Successful Treatment of a Balamuthia mandrillaris Cerebral Abscess in a Pediatric Patient With Complete Surgical Resection and Antimicrobial Therapy

Cuoco, Joshua A.; Klein, Brendan J.; LeBel, David P.; Faulhaber, Jason; Apfel, Lisa S.; Witcher, Mark R.

doi:10.1097/inf.0000000000003418

Cited by 6 publications

(4 citation statements)

References 10 publications

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“…A previous study examined the effects of the conjugation of amphotericin B on N. fowleri, revealing encouraging results; however, in this study, silver nanoparticles were utilized for the conjugation, and the cytotoxicity of the compounds alone was not evaluated [ 8 ]. Furthermore, until now, conjugated curcumin and amphotericin B have not been evaluated on B. mandrillaris , for which the number of reported cases is evident [ 45 , 46 , 47 ]. The nanocarriers utilized in this study also revealed greater drug loading efficiency, thus showing their capability for higher drug release to the desired target site [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Nanocarrier Drug Conjugates Exhibit Potent Anti-Naegleria fowleri and Anti-Balamuthia mandrillaris Properties

et al. 2023

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Given the opportunity and access, pathogenic protists (Balamuthia mandrillaris and Naegleria fowleri) can produce fatal infections involving the central nervous system. In the absence of effective treatments, there is a need to either develop new antimicrobials or enhance the efficacy of existing compounds. Nanocarriers as drug delivery systems are gaining increasing attention in the treatment of parasitic infections. In this study, novel nanocarriers conjugated with amphotericin B and curcumin were evaluated for anti-amoebic efficacy against B. mandrillaris and N. fowleri. The results showed that nanocarrier conjugated amphotericin B exhibited enhanced cidal properties against both amoebae tested compared with the drug alone. Similarly, nanocarrier conjugated curcumin exhibited up to 75% cidal effects versus approx. 50% cidal effects for curcumin alone. Cytopathogenicity assays revealed that the pre-treatment of both parasites with nanoformulated-drugs reduced parasite-mediated host cellular death compared with the drugs alone. Importantly, the cytotoxic effects of amphotericin B on human cells alone were reduced when conjugated with nanocarriers. These are promising findings and further suggest the need to explore nanocarriers as a means to deliver medicine against parasitic infections.

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Section: Discussionmentioning

confidence: 99%

Nanocarrier Drug Conjugates Exhibit Potent Anti-Naegleria fowleri and Anti-Balamuthia mandrillaris Properties

et al. 2023

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“…4 A small proportion of patients were diagnosed by CSF analysis or skin biopsy. We have summarized previous reports of B. mandrillaris encephalitis survivors 5,[11][12][13][14][15][16][17][18][19][20][21][22][23][24] (Table 2). Most of the survivors were diagnosed by early brain biopsy within 1 week of admission or by biopsy of preceding skin lesions.…”

Section: Discussionmentioning

confidence: 99%

Balamuthia mandrillarisamoebic encephalitis mimicking tuberculous meningitis

et al. 2023

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A 76‐year‐old female with no apparent immunosuppressive conditions and no history of exposure to freshwater and international travel presented with headache and nausea 3 weeks before the presentation. On admission, her consciousness was E4V4V6. Cerebrospinal fluid analysis showed pleocytosis with mononuclear cell predominance, elevated protein, and decreased glucose. Despite antibiotic and antiviral therapy, her consciousness and neck stiffness gradually worsened, right eye‐movement restriction appeared, and the right direct light reflex became absent. Brain magnetic resonance imaging revealed hydrocephalus in the inferior horn of the left lateral ventricle and meningeal enhancement around the brainstem and cerebellum. Tuberculous meningitis was suspected, and pyrazinamide, ethambutol, rifampicin, isoniazid, and dexamethasone were started. In addition, endoscopic biopsy was performed from the white matter around the inferior horn of the left lateral ventricle to exclude brain tumor. A brain biopsy specimen revealed eosinophilic round cytoplasm with vacuoles around blood vessels, and we diagnosed with amoebic encephalitis. We started azithromycin, flucytosine, rifampicin, and fluconazole, but her symptoms did not improve. She died 42 days after admission. In autopsy, the brain had not retained its structure due to autolysis. Hematoxylin and eosin staining of her brain biopsy specimen showed numerous amoebic cysts in the perivascular brain tissue. Analysis of the 16S ribosomal RNA region of amoebas from brain biopsy and autopsy specimens revealed a sequence consistent with Balamuthia mandrillaris. Amoebic meningoencephalitis can present with features characteristic of tuberculous meningitis, such as cranial nerve palsies, hydrocephalus, and basal meningeal enhancement. Difficulties in diagnosing amoebic meningoencephalitis are attributed to the following factors: (1) excluding tuberculous meningitis by microbial testing is difficult, (2) amoebic meningoencephalitis has low incidence and can occur without obvious exposure history, (3) invasive brain biopsy is essential in diagnosing amoebic meningoencephalitis. We should recognize the possibility of amoebic meningoencephalitis when evidence of tuberculosis meningitis cannot be demonstrated.

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“…Importantly, there is no specific drug targeting B. mandrillaris . Current treatments for GAE rely primarily on trial combinations of antimicrobial and antifungal drugs, resulting in variations in clinical outcomes ( Doyle et al, 2011 ; Cuoco et al, 2022 ). Thus, the development of more effective drugs remains a topic of intensive research ( Phan et al, 2021 ; Ferrins et al, 2023 ).…”

Section: Introductionmentioning

confidence: 99%

Phenotypic assay for cytotoxicity assessment of Balamuthia mandrillaris against human neurospheroids

Whangviboonkij,

Pengsart,

Chen

et al. 2023

Front. Microbiol.

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IntroductionThe phenotypic screening of drugs against Balamuthia mandrillaris, a neuropathogenic amoeba, involves two simultaneous phases: an initial step to test amoebicidal activity followed by an assay for cytotoxicity to host cells. The emergence of three-dimensional (3D) cell cultures has provided a more physiologically relevant model than traditional 2D cell culture for studying the pathogenicity of B. mandrillaris. However, the measurement of ATP, a critical indicator of cell viability, is complicated by the overgrowth of B. mandrillaris in coculture with host cells during drug screening, making it challenging to differentiate between amoebicidal activity and drug toxicity to human cells.MethodsTo address this limitation, we introduce a novel assay that utilizes three-dimensional hanging spheroid plates (3DHSPs) to evaluate both activities simultaneously on a single platform.Results and discussionOur study showed that the incubation of neurospheroids with clinically isolated B. mandrillaris trophozoites resulted in a loss of neurospheroid integrity, while the ATP levels in the neurospheroids decreased over time, indicating decreased host cell viability. Conversely, ATP levels in isolated trophozoites increased, indicating active parasite metabolism. Our findings suggest that the 3DHSP-based assay can serve as an endpoint for the phenotypic screening of drugs against B. mandrillaris, providing a more efficient and accurate approach for evaluating both parasite cytotoxicity and viability.

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Successful Treatment of a Balamuthia mandrillaris Cerebral Abscess in a Pediatric Patient With Complete Surgical Resection and Antimicrobial Therapy

Cited by 6 publications

References 10 publications

Nanocarrier Drug Conjugates Exhibit Potent Anti-Naegleria fowleri and Anti-Balamuthia mandrillaris Properties

Nanocarrier Drug Conjugates Exhibit Potent Anti-Naegleria fowleri and Anti-Balamuthia mandrillaris Properties

Balamuthia mandrillarisamoebic encephalitis mimicking tuberculous meningitis

Phenotypic assay for cytotoxicity assessment of Balamuthia mandrillaris against human neurospheroids

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