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Research Letter |

Response to Mold Contamination of Intravenous Magnesium Sulfate Produced by a Compounding Pharmacy FREE

John M. Boyce, MD1; Lorraine Lee, MHA, BSPharm1; Jeffrey Topal, MD1; David R. Peaper, MD, PhD1; Thomas Balcezak, MD1
[+] Author Affiliations
1Yale–New Haven Hospital, New Haven, Connecticut
JAMA Intern Med. 2014;174(4):630-631. doi:10.1001/jamainternmed.2013.13772.
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Published online

An increasing number of contaminated medications produced by compounding pharmacies have placed patients at risk, created unnecessary burdens on health care facilities, and illustrate the need for better oversight of the industry.13 We describe a hospital’s response to fungal contamination of intravenous magnesium sulfate (MgSO4) produced by a compounding pharmacy.

On March 13, 2013, a nurse discovered “floaters” in a bag of MgSO4. The hospital pharmacy immediately recalled all units of MgSO4 produced by the compounding pharmacy and found floaters in a second lot of MgSO4 recalled from a different hospital ward. The following day, pharmacy personnel recalled all 12 000 units of 44 types of products received from the compounding pharmacy from all patient care areas at the hospital and at 2 other system-related hospitals. Appropriate state agencies, the US Food and Drug Administration (FDA), and the Centers for Disease Control and Prevention (CDC) were notified. Products from the compounding pharmacy were sequestered and examined by hospital pharmacy employees and FDA personnel for visible evidence of contamination, and samples were obtained for investigation by the FDA and CDC. The hospital microbiology laboratory performed DNA sequencing of material from the contaminated MgSO4.

Because multiple lots of MgSO4 produced by the compounding pharmacy, including lots without visible contamination, were in use at the hospital concurrently, and lot numbers are not embedded in medication barcodes recorded in patient medical records, we could not identify only those patients who received MgSO4 from contaminated lots. Therefore, a list of all patients who received MgSO4 during the exposure period was generated. Hospital personnel notified potentially exposed patients by telephone and certified letter and informed their physicians by telephone. Prophylactic voriconazole was administered to patients with allogeneic stem cell transplants who were potentially exposed.

From mid-March through mid-June 2013, medical records of potentially exposed patients who were readmitted were reviewed for evidence of fungal infection, and microbiology laboratories at the 3 system hospitals reported growth of any mold from sterile body sites twice weekly to the infection control program.

DNA sequencing performed by the hospital microbiology laboratory directly on particulate material from contaminated bags and sequencing of fungal growth recovered from 2 lots of contaminated MgSO4 was consistent with Hamigera spp, subsequently identified by the CDC as Hamigera insecticola. Sequencing of fungal growth from 1 of the 2 lots also yielded an Aspergillus-like organism, identified by the CDC as Neosartorya hiratsukae. Investigations by the CDC and a reference laboratory used by the compounding pharmacy found that 4 lots of MgSO4 and a lot of dexamethasone sodium phosphate were contaminated with fungi, including Penicillium chrysogenum and Penicillium rubens (Table 1).

Table Graphic Jump LocationTable 1.  Contaminated Lots of Magnesium Sulfate From a Compounding Pharmacy and Fungal Contaminates Identified

A total of 1309 patients and 460 physicians were notified regarding possible exposures to contaminated MgSO4. As of mid-June 2013, responses to hotline calls, laboratory-based surveillance, and review of 545 readmissions of potentially exposed patients revealed no fungal infections attributable to the contaminating fungi. The hospital’s response involved an estimated 14 915 hours of personnel time, and estimated costs to the hospital system were $874 989 (Table 2). An FDA investigation revealed that the source of contamination was the compounding pharmacy, where all contaminated products prepared for our hospital were compounded on a separate (unique) laminar flow work bench, and uncovered unsanitary conditions and numerous violations of good manufacturing practice requirements for drugs.4

Table Graphic Jump LocationTable 2.  Hospital System Costs Associated With Fungal Contamination of Magnesium Sulfate

Fungal contamination of MgSO4 required extensive pharmacy, laboratory, infection control, and hospital administrative support; substantial hospital resources for patient and physician notification; ongoing surveillance; and prophylactic treatment of high-risk patients. Inclusion of lot numbers in medication barcodes would have greatly simplified notification and surveillance efforts by identifying only those patients who were exposed to contaminated lots. Our experience adds to the increasing body of evidence that improved oversight of compounding pharmacies by the FDA is needed.5,6

Corresponding Author: John M. Boyce, MD, Hospital Epidemiology and Infection Control, Yale–New Haven Hospital, 20 York St, New Haven, CT 06510 (John.Boyce@ynhh.org).

Published Online: February 3, 2014. doi:10.1001/jamainternmed.2013.13772.

Author Contributions: Dr Boyce and Ms Lee had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Boyce, Lee, Balcezak.

Acquisition of data: Lee, Topal, Peaper.

Analysis and interpretation of data: Boyce, Lee, Topal, Peaper.

Drafting of the manuscript: Boyce, Lee, Topal, Peaper.

Critical revision of the manuscript for important intellectual content: Boyce, Lee, Topal, Peaper, Balcezak.

Statistical analysis: Lee.

Administrative, technical, or material support: Boyce, Lee, Topal, Peaper, Balcezak.

Study supervision: Peaper.

Conflict of Interest Disclosures: None reported.

Additional Contributions: George Paci, RN, Kathleen Testa, RN, MPH, and Jessica Nuzzo, MPH, assisted with management of the hospital’s response to the episode of fungal contamination. Mary E. Brandt, PhD, Benjamin J. Park, MD, Nina Grossman, and Joyce Peterson from the Centers for Disease Control and Prevention, Atlanta, GA, identified and confirmed the fungi recovered from contaminated products produced by a compounding pharmacy. No individuals received compensation for their participation.

Staes  C, Jacobs  J, Mayer  J, Allen  J.  Description of outbreaks of health-care–associated infections related to compounding pharmacies, 2000-12. Am J Health Syst Pharm. 2013;70(15):1301-1312.
PubMed   |  Link to Article
Kainer  MA, Reagan  DR, Nguyen  DB,  et al; Tennessee Fungal Meningitis Investigation Team.  Fungal infections associated with contaminated methylprednisolone in Tennessee. N Engl J Med. 2012;367(23):2194-2203.
PubMed   |  Link to Article
Smith  RM, Schaefer  MK, Kainer  MA,  et al.  Fungal infections associated with contaminated methylprednisolone injections. N Engl J Med. 2012;369:1598-1609.
US Food and Drug Administration. MedPREP Consulting Inc., Tinton Falls, NJ, 483 issued 4/3/2013. http://www.fda.gov/downloads/About FDA/CentersOffices/officeofglobalregulatoryoperationsandpolicy/ora/oraelectronicreadingroom/ucm348230.pdf. Accessed Sptember 17, 2013.
Thompson  CA.  Compounding pharmacy industry has outgrown its regulatory system, ASHP and FDA say. Am J Health Syst Pharm. 2013;70(9):747-748.
PubMed   |  Link to Article
Traynor  K.  Compounding legislation clears first Senate hurdle. Am J Health Syst Pharm. 2013;70(13):1094-1096.
PubMed   |  Link to Article

Figures

Tables

Table Graphic Jump LocationTable 1.  Contaminated Lots of Magnesium Sulfate From a Compounding Pharmacy and Fungal Contaminates Identified
Table Graphic Jump LocationTable 2.  Hospital System Costs Associated With Fungal Contamination of Magnesium Sulfate

References

Staes  C, Jacobs  J, Mayer  J, Allen  J.  Description of outbreaks of health-care–associated infections related to compounding pharmacies, 2000-12. Am J Health Syst Pharm. 2013;70(15):1301-1312.
PubMed   |  Link to Article
Kainer  MA, Reagan  DR, Nguyen  DB,  et al; Tennessee Fungal Meningitis Investigation Team.  Fungal infections associated with contaminated methylprednisolone in Tennessee. N Engl J Med. 2012;367(23):2194-2203.
PubMed   |  Link to Article
Smith  RM, Schaefer  MK, Kainer  MA,  et al.  Fungal infections associated with contaminated methylprednisolone injections. N Engl J Med. 2012;369:1598-1609.
US Food and Drug Administration. MedPREP Consulting Inc., Tinton Falls, NJ, 483 issued 4/3/2013. http://www.fda.gov/downloads/About FDA/CentersOffices/officeofglobalregulatoryoperationsandpolicy/ora/oraelectronicreadingroom/ucm348230.pdf. Accessed Sptember 17, 2013.
Thompson  CA.  Compounding pharmacy industry has outgrown its regulatory system, ASHP and FDA say. Am J Health Syst Pharm. 2013;70(9):747-748.
PubMed   |  Link to Article
Traynor  K.  Compounding legislation clears first Senate hurdle. Am J Health Syst Pharm. 2013;70(13):1094-1096.
PubMed   |  Link to Article

Correspondence

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