Published Date: 2012-10-11 02:36:50
Subject: PRO/EDR> Aspergillus meningitis - USA (08)
Archive Number: 20121011.1335715
ASPERGILLUS MENINGITIS - USA (08)
A ProMED-mail post
ProMED-mail is a program of the
International Society for Infectious Diseases
Date: Wed 10 Oct 2012
Source: Centers for Disease Control and Prevention [CDC] [edited]
Status: ongoing Investigation
Infection: fungal meningitis
Facility type: outpatient setting
Case Count: 137
10 Oct 2012
Source: CDC [edited]
Interim guidance for CNS and/or parameningeal infections associated with injection of potentially contaminated products
The pathogens involved in this cluster of infections are still under investigation. At present, there is culture, PCR, and/or histopathologic evidence of fungal central nervous system (CNS) infection in at least 25 patients. The commonest pathogen identified in these patients to date is _Exserohilum_ spp.
One patient has documented evidence of _Aspergillus_ spp. infection. When initiating treatment for patients with meningitis (that is, CSF [cerebrospinal fluid] pleocytosis* regardless of glucose and protein levels), epidural abscess, and/or vertebral osteomyelitis of unknown etiology who received an epidural injection with a New England Compounding Center product, clinicians should continue to follow routine empiric treatment protocols to cover for potential bacterial pathogens and add empiric broad spectrum antifungal therapy to the treatment regimen because of the severe adverse outcomes of untreated invasive fungal infection.
These recommendations are based upon current evidence that at least 2 fungal pathogens are involved, and the possibility that additional pathogens may be identified as the investigation continues. CDC has consulted with national experts on treatment options for fungal CNS and/or parameningeal infections in patients associated with this cluster. The following represents interim guidance and may change as new information becomes available.
Consult an infectious disease physician to assist with diagnosis, management, and follow-up, which may be complex and prolonged.
After collecting cerebrospinal fluid for culture, initiate empiric combination antifungal therapy using the following regimen in addition to routine empiric treatment protocols to cover for potential bacterial pathogens until the etiology of the patient's CNS and/or parameningeal infection has been identified:
Voriconazole, preferably at a dose of 6mg/kg every 12 hours (IV initially) and to continue on this high dose for the duration of treatment, if possible. Regular monitoring of serum concentration (for example, weekly interval) is advisable.
Liposomal amphotericin B, preferably at a dose of 7.5 mg/kg IV daily (higher than standard dose). The liposomal preparation of amphotericin B [AmBisome] is preferred over other lipid formulations. If nephrotoxicity is a potential concern, particularly in older patients, the dose may be decreased to 5mg/kg IV daily. Administration of 1L normal saline prior to infusion may be considered to minimize risk of nephrotoxicity.
Avoid routine use of intrathecal amphotericin B, either the deoxycholate or the lipid formulations, due to limited data on its use and associated toxicities.
There is currently no clear evidence for the use of adjuvant steroid therapy. If used, careful monitoring of clinical status is warranted.
Adequate duration of antifungal treatment is unknown but likely will require prolonged therapy (for example, months) tailored by the clinical response to treatment. Individual management decisions, including choice of long-term antifungal regimen, should be made in consultation with infectious disease physicians experienced in the treatment of fungal infections. Clinicians should be vigilant for potential relapse of infection after completion of therapy.
At this time, CDC does not recommend initiation of antifungal prophylaxis in exposed patients who are asymptomatic. These patients should be closely monitored for development of symptoms, with a low threshold for performing lumbar puncture should the patient become symptomatic.
At this time, CDC does not recommend empiric antifungal therapy for symptomatic patients who have normal cerebrospinal fluid laboratory examination. These patients should be closely monitored and re-evaluated for progression of symptoms. Should the patient have progression of symptoms, a lumbar puncture should be repeated immediately.
*CSF WBC greater than 5 in a non-traumatic lumbar puncture. If a traumatic lumbar puncture is suspected, a corrected CSF WBC count can be calculated by subtracting one WBC for every 500 RBCs present in the CSF.
[It would be useful to know the date of administration of the contaminated corticosteroid and the date of initial onset of symptoms as well as the cell count, chemistries, and time to positive culture in documented cases. As well, the species of _Aspergillus_ mold and the number of cases with _Exserohilum_ species has not been reported. This is the 1st time that it has been reported that exserohilum may be commoner than aspergillus in this outbreak.
Related to the date of reporting (not date of onset), the number of cases, number of states involved and deaths is:
Date of report / Cases / States / Deaths
02 Oct 2012 / 12 / 2 / 2
04 Oct 2012 / 26 / 5 / 4
05 Oct 2012 / 35 / 5 / 5
06 Oct 2012 / 64 / 9 / 7
07 Oct 2012 / 91 / 9 / 7
08 Oct 2012 / 101 / 9 / 8
09 Oct 2012 / 119 / 10 / 11
10 Oct 2012 / 137 / 10 / 12
Total case fatality rate: 8.7 per cent - Mod.LL
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