CDC: Interim treatment guidance for osteoarticular infections
associated with injection of contaminated steroid products
Date: Tue 23 Oct 2012
Source: CDC [edited]
<http://www.cdc.gov/hai/outbreaks/clinicians/interim_guidance_osteoarticular_infections.html>
Rationale
- ---------
This is interim guidance for treatment of adult patients with
osteoarticular infections associated with intra-articular injections
of contaminated steroid products from the New England Compounding
Center [NECC]. Interim guidance may change as new information becomes
available.
These recommendations are based upon growing evidence that
_Exserohilum rostratum_ (a brown-black mold) is the predominant
pathogen in this outbreak, and expert opinion and published literature
indicating that voriconazole may be effective in treating infections
due to brown-black molds as well as infections due to _Aspergillus_
species. Recommendations are also based on considerations related to
the anatomic site of infection and pharmacokinetics of antifungal
agents. CDC continues to consult with national experts about treatment
options for fungal osteoarticular infections in patients associated
with this outbreak.
Infectious diseases physician consultation
- ------------------------------------------
Consult an infectious diseases physician to assist with patient
diagnosis, management, and follow up, which may be complex and
prolonged.
Diagnostic considerations
- -------------------------
Thorough diagnostic evaluation is essential, and should include
collection of synovial fluid and/or synovial tissue prior to
initiation of treatment. Samples should be sent or fungal culture,
molecular testing, and histopathological examination, in addition to
the standard tests for bacterial infection and crystal-induced
disease.
Physicians should use their best judgment in regard to imaging the
osteoarticular structure(s) that may be infected. For large joints,
such as knees, if there is a consideration of adjacent osteomyelitis,
then imaging should be performed. Imaging may be particularly
important in the evaluation of joint spaces such as the sacroiliac
joint, where osteomyelitis may be more common and from which obtaining
a diagnostic specimen of synovial fluid may be more difficult.
Similarly, for patients in whom complaints of back pain are worrisome
for the development of discitis/vertebral osteomyelitis, imaging
should be performed. In some of these cases, repeat imaging may be
required as the progression of the infection may be slow and imaging
findings suggestive or diagnostic of osteomyelitis may not be evident
for 2 weeks or more following initial presentation.
Note that a negative fungal culture or negative fungal polymerase
chain reaction (PCR) test from a diagnostic specimen obtained from a
joint space or bone does not rule out infection. Active fungal
infection may be present even when these tests are negative.
Empiric antifungal therapy
- --------------------------
Routine empiric antibacterial therapy should be used according to the
judgment of the physician while awaiting results of diagnostic
studies.
In clinically stable patients with peripheral joint infection, it may
be reasonable to wait 48-72 hours before initiating empiric antifungal
therapy, to allow time for identification of alternative diagnoses
(such as, bacterial arthritis, crystal-induced arthritis, etc.). This
decision should be made at the discretion of the provider.
When empiric antifungal therapy is initiated, the following regimen is
suggested until the etiology of the patient's septic arthritis has
been identified:
- - For discitis, vertebral osteomyelitis, and epidural abscess give
voriconazole at a dose of 6 milligrams per kilogram (mg/kg) every 12
hours. For osteoarticular infections that do not involve the spine,
give voriconazole, beginning with a loading dose of 6 mg/kg every 12
hours for 2 doses, followed by 4 mg/kg every 12 hours.
Dose adjustments may be needed for certain patients, including (but
not necessarily limited to): children (who often need a higher dose)
and patients with hepatic impairment (who may need a lower dose).
Dosing of voriconazole in obese patients should be discussed with an
infectious diseases physician. Oral voriconazole should be taken at
least one hour before or after a meal. Consult an infectious diseases
physician and refer to the manufacturer's instructions.
A blood specimen for serum voriconazole trough level measurement
should be collected on the 5th day of voriconazole treatment, and the
dose of voriconazole should be adjusted based on this trough level,
aiming for a trough level range of 2 to 5 micrograms per milliliter
(mcg/mL). Serum voriconazole trough levels greater than 5 mcg/mL
should be avoided because of the risk of neurotoxicity and other
drug-related adverse events.
Regular monitoring of serum voriconazole trough levels once per week
should occur for the initial 4-6 weeks of voriconazole treatment and
when dose adjustments are made. Dose adjustments should be made as
needed to maintain serum voriconazole trough levels within the range
of 2 to 5 mcg/mL.
Patients with more severe osteoarticular infection, clinical
instability, discitis, vertebral osteomyelitis, or epidural abscess
should be started on voriconazole IV. If the provider wants to
transition patients initially treated with IV voriconazole to oral
voriconazole, this should be done only after a patient is clinically
stable or improving, as long as no contraindications to oral therapy
exist.
Patients with mild osteoarticular infection not involving the spine
who are able to take oral voriconazole as prescribed and who are able
to be monitored closely may be started on oral voriconazole at the
provider's discretion. Patients on oral voriconazole should be treated
with a loading dose of 6 mg/kg every 12 hours for 2 doses, followed by
4 mg/kg every 12 hours, with monitoring of serum voriconazole trough
levels as above and dose adjustment as necessary. The target range for
serum voriconazole trough levels (2 to 5 mcg/mL) is readily achievable
using the oral form of the drug, but may require a slightly higher
dose and may take longer to achieve if unforeseen problems with
gastrointestinal intolerance or poor absorption are encountered.
Providers and patients should be aware of and monitor for potential
adverse effects of voriconazole, including (but not limited to)
hepatic toxicity and neurotoxicity. Liver function tests should be
closely monitored. The occurrence of hallucinations may be an
indication of neurotoxicity and elevated serum voriconazole levels,
and should prompt collection of a blood specimen for serum
voriconazole trough level measurement and voriconazole dose
adjustment.
Providers should carefully consider and manage the potential for
voriconazole drug interactions in all patients.
- - A lipid formulation of amphotericin B at a dose of 5 mg/kg IV daily
should be considered in addition to voriconazole in patients with
severe osteoarticular infection and/or patients with clinical
instability. Nephrotoxicity is a common complication of amphotericin B
therapy, including therapy with lipid formulations of amphotericin B.
Kidney function and electrolytes should be monitored closely in
patients receiving any amphotericin B formulation. Administration of 1
liter of normal saline IV prior to amphotericin B infusion may be
considered to minimize risk of nephrotoxicity. Providers and patients
should also be aware of and monitor for other potential adverse
effects of amphotericin B formulations.
- - Alternate therapies to consider for patients who are unable to
tolerate treatment with voriconazole include lipid formulations of
amphotericin B, posaconazole, and itraconazole. Therapeutic drug
monitoring should be performed for patients treated with posaconazole
or itraconazole. Consultation with an infectious diseases physician
should be sought regarding dosages and monitoring of these agents.
Fluconazole should NOT be used.
Other treatment considerations
- ------------------------------
Arthroscopy with joint lavage and debridement should be considered in
consultation with an orthopedic surgeon, or a neurosurgeon in the case
of vertebral osteomyelitis.
Considerations regarding duration of treatment
- ----------------------------------------------
Adequate duration of antifungal treatment is unknown, and it is likely
that patients will require prolonged therapy tailored by the clinical
response to treatment. Individual patient management decisions,
including choice of long-term antifungal treatment regimens, should be
made in consultation with infectious diseases physicians experienced
in the treatment of fungal infections. While adequate duration of
therapy is unknown and will likely vary substantially depending upon
individual patient circumstances, a minimum of 3 months of antifungal
treatment should be considered. Treatment may need to continue for
longer than 3 months in patients with more severe disease, bone
infection, underlying immunosuppression, etc. Clinicians should be
vigilant for potential relapse of infection after completion of
therapy.
- --
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