Sterile compounding: clinical, legal, and regulatory implications for patient safety.

BACKGROUND: Poor compounding practices by the New England Compounding Center resulted in the 2012-2013 fungal infections outbreak. Contaminated injectable methylprednisolone led to the diagnosis of fungal infections in 751 patients and 64 deaths. In the United States, pharmacy compounding has traditionally been regulated by state boards of pharmacy rather than the FDA. To minimize safety risks related to pharmacy compounding, the Drug Quality and Security Act (DQSA) was signed into law November 27, 2013, to improve regulation of compounding pharmacies. OBJECTIVES: To (a) review the literature regarding clinical, legal, and regulatory implications of pharmacy compounding for patient safety during the 2012-2013 fungal infections outbreak and (b) discuss strategies that managed care organizations (MCOs) can use to promote safe compounding practices.  METHODS: A literature search was conducted via PubMed for original articles on fungal infections related to drug compounding published October 2012 to March 2014. Specific search terms included "drug compounding and fungal infection" and "fungal meningitis outbreak." The FDA website was also utilized for material related to the Food, Drug, and Cosmetic Act and the DQSA.  RESULTS: Four articles met inclusion criteria. The 2012-2013 fungal infections outbreak was attributed to 3 lots of preservative-free methylprednisolone acetate, which comprised 17,675 vials distributed to 76 facilities across 23 states. Median incubation period (from time of last injection to initial diagnosis) was 47 days, ranging from 0 to 249 days. According to the FDA, a total of 30 recalls regarding compounded products were issued by pharmacies during March through December 2013. CONCLUSIONS: Pharmacy compounding has the potential for significant safety risks. The purpose of the DQSA is to improve regulation of compounding pharmacies. Since registration as an outsourcing facility is voluntary, uncertainty still remains regarding advancement in safe compounding practices. MCOs can employ multiple strategies to ensure patient safety and promote appropriate drug therapy.

How gaps in regulation of compounding pharmacy set the stage for a multistate fungal meningitis outbreak.

OBJECTIVE: To provide an overview of the regulation issues surrounding compounding pharmacy that allowed the United States fungal meningitis outbreak to occur and the changes in regulation that ensued. SUMMARY: In September 2012, a single case report sparked an investigation into a nationwide outbreak of fungal meningitis due to contaminated injectable drugs. The source of the contamination, New England Compounding Center (NECC), was in violation of several state and federal laws and had a history of such violations. The regulation of compounding pharmacies has historically been left to the states, while manufacturing fell under the jurisdiction of the Food and Drug Administration. However, as more compounders took part in large-scale interstate distribution of drugs, the current state-based regulatory system became less equipped to provide oversight. The lack of a clear definition of "compounding pharmacy" further obscures proper oversight and regulation. Congress and several states have taken steps to build safeguards against large-scale compounding by increasing inspections, adopting stricter licensing requirements, and enacting the Drug Quality and Security Act of 2013. CONCLUSION: While the current compounding regulation changes are a necessary step forward, it remains to be seen how effective they will be in safeguarding the public.

A hybrid strategy for surveillance of individuals potentially exposed to contaminated methylprednisolone acetate--Virginia, 2012.

In September 2012, a multistate outbreak of fungal infections associated with the use of contaminated steroid products resulted in 675 exposed persons in Virginia and 53 cases of fungal infections, including 2 deaths. This article describes the design and implementation of a "hybrid" active public health surveillance system and related communication activities in partnership with key clinical stakeholders in Virginia. Strong collaboration with clinical partners is critical in establishing and implementing a surveillance system for an evolving outbreak. While clinicians focused on diagnosis, treatment, and routine follow-up of patients who presented with symptoms consistent with the outbreak case definition, public health took on the responsibility of weekly surveillance phone calls to all exposed persons who did not enter clinical care. Communication between clinical partners and public health was essential and included the somewhat atypical role of public health actively performing assessment and referral to care functions during an outbreak.

Epidemiology of central nervous system infection.

In cases of central nervous system infection, it is crucial for the neuroradiologist to provide an accurate differential diagnosis of the possible pathogens involved so that treating physicians can be aided in the choice of empiric therapy. This approach requires the radiologist to be aware of local epidemiology and have knowledge of infectious agents that are endemic to their area of practice. This article reviews and discusses the changing epidemiology of pathogens most often observed in meningitis, brain abscess, epidural abscess, postoperative infections, and human immunodeficiency virus infection.

Successful kidney transplantation after coccidioidal meningitis.

Coccidioidomycosis is a fungal infection primarily found in residents or visitors to geographic areas where Coccidioides species are endemic, including the southwestern United States, northwestern Mexico, and certain areas of Central and South America. The infection rarely disseminates, but certain populations are at higher risk of dissemination. One population at high risk of disseminated disease is solid organ transplant recipients. At our transplant center in Arizona, patients with proven coccidioidal infection before transplantation undergo thorough counseling about the risks of dissemination and possible death from coccidioidomycosis subsequent to the use of immunosuppressive medications after transplantation. Currently, patients with coccidioidal infection before transplantation are maintained on lifelong infection suppression with triazole therapy. We present the first successful case of a kidney transplant in a patient after treatment for coccidioidal meningitis without post-transplant reactivation of the coccidioidal infection.

Iatrogenic meningitis after lumbar puncture-a preventable health hazard.

Iatrogenic meningitis (IM) is a rare complication of diagnostic and therapeutic lumbar puncture (LP). This study includes cases of IM managed in the Departments of Neurology, of two referral hospitals, in India between January 1984 and April 2002. The diagnosis of IM was made when symptoms of meningitis occurred 24 h to 21 days after LP. All the procedures were performed in the peripheral hospitals before they were referred to the two centres. There were 17(63%) women and 10(37%) men. The age range was 19-50 years with a mean age of 31. The precipitating event was spinal anaesthesia for pelvic and intra-abdominal surgeries (Caesarean section 11 cases, hysterectomy three cases, herniorraphy two cases, appendicectomy two cases, anal fissurectomy one case, varicocelectomy one case and hydrocelectomy one case) laminectomy in two and diagnostic myelogram in four patients. The cerebrospinal fluid (CSF) culture was positive in six (22%) patients. The organisms were Pseudomonas aeruginosa in one case, Staphylococcus aureus in three cases, Acinetobacter spp. in one case and Mycobacterium tuberculosis in one case. In five individuals, mycotic aneurysms with subarachnoid haemorrhage due to invasive aspergillosis was documented at autopsy. The mean follow-up was 10.6 months (range 1-18). Seventeen (63%) patients received conventional antibiotics alone, while 10 patients received antibiotics and anti-tuberculous drugs when the meningitis became chronic. The mortality was 36%. The poor prognostic factors were women who underwent Caesarean section (P < 0.04) presence of hemiplegia (P < 0.04) and altered mental status (P < 0.0004). This study shows high morbidity and mortality of IM after LP. Simple aseptic precautions under- taken before the procedure can prevent IM. The urgent need for increasing the awareness among medical personnel in peripheral hospitals of developing countries cannot be over emphasized.