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Fulltext Unilateral rhino-orbital-cerebral mucormycosis with contralateral endogenous fungal endophthalmitis

Ho HC, Liew OH, Teh SS, Hanizasurana H, Ibrahim M, Shatriah I

Clin Ophthalmol, 2015;9:553-6.
PMID: 25848206 DOI: 10.2147/OPTH.S82204

Rhino-orbital-cerebral mucormycosis (ROCM) is an uncommon but fatal fungal infection. We report a rare case of unilateral ROCM with ipsilateral central retinal artery occlusion and contralateral choroiditis, which later progressed to endogenous fungal endophthalmitis. The patient was successfully treated with sinuses debridement, systemic liposomal amphotericin B, and intravitreal amphotericin B. The endophthalmitis completely resolved with good vision, but the ROCM eye remained blind due to central retinal artery occlusion.

Matched MeSH terms: Amphotericin B
Trichosporon Asahii fungaemia in an immunocompetent polytrauma patient who received multiple antibiotics

Ding CH, Khaithir TMN, Wahab AA, Faiz MA, Saarah WR

Malays J Pathol, 2020 Aug;42(2):293-296.
PMID: 32860385

Trichosporon asahii is a yeast-like fungus that is emerging as an important cause of invasive infections in tertiary medical centres. A 58-year-old Chinese man with no known medical illnesses presented with liver lacerations and multiple fractures following an alleged 12-foot fall at a construction site. The gravity of his injuries and poor haemodynamic status necessitated an intensive care unit (ICU) admission, during which several febrile episodes were detected and multiple antibiotics were administered. After being in the ICU for at least two weeks, a urease-positive yeast was isolated from the patient's blood. The yeast formed dry, fuzzy and wrinkled white colonies on Sabouraud dextrose agar following prolonged incubation, and produced blastoconidia, true hyphae, pseudohyphae and arthroconidia on slide culture. It was identified biochemically by the ID 32 C kit as T. asahii. The yeast had elevated minimal inhibitory concentration (MIC) values to fluconazole, amphotericin B, flucytosine and all echinocandins tested. In view of this, the patient was treated with voriconazole and was successfully transferred to the general medical ward.

Matched MeSH terms: Amphotericin B/pharmacology
Tongue necrosis secondary to mucormycosis in a diabetic patient: A first case report in Malaysia

Fattah SY, Hariri F, Ngui R, Husman SI

J Mycol Med, 2018 Sep;28(3):519-522.
PMID: 30205883 DOI: 10.1016/j.mycmed.2018.06.004

Mucormycosis is a rare fungal infection and high mortality that commonly affects patients with the weakened immune system. We present an unusual case of tongue necrosis probably due to the healthcare-associated mucormycosis (HCM) in a diabetic patient. Although cannot be proved with certainty, we surmise that intubation as a risk factor in our case. The diagnosis was confirmed by histopathological examination (HPE) of the necrotic tissue specimen. The patient was responded well to lipid complex amphotericin B (250mg) regime after surgery. Subsequent follow up revealed that no signs of recurrence. Early, recognition, diagnosis, prompt treatment and awareness among clinician are representing the most effective way of managing the disease.

Matched MeSH terms: Amphotericin B/administration & dosage; Amphotericin B/therapeutic use
Fulltext The Development of Drugs against Acanthamoeba Infections

Siddiqui R, Aqeel Y, Khan NA

Antimicrob Agents Chemother, 2016 11;60(11):6441-6450.
PMID: 27600042 DOI: 10.1128/AAC.00686-16

For the past several decades, there has been little improvement in the morbidity and mortality associated with Acanthamoeba keratitis and Acanthamoeba encephalitis, respectively. The discovery of a plethora of antiacanthamoebic compounds has not yielded effective marketed chemotherapeutics. The rate of development of novel antiacanthamoebic chemotherapies of translational value and the lack of interest of the pharmaceutical industry in developing such chemotherapies have been disappointing. On the other hand, the market for contact lenses/contact lens disinfectants is a multi-billion-dollar industry and has been successful and profitable. A better understanding of drugs, their targets, and mechanisms of action will facilitate the development of more-effective chemotherapies. Here, we review the progress toward phenotypic drug discovery, emphasizing the shortcomings of useable therapies.

Matched MeSH terms: Amphotericin B/pharmacology
Fulltext The Current Status of Feline Sporotrichosis in Malaysia

Siew HH

Nihon Ishinkin Gakkai Zasshi, 2017;58(3):E107-E113.
PMID: 28855477 DOI: 10.3314/mmj.17.014

Feline sporotrichosis has been reported in Malaysia since the 1990's. Since then, studies have revealed that clinical clade D, Sporothrix schenckii sensu stricto, of a single clonal strain is the most common cause of this disease in Malaysia. The prevalence of a single clonal strain from a clinical clade was never before reported in Asia in a specific geographical niche. This raises the possibility of a process of purifying selection and subsequent clonal proliferation. While agricultural practices may serve as the selective pressure, direct causality has yet to be established. Studies into the thermo-tolerability of the Malaysian clonal strain of S. schenckii sensu stricto revealed that a small minority of clinical isolates have the capacity to grow at 37℃, while the majority displayed low susceptibility to commonly used antifungals in clinical practice, such as itraconazole (ITZ) and terbinafine (TRB). Despite unestablished breakpoints, suspected resistance (MIC > 4 mg/mL) towards amphotericin B (AMB) and fluconazole (FLC) was recorded in the isolates. This explains the often lack of clinical response in feline patients treated with recommended doses of antifungals, including ITZ. Coupled with the potential zoonotic transmission to clients and veterinarians, protracted treatment period, and subsequent cost of treatment, prognosis of feline sporotrichosis is often regarded to be poor. The use of a higher dose of ITZ has been reported, and an adoption of this high-dose treatment regime is reported in this manuscript, with complete cure achieved in cases of recalcitrant and/or unresponsive feline sporotrichosis, which would otherwise be euthanized.

Matched MeSH terms: Amphotericin B/pharmacology
Talaromyces (Penicillium) species infection in the central nervous system

Chuah CH, Ong YC, Kong BH, Woo YY, Wong PS, Leong KN, et al.

J R Coll Physicians Edinb, 2020 Jun;50(2):138-140.
PMID: 32568283 DOI: 10.4997/JRCPE.2020.211

Talaromycosis typically occurs as an opportunistic infection among immunocompromised individuals. Infection caused by species other than T. marneffei is uncommon. While most reported cases describe infection in the lungs, we report an extremely rare intracranial Talaromyces species infection. This 61-year-old with end-stage renal disease who was unwell for the previous two months, presented with fever and worsening confusion lasting for three days. Lumbar puncture was suggestive of meningitis. Cerebrospinal fluid (CSF) culture was later confirmed to be Penicillium chrysogenum. The patient was co-infected with Group B Streptococcus sepsis. He improved with amphotericin B and ceftriaxone and was discharged with oral itraconazole for four weeks. However, he died of unknown causes two weeks later at home. Talaromyces species infection in the central nervous system is uncommon. This case highlighted a rare but life-threatening fungal meningitis. Among the four reported cases worldwide, none of the patients survived.

Matched MeSH terms: Amphotericin B
Systemic fusarium infection in cancer patients : a report of two cases

Mohamed, M., Ariffin, H., Arasu, A., Tuck Soon, S.H., Abdullah, W.A., Lin, H.P.

Malaysian Journal of Paediatrics and Child Health, 1998;10(2):55-58.
MyJurnal

Fusarium species is an emerging genus of fungal pathogens which until recently were rare causes of human disease apart from localized infection of the skin and nails. Two cases of fungaemia due to Fusarium sp. in children are described. The first child, an 8-year old girl with acute myeloid leukaemia developed character-sitic pyoderma gangrenosum-like skin lesions before succumbing to disseminated Fusarium infection and acute respiratory distress syndrome. The second child, a 5-month old boy, developed pneumonia associated with a transient erythematous skin rash while on chemother-apy for congenital leukaemia. Both patients had Fusarium isolated from blood. The second child improved after six weeks of treatment with ampho-tericin B and granulocyte-macrophage colony stimulat-ing factor but ultimately she died of the disease follow-ing discharge. Fusarium spp should be recognised as an opportunistic pathogen in immunocompromised patients. Current literature suggests that liposomal amphotericin B in conjunction with leukocyte growth factors are the treatment of choice in this potentially fatal infection.

Matched MeSH terms: Amphotericin B
Fulltext Successful treatment of Candida albicans endocarditis in a child with leukemia--a case report and review of the literature

Ariffin H, Ariffin W, Tharam S, Omar A, de Bruyne J, Lin HP

Singapore Med J, 1999 Aug;40(8):533-6.
PMID: 10572495

Candida species is now being increasingly recognised as an important cause of endocarditis especially in immunocompromised patients. A case of Candida albicans endocarditis in a child with acute lymphoblastic leukemia (ALL) is reported. The child did not have a central venous catheter at any time. Treatment consisted of intravenous amphotericin B and fluconazole for 3 weeks followed by oral fluconazole for 2 weeks. No surgical resection was necessary. We highlight here the importance of echocardiography in the management of prolonged febrile neutropenia and discuss the dilemma of continuing chemotherapy in such patients.

Matched MeSH terms: Amphotericin B/administration & dosage*
Silver nanoparticle conjugation affects antiacanthamoebic activities of amphotericin B, nystatin, and fluconazole

Anwar A, Siddiqui R, Hussain MA, Ahmed D, Shah MR, Khan NA

Parasitol Res, 2018 Jan;117(1):265-271.
PMID: 29218442 DOI: 10.1007/s00436-017-5701-x

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

Matched MeSH terms: Amphotericin B/pharmacology*; Amphotericin B/chemistry
Fulltext Rhino-orbito-cerebral mucormycosis: a treatment dilemma

Jeevanan J, Gendeh BS, Faridah HA, Vikneswaran T

Med J Malaysia, 2006 Mar;61(1):106-8.
PMID: 16708746 MyJurnal

A case of rhino-orbito-cerebral mucormycosis is presented showing its aggressive nature and progression of disease. The typical clinical features, neuroimaging and histological findings are highlighted in this report. Amphotericin B and surgical debridement remain the mainstay of treatment. However, associated co-morbidities need to be addressed.

Matched MeSH terms: Amphotericin B/therapeutic use*
Repurposing of Drugs Is a Viable Approach to Develop Therapeutic Strategies against Central Nervous System Related Pathogenic Amoebae

Anwar A, Khan NA, Siddiqui R

ACS Chem Neurosci, 2020 08 19;11(16):2378-2384.
PMID: 32073257 DOI: 10.1021/acschemneuro.9b00613

Brain-eating amoebae including Acanthamoeba spp., Naegleria fowleri, and Balamuthia mandrillaris cause rare infections of the central nervous system that almost always result in death. The high mortality rate, lack of interest for drug development from pharmaceutical industries, and no available effective drugs present an alarming challenge. The current drugs employed in the management and therapy of these devastating diseases are amphotericin B, miltefosine, chlorhexidine, pentamidine, and voriconazole which are generally used in combination. However, clinical evidence shows that these drugs have limited efficacy and high host cell cytotoxicity. Repurposing of drugs is a practical approach to utilize commercially available, U.S. Food and Drug Administration approved drugs for one disease against rare diseases caused by brain-eating amoebae. In this Perspective, we highlight some of the success stories of drugs repositioned against neglected parasitic diseases and identify future potential for effective and sustainable drug development against brain-eating amoebae infections.

Matched MeSH terms: Amphotericin B
Fulltext Refractory Scedosporium apiospermum Keratitis Successfully Treated with Combination of Amphotericin B and Voriconazole

Fadzillah MT, Ishak SR, Ibrahim M

Case Rep Ophthalmol Med, 2013;2013:413953.
PMID: 23509650 DOI: 10.1155/2013/413953

Aim. To report a case of refractory fungal keratitis caused by Scedosporium apiospermum. Methods. Interventional case report. Results. A 47-year-old Malay housewife presented with left eye cornea ulcer as her first presentation of diabetes mellitus. There was no history of ocular trauma, contact lens used, or cornea foreign body. Scedosporium apiospermum was isolated from the cornea scrapping. Her cornea ulcer initially responded well to topical Amphotericin B within 3 days but subsequently worsened. Repeat cornea scrapping also yields Scedosporium apiospermum. This refractory keratitis was successfully treated with a combination of topical Amphotericin B and Voriconazole over 6 weeks. Conclusion. Scedosporium apiospermum keratitis is an opportunistic infection, which is difficult to treat despite tight control of diabetes mellitus and intensive antifungal treatment. The infection appeared to have very quick onset but needed long duration of treatment to completely heal. Surgical debridement always plays an important role as a therapeutic procedure as well as establishes the diagnosis through repeat scrapping.

Matched MeSH terms: Amphotericin B
Fulltext Rare Kodamaea ohmeri keratitis following a trivial vegetative trauma

Saud Al-Abbas AH, Ling JL, Muhammed J, Hussein A

BMJ Case Rep, 2019 Jun 22;12(6).
PMID: 31229985 DOI: 10.1136/bcr-2019-229660

Kodamaea ohmeri keratitis is an opportunistic pathogen seen in patients who have undergone invasive procedures and immunocompromised state. It has been identified in septicemia patients, resulting in mortality. To the best of our knowledge, we identified the first case of K. ohmeri keratitis following an injury with vegetative material. A 57-year-old woman with underlying, poorly controlled diabetes mellitus was gardening when a tree leaf accidentally poked her in the eye. Two weeks later, the patient presented with right eye pain, redness and progressive blurring of vision due to a traumatised right cornea. Slit-lamp examination showed a small inferior paracentral corneal stromal infiltrate with overlying epithelial defect. A corneal scraping sample yielded K. ohmeri from Analytical Profile Index (API) 20C yeast identification system. She was treated with intensive topical amphotericin B and fluconazole. After 6 weeks of treatment, the keratitis resolved with faint scar tissue, and her visual acuity improved.

Matched MeSH terms: Amphotericin B/administration & dosage; Amphotericin B/therapeutic use
Fulltext Properties of An Oral Nanoformulation of A Molecularly Dispersed Amphotericin B Comprising A Composite Matrix of Theobroma Oil and Bee'S Wax

Tan CS, Billa N, Roberts CJ, Scurr DJ

Nanomaterials (Basel), 2014 Dec 19;4(4):905-916.
PMID: 28344257 DOI: 10.3390/nano4040905

An amphotericin B-containing (AmB) solid lipid nanoparticulate drug delivery system intended for oral administration, comprised of bee's wax and theobroma oil as lipid components was formulated with the aim to ascertain the location of AmB within the lipid matrix: (a) a homogenous matrix; (b) a drug-enriched shell; or (c) a drug enriched core. Both the drug-loaded and drug-free nanoparticles were spherical with AmB contributing to an increase in both the z-average diameter (169 ± 1 to 222 ± 2 nm) and zeta potential (40.8 ± 0.9 to 50.3 ± 1.0 mV) of the nanoparticles. A maximum encapsulation efficiency of 21.4% ± 3.0%, corresponding to 10.7 ± 0.4 mg encapsulated AmB within the lipid matrix was observed. Surface analysis and electron microscopic imaging indicated that AmB was dispersed uniformly within the lipid matrix (option (a) above) and, therefore, this is the most suitable of the three models with regard to modeling the propensity for uptake by epithelia and release of AmB in lymph.

Matched MeSH terms: Amphotericin B
Fulltext Prevalence, virulence and antifungal activity of C. albicans isolated from infected root canals

Abraham SB, Al Marzooq F, Himratul-Aznita WH, Ahmed HMA, Samaranayake LP

BMC Oral Health, 2020 12 01;20(1):347.
PMID: 33256696 DOI: 10.1186/s12903-020-01347-5

BACKGROUND: There is limited data on the prevalence of Candida species in infected root canal systems of human teeth. We attempted to investigate the prevalence, genotype, virulence and the antifungal susceptibility of Candida albicans isolated from infected root canals of patients with primary and post-treatment infections in a UAE population.
METHODS: Microbiological samples from 71 subjects with infected root canals were aseptically collected, and cultured on Sabouraud dextrose agar, and C. albicans was identified using multiplex polymerase chain reaction, and the isolates were further subtyped using ABC genotyping system. Their relative virulence was compared using further four archival samples of endodontic origin from another geographical region, and four more salivary isolates, as controls. The virulence attributes compared were biofilm formation, and production of phospholipase and haemolysin, and the susceptibility to nystatin, amphotericin B, ketoconazole, and fluoconazole was also tested.
RESULTS: 4 out of 71 samples (5.6%) yielded Candida species. On analysis of variance among the groups, the intracanal isolates, mainly Genotype A, possessed a high degree of phospholipase and haemolysin activity (p

Matched MeSH terms: Amphotericin B
Prevalence of albicans and non-albicans candiduria in a Malaysian medical centre

Ding CH, Wahab AA, Muttaqillah NA, Tzar MN

J Pak Med Assoc, 2014 Dec;64(12):1375-9.
PMID: 25842581

To determine the proportion of albicans and non-albicans candiduria in a hospital setting and to ascertain if fluconazole is still suitable as empirical antifungal therapy based on antifungal susceptibility patterns of Candida species.

Matched MeSH terms: Amphotericin B/therapeutic use
Pharmacokinetics and tissue distribution of an orally administered mucoadhesive chitosan-coated amphotericin B-Loaded nanostructured lipid carrier (NLC) in rats

Tan JSL, Roberts C, Billa N

J Biomater Sci Polym Ed, 2020 02;31(2):141-154.
PMID: 31612804 DOI: 10.1080/09205063.2019.1680926

Oral delivery of amphotericin B (AmpB) is desirable because it provides a more patient-friendly mode of administration compared to the current delivery approach akin with the marketed AmpB formulations. The goal of the study was to investigate the pharmacokinetics and tissue distribution of orally administered chitosan-coated AmpB-loaded nanostructured lipid carriers (ChiAmpB NLC) administered to Sprague Dawley rats at a dose of 15 mg/kg. Orally administered ChiAmpB NLC resulted in a two-fold increase in the area under the curve (AUC0-∞) compared to the uncoated AmpB NLC and marketed Amphotret®. This enhanced bioavailability of AmpB suggests prolonged transit and retention of ChiAmpB NLC within the small intestine through mucoadhesion and subsequent absorption by the lymphatic pathway. The results show that mean absorption and residence times (MAT & MRT) were significantly higher from ChiAmpB NLC compared to the other two formulations, attesting to the mucoadhesive effect. The ChiAmpB NLC presented a lower nephrotic accumulation with preferential deposition in liver and spleen. Thus, the limitations of current marketed IV formulations of AmpB are potentially addressed with the ChiAmpB NLC in addition to utilizing this approach for targeting internal organs in visceral leishmaniasis.

Matched MeSH terms: Amphotericin B/administration & dosage; Amphotericin B/pharmacokinetics*; Amphotericin B/chemistry*
Fulltext Penicilliosis in lupus patients presenting with unresolved fever: a report of 2 cases and literature review

Chong YB, Tan LP, Robinson S, Lim SK, Ng KP, Keng TC, et al.

Trop Biomed, 2012 Jun;29(2):270-6.
PMID: 22735849 MyJurnal

Penicilliosis is a rare occurrence among non human immunodeficiency virus (HIV) infected patients. We report here two cases of Penicillium marneffei infection in patients with systemic lupus erythematosus (SLE). Both patients had a recent flare of lupus and were on immunosuppressive drugs when they presented with prolonged fever without an obvious foci of infection, unresponsive to broad-spectrum antibiotics. They were leucopaenic upon admission, with rapid deterioration during the course of the illness. Diagnosis of penicilliosis via fungal isolation from blood culture was delayed resulting in the late initiation of antifungal agents. While both patients ultimately recovered, the delay in diagnosis led to a prolonged hospital stay with increased morbidity. Clinicians should be aware of this uncommon but emerging fungal pathogen in SLE patients and maintain a high index of suspicion in diagnosing this potentially fatal but treatable disease.

Matched MeSH terms: Amphotericin B/therapeutic use
Paecilomyces lilacinus fungaemia in an AIDS patient: the importance of mycological diagnosis

Ding CH, Tzar MN, Rahman MM, Muttaqillah NA, Redzuan SR, Periyasamy P

Pak J Med Sci, 2014 Jul;30(4):914-6.
PMID: 25097544

Fungaemia due to Paecilomyces lilacinus is generally not considered in AIDS patients because this condition is not categorised as an AIDS-indicator illness. We report a case of a 25-year-old lady who presented to our hospital with Guillain-Barré Syndrome, with the subsequent development of refractory fungaemia, multi-organ failure and disseminated intravascular coagulopathy. Amphotericin B was given as empirical antifungal therapy. HIV screening was reactive and Paecilomyces lilacinus was isolated from her blood. The fungaemia did not resolve after one week of amphotericin B treatment. The addition of itraconazole was also unsuccessful in clearing the fungaemia. Accurate mycological diagnosis is important in the care of AIDS patients with fungaemia because of the risk of treatment failure with empirical therapy.

Matched MeSH terms: Amphotericin B
Mucoadhesive chitosan-coated nanostructured lipid carriers for oral delivery of amphotericin B

Ling Tan JS, Roberts CJ, Billa N

Pharm Dev Technol, 2019 Apr;24(4):504-512.
PMID: 30132723 DOI: 10.1080/10837450.2018.1515225

This study describes the properties of an amphotericin B-containing mucoadhesive nanostructured lipid carrier (NLC), with the intent to maximize uptake within the gastrointestinal tract. We have reported previously that lipid nanoparticles can significantly improve the oral bioavailability of amphotericin B (AmpB). On the other hand, the aggregation state of AmpB within the NLC has been ascribed to some of the side effects resulting from IV administration. In the undissolved state, AmpB (UAmpB) exhibited the safer monomeric conformation in contrast to AmpB in the dissolved state (DAmpB), which was aggregated. Chitosan-coated NLC (ChiAmpB NLC) presented a slightly slower AmpB release profile as compared to the uncoated formulation, achieving 26.1% release in 5 hours. Furthermore, the ChiAmpB NLC formulation appeared to prevent the expulsion of AmpB upon exposure to simulated gastrointestinal pH media, whereby up to 63.9% of AmpB was retained in the NLC compared to 56.1% in the uncoated formulation. The ChiAmpB NLC demonstrated mucoadhesive properties in pH 5.8 and 6.8. Thus, the ChiAmpB NLC formulation is well-primed for pharmacokinetic studies to investigate whether delayed gastrointestinal transit may be exploited to improve the systemic bioavailability of AmpB, whilst simultaneously addressing the side-effect concerns of AmpB.

Matched MeSH terms: Amphotericin B/administration & dosage; Amphotericin B/chemistry*

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