Setting: emergency department (ED)
CC: “I’ve got fluid coming out of an ulcer in my leg.”
VS: BP: T: 98°F; R: 14 breaths/minute
HPI: A 64-year-old man with long-standing diabetes and peripheral arterial disease (PAD) comes to the ED with drainage coming out of an area of ulcer over the tibial area. He has had recurrent ulcers in this area off and on for years. Most have responded to local wound care. Occasionally he has used antibiotics. He did not go see his doctor for this one, and decided on his own to come to the ED.
PMHX:
Diabetes
Hypertension
PAD
Medications:
Aspirin, cilostazol
Metformin, glyburide, and sitagliptin
PE:
General: comfortable, sitting upright, no distress
Chest: clear bilaterally
Extremities: 2-cm ulcer over anterior surface of lower left leg, halfway between knee and ankle; modest warmth in the area, little tenderness. Draining sinus tract is visible in the center. Bone is not visible.
Diabetes + PAD = Ulcers ± Osteomyelitis
The first question to ask yourself when confronted with a patient with a diabetic ulcer is:
• Osteomyelitis: yes or no?
Neutrophils do not function normally in diabetes.
Initial Orders:
X-ray of leg
Complete blood count (CBC), basic metabolic panel (CHEM-7)
Restart outpatient medications
On the computer-based case simulation (CCS), if you do not order something, it is not being given or done. In this case, unless you order the PAD and diabetes medications, you should not assume they are automatically continued. Nothing is automatically continued on CCS, unless you have ordered it. You will be able to see on the order screen in front of you every medication that is ordered, and every laboratory test that is pending.
Probing straight to bone
• Highly suggestive of osteomyelitis
• Will not give specific organism
Which of these is useless in osteomyelitis evaluation?
a. Gallium scan
b. Indium scan
c. Swab culture of ulcer
d. Computed tomography (CT) scan
e. Technetium-99 scan
Answer c. Swab culture of ulcer
Culturing the surface of an ulcer generates irrelevant and misleading data. The ulcer will definitely grow organisms, but it will not tell you what is in the bone. That makes it distracting. The other scans are not as accurate as magnetic resonance imaging (MRI), but they can be useful to determine if there is bone involvement or if the infection is limited just to the skin.
Do not give antibiotics just for a bone infection. Osteomyelitis in a diabetic patient is a chronic infection that takes weeks to months to develop, and needs weeks to months to cure. It is more important to get a specific microbiologic identification, than to start empiric therapy that might be incorrect.
Move the clock forward to get x-ray results.
• Bone loss needs 1 to 2 weeks to show as abnormal on x-ray.
• For the x-ray to be abnormal, 50% to 70% of bone calcium must be lost.
Report:
X-ray: no destruction of bone detected
CBC: normal white blood cell (WBC) count, no anemia
Chemistry: normal except glucose 138 mg/dL
What is an abnormality shown on MRI based on?
a. Calcium
b. Water
c. Sodium and potassium
d. Nuclear isotope deposition
e. Glucose metabolism
Answer b. Water
The MRI is based on an alteration of the spin of hydrogen ions in molecules when exposed to different magnetic frequencies. The spin or “flip” in the ion occurs under different magnetic intensity based on its water content. Bone actually swells in 2 to 3 days after infection begins. The swelling of bone changes its water content very early and very clearly and this is why it shows as an abnormality on MRI so early. CT and x-ray are based on calcium content. The positron emission tomography (PET) scan is based on the metabolism of 18-fluorodeoxyglucose. Cancer generally has a higher rate of glucose metabolism than surrounding tissues and that is why it lights up with PET scan.
• MRI is based on tissue water content.
• PET is based on glucose metabolism.
Orders:
MRI
Only do a nuclear bone scan if an MRI cannot be done, for example, because of the presence of a pacemaker.
Hold antibiotics until you get a bone sample.
On your clinical rotations you will see doctors treating with antibiotics before a bone sample is obtained. Do not do this on your Step 3 examination test. Advance the clock to get MRI results.
The CCS order screen will always tell you the precise time, down to the minute, when a test result will come back.
Report:
MRI: abnormal uptake in the tibia consistent with osteomyelitis
The culture of the surface of an ulcer does not reveal what is in the bone.
Orders:
Bone biopsy
Erythrocyte sedimentation rate (ESR)
Gram-negative bacilli causes 30% of osteomyelitis in diabetes.
Only biopsy can tell if Staphylococcus is sensitive or resistant.
Move the clock forward until the biopsy is obtained. You do not have to wait for the results to start antibiotics. You just have to take the sample before the start of antibiotics so that you know it will be accurate.
After the bone biopsy is obtained, order antibiotics.
CCS will tell you that it will be 1 to 2 days before the culture and pathology reports are back. The culture will give you the organisms and the sensitivity. Pathology will tell you whether osteomyelitis is present on the microscopic examination of the slides.
Osteomyelitis Pathology
• Neutrophils infiltrating bone
Organisms
1. Staphylococcus: both sensitive and resistant
2. Gram-negative rods
3. Fungus, mycobacterial, mixed
Orders:
Vancomycin or linezolid or daptomycin and
Piperacillin/Tazobactam or cefepime or quinolone (levofloxacin, ciprofloxacin)
If a rash is associated with the use of penicillin, cephalosporin is safe to use.
Move the clock forward to obtain the results of the bone biopsy. Antibiotics should be continued intravenously until results are obtained.
Reports:
ESR: 110 mm/h
Bone biopsy:
Pathology shows neutrophils.
The culture is Staphylococcus aureus.
It is sensitive to oxacillin.
What is the mechanism of vancomycin?
a. DNA gyrase
b. RNA polymerase
c. Cell wall
d. Ribosome
Answer c. Cell wall
Vancomycin inhibits the formation of the cell wall by a mechanism different than that of penicillin or cephalosporin (Figure 10-1). Despite them both working by inhibiting the cell wall, beta-lactam antibiotics are more effective and bactericidal at inhibiting growth of organisms that are sensitive to oxacillin. For this reason, it is imperative that you switch vancomycin to a beta-lactam antibiotic if the organism is sensitive. Vancomycin has a greater failure rate in controlling sensitive microorganisms that are oxacillin (methicillin) sensitive.
Figure 10-1. Inhibition of bacterial cell wall synthesis: vancomycin and beta-lactam agents. Vancomycin inhibits the polymerization or transglycosylase reaction (A) by binding to the D-alanyl-D-alanine terminus of the cell wall precursor unit attached to its lipid carrier and blocks linkage to the glycopeptide polymer (indicated by the subscript n). These (NAM–NAG)n peptidoglycan polymers are located within the cell wall. Van A-type resistance is due to the expression of enzymes that modify the cell wall precursor by substituting a terminal D-lactate for D-alanine, reducing vancomycin binding affinity by 1000 times. Beta-lactam antibiotics inhibit the cross-linking or transpeptidase reaction (B) that links glycopeptide polymer chains by formation of a cross-bridge with the stem peptide (the five glycines in this example) of one chain, displacing the terminal D-alanine of an adjacent chain. (Reproduced with permission from Brunton LL, et al. Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 12th ed. New York: McGraw-Hill; 2011.)
The patient can be sent home on antibiotics intravenously. Only gram-negative osteomyelitis can be reliably treated with oral antibiotics such as a quinolone. Staphylococci, whether sensitive or resistant, must be treated with intravenous (IV) antibiotics.
Orders:
Discontinue vancomycin.
Discontinue piperacillin/tazobactam.
Start IV oxacillin (or nafcillin) or ceftriaxone.
Transfer the patient home.
CCS is easier than real life in that you do not have to worry about dosing of antibiotics. Oxacillin, nafcillin, cefazolin, and ceftriaxone are all IV antibiotics that effectively cover sensitive staphylococcus. Any one of them is acceptable on CCS based on the sensitivities that are reported to you.
Move the clock forward at 1- to 2-week intervals. You should not repeat the x-ray or MRI to follow the effect of treatment. Use the ESR. If the ESR comes down slowly over 4 weeks, you can stop antibiotics. If, at 3 weeks, the ESR is still elevated, continue IV treatment to 6 weeks. If the ESR is still elevated at 5 and 6 weeks, then repeat the MRI and evaluate for surgical debridement. Persistently high ESR may indicate necrotic bone or abscess formation.
Bone biopsy is the key to osteomyelitis management!
You will feel stupid if you did not biopsy the bone, and the treatment fails at 6 weeks.