Nov 13, 2012 (CIDRAP News) – Clinicians at a Virginia hospital that screened 172 patients who were exposed to contaminated injectable steroids provided an early snapshot yesterday of patients' clinical courses and more evidence that the organism is invasive, putting patients at risk for strokes.
Two Virginia clinics used the recalled methylprednisolone acetate injections that have been linked to a multistate fungal meningitis outbreak, and most of the 673 patients who were exposed to the drugs were screened at two of the state's hospitals. Researchers from one of the facilities published observations from their experience in the Annals of Internal Medicine.
In another outbreak-related development yesterday, the US Food and Drug Administration (FDA) released an inspection report of Ameridose, a second compounding pharmacy that hasn't been linked to the illnesses but had business ties to the firm that produced the tainted drugs.
Ameridose recalled all of its products on Oct 31 after an initial FDA inspection flagged problems, and the newly released inspection detailed some of the issues, such as a repeated failure to follow up on sterility test problems.
Tracking clinical courses
The Virginia group's work adds to a growing body of knowledge about the clinical course of the unusual infections and lessons learned from treating affected patients. On Nov 7 clinicians from Tennessee—where the first outbreak cases were identified—reported in the New England Journal of Medicine on their findings from the first 66 patients they treated.
So far 438 outbreak cases, including 32 deaths, have been reported from 19 states, according to the most recent update from the US Centers for Disease Control and Prevention (CDC). The contaminated injections were produced by New England Compounding Center (NECC) and were used as epidural treatment for back pain and as peripheral injections for joint problems.
On Oct 4 after federal officials sent an urgent warning about the infections to clinicians, the Virginia hospital set up a hotline to field calls from the public and health providers and established a protocol for screening patients who were exposed to the tainted injections and sought evaluation and care in the emergency department.
Of 172 patients who were seen in the emergency department, 131 underwent lumbar puncture, and of that group, 25 patients met the meningitis case definition. The mean incubation period was 23 days, with a median of 19 days.
Two other patients linked to the outbreak were seen at the hospital but not included in the case series. One of those was admitted moribund with a subarachnoid hemorrhage and wasn't diagnosed until after death, and the other was transferred from another facility but died from a stroke on the day of admission.
All 25 patients had received at least one injection from one of the recalled lots, and two of them also received injections from one of the other two contaminated lots.
All of the 25 patients described the headaches as the worst they ever had. Brain imaging was done on 23 of the patients, with abnormal findings in 9 of the cases. Magnetic resonance imaging was done on 18 patients who reported severe back pain, and results showed that 9 had arachnoiditis and 1 had myelitis.
Clinicians started all 25 of the patients on intravenous voriconazole, but held off on coadministering amphotericin B because of the theoretical risk of antagonism. Five of seven patients with elevated transaminase levels were switched to amphotericin. Sixteen of the 25 patients experienced hallucinations during voriconazole therapy.
Fifteen of the patients are still undergoing voriconazole treatment. Patients who showed worsening clinical symptoms or other parameters were switched to amphotericin. The group observed that patients who were able to remain on voriconazole therapy were discharged more quickly than those who needed a treatment change.
Some of the patients have been transferred to rehabilitation facilities for physical therapy before returning home. The researchers noted that the patients' most common complaint is extreme fatigue.
They noted that recovery is slow but varies widely. "Many patients have improved to the point that their major complaint has become one of boredom as wary clinicians waited for better CSF [cerebrospinal fluid] parameters," the group wrote. "However, others remain very symptomatic, primarily with arachnoiditis and urinary retention, and three have had strokes."
Though initial treatment with voriconazole seems like a solid recommendation, close monitoring is needed, decisions need to be individualized, and other options for treatment need to be explored, the group said. They added that many questions are still unanswered, such as the recommended length of treatment and when patients are considered "cured."
Inspection report
Meanwhile, the FDA's investigation report of the Ameridose facility also found that the company failed to adequately investigate complaints about its products. The team also found that Ameridose didn't have procedures and controls for ensuring drug potency or purity. The 20-page report details 15 observations.
Inspectors also flagged several examples of equipment not being cleaned enough to prevent contamination, such as thick, different-colored residues on the intakes of hoods used in the drug preparation areas. They also found insects where finished products were stored and near where sterile products were being prepared.
See also:
Nov 12 Ann Intern Med report
Nov 12 FDA 483 inspection report on Ameridose
Nov 9 CDC outbreak update
Nov 7 CIDRAP News story "Meningitis outbreak investigators say quick work paid off"
