Download Michigan Pain Clinics

Fungal Infections Associated with
Contaminated Methylprednisolone
Acetate in Michigan, 2012-2013
Joseph R. Coyle, MPH
Michigan Department of Community Health
Exserohilum rostratum
2
Acknowledgements
• Michigan Outbreak Response Team:
▫
▫
▫
▫
Brenda Brennan
Jim Collins
Joe Coyle
Jay Fiedler
▫
▫
▫
▫
▫
Jennie Finks
Shannon Johnson
Jevon McFadden
Mawuli Nyaku
Many others…
• Michigan Pain Clinics and Staff
• Michigan Hospitals- Administrators, Clinicians, IPs
• State Health Departments
• Centers for Disease Control and Prevention
3
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
4
Outline
Case Count October 8th, 2012
Case Count June 3rd, 2013
5
Outbreak Timeline
6
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)
7
Outbreak Timeline
• 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 (subacute meningitis with pleocytosis) with a common
exposure (NECC MPA)
8
Outbreak Timeline
• 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
9
Role of the Michigan Department
Community Health
10
MDCH Role
• 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
11
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
12
Michigan Pain Clinics
13
Michigan Pain Clinics
Location
Recalled Product Received
Lot Number
Clinic A
Clinic B
Clinic C
Clinic D
Amount
Product
Patients
Injections
638
759
1,032
1,668
102
114
32
40
1,804
2,581
06292012
400 vials
MPA 80mg/mL – 5mL PF
05212012
1,000 vials
MPA 80mg/mL – 1mL PF
06292012
500 vials
MPA 80mg/mL – 1mL PF
05212012
100 vials
MPA 80mg/mL – 1mL PF
06292012
100 vials
MPA 80mg/mL – 1mL PF
08102012
100 vials
MPA 80mg/mL – 1mL PF
05212012
25 vials
MPA 80mg/mL – 1mL PF
MI TOTAL
*Estimates
2,225 vials
Exposures*
14
Michigan Pain Clinics
Location
Recalled Product Received
Lot Number
Clinic A
Clinic B
Clinic C
Clinic D
Amount
Product
Patients
Injections
638
759
1,032
1,668
102
114
32
40
1,804
2,581
06292012
400 vials
MPA 80mg/mL – 5mL PF
05212012
1,000 vials
MPA 80mg/mL – 1mL PF
06292012
500 vials
MPA 80mg/mL – 1mL PF
05212012
100 vials
MPA 80mg/mL – 1mL PF
06292012
100 vials
MPA 80mg/mL – 1mL PF
08102012
100 vials
MPA 80mg/mL – 1mL PF
05212012
25 vials
MPA 80mg/mL – 1mL PF
MI TOTAL
*Estimates
2,225 vials
Exposures*
15
Michigan Shipments of NECC MPA
Lot 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%
16
Michigan Shipments of NECC MPA
Lot 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%
• Preliminary data analysis indicated lot 06292012 had
the highest attack rate of the three recalled lots1,2
1Smith
et al. “Fungal Infections Associated with Contaminated Methylprednisolone
Injections – Preliminary Report”. New England Journal of Medicine. 2012.
2Kainer et al. “Fungal Infections Associated with Contaminated Methylprednisolone
in Tennessee”. New England Journal of Medicine 367(23):2194-203
17
Patient Notification
• 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
18
Patient Notification
100.0%
1750
1500
80.0%
1250
60.0%
1000
750
40.0%
500
20.0%
250
0
0.0%
10/2
10/9
10/16
10/23
10/30
11/6
• 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
Percentage of Patients Notified
Number of Patients Notified
Michigan NECC Patient Notification Estimates
19
Identifying and Counting Cases
20
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)
21
Case Identification
(http://www.cdc.gov/hai/outbreaks/clinicians/casedef_multistate_outbreak.html )
• Case definitions are not mutually exclusive
▫ e.g. a patient could have both meningitis and a paraspinal 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
22
Case Identification
(http://www.cdc.gov/hai/outbreaks/clinicians/casedef_multistate_outbreak.html )
• 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
23
Epidemiology of Fungal
Infections in Michigan
24
Case Count
(as of June 3rd, 2013 - http://www.cdc.gov/hai/outbreaks/meningitis-map-large.html)
25
Case Count
(as of June 3rd, 2013 - http://www.cdc.gov/hai/outbreaks/meningitis-map-large.html)
State
Meningitis +
Stroke w/out
Peripheral
Total Case Meningitis
Paraspinal/Spinal
Paraspinal/Spinal Lumbar Puncture
Joint Infection
Count
Only
Infection only
Infection
Only
Only
Paraspinal/Spinal
Infection +
Peripheral Joint
Infection
Deaths
Florida (FL)
Georgia (GA)
Idaho (ID)
Illinois (IL)
Indiana (IN)
Maryland (MD)
Michigan (MI)
Minnesota (MN)
North Carolina (NC)
New Hampshire (NH)
New Jersey (NJ)
New York (NY)
Ohio (OH)
Pennsylvania (PA)
Rhode Island (RI)
South Carolina (SC)
Tennessee (TN)
Texas (TX)
Virginia (VA)
West Virginia (WV)
25
1
1
2
88
26
264
12
18
14
51
1
20
1
3
3
152
2
54
7
22
1
1
2
30
23
23
10
1
9
30
0
12
1
1
2
21
2
41
0
1
0
0
0
17
1
44
0
3
0
11
0
3
0
1
0
58
0
8
2
1
0
0
0
1
0
2
0
0
0
0
0
0
0
0
0
3
0
0
0
1
0
0
0
40
2
168
2
14
0
9
1
5
0
1
1
68
0
4
5
0
0
0
0
0
0
25
0
0
5
1
0
0
0
0
0
2
0
0
0
0
0
0
0
0
0
2
0
0
0
0
0
0
0
0
0
0
0
0
0
5
0
0
0
11
3
16
1
1
0
0
0
1
0
0
0
15
0
5
0
TOTAL
745
232
150
7
321
33
2
58*
26
Case Count
(as of June 3rd, 2013 - http://www.cdc.gov/hai/outbreaks/meningitis-map-large.html)
State
Meningitis +
Stroke w/out
Peripheral
Total Case Meningitis
Paraspinal/Spinal
Paraspinal/Spinal Lumbar Puncture
Joint Infection
Count
Only
Infection only
Infection
Only
Only
Paraspinal/Spinal
Infection +
Peripheral Joint
Infection
Deaths
Florida (FL)
Georgia (GA)
Idaho (ID)
Illinois (IL)
Indiana (IN)
Maryland (MD)
Michigan (MI)
Minnesota (MN)
North Carolina (NC)
New Hampshire (NH)
New Jersey (NJ)
New York (NY)
Ohio (OH)
Pennsylvania (PA)
Rhode Island (RI)
South Carolina (SC)
Tennessee (TN)
Texas (TX)
Virginia (VA)
West Virginia (WV)
25
1
1
2
88
26
264
12
18
14
51
1
20
1
3
3
152
2
54
7
22
1
1
2
30
23
23
10
1
9
30
0
12
1
1
2
21
2
41
0
1
0
0
0
17
1
44
0
3
0
11
0
3
0
1
0
58
0
8
2
1
0
0
0
1
0
2
0
0
0
0
0
0
0
0
0
3
0
0
0
1
0
0
0
40
2
168
2
14
0
9
1
5
0
1
1
68
0
4
5
0
0
0
0
0
0
25
0
0
5
1
0
0
0
0
0
2
0
0
0
0
0
0
0
0
0
2
0
0
0
0
0
0
0
0
0
0
0
0
0
5
0
0
0
11
3
16
1
1
0
0
0
1
0
0
0
15
0
5
0
TOTAL
745
232
150
7
321
33
2
58*
27
Case Breakdown
Michigan Fungal Infections be Case Definition (n=264a,b)
25
9%
2
1%
23
9%
Meningitis Only
44
17%
Meningitis + Paraspinal/Spinal
Infection
Stroke w/out Lumbar Puncture Only
2
1%
Paraspinal/Spinal Infection only
Peripheral Joint Infection Only
Paraspinal/Spinal Infection +
168
Peripheral Joint Infection
63%
a 16 deaths among persons meeting one of the case definitions
b 83 (31.8%) cases laboratory confirmed by culture, histopathology or molecular assay
28
Case Count
(as of June 3rd, 2013 - http://www.cdc.gov/hai/outbreaks/meningitis-map-large.html)
Meningitis (with or without other
infection)
Michigan
Nationwide
Paraspinal/Spinal Infection only
Peripheral Joint Infection Only
Total Case Count
0
100
200
300
400
500
600
700
800
60
70
Deaths
0
10
20
30
40
50
29
Case Breakdown
25
9%
2
1%
23
9%
Michigan
N=264
44
17%
4
0
8%
0%
0
0%
Virginia
N=54
8
15%
2
1%
168
63%
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
41
77%
30
Case Count
(as of June 3rd, 2013 - http://www.cdc.gov/hai/outbreaks/meningitis-map-large.html)
Patients Exposed1
Patients Infected
13.3%
35.4%
64.6%
86.7%
Michigan
1Smith
Nationwide
et al. “Fungal Infections Associated with Contaminated Methylprednisolone
Injections – Preliminary Report”. New England Journal of Medicine. 2012.
31
Epi Curve
• Change in case presentation from meningitis to primarily paraspinal infections around late October prompted one hospital to
recommend screening MRIs for all asymptomatic patients
potentially exposed at Clinic A
32
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
Preliminary Results on Screening MRIs (n=292)
16%
Normal
Equivocal
18%
Abnormal
66%
Represents approximately
50 patients who may not
have been otherwise
identified
33
Infection Timeline
N=5
N=41
34
Infection Timeline
N=73
N=214
35
Infection Timeline
N=255
36
Case Demographics
Age (n=264)
Median
66
Range
28-89
Sex (n=264)
Female
154
58.3 %
Male
110
41.7 %
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 %
Race (n=264)
37
Clinic Attack Rates
Location
Clinic A
Clinic B
Clinic C
Clinic D
Recalled Product Received
Lot
Number
Amount
(vials)
06292012
400
MPA 80mg/mL – 5mL
05212012
1,000
MPA 80mg/mL – 1mL
06292012
500
MPA 80mg/mL – 1mL
05212012
100
MPA 80mg/mL – 1mL
06292012
100
MPA 80mg/mL – 1mL
08102012
100
MPA 80mg/mL – 1mL
05212012
25
MPA 80mg/mL – 1mL
Product
Exposures*
Infections
Patients
Cases
Attack
Rate
638
212
33.2 %
1,032
52
5.0 %
102
0
0.0 %
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
*Estimates
3http://www.cdc.gov/hai/outbreaks/meningitis-map-large.html
38
Clinic Attack Rates
Location
Clinic A
Clinic B
Clinic C
Clinic D
Recalled Product Received
Lot
Number
Amount
(vials)
06292012
400
MPA 80mg/mL – 5mL
05212012
1,000
MPA 80mg/mL – 1mL
06292012
500
MPA 80mg/mL – 1mL
05212012
100
MPA 80mg/mL – 1mL
06292012
100
MPA 80mg/mL – 1mL
08102012
100
MPA 80mg/mL – 1mL
05212012
25
MPA 80mg/mL – 1mL
Product
Exposures*
Infections
Patients
Cases
Attack
Rate
638
212
33.2 %
1,032
52
5.0 %
102
0
0.0 %
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
*Estimates
3http://www.cdc.gov/hai/outbreaks/meningitis-map-large.html
39
Factors contributing to burden of
cases in Michigan
• 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
1Smith
et al. “Fungal Infections Associated with Contaminated Methylprednisolone Injections –
Preliminary Report”. New England Journal of Medicine. 2012.
40
Summary
41
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
42
Contributions from MDCH
• 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
43
Contributions from MDCH
• Facilitated patient notification which led to early
diagnosis and treatment
http://www.cdc.gov/hai/outbreaks/infographic.html
44
Thanks!
45
Questions?