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Meningitis: Risk Factors Emerge, Cases Top 420

On Behalf of | Nov 8, 2012 | Fungal Meningitis

The first analysis of a large number of patients in the continuing fungal meningitis outbreak — which has now sickened 424 — offers clues to why some became ill and others did not.

Exposure to one lot of the tainted steroid — the so-called 06 lot — was associated with a fourfold increase in risk, compared with exposure to one of the other two lots implicated in the outbreak, according to Marion Kainer, MBBS, of the Tennessee Department of Health in Nashville, and colleagues.

Other risk factors include higher doses of the steroid, multiple procedures, the use of older vials of lot 06, and a translaminar approach to epidural glucocorticoid injection, Kainer and colleagues reported online in the New England Journal of Medicine.

The analysis is based on the first 66 patients in Tennessee, including the man in his 50s who became the index case for the outbreak, which has now sickened 424 people in 19 states, and claimed 31 lives.

The outbreak is being blamed on fungal contamination of three lots of preservative-free methylprednisolone acetate, made by the New England Compounding Center in Framingham Mass., and shipped to pain clinics in 23 states.

The steroid was most commonly given via epidural or paraspinal injection to control chronic pain, and the CDC says that use has been linked to 414 cases of disease — mainly fungal meningitis, but including posterior circulation stroke, spinal osteomyelitis, or epidural abscess — as well as all 31 deaths.

The tainted steroid was occasionally injected into peripheral joints and has been linked to 10 infections, but no deaths, the CDC says.

None of the 66 patients in the current analysis — those who met the case definition up to Oct. 19 — had peripheral joint infections, Kainer and colleagues reported.

Instead, 73% had meningitis alone, 15% had either the cauda equine syndrome or focal infection, and 12% had a posterior circulation stroke with or without meningitis.

All 66 had been patients at one of three pain clinics in the state, where a total of 1,009 people had been given the tainted steroid. Kainer and colleagues reported:

  • Median age was 69, with a range from 23 to 91
  • 71% were women
  • The 66 patients had 124 procedures between July 3 and Sept. 26, including 110 lumbar epidural injections, 12 cervical epidural injections, 1 sacroiliac-joint injection, and 1 recorded as “other”
  • Median time from the last injection to symptom onset was 18 days, with a range from 0 to 56
  • 8 of the 66 died, including 7 of the 13 who had a stroke. The eighth was a patient with meningitis who developed fatal paroxysmal atrial fibrillation
  • 61 were treated initially with voriconazole (Vfend) and 35 were also treated with liposomal amphotericin B

The researchers conducted a cohort analysis of all patients treated at the clinic where most of the steroid was used – dubbed Clinic A – in order to tease out risk factors, Kainer and colleagues reported.

All told, 817 people had a total of 1,335 procedures at Clinic A between July 1 and Sept. 20, but 124 did not receive methylprednisolone acetate. No case patients were among the group that did not get the steroid, the researchers reported.

Univariate analysis showed:

  • Patients who had multiple procedures had nearly a threefold increased risk of a fungal infection (RR 2.9, 95% CI 1.7 to 5.0)
  • Attack rates were 5% among those who had one procedure, 8.4% in those who had two procedures, 13.7% with three procedures, and 14.3% with four
  • Those who been given the drug with a translaminar approach were more than twice as likely to develop fungal infection as those who were never treated that way (RR 2.5, 95% CI 1.3 to 4.8)
  • Women were nearly twice as likely as men to develop infection (RR 1.9, 95% CI 1.1 to 3.4)
  • Age also played a role: those older than 60 were four times as likely to become case patients as those 60 or younger (RR 4.1, 95% CI 2.1 to 7.7)

The researchers also reported significant risk associated with the use of steroid from lot [email protected] – the 06 lot – compared with drug from lots [email protected] or [email protected]

Specifically, infections developed in 51 of the 424 patients who got methylprednisolone acetate from the 06 lot, versus 7 of 231 who had injections from one of the other lots (RR 4.0 95% CI 1.8 to 8.6).

Within the group who got lot 06 injections, attack rates were higher the older the vial, the researchers reported — 29 of 149 patients, or 19%, who got methylprednisolone from vials older than 50 days developed infection, versus 6 of 190, or 3%, whose injections came from newer vials.

Kainer and colleagues noted that more rapid treatment appeared to reduce the risk of death. All eight of the fatal cases were early in the outbreak and had “delayed, minimal, or no treatment.”

The researchers cautioned that estimates of risk might change over time, since the outbreak is continuing. Indeed, Tennessee now has 79 reported cases, according to the CDC.

They also noted that laboratory confirmation of fungal infection exists for only 22 patients.

The index patient had a culture-confirmed infection with Aspergillus fumigatus and the remaining 21 were infected with Exserohilum rostratum. But of that group, only six confirmations came from culture; the CDC determined the remainder using an investigational method whose sensitivity is not known.

Kainer and colleagues also cautioned that long-term outcome data are not yet available and the clinical status of patients — including complications — is still changing.

Primary source: New England Journal of Medicine
Source reference:
Kainer MA, et al “Fungal infections associated with contaminated methylprednisolone in Tennessee” N Engl J Med 2012; DOI: 10.1056/NEJMoa1212972.

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