Disseminated Balamuthia mandrillaris Infection

Abstract

f Balamuthia mandrillaris is a rare cause of human infection, but when infections do occur, they result in high rates of morbidity and mortality. A case of disseminated Balamuthia infection is presented. Early diagnosis and initiation of recommended therapy are essential for increased chances of successful outcomes. CASE REPORTT he patient was an 82-year-old white male with a history of necrobiosis lipoidica versus granuloma annulare of the right hand who was admitted in April 2012 for acute onset of fevers, chills, nausea, vomiting, lethargy, and altered mental status (AMS). He initially presented to an outside-hospital emergency department with a temperature of 38.5°C, a heart rate of 97 beats per min, and oxygen saturation of 88% on room air. His oxygen saturation improved with administration of nasal cannula oxygen. A chest X-ray (CXR) procedure was performed and demonstrated findings concerning for granulomatous disease. Due to his condition, he was transferred to our tertiary care center for further evaluation and treatment.Per his family, he had been healthy and without complaints prior to his current presentation. For approximately 15 months, he had been treated by a dermatologist for skin lesions located on his right thigh and hand as well as left upper extremity (LUE) and abdomen. He had multiple skin biopsy specimens from the right hand, LUE, and right thigh with negative bacterial, acid-fast bacillus (AFB), and fungal analysis results. During this period of time, he took itraconazole for 3 months without clinical response and was thus started on prednisone. All lesions resolved except those on his right hand. He was treated with a 14-day course of doxycycline and cephalexin for possible cellulitis of the right hand prior to this admission. Previous workup included a negative syphilis screen and a normal angiotensin-converting enzyme (ACE) level (drawn for possible sarcoidosis). A CXR performed at that time revealed nonspecific interstitial changes.A review of the patient's symptoms was obtained from family members given the patient's AMS. Per their report, the patient reported a headache but no neck pain or stiffness. He had no history of mouth sores or genital ulcers and had a remote history of shingles. He had had an episode of bronchitis 1 month prior to admission (PTA) that was slow to improve but gradually resolved.In terms of exposures, he had no history of international travel but did have seawater exposure on the Gulf Coast of Alabama 1 month prior to admission. He had no pets but had been mowing grass and spreading grass seed PTA. He had no known tick bites but spent time outdoors using a metal detector for treasure hunting and digging in soil. Previously, he had taught a bible study group in a prison but had no known tuberculosis (TB) exposure and no previous TB testing.In an initial physical examination, he was febrile to 38.2°C and his oxygen saturation was 94% with 2 liters of oxygen administered using a nasal cannula. He was initially agitated and confused but progressed to somnolence o...

Functional Assessment of 2,177 U.S. and International Drugs Identifies the Quinoline Nitroxoline as a Potent Amoebicidal Agent against the Pathogen Balamuthia mandrillaris

“…While systematic ecological studies of B. mandrillaris have not been performed, free-living B. mandrillaris amoebae have been isolated from water, soil, and dust across all continents ( 10 – 18 ). Cases of human and animal infections are also reported on all continents but are most common in South America and the southern United States ( 19 – 35 ) (reviewed in references 31 , 32 , and 33 ). B. mandrillaris is thought to be transmitted by inhalation of contaminated aerosols or exposure via broken skin ( 36 ).…”

“…In vitro studies performed with the CDC-recommended drugs have shown little to no inhibition of amoebic growth by fluconazole, sulfadiazine, and flucytosine, while azithromycin, pentamidine isethionate, miltefosine, and voriconazole (a fluconazole derivative) exhibit amoebicidal or amoebistatic activity ( 11 , 42 , 51 ). Current treatments for B. mandrillaris CNS infections employing experimental combinations of these drugs have produced inconsistent outcomes, including survival in some cases and fatality in others ( 7 , 19 , 23 , 27 , 29 , 30 , 34 , 54 – 62 ). As the efficacy and specificity of current treatments remain uncertain, there is a clear need to identify additional drugs that can improve patient outcomes.…”

Repurposing the quinoline antibiotic nitroxoline to treat infections caused by the brain-eating amoebaBalamuthia mandrillaris

“…Because encystment appears to occur as a response to certain drug treatments, we also assessed the ability of each drug to inhibit the viability of pre-formed B. mandrillaris cysts. We Because there is no established treatment for GAE, patients commonly receive experimental combinations of antimicrobial agents in aggressive and prolonged treatment regimens with mixed outcomes (7,19,23,27,29,30,34,(53)(54)(55)(56)(57)(58)(59)(60)(61). In the present study, we aimed to address the critical need for new treatments of GAE by identifying novel amoebicidal compounds amongst known drugs using a high-throughput screening approach.…”

“…Laurie and White et al, Inhibition of Balamuthia mandrillaris by nitroxoline 6 sulfadiazine and flucytosine while azithromycin, pentamidine isethionate, miltefosine, and voriconazole (fluconazole derivative) exhibit amoebicidal or amoebistatic activity (11,41,50). Current treatments for B. mandrillaris CNS infections employing experimental combinations of these drugs have produced inconsistent outcomes including survival in some cases and fatality in others (7,19,23,27,29,30,34,(53)(54)(55)(56)(57)(58)(59)(60)(61). As the efficacy and specificity of current treatments remains uncertain, there is a clear need to identify additional drugs that can improve patient outcomes.…”

“…Cysts with little to no motility are observed outside the boundaries of tissues (Movie S2). While these findings are qualitative, the largescale differences in tissue morphology observed in this experiment are consistent with the possibility that nitroxoline has a protective effect towards host tissue in the context of B. mandrillaris infection.DiscussionGAE caused by Balamuthia mandrillaris is almost always fatal(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34).Laurie and White et al, Inhibition of Balamuthia mandrillaris by nitroxoline 21…”