BETHESDA, MD 15 Nov 2012—Pharmacists involved in the care of patients with fungal meningitis say both clinical and administrative issues are important in the response to the outbreak.
Before the infections were linked to tainted injectable medications made by the New England Compounding Center (NECC) of Framingham, Massachusetts, no one knew what was making the patients sick.
"Initially, just trying to figure out what was wrong with these patients—that was really the hard time [for us]," said Mark Sullivan, director of pharmacy operations at Vanderbilt University Medical Center in Nashville, Tennessee.
The medical center was the treatment site of the first patient with fungal meningitis identified during the outbreak. According to a report in the October 19 New England Journal of Medicine, the 50-year-old index patient had neutrophilic meningitis, a condition that is usually caused by bacterial infection but, in this case, did not respond to broad-spectrum antimicrobial therapy.
David Gregory, the medical center's director for education, research, and clinical pharmacy services, credited an astute physician with ordering a test that confirmed the presence of a fungus in the index patient's cerebrospinal fluid.
The patient was one of thousands across the nation who were treated with methylprednisolone acetate injection made by NECC. FDA in October confirmed the presence of fungi in unopened vials of the corticosteroid medication and described unsanitary conditions at NECC.
All NECC-made products have been recalled.
Treatment. Sullivan said Vanderbilt has been following treatment recommendations from the Centers for Disease Control and Prevention (CDC), guidance that has evolved over the course of the outbreak. CDC initially recommended high-dose therapy with both voriconazole and liposomal amphotericin B but later said voriconazole monotherapy is probably effective for patients who are not seriously ill.
Vanderbilt's antimicrobial stewardship and therapeutic drug monitoring pharmacists work closely with other clinicians to provide the most appropriate therapy. Gregory said the treatment regimen—usually voriconazole—is guided by drug-sensitivity test results as well as the patient's renal and hepatic function and other factors.
A similar process is in place at St. Joseph Mercy Health System (SJMHS) in Michigan, said Chris Cook, pharmacy director for the Ann Arbor and Livingston hospitals.
"We have a dedicated 24-hour pharmacist that looks at every one of these patients," Cook said. "They follow up on all dosing. And the pharmacy develops all the doses based on voriconazole levels, based on toxicities, upon heart, kidney, liver—all the organ functions, to make sure it's appropriate."
He said the higher-than-normal dosages of voriconazole and liposomal amphotericin B that are needed to fight the fungus make it critical to closely monitor how well patients tolerate the therapy.
"Those drugs are tough to handle," Cook said. "They're hard to monitor, and you have to monitor them."
Cook estimated that nearly 70 patients with meningitis or joint infections related to the outbreak had received care at SJMHS through late October.
"Clinical pharmacy is very heavily involved in every one of these patients," Cook said.
One of the biggest jobs for clinical pharmacists at SJMHS has been developing and updating treatment algorithms for the health system's electronic medical record and computerized prescriber-order-entry system.
SJMHS has also set up an outpatient clinic for patients who have been discharged from the hospital as well as those in the community who received tainted injections. Cook said pharmacists spend four hours a day at the clinic and may ultimately help care for more than 600 patients affected by the outbreak.
CDC said in October that most infections have been evident, on average, about six weeks after the patient was treated with NECC-made methylprednisolone; this raised optimism at the time that the end of the outbreak was in sight.
"That's heartening, given what we've dealt with in the last three weeks," Sullivan said in late October.
But at SJMHS, Cook said, the discovery of the six-week window coincided with a new phenomenon—recrudescent symptoms in patients with meningitis or joint infections who had previously been discharged from the hospital on voriconazole monotherapy.
"The intensity of what we're doing went into a lull, but it's picking up again," Cook said. "For a while, we were trying to get as many people off of dual therapy as possible. But now we're starting to put people back on dual therapy."
He said about four or five patients had amphotericin B added back to their regimen the previous day and another four or five were expected to resume dual therapy imminently.
Uncertainty about the necessary duration of treatment has been an issue since the start of the outbreak, because the fungi causing the infections are not normally found in the human body. CDC recommends treating patients for at least three months, or even longer for patients with severe disease.
Staffing. Gregory said Vanderbilt, with its fairly small outbreak-related caseload, hasn't needed additional pharmacy staff to cope with the fungal infections.
That hasn't been the case at SJMHS.
"We had to increase our staff. We got approval from administration to increase some of our part-time people to temporary, full-time staff," Cook said.
He said additional pharmacy staff were needed for the outpatient clinic. And on the inpatient side, the demand for liposomal amphotericin B injection caused problems for the staff.
"It takes a long time to go into solution, and it really decreases the productivity of the inpatient staff," Cook said of the drug. "We actually had to bring in extra technicians and pharmacists so we could keep up with the demand for amphotericin."
Although public health officials have said that ample national supplies of amphotericin B and voriconazole are available, Cook worried that the situation will change if the outbreak continues. He said oral voriconazole is available only on allocation from his wholesaler, raising the question of whether large numbers of patients can be successfully managed on long-term treatment with the drug.
"If this extends for three months for everybody . . . is there going to be enough oral voriconazole?" he asked.
Looking ahead. The outbreak has brought home to pharmacy leadership the need to examine their policies on outsourcing and inhouse production of compounded drugs.
"I think that's the biggest thing that's hitting pharmacy" from the outbreak, Gregory said. He said Vanderbilt has brought inhouse some of the compounding work formerly done by Massachusetts-based Ameridose, a sister company of NECC and also a focus of the outbreak investigation. Ameridose recalled all of its products on October 31.
Sullivan said Vanderbilt's pharmacy administration team is spending a lot of time on efforts "to make sure we've got everything in place for anything in the future that we need to do to protect our patients."
Cook said SJMHS is also rethinking its relationships with compounding pharmacies.
"We've used NECC," he said. "We haven't had any steroid injections from NECC. But we've used [NECC] because compounding pharmacies do offer a niche," especially for medications that are in short supply.