amphotericin-b and Amebiasis

Pathogenic free-living amoebae (FLA), namely Acanthamoeba sp., Naegleria fowleri and Balamuthia mandrillaris are distributed worldwide. These neurotropic amoebae can cause fatal central nervous system (CNS) infections in humans. This review deals with the demographic characteristics, symptoms, diagnosis, and treatment outcomes of patients with CNS infections caused by FLA documented in India. There have been 42, 25, and 4 case reports of Acanthamoeba granulomatous amoebic encephalitis (GAE), N. fowleri primary amoebic meningoencephalitis (PAM), and B. mandrillaris meningoencephalitis (BAE), respectively. Overall, 17% of Acanthamoeba GAE patients and one of the four BAE patients had some form of immunosuppression, and more than half of the N. fowleri PAM cases had history of exposure to freshwater. Acanthamoeba GAE, PAM, and BAE were most commonly seen in males. Fever, headache, vomiting, seizures, and altered sensorium appear to be common symptoms in these patients. Some patients showed multiple lesions with edema, exudates or hydrocephalus in their brain CT/MRI. The cerebrospinal fluid (CSF) of these patients showed elevated protein and WBC levels. Direct microscopy of CSF was positive for amoebic trophozoites in 69% of Acanthamoeba GAE and 96% of PAM patients. One-fourth of the Acanthamoeba GAE and all the BAE patients were diagnosed only by histopathology following autopsy/biopsy samples. Twenty-one Acanthamoeba GAE survivors were treated with cotrimoxazole, rifampicin, and ketoconazole/amphotericin B, and all eleven PAM survivors were treated with amphotericin B alongside other drugs. A thorough search for these organisms in CNS samples is necessary to develop optimum treatment strategies.

Topics: Acanthamoeba; Amebiasis; Amoeba; Amphotericin B; Balamuthia mandrillaris; Central Nervous System Infections; Humans; Male

Disseminated acanthamoebiasis is a rare, often fatal, infection most commonly affecting immunocompromised patients. We report a case involving sinuses, skin, and bone in a 60-year-old woman 5 months after heart transplantation. She improved with a combination of flucytosine, fluconazole, miltefosine, and decreased immunosuppression. To our knowledge, this is the first case of successfully treated disseminated acanthamoebiasis in a heart transplant recipient and only the second successful use of miltefosine for this infection among solid organ transplant recipients. Acanthamoeba infection should be considered in transplant recipients with evidence of skin, central nervous system, and sinus infections that are unresponsive to antibiotics. Miltefosine may represent an effective component of a multidrug therapeutic regimen for the treatment of this amoebic infection.

Topics: Acanthamoeba; Amebiasis; Amebicides; Amphotericin B; Anti-Bacterial Agents; Antilymphocyte Serum; Biopsy; Cardiomyopathies; Drugs, Investigational; Endoscopy; Female; Fluconazole; Flucytosine; Heart Transplantation; Humans; Immunocompromised Host; Immunosuppressive Agents; Magnetic Resonance Imaging; Metacarpal Bones; Metronidazole; Middle Aged; Phosphorylcholine; Polymerase Chain Reaction; Radiography; Sinusitis; Skin

Primary amoebic meningoencephalitis (PAM) due to Naegleria fowleri was detected in a 36-year-old, Indian countryman who had a history of taking bath in the village pond. He was admitted in a semi comatosed condition with severe frontal headache, neck stiffness, intermittent fever, nausea, vomiting, left hemiparesis and seizures. Computerized tomography (CT) scan of brain showed a soft tissue non-enhancing mass with erosion of sphenoid sinus. However CSF findings showed no fungal or bacterial pathogen. Trophozoites of Naegleria fowleri were detected in the direct microscopic examination of CSF and these were grown in culture on non-nutrient agar. The patient was put on amphotericin-B, rifampicin and ceftazidime but his condition deteriorated and was taken home by his relatives in a moribund condition against medical advice and subsequently died. A literature review of 7 previous reports of PAM in India is also presented. Four of theses eight cases were non lethal. The mean age was 13.06 years with male: female ratio of 7:1. History of contact with water was present in four cases. Trophozoites could be identified in all 8 cases in this series.

Topics: Adult; Amebiasis; Amphotericin B; Animals; Ceftazidime; Central Nervous System Protozoal Infections; Cerebrospinal Fluid; Drug Therapy, Combination; Fatal Outcome; Humans; Male; Naegleria fowleri; Rifampin; Tomography, X-Ray Computed; Treatment Refusal

Topics: Amebiasis; Amphotericin B; Animals; Antifungal Agents; Brain; Humans; Meningoencephalitis; Miconazole; Naegleria fowleri; Prognosis

Primary amebic meningoencephalitis (PAM) is a rapidly progressive and potentially fatal infection frequently contracted by swimming in bodies of warm fresh water. The etiological agent in most reported cases of PAM is the ameboflagellate Naegleria fowleri. Infection with this organism closely mimics and is often mistaken for a bacterial or a viral pyogenic meningitis. Recovery is rare and depends on rapid diagnosis and treatment. Physicians treating individuals who present with an acute pyogenic meningitis should consider the diagnosis of PAM, particularly if the patient has a recent history of swimming in warm fresh water. We review the recent literature for cases of PAM and the discuss ecology of N. fowleri and the clinical presentation, diagnosis, and treatment of PAM.

Topics: Amebiasis; Amphotericin B; Animals; Central Nervous System Protozoal Infections; Fresh Water; Humans; Naegleria fowleri; Rifampin

Two children with primary amoebic meningoencephalitis secondary to Naegleria fowleri are reported. Both children died, and the causative agent was identified at autopsy. Presentation and outcome conformed to the usual course of primary amoebic meningoencephalitis and reaffirm the gravity and rapid progression of this infection. The epidemiology, microbiology, diagnostic considerations, and treatment are discussed. Primary amoebic meningoencephalitis should be considered in the differential diagnosis of children with meningitis or encephalitis.

Topics: Amebiasis; Amebicides; Amphotericin B; Animals; Arizona; Child; Fatal Outcome; Female; Humans; Infant; Meningoencephalitis; Naegleria fowleri

Primary amebic meningoencephalitis is a disease caused by the free-living amebae of the genera Naegleria or Acanthamoeba. The clinical course may result in death a few days after presentation or it may be insidious, with progressive neurologic deterioration and death after a chronic course. This article describes the organisms involved, the clinical course, pathology, diagnosis, and treatment of the disease.

Topics: Adolescent; Adrenal Cortex Hormones; Amebiasis; Amoeba; Amphotericin B; Blood; Cerebrospinal Fluid; Child; Female; Humans; Meningoencephalitis; Swimming Pools; Water Microbiology

Primary amoebic meningoencephalitis is a fulminant and rapidly fatal diseases which principally affects children and young adults. The causative organism is Naegleria fowleri, an amoebo-flagellate found in most soil and freshwater habitats. The portal of entry is the nasopharynx from which the amoeba makes its way into the brain by penetration of the olfactory mucosa and cribriform plate. Diagnosis should be suspected in all cases of purulent meningitis and meningoencephalitis in which bacteria are not evident in the cerebrospinal fluid. Diagnosis can be made by microscopic examination of a fresh specimen of cerebrospinal fluid, or a specimen strained with Wright's or Gram's stain. Combination chemotherapy with amphotericin B and tetracycline, or amphotericin B and rifamycin, by intravenous, intrathecal, and when possible, intraventricular instillation, may offer some hope of success. Preventive measures include constant surveillance of domestic water supplies and swimming pools for amoebic contamination, and education of the public to avoid swimming in contaminated areas.

Topics: Amebiasis; Amphotericin B; Humans; Meningoencephalitis; Tetracycline

Topics: Amebiasis; Amphotericin B; Brain; Cerebral Cortex; Cerebrospinal Fluid; Humans; Meningoencephalitis

Balamuthia mandrillaris and Naegleria fowleri are protist pathogens that can cause fatal infections. Despite mortality rate of > 90%, there is no effective therapy. Treatment remains problematic involving repurposed drugs, e.g., azoles, amphotericin B and miltefosine but requires early diagnosis. In addition to drug discovery, modifying existing drugs using nanotechnology offers promise in the development of therapeutic interventions against these parasitic infections. Herein, various drugs conjugated with nanoparticles were developed and evaluated for their antiprotozoal activities. Characterizations of the drugs' formulations were accomplished utilizing Fourier-transform infrared spectroscopy, efficiency of drug entrapment, polydispersity index, zeta potential, size, and surface morphology. The nanoconjugates were tested against human cells to determine their toxicity in vitro. The majority of drug nanoconjugates exhibited amoebicidal effects against B. mandrillaris and N. fowleri. Amphotericin B-, Sulfamethoxazole-, Metronidazole-based nanoconjugates are of interest since they exhibited significant amoebicidal effects against both parasites (p < 0.05). Furthermore, Sulfamethoxazole and Naproxen significantly diminished host cell death caused by B. mandrillaris by up to 70% (p < 0.05), while Amphotericin B-, Sulfamethoxazole-, Metronidazole-based drug nanoconjugates showed the highest reduction in host cell death caused by N. fowleri by up to 80%. When tested alone, all of the drug nanoconjugates tested in this study showed limited toxic effects against human cells in vitro (less than 20%). Although these are promising findings, prospective work is warranted to comprehend the mechanistic details of nanoconjugates versus amoebae as well as their in vivo testing, to develop antimicrobials against the devastating infections caused by these parasites.

Topics: Amebiasis; Amebicides; Amphotericin B; Balamuthia mandrillaris; Humans; Metronidazole; Naegleria fowleri; Nanoconjugates; Prospective Studies; Sulfamethoxazole

Primary amebic meningoencephalitis, caused by brain infection with a free-living ameba,

Topics: Amebiasis; Amphotericin B; Auranofin; Central Nervous System Protozoal Infections; Europe; Genotype; Humans; Naegleria fowleri

Infectious diseases are the leading cause of morbidity and mortality, killing more than 15 million people worldwide. This is despite our advances in antimicrobial chemotherapy and supportive care. Nanoparticles offer a promising technology to enhance drug efficacy and formation of effective vehicles for drug delivery. Here, we conjugated amphotericin B, nystatin (macrocyclic polyenes), and fluconazole (azole) with silver nanoparticles. Silver-conjugated drugs were synthesized successfully and characterized by ultraviolet-visible spectrophotometry, Fourier transform infrared spectroscopy, and atomic force microscopy. Conjugated and unconjugated drugs were tested against Acanthamoeba castellanii belonging to the T4 genotype using amoebicidal assay and host cell cytotoxicity assay. Viability assays revealed that silver nanoparticles conjugated with amphotericin B (Amp-AgNPs) and nystatin (Nys-AgNPs) exhibited significant antiamoebic properties compared with drugs alone or AgNPs alone (P < 0.05) as determined by Trypan blue exclusion assay. In contrast, conjugation of fluconazole with AgNPs had limited effect on its antiamoebic properties. Notably, AgNP-coated drugs inhibited amoebae-mediated host cell cytotoxicity as determined by measuring lactate dehydrogenase release. Overall, here we present the development of a new formulation of more effective antiamoebic agents based on AgNPs coated with drugs that hold promise for future applications.

Topics: Acanthamoeba castellanii; Amebiasis; Amebicides; Amphotericin B; Fluconazole; Humans; Metal Nanoparticles; Microscopy, Atomic Force; Nystatin; Silver; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared

The free-living amoeba (FLA) Acanthamoeba sp. is an opportunistic pathogen that can cause amoebic keratitis (AK) or granulomatous amoebic encephalitis (GAE). While current treatments of AK are long with some relapses, no consensus therapy has been developed for GAE remaining lethal in 90% of the cases. In this context, efficient antiacanthamoebal drugs have to be identified. In this work, 15 drugs used in the treatment of AK or GAE or in other parasitic diseases were evaluated for their in vitro activity on A. castellanii. Hexamidine, voriconazole and clotrimazole exhibited the highest activities with IC

Topics: Acanthamoeba castellanii; Acanthamoeba Keratitis; Amebiasis; Amphotericin B; Anti-Infective Agents; Benzamidines; Humans; Inhibitory Concentration 50; Parasitic Sensitivity Tests; Voriconazole

Primary amoebic meningoencephalitis (PAM) is a rare and almost always fatal disease that is caused by Naegleria fowleri, a freshwater thermophilic amoeba. Our case involves an adolescent female who presented with fever of unknown origin. A lumbar puncture was performed, and the Wright-Giemsa and Gram stained cerebrospinal fluid (CSF) cytospin slides showed numerous organisms. Experienced medical technologists in the microbiology and hematology laboratories identified the organisms as morphologically consistent with Naegleria species. The laboratory made a rapid diagnosis and alerted emergency department care providers within 75 minutes. The patient was treated for PAM with amphotericin, rifampin, azithromycin, fluconazole and aggressive supportive therapy including dexamethasone. The Centers for Disease Control and Prevention (CDC) was contacted, and miltefosine, an investigational medication, was started. Additional treatment included an intraventricular shunt and controlled hypothermia in order to mitigate potential cerebral edema. Our patient is a rare success story, as she was diagnosed swiftly, successfully treated, and survived PAM.

Topics: Amebiasis; Amphotericin B; Antiprotozoal Agents; Azithromycin; Central Nervous System Protozoal Infections; Cerebrospinal Fluid; Cerebrospinal Fluid Shunts; Child; Early Diagnosis; Female; Fluconazole; Humans; Hypothermia, Induced; Meningoencephalitis; Naegleria fowleri; Phosphorylcholine; Rifampin

Acanthamoeba infections are rare and mostly occur in immunocompromised patients. Most of the reported cases after stem cell transplantation have been diagnosed postmortem. We present the case of a 3-year-old boy with chronic graft versus host disease post hematopoietic transplantation, who was successfully treated for Acanthamoeba.

Topics: Acanthamoeba; Amebiasis; Amebicides; Amphotericin B; Child, Preschool; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Male; Nasal Mucosa; Sinusitis

Naegleria fowleri is a free living parasite which habitats in fresh water reservoirs. It causes a fatal nervous system infection known as primary amoebic meningoencephalitis by invading through cribriform plate of nose and gaining entry into brain. We report a case of primary amoebic meningoencephalitis caused by Naegleria fowleri in Karachi, Pakistan, in a 42 years old male poultry farm worker having no history of swimming. Clinical course was fulminant and death occurred within one week of hospital admission. Naegleria fowleri was detected by wet mount technique in the sample of cerebrospinal fluid collected by lumbar puncture of patient. This is a serious problem and requires immediate steps to prevent general population to get affected by this lethal neurological infection.

Topics: Adult; Amebiasis; Amebicides; Amphotericin B; Central Nervous System Protozoal Infections; Dexamethasone; Fatal Outcome; Glucocorticoids; Humans; Male; Naegleria fowleri; Pakistan

Primary amebic meningoencephalitis (PAM) is a rapidly fatal infection caused by the free-living ameba Naegleria fowleri. The drug of choice in treating PAM is the antifungal antibiotic amphotericin B, but its use is associated with severe adverse effects. Moreover, few patients treated with amphotericin B have survived PAM. Therefore, fast-acting and efficient drugs are urgently needed for the treatment of PAM. To facilitate drug screening for this pathogen, an automated, high-throughput screening methodology was developed and validated for the closely related species Naegleria gruberi. Five kinase inhibitors and an NF-kappaB inhibitor were hits identified in primary screens of three compound libraries. Most importantly for a preclinical drug discovery pipeline, we identified corifungin, a water-soluble polyene macrolide with a higher activity against Naegleria than that of amphotericin B. Transmission electron microscopy of N. fowleri trophozoites incubated with different concentrations of corifungin showed disruption of cytoplasmic and plasma membranes and alterations in mitochondria, followed by complete lysis of amebae. In vivo efficacy of corifungin in a mouse model of PAM was confirmed by an absence of detectable amebae in the brain and 100% survival of mice for 17 days postinfection for a single daily intraperitoneal dose of 9 mg/kg of body weight given for 10 days. The same dose of amphotericin B did not reduce ameba growth, and mouse survival was compromised. Based on these results, the U.S. FDA has approved orphan drug status for corifungin for the treatment of PAM.

Topics: Amebiasis; Aminoglycosides; Amphotericin B; Animals; Antiprotozoal Agents; Brain; Cell Membrane; Central Nervous System Protozoal Infections; Drug Administration Schedule; High-Throughput Screening Assays; Humans; Injections, Intraperitoneal; Macrolides; Mice; Microscopy, Electron, Transmission; Mitochondria; Naegleria; Naegleria fowleri; NF-kappa B; Protein Kinase Inhibitors; Protein Kinases; Small Molecule Libraries; Survival Rate; Trophozoites

To evaluate the disinfectant effect of methylene blue (MB)-mediated photodynamic therapy (PDT) on a pathogenic strain of Acanthamoeba.. Acanthamoeba castellanii (ATCC 50370) used in this study were treated under one of four experimental conditions: light irradiation and incubation in MB (L+M+), light irradiation and incubation in physiologic solution (L+M-), incubation in MB only (L-M+), and incubation in physiologic solution (L-M-). M+ trophozoites were incubated in either 0.25 or 0.5 mM MB for 10 minutes. L+ organisms were irradiated for 30 minutes following incubation in solution. A halogen lamp (660 ± 10 nm) with a maximum output of 6 mW/cm(2) was used as the PDT light source. After treatment, antiacanthamoeba activity was evaluated by checking the respiratory activity of the amoeba with 5-cyano-2,3-tetrazolium chloride (CTC) staining. We also determined whether the effect of PDT with MB had been retained or augmented when it was performed in combination with conventional antiamoebic agents.. MB-PDT suppressed the respiratory activity of trophozoites in an MB-concentration-dependent manner at total light doses of 10.8 J/cm(2). The respiratory activity of each group as a percentage of that of L-M- is as follows: L+M+ 11.6% (0.5 mM), 60.9% (0.25 mM); L-M+ 116.5% (0.5 mM), 105.5% (0.25 mM); L+M- 107.6%; and L-M- 106.3%. (L+M+ versus L-M- P < 0.05). MB-PDT had a synergistic effect when used in combination with polyhexamethylene biguanide (PHMB) or amphotericin B, but not with voriconazole.. MB-PDT is effective against Acanthamoeba in vitro and has synergistic effects with PHMB and amphotericin B.

Topics: Acanthamoeba castellanii; Amebiasis; Amebicides; Amphotericin B; Animals; Antifungal Agents; Drug Therapy, Combination; Enzyme Inhibitors; Guanidines; Humans; In Vitro Techniques; Keratitis; Methylene Blue; Mice; Mice, Inbred C57BL; Photochemotherapy; Photosensitizing Agents; Polymers; Pyrimidines; Riboflavin; Triazoles; Ultraviolet Therapy; Voriconazole

Amphotericin B was formulated as nanosuspensions to develop a nanoparticulate brain delivery system. Nanosuspensions were produced with different surfactant solutions by high-pressure homogenization and then characterized by laser diffractometry and photon correlation spectroscopy. Before in vitro and in vivo testing all nanosuspensions were investigated for protein adsorption by two-dimensional polyacrylamide gel electrophoresis to predict brain-targeting capacities. Selected nanosuspensions were tested for amebicidal activity against Balamuthia mandrillaris, an agent of lethal encephalitis. Our results indicate that nanosuspensions coated with polysorbate 80 and sodium cholate markedly increased drug brain delivery and inhibited the parasite in vitro, though less in vivo. From the clinical editor: The antifungal Amphotericin B was formulated as nanosuspensions to develop a nanoparticulate brain delivery system. The results indicate that nanosuspensions coated with polysorbate 80 and sodium cholate markedly increased drug brain delivery and inhibited the parasite in vitro, though less in vivo.

Topics: Amebiasis; Amebicides; Amoebozoa; Amphotericin B; Animals; Brain; Drug Delivery Systems; Female; Mice; Mice, Inbred C57BL; Nanostructures; Polysorbates

Naegleria fowleri is a ubiquitous, pathogenic free-living amoeba; it is the most virulent Naegleria species and causes primary amoebic meningoencephalitis (PAME) in laboratory animals and humans. Although amphotericin B is currently the only agent available for the treatment of PAME, it is a very toxic antibiotic and may cause many adverse effects on other organs. In order to find other potentially therapeutic agents for N. fowleri infection, the present study was undertaken to evaluate the in vitro and in vivo efficacies of miltefosine and chlorpromazine against pathogenic N. fowleri. The result showed that the growth of the amoeba was effectively inhibited by treatment with amphotericin B, miltefosine, and chlorpromazine. When N. fowleri trophozoites were treated with amphotericin B, miltefosine, and chlorpromazine, the MICs of the drug were 0.78, 25, and 12.5 microg/ml, respectively, on day 2. In experimental meningoencephalitis of mice that is caused by N. fowleri, the survival rates of mice treated with amphotericin B, miltefosine, and chlorpromazine were 40, 55, and 75%, respectively, during 1 month. The average mean time to death for the amphotericin B, miltefosine, and chlorpromazine treatments was 17.9 days. In this study, the effect of drugs was found to be optimal when 20 mg/kg was administered three times on days 3, 7, and 11. Finally, chlorpromazine had the best therapeutic activity against N. fowleri in vitro and in vivo. Therefore, it may be a more useful therapeutic agent for the treatment of PAME than amphotericin B.

Topics: Amebiasis; Amebicides; Amphotericin B; Animals; Central Nervous System Protozoal Infections; Chlorpromazine; Female; In Vitro Techniques; Mice; Mice, Inbred BALB C; Naegleria fowleri; Parasitic Sensitivity Tests; Phosphorylcholine

Acanthamoeba species are known to cause 2 well-described entities: (1) granulomatous amoebic encephalitis (GAE), which usually affects immunocompromised hosts, and (2) keratitis, which typically follows trauma associated with contamination of water or contact lenses. Less common manifestations include pneumonitis and a subacute granulomatous dermatitis. We describe a case of granulomatous dermatitis secondary to Acanthamoeba infection in a lung transplant recipient and a successful outcome following treatment with lipid formulation of amphotericin B and voriconazole. We believe this is the second case report describing disseminated Acanthamoeba infection in a lung transplant recipient. We also describe successful outcome with a combination of lipid formulation of amphotericin B and voriconazole, drugs that have not been previously reported to treat Acanthamoeba.

Topics: Acanthamoeba; Acute Disease; Amebiasis; Amphotericin B; Animals; Antiprotozoal Agents; Chemistry, Pharmaceutical; Female; Humans; Injections, Intravenous; Lipids; Lung Transplantation; Middle Aged; Postoperative Complications; Pyrimidines; Skin Diseases, Parasitic; Treatment Outcome; Triazoles; Voriconazole

Acanthamoeba infection is a rare, difficult-to-treat, and often fatal, opportunistic parasitic infection in immunocompromised hosts, such as patients infected with HIV. We describe an aggressive nasal and sinus infection by Acanthamoeba spp. in a person with AIDS. The resolution of this Acanthamoeba infection was secondary to a multidisciplinary treatment approach involving a combination of surgery as well as high-dose amphotericin B plus 5-fluorocytosine. In the era of the HIV/AIDS pandemic, the present report underscores the need for early identification and prompt aggressive treatment to ensure successful management of this rare but potentially fatal opportunistic infection.

Topics: Acanthamoeba; Adult; AIDS-Related Opportunistic Infections; Amebiasis; Amebicides; Amphotericin B; Animals; Flucytosine; HIV Infections; Humans; Male; Rhinitis; Sinusitis; Treatment Outcome

This report describes a case of primary amoebic meningoencephalitis in a patient with systemic lupus erythematosus. No specific exposure was identified. Treatment with intravenous amphotericin B was associated with marked clinical improvement, but subsequent fatal relapse while still on therapy.

Topics: Adult; Amebiasis; Amphotericin B; Animals; Disease Progression; Fatal Outcome; Female; Humans; Immunocompromised Host; Lupus Erythematosus, Systemic; Meningoencephalitis; Naegleria; Recurrence; Treatment Outcome

Inhalation of water contaminated with Naegleria fowleri may lead to a potentially fatal infection of the central nervous system known as primary amebic meningoencephalitis (PAM). Amphotericin B (AMB), an antifungal drug, is the only agent with established clinical efficacy in the treatment of PAM, though therapy with this drug is not always effective and has been associated with adverse effects on the kidneys and other organs. We investigated the activity of various therapeutic agents against N. fowleri in an attempt to identify other useful agents for treating PAM. Several of these agents exhibited in vitro activity against the Lee (M67) strain of N. fowleri. The minimum inhibitory concentrations of these agents were 0.1 microg/ml (ketoconazole), 1 microg/ml (liposomal AMB), and 10 microg/ml (minocycline, quinupristin-dalfopristin, and trifluoperazine). Other agents had a minimum inhibitory concentration > 10 microg/ml (linezolid) or > 100 microg/ml (rifampin). In a mouse model of PAM, none of the untreated control mice survived, whereas the survival of treated animals was 50% (quinupristin-dalfopristin), 30% (ketoconazole and liposomal AMB), 20% (trifluoperazine), and 10% (linezolid and minocycline). Further studies are needed to ascertain whether these agents have synergistic activity with AMB in vitro and in vivo.

Topics: Acetamides; Adolescent; Amebiasis; Amebicides; Amphotericin B; Animals; Central Nervous System Protozoal Infections; Disease Models, Animal; Drug Therapy, Combination; Female; Humans; Ketoconazole; Linezolid; Liposomes; Male; Mice; Minocycline; Naegleria fowleri; Oxazolidinones; Trifluoperazine; Virginiamycin

Acute amebic meningoencephalitis caused by free-living amebae naegleria fowleri is extremely rare and uniformly fatal with only seven survivals reported till date. An interesting case of naegleria meningitis diagnosed by wet mount cytology of cerebrospinal fluid (CSF) and treated with amphoterecin B, rifampicin and ornidazole with complete recovery is presented. In cases of suspected pyogenic meningitis, if CSF staining, antigen detection or culture is negative for bacteria, a wet mount cytology of CSF for naegleria is suggested. Early treatment with amphoterecin B and rifampicin may improve survival.

Topics: Adult; Amebiasis; Amebicides; Amphotericin B; Animals; Antiprotozoal Agents; Drug Therapy, Combination; Female; Humans; Meningitis; Naegleria fowleri; Ornidazole; Rifampin

Artemisinin and its derivative alpha, beta-arteether have been evaluated for activity against experimental primary amoebic meningoencephalitis. In vivo experiments have shown that amphotericin B at dose of 2.5 mg/kg for 5 days produced 100% protection. Artemisinin and alpha, beta-arteether, even when tested at a high doses (60-120 mg/kg x 5 days and 90-180 mg/x 5 days) respectively, were not curative and showed only slight protection as indicated by extension of mean survival time.

Topics: Amebiasis; Amebicides; Amphotericin B; Animals; Artemisinins; Meningoencephalitis; Mice; Naegleria fowleri; Sesquiterpenes

Topics: Amebiasis; Amphotericin B; Animals; Antiprotozoal Agents; Child; Humans; Hydrocephalus; Injections, Spinal; Male; Meningitis; Naegleria fowleri

A cell-free growth medium for the opportunistic pathogenic ameba Balamuthia mandrillaris is presented. This represents an advance over the use of monkey kidney cells for growth of the amebas and can be helpful in isolation of these amebas from brain tissue from cases in which amebic meningoencephalitis is a diagnostic possibility, as well as for biochemical and molecular biological studies. Three isolates of Balamuthia have been cultured in this medium. The cell-free growth system was also used to screen cultures for sensitivity to a variety of antimicrobial agents. Of the various drugs tested, pentamidine isethionate was most effective against amebas (ca. 90% inhibition after 6 days of exposure), but the drug was amebastatic and not amebacidal in the axenic system at the highest concentration tested (10 micrograms/ml).

Topics: Amebiasis; Amoeba; Amphotericin B; Animals; Antiprotozoal Agents; Benzamidines; Cell-Free System; Culture Media; Drug Resistance; Humans; Meningoencephalitis; Microbial Sensitivity Tests; Opportunistic Infections; Pentamidine

Artemisinin and its derivatives, beta-arteether and sodium artesunic acid, have been evaluated for activity against experimental primary amebic meningoencephalitis and the efficacy of these compounds has been compared with that of the standard drug amphotericin B. In vivo experiments in Swiss mice have shown that amphotericin B at a dose of 2.5 mg/kg for 5 days produced 100% protection in the mice infected intranasally with Naegleria fowleri. Artemisinin, beta-arteether, and sodium artesunic acid, even when tested at high doses (60-180 mg/kg x 5 days), were not curative and showed only slight protection as indicated by extension of mean survival time.

Topics: Amebiasis; Amebicides; Amphotericin B; Animals; Artemisinins; Artesunate; Dose-Response Relationship, Drug; Meningoencephalitis; Mice; Naegleria fowleri; Sesquiterpenes

Acanthamoeba, a free-living ameba of soil and water, produces the rare infections of granulomatous amebic encephalitis and amebic keratitis. We report a 38-year-old white man with the acquired immunodeficiency syndrome (AIDS) who experienced Acanthamoeba infection that presented as multiple skin nodules without associated encephalitis. Histologic examination revealed necrotizing granulomatous inflammation with numerous amebic organisms that were cultured and identified as Acanthamoeba group 2, probably Acanthamoeba castellani by monoclonal antibodies. Results of in vitro susceptibility testing demonstrated resistance to all six tested drugs. A partial clinical response, however, was obtained with multidrug therapy.

Topics: Acanthamoeba; Adult; AIDS-Related Opportunistic Infections; Amebiasis; Amebicides; Amphotericin B; Animals; Anti-Bacterial Agents; Antimetabolites; Antiparasitic Agents; Drug Therapy, Combination; Flucytosine; Humans; Male; Rifampin

Primary amoebic meningoencephalitis due to Naegleria fowleri was found in a 38-year-old Chinese man living in Hong Kong who presumably acquired the infection from swimming in a hot spring in neighbouring China. Amoebic cysts were identified in tissue taken from a brain abscess. The patient responded to surgical drainage and a 6-week course of amphotericin B, rifampicin and chloramphenicol. This is one of 6 cases of successful treatment of primary amoebic meningoencephalitis documented in the medical literature.

Topics: Adult; Amebiasis; Amphotericin B; Animals; Brain Abscess; Chloramphenicol; Combined Modality Therapy; Craniotomy; Drainage; Drug Therapy, Combination; Hong Kong; Humans; Male; Meningoencephalitis; Naegleria fowleri; Rifampin

Topics: Adolescent; Amebiasis; Amphotericin B; Animals; Cerebrospinal Fluid; Drug Therapy, Combination; Female; Humans; Itraconazole; Meningoencephalitis; Naegleria; Rifampin

Six cases of primary amoebic meningoencephalitis were diagnosed and treated at the Balimo Health Centre between December 1986 and September 1988. This disease has not previously been reported in Papua New Guinea although from information derived from other studies it should be occurring in the lowlands of Papua New Guinea from time to time. Although less than optimum treatment was given to the early cases the case fatality rate in the series was only 66%. This compares very favorably with a case fatality rate of nearly 100% from other studies. Early diagnosis and prompt treatment should help to reduce mortality.

Topics: Amebiasis; Amphotericin B; Animals; Climate; Female; Humans; Infant; Male; Meningoencephalitis; Papua New Guinea

The fourth documented survivor of primary amebic meningoencephalitis, a young man with a history of waterskiing in a stagnant freshwater lake in northeastern Pennsylvania, is presented. Early consideration of this unusual diagnosis, based on historical factors (recent contact with warm fresh water), coupled with prompt aggressive therapy with high-dose amphotericin B is emphasized in achieving a successful outcome.

Topics: Adult; Amebiasis; Amphotericin B; Animals; Humans; Male; Meningoencephalitis; Naegleria

The fifth nonlethal case of primary amoebic meningoencephalitis was reported. He was a 61-year-old gardener from northeast Thailand who had an abrupt onset of high fever, headache and stupor. Lumbar puncture showed numerous naegleria in the cerebrospinal fluid. The combination of 0.5 mg/kg/day of intravenous amphotericin B for 14 days, oral rifampicin and oral ketoconazole for 1 month cured the patient with no recurrence after one year of follow-up. The authors emphasise the regimen of low dose amphotericin B for a prolonged period instead of a high dose over a short period.

Topics: Amebiasis; Amphotericin B; Animals; Humans; Male; Meningoencephalitis; Middle Aged; Naegleria; Survival Rate; Thailand

Topics: Amebiasis; Amoeba; Amphotericin B; Humans; Meningoencephalitis

Topics: Amebiasis; Amphotericin B; Animals; Anti-Bacterial Agents; Drug Therapy, Combination; Female; Male; Meningoencephalitis; Mice; Rifampin; Tetracycline

Topics: Amebiasis; Amphotericin B; Animals; Brain; Hydrolases; Lipid Peroxides; Mice; Paromomycin

Topics: Amebiasis; Amebicides; Amoeba; Amphotericin B; Animals; Drug Resistance; Endolimax; Female; Male; Mice; Paromomycin; Polymyxin B

Topics: Amebiasis; Amphotericin B; Child; Female; Humans; Meningoencephalitis; Miconazole; Rifampin

In the summer of 1978, two children who had recently been swimming in freshwater lakes in Florida died from primary amoebic meningoencephalitis. Despite early and intensive treatment with amphotericin B, both patients died three to five days after the onset of illness. Amoebae were observed in wet preparations of cerebrospinal fluid and in sections of cerebral tissue and were identified as Naegleria fowleri by the indirect immunofluorescent antibody technique. The amoebae were highly virulent in mice. The isolate of N. fowleri was extremely sensitive in vitro to amphotericin B (minimal inhibitory concentration [MIC], 0.15 microgram/ml), somewhat sensitive to miconazole (MIC, 25 micrograms/ml), and resistant to rifampin (MIC, less than or equal to 100 micrograms/ml). Treatment with amphotericin B (7.5 mg/kg of body weight per day) administered intraperitoneally protected 60% of the mice. Lower doses of amphotericin B alone or in combination with miconazole (100 mg/kg) or rifampin (220 mg/kg) were not protective. These results suggest that amphotericin B remains the single effective agent in treatment of primary amoebic meningoencephalitis.

Topics: Adolescent; Amebiasis; Amphotericin B; Animals; Child; Humans; Male; Meningoencephalitis; Mice; Miconazole; Rifampin; Serologic Tests; Swimming

The treatment of primary amoebic meningoencephalitis was examined using a mouse model. Rifamycin by itself was ineffective. However, a synergistic effect was observed when used in combination with amphotericin B. This finding may prove useful in the treatment of patients with primary amoebic meningoencephalitis, for which satisfactory treatment is currently unavailable.

Topics: Amebiasis; Amphotericin B; Animals; Drug Synergism; Drug Therapy, Combination; Meningoencephalitis; Mice; Mice, Inbred BALB C; Rifamycins

Two cases of PAME in children occurring during dusty harmattan period in Northern Nigeria are reported. In the absence of history of swimming or any other water related sport, and as suggested in our two previous reports, a dustbone infection as an important route of infection in PAME in this area is stressed. A need to fully investigate any atypical case of meningitis and meningoencephalitis in this area is emphasised.

Topics: Amebiasis; Amoeba; Amphotericin B; Cerebrospinal Fluid; Child, Preschool; Female; Humans; Infant; Meningoencephalitis; Nigeria

Topics: Amebiasis; Amphotericin B; Animals; Drug Synergism; Drug Therapy, Combination; Male; Meningoencephalitis; Mice; Mice, Inbred BALB C; Tetracycline; Time Factors

Primary amebic meningoencephalitis a rapidly fatal CNS infection caused by the free-living ameba Naegleria fowleri. The disease is acquired by swimming in fresh water and is being recognized with increasing frequency. Results of early diagnosis and treatment with amphotericin and other drugs suggest therapeutic optimism. Epidemiological surveys have shown the organism to be commonly present in fresh-water lakes in the warmer parts of the world. Prompt recognition and treatment is vital.

Topics: Adolescent; Amebiasis; Amphotericin B; Child; Humans; Male; Meningoencephalitis

A case of primary amebic meningoencephalomyelitis due to Naegleria sp observed in a 14 years old boy is reported. Symptoms due to myelitis at the dorsal level assumed ascending character during the first days of disease. Manifestations due to encephalic involvemente were discrete. Cerebrospinal fluid changes were marked by pleocytosis, and the eosinophil cells participation in the cytomorphological profile was persitently high. Amphotericin-B was used intravenously (25 mgm/day) until 1,500 mgm of total dosis. Remission of encephalitis manifestations was prompt, as well as of meningeal signs. Cerebrospinal fluid changes disappeared progressively. Sensitive-motor changes due to spinal cord involvement persisted as permanent sequelae. Naegleria sp., was isolated from the cerebrospinal fluid in the acute stage of the disease, as well as, from the water of a lagoon where the patient used to swim.

Topics: Adolescent; Amebiasis; Amphotericin B; Encephalomyelitis; Humans; Male; Meningoencephalitis

The efficacy of tetracycline and amphotericin B in the treatment of primary amoebic meningoencephalitis was studied by means of a mouse model. The results showed marked synergism between these two drugs. Mice who recieved 50 microgram amphotericin B daily succumbed to the infection with only 28.6% survival compared to 0% in untreated controls. In contrast, survival percentage was increased to 66.7% and 84.6% in mice receiving the combined dosage schedule of 50 microgram amphotericin B with 2 tetracycline, and 50 microgram amphotericin B with 3 mg tetracycline, respectively. The finding of synergism between tetracycline and amphotericin may provide a better means for the treatment of this disease.

Topics: Amebiasis; Amphotericin B; Animals; Drug Synergism; Drug Therapy, Combination; Male; Meningoencephalitis; Mice; Mice, Inbred BALB C; Tetracycline

Topics: Amebiasis; Amoeba; Amphotericin B; Animals; Mice; Mice, Inbred C3H; Temperature; Virulence

Topics: Amebiasis; Amphotericin B; Humans; Meningoencephalitis

Topics: Adolescent; Adult; Amebiasis; Amoeba; Amphotericin B; Animals; Brain; Child; Child, Preschool; Female; Guinea Pigs; Humans; Infant; Male; Meningoencephalitis; Nasal Mucosa; Prognosis; Virulence

Topics: Amebiasis; Amebicides; Amoeba; Amphotericin B; Antifungal Agents; Humans; Imidazoles; In Vitro Techniques; Meningoencephalitis; Trityl Compounds

Topics: Amebiasis; Amoeba; Amphotericin B; Animals; Methacycline; Mice; Poland; Polymyxins; Time Factors; Virulence; Water Microbiology

Topics: Adolescent; Amebiasis; Amoeba; Amphotericin B; Female; Humans; Male; Meningoencephalitis; Swimming Pools; Water Microbiology

Topics: Amebiasis; Amebicides; Amoeba; Amphotericin B; Brain; Brain Stem; Central Nervous System Diseases; Cerebrospinal Fluid Proteins; Encephalitis; Humans; Leukocyte Count; Lymphocytosis; Male; Middle Aged; Necrosis; Temporal Lobe; Water Pollution

Topics: Amebiasis; Amoeba; Amphotericin B; Australia; Humans; Meningoencephalitis; Water Microbiology; Water Supply

Topics: Amebiasis; Amphotericin B; Animals; Autopsy; Belgium; Child; Female; Humans; Male; Meningoencephalitis; Mice; Swimming Pools

Topics: Amebiasis; Amoeba; Amphotericin B; Anti-Bacterial Agents; Cerebrospinal Fluid; Disease Models, Animal; Humans; Meningoencephalitis; Respiratory Tract Infections; Sports Medicine; Staining and Labeling; Swimming; United States

Topics: Amebiasis; Amphotericin B; Animals; Meningoencephalitis; Mice; Nitrofurazone; Paromomycin; Pyrimethamine; Sulfadiazine

Topics: Adolescent; Adult; Amebiasis; Amebicides; Amoeba; Amphotericin B; Anti-Bacterial Agents; Brain; Cerebrospinal Fluid; Environmental Exposure; Female; Humans; Male; Meningoencephalitis; Nasal Mucosa; Spinal Cord; Swimming Pools; Virginia

Topics: Adult; Amebiasis; Amoeba; Amphotericin B; Child; Eukaryota; Humans; Male; Meningoencephalitis; Protozoan Infections; United Kingdom

Meningoencephalitis proved to be due to an amoeba (Naegleria) has been diagnosed in Great Britain for the first time. The first patient (a boy of 2) survived longer than any previously recorded cases, but in spite of early diagnosis and treatment he died 15 days after the onset of meningeal symptoms.Two other children who were exposed to the same possible source of infection (a warm, muddy puddle) had similar symptoms and developed mild meningitis. A naegleria was isolated from the cerebrospinal fluid of one of them. Both recovered after treatment with amphotericin.

Topics: Amebiasis; Amoeba; Amphotericin B; Autopsy; Brain; Child; Child, Preschool; Eukaryota; Humans; Male; Meningoencephalitis; Protozoan Infections; Respiratory Tract Infections; United Kingdom

An amoeba of the genus Naegleria causing fatal meningoencephalitis in a human subject has been investigated for its sensitivity to several drugs. Penicillin, sulphadiazine, chloramphenicol, oxytetracycline hydrochloride, streptomycin, methotrexate, emetine, quinine, and metronidazole had no effect on the organism in vitro at levels in excess of those likely to be attained therapeutically in the brain. Amphotericin B was highly amoebicidal in vitro and protected mice from infection with the organism. Used in high dosage by the intraventricular as well as the intravenous route, this drug might be successful in the treatment of further cases of primary amoebic meningoencephalitis.

Topics: Amebiasis; Amoeba; Amphotericin B; Animals; Chloramphenicol; Emetine; Humans; Meningoencephalitis; Methotrexate; Metronidazole; Mice; Oxytetracycline; Penicillins; Quinine; Streptomycin; Sulfadiazine

Topics: Amebiasis; Amphotericin B; Animals; Cerebrospinal Fluid; Culture Techniques; Diet Therapy; Emetine; Eukaryota; Flagella; Haplorhini; Humans; Mice; Microscopy, Phase-Contrast; Rabbits; Sulfadiazine; Virulence