainage of the infected area
is not carried out as soon as possible. Furthermore, without initial surgical removal
of necrotic bone (sequestrum) and other poorly vascularized, infected material, even
the most optimal IV antibiotics are likely to fail.
After surgery, antibiotic therapy directed against the pathogens isolated in the
surgical specimens should be started. The regimen choice should not be based on the
sinus tract culture results because these isolates may not correlate with the actual
causative organisms. J.F. should be treated initially with IV antibiotics because of
relatively poor blood flow at the infection site. Although the optimal duration of
therapy for chronic osteomyelitis is not well established, the standard
recommendation has been parenteral therapy for 6 weeks, followed by oral antibiotic
therapy, depending on the healing rate.
19 However, based on more recent data with
oral antibiotics in chronic osteomyelitis, the susceptibility of the antibiotic for the
organism is more relevant than the route of administration.
be evaluated by an orthopedic surgeon because he may require further surgical
treatment to eradicate chronically infected bone.
CASE 73-4, QUESTION 3: What would be reasonable antibiotic therapy for J.F.?
On the basis of the bone culture and sensitivity results, J.F. needs high-dose
therapy directed at P. mirabilis and B. fragilis. For convenience and possible future
home therapy, ceftriaxone (2 g IV every 24 hours) could be started for coverage of
Proteus and metronidazole (500 mg IV every 8 hours) also should be started for
coverage of B. fragilis. Because of excellent oral bioavailability, the metronidazole
can be rapidly converted to oral therapy at the same dose before discharge.
Ertapenem could be an alternative choice for home IV therapy assuming that the
Proteus isolate is sensitive. This agent also provides excellent anaerobic activity,
and its once-daily dosing (1 g IV every 24 hours) is convenient for home therapy.
After 6 to 8 weeks of home parenteral therapy, J.F. should be evaluated for
additional 6 to 8 weeks or longer depending on resolution of the sinus tract drainage,
pain, and tenderness in J.F.’s arm. Under these circumstances, he should be
monitored closely for possible long-term adverse drug effects (e.g., hepatitis,
cytopenias, neuropathy). If the sinus tract does not heal or if J.F. remains
symptomatic, surgical exploration and bone cultures must be repeated.
PMMA beads) inserted during J.F.’s orthopedic surgery?
To deliver high concentrations of antibiotics to poorly vascularized bone infection
sites, various materials containing antibiotics can be placed at the infection site
during surgery. Plaster pellets, fibrin, collagen, hydroxyapatite, and PMMA
impregnated with antibiotic, usually an aminoglycoside or vancomycin, have been
used. The dosage form is designed for the slow release of antibiotics from the
material. The most commonly reported experience with local antibiotic delivery has
been with antibiotic-impregnated PMMA cement or beads inserted during joint
arthroplasty. Local delivery of antibiotics should not replace systemic antibiotics in
the treatment of chronic osteomyelitis.
Osteomyelitis Associated with Prosthetic Material
removal of her prosthetic joint. Does A.T. have a prosthetic joint infection?
Joint replacement surgery is commonly performed for patients with significant
joint destruction as a result of arthritis and other disabling diseases. Prosthetic knee,
exogenous inoculation of bacteria perioperatively, via hematogenous dissemination
of bacteria, or by contiguous spread from a topical wound. Bacteria infect bone
adjacent to the joint prosthesis, including the bone–cement interface, resulting in a
loosened and less functional prosthesis.
22 Staphylococcus species including
coagulase-negative species such as S. epidermidis are most commonly involved in
prosthetic joint infections, followed by Streptococcus species, gram-negative bacilli,
and anaerobes. Although coagulase-negative staphylococci are usually considered a
contaminant in culture, this organism readily adheres to prosthetic material and
should be considered pathogenic when cultured from prostheses. Coagulase-negative
staphylococci are often methicillin-resistant but susceptible to vancomycin.
Chronic pain, swelling, erythema, and tenderness over a prosthetic joint are
typical findings associated with prosthetic joint infection. Persistent wound drainage
may also be present. A.T. has had a relatively lengthy duration of symptoms
associated with her left knee, which could be caused by joint loosening, but the cell
count and differential from the joint aspirate suggest joint infection. Consistent with
infected prosthesis is also the predominance of neutrophils in her joint fluid and
gram-positive cocci on a Gram stain. As is often the case, she has no obvious
preceding source of infection from which bacteria may have originated.
Occasionally, sources of infection with hematogenous dissemination to the prosthetic
joint are identified, such as dental infections, cellulitis, or urinary tract infections.
Given the Gram stain result, A.T. should receive coverage for Staphylococcus and
Streptococcus species with vancomycin while awaiting the results of cultures and
CASE 73-5, QUESTION 2: Does A.T. need surgery and antibiotics to cure her infection?
Surgical removal of A.T.’s knee prosthesis in conjunction with intravenous
antibiotics for 6 weeks is the current recommendation for optimal eradication of
23 A two-stage orthopedic procedure is frequently used
that involves removal of the infected prosthesis, placement of an antibiotic-filled
spacer, joint immobilization, and antibiotics for 6 weeks. If the joint space remains
culture negative after 2 weeks of antibiotics, a new joint prosthesis is then reinserted.
Because avascular bone cement and prosthetic material can become seeded with
bacteria, complete removal of this material is necessary to have the greatest chance
of curing the infection. Six weeks of systemic antibiotic therapy in combination with
orthopedic surgery results in restoration of joint function in 80% to 90% of cases.
High rates of treatment failure occur if the joint prosthesis is not removed, if the
antibiotic duration is too short, and if chronic suppressive antibiotics are not
CASE 73-5, QUESTION 3: The surgeon is unable to completely remove A.T.’s prosthetic joint. The
be used? How long should A.T. be treated?
Because A.T.’s prosthesis cannot be removed, she will need 2 to 6 weeks of
vancomycin (15 mg/kg IV Q12 hours) plus oral rifampin (300–450 mg PO BID),
followed by 6 months of oral antibiotics plus rifampin.
daily) or linezolid (600 mg PO/IV Q12 hours) may be considered alternatives to
vancomycin, depending on pathogen susceptibility, drug allergies or intolerances,
and potential drug–drug interactions.
effects, such as creatine kinase elevations (daptomycin) and bone marrow
suppression and neuropathy (linezolid).
22 Combination therapy with rifampin should
be used for prosthetic joint infection caused by staphylococci, particularly if removal
of the infected prosthesis is not possible, because rifampin penetrates bacterial
membranes and biofilms to enhance the bactericidal activity of the antibiotic
regimen. Monotherapy with rifampin should never be used because of rapid
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