Assessment of blood-brain barrier penetration of miltefosine used to treat a fatal case of granulomatous amebic encephalitis possibly caused by an unusual Balamuthia mandrillaris strain.

Balamuthia mandrillaris, a free-living ameba, causes rare but frequently fatal granulomatous amebic encephalitis (GAE). Few patients have survived after receiving experimental drug combinations, with or without brain lesion excisions. Some GAE survivors have been treated with a multi-drug regimen including miltefosine, an investigational anti-leishmanial agent with in vitro amebacidal activity. Miltefosine dosing for GAE has been based on leishmaniasis dosing because no data exist in humans concerning its pharmacologic distribution in the central nervous system. We describe results of limited cerebrospinal fluid (CSF) and serum drug level testing performed during clinical management of a child with fatal GAE who was treated with a multiple drug regimen including miltefosine. Brain biopsy specimens, CSF, and sera were tested for B. mandrillaris using multiple techniques, including culture, real-time polymerase chain reaction, immunohistochemical techniques, and serology. CSF and serum miltefosine levels were determined using a liquid chromatography method coupled to tandem mass spectrometry. The CSF miltefosine concentration on hospital admission day 12 was 0.4 µg/mL. The serum miltefosine concentration on day 37, about 80 h post-miltefosine treatment, was 15.3 µg/mL. These are the first results confirming some blood-brain barrier penetration by miltefosine in a human, although with low-level CSF accumulation. Further evaluation of brain parenchyma penetration is required to determine optimal miltefosine dosing for Balamuthia GAE, balanced with the drug's toxicity profile. Additionally, the Balamuthia isolate was evaluated by real-time polymerase chain reaction (PCR), demonstrating genetic variability in 18S ribosomal RNA (18S rRNA) sequences and possibly signaling the first identification of multiple Balamuthia strains with varying pathogenicities.

A national outbreak of Ralstonia mannitolilytica associated with use of a contaminated oxygen-delivery device among pediatric patients.

OBJECTIVES: In August 2005, the Centers for Disease Control and Prevention was notified of a Ralstonia species outbreak among pediatric patients receiving supplemental oxygen therapy with the Vapotherm 2000i (Vapotherm, Inc, Stevensville, MD). The Vapotherm 2000i is a reusable medical device that was used in >900 hospitals in the United States in 2005. Ralstonia are waterborne bacilli that have been implicated in hospital-acquired infections. We initiated an investigation to determine the source of the outbreak and implement infection control and prevention measures. PATIENTS AND METHODS: We performed a case-control study at 1 hospital and conducted national case findings to obtain clinical and environmental samples for laboratory analysis. Case-patients had health care-acquired Ralstonia colonization or infection. Isolates were compared by using pulsed-field gel electrophoresis. We tested manufacturer-recommended disinfection protocols for the Vapotherm 2000i under simulated-use conditions. RESULTS: Case-patients at the hospital (n = 5) were more likely to have received Vapotherm therapy than controls. Nationally, Ralstonia mannitolilytica was confirmed in 38 patients (aged 5 days to 7 years); 35 (92%) of the patients were exposed to the Vapotherm 2000i before recovery of the organism. Pulsed-field gel electrophoresis showed related R. mannitolilytica strains from isolates sent from 18 hospitals in 12 states. A Vapotherm machine reprocessed with a protocol proposed by the manufacturer grew Ralstonia spp after 7 days of simulated use. In December 2005, Vapotherm recalled the 2000i. CONCLUSIONS: Our findings suggest intrinsic contamination of Vapotherm devices with Ralstonia spp. New medical devices may provide therapy equivalent to current devices yet pose novel reprocessing challenges.