Fungal Infections Associated with Contaminated Methylprednisolone Acetate in Michigan, 2012-2013Joseph R. Coyle, MPHMichigan Department of Community Health

Exserohilum rostratum

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•Michigan Outbreak Response Team:▫Brenda Brennan▫Jim Collins▫Joe Coyle▫Jay Fiedler

•Michigan Pain Clinics and Staff

•Michigan Hospitals- Administrators, Clinicians, IPs

•State Health Departments

•Centers for Disease Control and Prevention

▫Jennie Finks▫Shannon Johnson▫Jevon McFadden▫Mawuli Nyaku▫Many others…

Acknowledgements

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Outline•Outbreak Timeline

•Role of the MDCH

•Michigan Pain Clinics▫Patient Notification

• Identifying and Counting Cases▫Surveillance definitions

•Characterization and Epidemiology of Fungal Infections in Michigan

•Summarizing the MDCH Contribution

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Case Count October 8th, 2012

Case Count June 3rd, 2013

Outline

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Outbreak Timeline

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Outbreak Timeline•September 18th, 2012 – Tennessee Department of

Health (TDH) receives report of 56-year old patient with Aspergillus meningitis

•September 25th, 2012 – TDH identified an additional 7 patients with meningitis

▫All TN patients received an epidural steroid injection from a common Ambulatory Surgery Center

▫All injections were from three lots of methylprednisolone acetate (MPA) from the New England Compounding Center (NECC)

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•September 26th, 2012 – NECC voluntarily recalls three lots of MPA (05212012, 06292012, and 08102012)

•September 27th, 2012 – North Carolina Department of Health and Human Services identifies a patient with meningitis also exposed to one of the three recalled lots of MPA

TN and NC patients had similar presentations (sub-acute meningitis with pleocytosis) with a common exposure (NECC MPA)

Outbreak Timeline

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•September 28th, 2012 – Growing evidence of connection between meningitis cases and NECC MPA shared on multi-state call with CDC

•October 1st, 2012 –NECC customer invoice list shared with the Michigan Department of Community Health (MDCH) Bureau of Epidemiology

•October 2nd, 2012 – MDCH begins contacting Michigan clinics who were recipients of recalled lots of NECC MPA

Outbreak Timeline

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Role of the Michigan Department Community Health

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•Maintaining daily contact with CDC (Epi, Lab, and Clinical)

•Retrospectively and prospectively identifying cases and maintaining case count / line list

•Coordinating with Michigan hospitals and clinicians

•Sharing information via the Michigan Health Alert Network (MIHAN)

•Updating media via press releases and our PIO

•Collection of specimens to be forwarded to CDC lab for testing

MDCH Role

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MDCH Role•Chart abstraction and data collection

•Patient Notification and Coordinating with Michigan Clinics:▫Re-enforcing recall and instructing clinics to pull any

recalled product from circulation

▫Identifying a point-of-contact at each pain clinic

▫Working with clinics to determine a list of patients potentially exposed to a recalled lot of NECC MPA

▫Assisting clinics with direct patient notification: Direct contact via phone (voicemail not sufficient) Registered letter

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Michigan Pain Clinics

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Michigan Pain ClinicsLocation Recalled Product Received Exposures*

Lot Number Amount Product Patients Injections

Clinic A 06292012 400 vials MPA 80mg/mL – 5mL PF 638 759

Clinic B05212012 1,000 vials MPA 80mg/mL – 1mL PF

1,032 1,66806292012 500 vials MPA 80mg/mL – 1mL PF

Clinic C

05212012 100 vials MPA 80mg/mL – 1mL PF

102 11406292012 100 vials MPA 80mg/mL – 1mL PF

08102012 100 vials MPA 80mg/mL – 1mL PF

Clinic D 05212012 25 vials MPA 80mg/mL – 1mL PF 32 40

MI TOTAL 2,225 vials 1,804 2,581

*Estimates

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Michigan Pain ClinicsLocation Recalled Product Received Exposures*

Lot Number Amount Product Patients Injections

Clinic A 06292012 400 vials MPA 80mg/mL – 5mL PF 638 759

Clinic B05212012 1,000 vials MPA 80mg/mL – 1mL PF

1,032 1,66806292012 500 vials MPA 80mg/mL – 1mL PF

Clinic C

05212012 100 vials MPA 80mg/mL – 1mL PF

102 11406292012 100 vials MPA 80mg/mL – 1mL PF

08102012 100 vials MPA 80mg/mL – 1mL PF

Clinic D 05212012 25 vials MPA 80mg/mL – 1mL PF 32 40

MI TOTAL 2,225 vials 1,804 2,581

*Estimates

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Michigan Shipments of NECC MPALot Number Michigan (mLs) Nationwide (mLs)1 MI % of Nation

05212012 1,125 11,622 9.7%

06292012 2,600 10,665 24.4%

08102012 100 4,303 2.3%

TOTAL 3,825 26,591 14.4%

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Michigan Shipments of NECC MPALot Number Michigan (mLs) Nationwide (mLs)1 MI % of Nation

05212012 1,125 11,622 9.7%

06292012 2,600 10,665 24.4%

08102012 100 4,303 2.3%

TOTAL 3,825 26,591 14.4%

1Smith et al. “Fungal Infections Associated with Contaminated Methylprednisolone Injections – Preliminary Report”. New England Journal of Medicine. 2012.

•Preliminary data analysis indicated lot 06292012 had the highest attack rate of the three recalled lots1,2

2Kainer et al. “Fungal Infections Associated with Contaminated Methylprednisolone in Tennessee”. New England Journal of Medicine 367(23):2194-203

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•Objectives:▫Explain patient’s exposure and evaluate individual for

current signs and symptoms of meningitis or localized infection

▫If the patient is symptomatic: Refer patient to receive immediate medical evaluation

▫If the patient is asymptomatic: Discuss signs and symptoms of disease Inform patients to receive immediate medical evaluation

if they experience symptoms in the future

▫Answer any other questions or concerns patients might have

Patient Notification

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•MDCH staff helped a Clinic A place phone calls on 10/6•MDCH and Local Health Department staff dispatched to

Clinic B from 10/8 to 10/10 to aid in contacting patients • Patients hard to reach by phone sent registered letter

Patient Notification

10/2 10/9 10/16 10/23 10/30 11/60

250

500

750

1000

1250

1500

1750

0.0%

20.0%

40.0%

60.0%

80.0%

100.0%

Michigan NECC Patient Notification Estimates

Num

ber o

f Pati

ents

Noti

fied

Perc

enta

ge o

f Pati

ents

Noti

fied

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Identifying and Counting Cases

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Case Definitions (http://www.cdc.gov/hai/outbreaks/clinicians/casedef_multistate_outbreak.html )

An individual potentially exposed to one of the three recalled lots of NECC MPA who meets one of the following criteria:

•Meningitis - Meningitis of unknown etiology

• Stroke - Posterior circulation stroke without a cardioembolic source and without documentation of a normal cerebrospinal fluid (CSF) profile

• Paraspinal Infection - Osteomyelitis, abscess or other infection (e.g., soft tissue infection), in the spinal or paraspinal structures at or near the site of injection

• Joint Infection - Osteomyelitis or worsening inflammatory arthritis of a peripheral joint (e.g., knee, shoulder, or ankle)

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•Case definitions are not mutually exclusive▫e.g. a patient could have both meningitis and a para-

spinal infection

•Cases were counted in the state where they received their injection▫e.g. Michigan residents who received NECC injections

in Indiana are counted as Indiana cases

•Deaths reported are from all causes among persons who meet at least one of the case definitions▫Deaths are not necessarily directly attributed to a

fungal infection or treatment complications

Case Identification(http://www.cdc.gov/hai/outbreaks/clinicians/casedef_multistate_outbreak.html )

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•Determination of infection was made by clinical teams, including neuroradiologists and infectious disease specialists, who interpreted findings in the context of patient signs and symptoms

•For example:▫Clinical judgment – determining what is an infectious

versus non-specific enhancement on MRI

▫Patient judgment – determining new or worsening pain beyond baseline

•MDCH counted cases, but did not ‘call’ cases

Case Identification (http://www.cdc.gov/hai/outbreaks/clinicians/casedef_multistate_outbreak.html )

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Epidemiology of Fungal Infections in Michigan

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Case Count (as of June 3rd, 2013 - http://www.cdc.gov/hai/outbreaks/meningitis-map-large.html)

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StateTotal Case

CountMeningitis

Only

Meningitis + Paraspinal/Spinal

Infection

Stroke w/out Lumbar Puncture

Only

Paraspinal/Spinal Infection only

Peripheral Joint Infection

Only

Paraspinal/Spinal Infection +

Peripheral Joint Infection

Deaths

Florida (FL) 25 22 1 1 1 0 0 5Georgia (GA) 1 1 0 0 0 0 0 0

Idaho (ID) 1 1 0 0 0 0 0 0Illinois (IL) 2 2 0 0 0 0 0 0

Indiana (IN) 88 30 17 1 40 0 0 11Maryland (MD) 26 23 1 0 2 0 0 3Michigan (MI) 264 23 44 2 168 25 2 16

Minnesota (MN) 12 10 0 0 2 0 0 1North Carolina (NC) 18 1 3 0 14 0 0 1

New Hampshire (NH) 14 9 0 0 0 5 0 0New Jersey (NJ) 51 30 11 0 9 1 0 0New York (NY) 1 0 0 0 1 0 0 0

Ohio (OH) 20 12 3 0 5 0 0 1Pennsylvania (PA) 1 1 0 0 0 0 0 0Rhode Island (RI) 3 1 1 0 1 0 0 0

South Carolina (SC) 3 2 0 0 1 0 0 0Tennessee (TN) 152 21 58 3 68 2 0 15

Texas (TX) 2 2 0 0 0 0 0 0Virginia (VA) 54 41 8 0 4 0 0 5

West Virginia (WV) 7 0 2 0 5 0 0 0

TOTAL 745 232 150 7 321 33 2 58*

Case Count (as of June 3rd, 2013 - http://www.cdc.gov/hai/outbreaks/meningitis-map-large.html)

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Case Count (as of June 3rd, 2013 - http://www.cdc.gov/hai/outbreaks/meningitis-map-large.html)

StateTotal Case

CountMeningitis

Only

Meningitis + Paraspinal/Spinal

Infection

Stroke w/out Lumbar Puncture

Only

Paraspinal/Spinal Infection only

Peripheral Joint Infection

Only

Paraspinal/Spinal Infection +

Peripheral Joint Infection

Deaths

Florida (FL) 25 22 1 1 1 0 0 5Georgia (GA) 1 1 0 0 0 0 0 0

Idaho (ID) 1 1 0 0 0 0 0 0Illinois (IL) 2 2 0 0 0 0 0 0

Indiana (IN) 88 30 17 1 40 0 0 11Maryland (MD) 26 23 1 0 2 0 0 3Michigan (MI) 264 23 44 2 168 25 2 16

Minnesota (MN) 12 10 0 0 2 0 0 1North Carolina (NC) 18 1 3 0 14 0 0 1

New Hampshire (NH) 14 9 0 0 0 5 0 0New Jersey (NJ) 51 30 11 0 9 1 0 0New York (NY) 1 0 0 0 1 0 0 0

Ohio (OH) 20 12 3 0 5 0 0 1Pennsylvania (PA) 1 1 0 0 0 0 0 0Rhode Island (RI) 3 1 1 0 1 0 0 0

South Carolina (SC) 3 2 0 0 1 0 0 0Tennessee (TN) 152 21 58 3 68 2 0 15

Texas (TX) 2 2 0 0 0 0 0 0Virginia (VA) 54 41 8 0 4 0 0 5

West Virginia (WV) 7 0 2 0 5 0 0 0

TOTAL 745 232 150 7 321 33 2 58*

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Case Breakdown

a 16 deaths among persons meeting one of the case definitionsb 83 (31.8%) cases laboratory confirmed by culture, histopathology or molecular assay

239%

4417%

21%

16864%

259%

21%

Michigan Fungal Infections be Case Definition (n=264a,b)

Meningitis Only

Meningitis + Paraspinal/Spinal Infection

Stroke w/out Lumbar Puncture Only

Paraspinal/Spinal Infection only

Peripheral Joint Infection Only

Paraspinal/Spinal Infection + Peripheral Joint Infection

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Case Count (as of June 3rd, 2013 - http://www.cdc.gov/hai/outbreaks/meningitis-map-large.html)

Total Case Count

Peripheral Joint Infection Only

Paraspinal/Spinal Infection only

Meningitis (with or without other infection)

0 100 200 300 400 500 600 700 800

MichiganNationwide

Deaths

0 10 20 30 40 50 60 70

29

239%

4417%

21%

16864%

259%

21%

Meningitis OnlyMeningitis + Paraspinal/Spinal InfectionStroke w/out Lumbar Puncture OnlyParaspinal/Spinal Infection onlyPeripheral Joint Infection OnlyParaspinal/Spinal Infection + Peripheral Joint Infection

4177%

815%

48%

MichiganN=264

VirginiaN=54

Case Breakdown

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13.3%

86.7%

Patients Exposed1 Patients Infected

Michigan Nationwide

Case Count (as of June 3rd, 2013 - http://www.cdc.gov/hai/outbreaks/meningitis-map-large.html)

1Smith et al. “Fungal Infections Associated with Contaminated Methylprednisolone Injections – Preliminary Report”. New England Journal of Medicine. 2012.

35.4%

64.6%

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Epi Curve

• Change in case presentation from meningitis to primarily para-spinal infections around late October prompted one hospital to recommend screening MRIs for all asymptomatic patients potentially exposed at Clinic A

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Screening MRIs•Approach initiated by a single Michigan hospital

•414 asymptomatic patients targeted as part of outreach▫Preliminary data on 292 patients who received MRI

screens

66%

16%

18%

Preliminary Results on Screening MRIs (n=292)

Normal

Equivocal

Abnormal

Represents approximately 50 patients who may not have been otherwiseidentified

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Infection Timeline

N=5 N=41

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Infection Timeline

N=73 N=214

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Infection Timeline

N=255

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Case Demographics

Age (n=264)Median 66

Range 28-89

Sex (n=264)Female 154 58.3 %

Male 110 41.7 %

Race (n=264)American Indian / Alaskan Native 1 0.4 %

Asian 1 0.4 %

Black / African American 4 1.5 %

Caucasian 247 93.6 %

Unknown 11 4.2 %

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Clinic Attack RatesLocation Recalled Product Received Exposures* Infections

Lot Number

Amount (vials) Product Patients Cases Attack

Rate

Clinic A 06292012 400 MPA 80mg/mL – 5mL 638 212 33.2 %

Clinic B05212012 1,000 MPA 80mg/mL – 1mL

1,032 52 5.0 %06292012 500 MPA 80mg/mL – 1mL

Clinic C

05212012 100 MPA 80mg/mL – 1mL

102 0 0.0 %06292012 100 MPA 80mg/mL – 1mL

08102012 100 MPA 80mg/mL – 1mL

Clinic D 05212012 25 MPA 80mg/mL – 1mL 32 0 0.0 %

MI Total 2,225 1,804 264 14.6 %

Nationwide 26,5911 13,5342 7453 5.5 %

1Smith et al. “Fungal Infections Associated with Contaminated Methylprednisolone Injections – Preliminary Report”. New England Journal of Medicine. 2012. 2http://www.cdc.gov/hai/outbreaks/infographic.html 3http://www.cdc.gov/hai/outbreaks/meningitis-map-large.html

*Estimates

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Location Recalled Product Received Exposures* Infections

Lot Number

Amount (vials) Product Patients Cases Attack

Rate

Clinic A 06292012 400 MPA 80mg/mL – 5mL 638 212 33.2 %

Clinic B05212012 1,000 MPA 80mg/mL – 1mL

1,032 52 5.0 %06292012 500 MPA 80mg/mL – 1mL

Clinic C

05212012 100 MPA 80mg/mL – 1mL

102 0 0.0 %06292012 100 MPA 80mg/mL – 1mL

08102012 100 MPA 80mg/mL – 1mL

Clinic D 05212012 25 MPA 80mg/mL – 1mL 32 0 0.0 %

MI Total 2,225 1,804 264 14.6 %

Nationwide 26,5911 13,5342 7453 5.5 %

1Smith et al. “Fungal Infections Associated with Contaminated Methylprednisolone Injections – Preliminary Report”. New England Journal of Medicine. 2012. 2http://www.cdc.gov/hai/outbreaks/infographic.html 3http://www.cdc.gov/hai/outbreaks/meningitis-map-large.html

Clinic Attack Rates

*Estimates

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•Michigan had the highest number of potentially exposed patients1

•Michigan received a disproportionate amount of the 06292012 ‘Hot Lot’

•Potentially higher contamination in 5mL vials of MPA?

•Enhanced surveillance and MRI screenings may have identified cases that might have otherwise been missed

Factors contributing to burden of cases in Michigan

1Smith et al. “Fungal Infections Associated with Contaminated Methylprednisolone Injections – Preliminary Report”. New England Journal of Medicine. 2012.

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Summary

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Contributions from MDCH•MDCH dedicated ~4,000 hours during the first three

months of the outbreak (equivalent of two FTEs)

•Case report form completion – over 10,000 pages of hospitalization information from fungal cases abstracted from medical records sent to CDC:▫264 case report forms, each a minimum of 27 pages in

length – totaling ~7,128 pages▫277 additional admission case report forms, each a

minimum of 12 pages in length – totaling ~3,324 pages

•Sharing information to help inform national guidelines and recommendations

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•Providing hospital assistance and support clinical decision making:

▫MDCH Certificates of Need through Licensing and Regulatory Affairs Allowed hospital to obtain an additional mobile MRI Allowed hospital to open an additional operating suite

▫Redirected patients to hospitals with lower burden of infected patients

▫Assisted with staffing augmentation at overburdened facilities FEP Volunteer Management expedited out-of-state nurse

licensure

Contributions from MDCH

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•Facilitated patient notification which led to early diagnosis and treatment

Contributions from MDCH

http://www.cdc.gov/hai/outbreaks/infographic.html

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Thanks!

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Questions?