The CDC has issued guidance for clinicians(www.cdc.gov) in the wake of a fungal meningitis outbreak that has caused more than 110 illnesses and 11 deaths in 10 states as of Oct. 10.
The cases are associated with a potentially contaminated steroid -- methylprednisolone acetate -- manufactured by New England Compounding Center in Framingham, Mass. On Sept. 25, the company initially recalled three lots of methylprednisolone acetate (PF) 80 mg/ml: 05212012@68, BUD 11/17/2012; 06292012@26, BUD 12/26/2012; and 08102012@51, BUD 2/6/2013.
The company now has expanded that recall to include all products that were compounded at and distributed from its Framingham facility. The CDC said health care professionals should cease use of any product produced by New England Compounding Center.
- The CDC has issued guidance for physicians in response to an expanding outbreak of fungal meningitis.
- More than 110 cases and 11 deaths have been reported in 10 states as of Oct. 10.
- The illnesses have been linked to a potentially contaminated steroid -- methylprednisolone acetate -- produced by New England Compounding Center.
- The manufacturer has expanded its recall to include all products compounded and distributed from its Framingham, Mass., facility.
The CDC also said physicians should contact patients who have received the recalled medications to determine if they are having symptoms, including fever, new or worsening headache, neck stiffness, sensitivity to light, new weakness or numbness, increasing pain, or redness or swelling at the injection site. "All patients who may have received these medications need to be tracked down immediately," said Benjamin Park, M.D., medical officer of the Mycotic Diseases Branch in a press release(www.cdc.gov). "It is possible that if patients with infection are identified soon and put on appropriate antifungal therapy, lives may be saved."
The potentially contaminated products first became available May 21. Patients have had symptoms within one to four weeks after their injection. Several patients have suffered strokes(emergency.cdc.gov) resulting from the infection, according to the CDC. Not all patients who received the medicine will become sick, and this form of meningitis is not contagious, the agency noted.
The CDC said in its interim guidance that physicians should consult an infectious disease physician to assist with diagnosis, management and follow up, which may be complex and prolonged.
Cerebrospinal fluid obtained from infected patients has typically shown elevated white cell count, low glucose and elevated protein. After collecting cerebrospinal fluid for culture, the agency said physicians should 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 central nervous system and/or parameningeal infection has been identified.
- Voriconazole, initially by IV, at a dose of 6mg/kg every 12 hours and to continue on this high dose for the duration of treatment, if possible. Weekly monitoring of serum concentration is advisable.
- Liposomal amphotericin B, preferably at a dose of 7.5 mg/kg by IV daily. The liposomal preparation of amphotericin B (AmBisome) is preferred to 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 1 L of normal saline before infusion may be considered to minimize risk of nephrotoxicity.
The agency also offered the following recommendations:
- avoid routine use of intrathecal amphotericin B, either the deoxycholate or the lipid formulations, due to limited data on its use and associated toxicities;
- although there is no clear evidence for the use of adjuvant steroid therapy, monitoring is warranted if this therapy is used;
- adequate duration of antifungal treatment is unknown but likely will require prolonged therapy tailored by the patient's response to treatment, so individual management decisions, including choice of long-term antifungal regimen, should be made in consultation with infectious disease physicians, and clinicians should be vigilant for potential relapse of infection after therapy completion.
- antifungal prophylaxis in exposed patients who are asymptomatic is not recommended, but these patients should be closely monitored for development of symptoms with a low threshold for performing lumbar puncture should the patient become symptomatic; and
- empiric antifungal therapy is not recommended for symptomatic patients who have normal cerebrospinal fluid, but these patients should be closely monitored and re-evaluated for progression of symptoms.
In addition to its guidance document, the CDC has developed a frequently-asked-questions sheet for physicians(www.cdc.gov) and for patients(www.cdc.gov).
Physicians and patients are encouraged to report adverse events associated with methylprednisolone acetate to the FDA's MedWatch program(www.fda.gov).