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Iatrogenic Fungal Meningitis: Tragedy Repeated<!--Author Name-->
<!--David J. Graham MD, MPH; Rita Quellet-Hellstrom PhD; Thomas E. MaCurdy PhD; Farzana Ali BA; Christopher Sholley BS; Christopher Worrall BS;Jeffery A. Kelman MD, MMSc-->
John R. Perfect, MD
<!--this section is to display disclosure and other info-->[+-] Article and Author Information
Ann Intern Med. 18 October 2012
Recent reports of fungal meningitis cases caused by contaminated corticosteroid injections demand that we remember prior lessons learned, while scrambling to care for currently affected persons even before all the facts are in hand. In 2002, the Centers for Disease Control and Prevention (CDC) detailed 5 cases of Exophiala (Wangiella) dermatitidis meningitis or arthritis related to contaminated, injectable, preservative-free methylprednisolone acetate prepared from a compounding pharmacy (1). I was involved in the recognition and management of some of these patients. We learned, or thought we learned, several important lessons from the outbreak: that compounding of preservative-free corticosteroids requires meticulous sterility to ensure lack of fungal contamination; in the absence of that level of sterility and in an environment of highly concentrated steroids, fungi grow aggressively (2) (this has also been occasionally observed in ophthalmology with the accidental treatment of fungal keratitis with topical steroids); and injection of fungus-contaminated corticosteroid solution into the parameninges allows fungus to travel through tissue planes into the subarachnoid space, leading to invasive mycosis. We also learned that the incubation period for appearance of disease from the time of exposure could be up to 6 months, that many persons in several states were exposed but the attack rate for disease was low, and that voriconazole successfully treated these cases of iatrogenic fungal meningitis except for 1 fatality. However, the cost in patient worry and suffering, medical expenses, and public health surveillance of the 2002 outbreak was high, and the public's trust that medications are safe from microbial contamination was shaken.
The present fungal meningitis outbreak, first recognized in September 2012, seems to be caused by Exserohilum rostratum inoculated from contaminated lots of preservative-free methylprednisolone acetate, although it remains possible that other fungi have been involved in some cases. The injections were primarily given as epidural injections to older adults with low back pain and possibly as intra-articular injections...
...
Patients will need to be followed closely and management refined in real-time. The details of the epidemiology, including the attack rate, remain unclear. The natural history of resultant infections is only now coming into focus, and the manner by which exposed patients should be followed and managed is a work in progress. Unfortunately, the incubation period for these infections, based on prior experience, may extend to months after exposure. Therefore, exposed patients will need to be followed for a long time. The appropriate duration of therapy is similarly unknown, as are such questions as whether to screen with lumbar puncture or joint aspiration and appropriate use of empirical voriconazole. The bottom line is that management will need to be individualized for patients for some time to come.
...
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<!--David J. Graham MD, MPH; Rita Quellet-Hellstrom PhD; Thomas E. MaCurdy PhD; Farzana Ali BA; Christopher Sholley BS; Christopher Worrall BS;Jeffery A. Kelman MD, MMSc-->
John R. Perfect, MD
<!--this section is to display disclosure and other info-->[+-] Article and Author Information
Ann Intern Med. 18 October 2012
Recent reports of fungal meningitis cases caused by contaminated corticosteroid injections demand that we remember prior lessons learned, while scrambling to care for currently affected persons even before all the facts are in hand. In 2002, the Centers for Disease Control and Prevention (CDC) detailed 5 cases of Exophiala (Wangiella) dermatitidis meningitis or arthritis related to contaminated, injectable, preservative-free methylprednisolone acetate prepared from a compounding pharmacy (1). I was involved in the recognition and management of some of these patients. We learned, or thought we learned, several important lessons from the outbreak: that compounding of preservative-free corticosteroids requires meticulous sterility to ensure lack of fungal contamination; in the absence of that level of sterility and in an environment of highly concentrated steroids, fungi grow aggressively (2) (this has also been occasionally observed in ophthalmology with the accidental treatment of fungal keratitis with topical steroids); and injection of fungus-contaminated corticosteroid solution into the parameninges allows fungus to travel through tissue planes into the subarachnoid space, leading to invasive mycosis. We also learned that the incubation period for appearance of disease from the time of exposure could be up to 6 months, that many persons in several states were exposed but the attack rate for disease was low, and that voriconazole successfully treated these cases of iatrogenic fungal meningitis except for 1 fatality. However, the cost in patient worry and suffering, medical expenses, and public health surveillance of the 2002 outbreak was high, and the public's trust that medications are safe from microbial contamination was shaken.
The present fungal meningitis outbreak, first recognized in September 2012, seems to be caused by Exserohilum rostratum inoculated from contaminated lots of preservative-free methylprednisolone acetate, although it remains possible that other fungi have been involved in some cases. The injections were primarily given as epidural injections to older adults with low back pain and possibly as intra-articular injections...
...
Patients will need to be followed closely and management refined in real-time. The details of the epidemiology, including the attack rate, remain unclear. The natural history of resultant infections is only now coming into focus, and the manner by which exposed patients should be followed and managed is a work in progress. Unfortunately, the incubation period for these infections, based on prior experience, may extend to months after exposure. Therefore, exposed patients will need to be followed for a long time. The appropriate duration of therapy is similarly unknown, as are such questions as whether to screen with lumbar puncture or joint aspiration and appropriate use of empirical voriconazole. The bottom line is that management will need to be individualized for patients for some time to come.
...
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