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Fulltext Brief report: nail sampling technique and its interpretation

Leelavathi M, Tzar MN

Malays Fam Physician, 2011;6(2-3):58-9.
PMID: 25606224

The clinical suspicion of onychomyosis based on appearance of the nails, requires culture for confirmation. This is because treatment requires prolonged use of systemic agents which may cause side effects. One of the common problems encountered is improper nail sampling technique which results in loss of essential information. The unfamiliar terminologies used in reporting culture results may intimidate physicians resulting in misinterpretation and hamper treatment decision. This article provides a simple guide on nail sampling technique and the interpretation of culture results.
Fulltext Candidaemia and antifungal susceptibility testing in a teaching hospital

Tzar MN, Shamim AS

Med J Malaysia, 2009 Mar;64(1):61-4.
PMID: 19852325 MyJurnal

We reviewed cases of candidaemia at Universiti Kebangsaan Malaysia Medical Centre from 1st January 2005 to 30th June 2006. All blood cultures positive for Candida species or its teleomorphs within the study period were identified and antifungal susceptibility testing was performed. Out of 50 blood isolates, 20 (40%) were identified as Candida albicans, 16 (32%) C. tropicalis, five (10%) C. parapsilosis, three (6%) C. famata, two (4%) C. glabrata, two (4%) Pichia ohmeri, one (2%) C. krusei and one (2%) P. etchell/carsonii. Susceptibility to amphotericin B was 100%, fluconazole 90%, itraconazole 40%, ketoconazole 88%, 5-flucytosine 98% and voriconazole 98%.
Fulltext Ochrobactrum anthropi catheter-related bloodstream infection: the first case report in malaysia

Siti Rohani AH, Tzar MN

Med J Malaysia, 2013 Jun;68(3):267-8.
PMID: 23749021 MyJurnal

A 60-year old Malay man presented with an intermittent lowgrade fever for 3 days and worsening of right ankle ulcers. He was known to have ischaemic heart disease, diabetes mellitus type 2, hypertension and end stage renal failure and was on regular haemodialysis. The organisms isolated from the peripheral and central blood specimens were identified as Ochrobactrum anthropi, a rarely encountered gramnegative bacillus with a unique antibiotic susceptibility profile. His condition improved after removal of the catheters and administration of antibiotic therapy. This case report highlights the importance of being wary of such rare, opportunistic pathogens and good communication between the microbiologists and the clinicians.
Fulltext Antibacterial activities of the extracts, fractions and isolated compounds from Canarium patentinervium Miq. against bacterial clinical isolates

Mogana R, Adhikari A, Tzar MN, Ramliza R, Wiart C

BMC Complement Med Ther, 2020 Feb 14;20(1):55.
PMID: 32059725 DOI: 10.1186/s12906-020-2837-5

BACKGROUND: Canarium patentinervium leaves are used by the local indigenous people of Malaysia for wound healing. The current study is undertaken to screen the comprehensive antibacterial activity of the leaves and barks extracts, fractions and isolated compounds from this plant. Bioassay guided fractionation was also undertaken to deeply evaluate the antibacterial activity of the water fraction of the leaves extract. This is to provide preliminary scientific evidence to the ethnopharmacology usage of this plant by investigating antibacterial properties of the plant and its isolated constituents.
METHODS: Bio-assay guided fractionation and subsequent isolation of compounds using open column chromatography. The antibacterial activity against gram positive and gram negative ATCC strain and resistant clinical strains were evaluated using microtiter broth dilution method to determine minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and time-kill assay. The chemical structure of the isolated compounds from the water fraction of the ethanol extract of leaves was elucidated using Nuclear Magnetic Resonance (NMR).
RESULTS: The ethanol extract of the leaves and barks showed antimicrobial activity against all four ATCC and eight clinical isolates. The ethanol extract of the leaves and the corresponding water fraction had good activity against MRSA S. aureus. (MIC: 250 μg/ml) and had bactericidal effect on eight of the clinical strains (MSSA,MRSA, oxacillin-resistant CONS, oxacillin-sensitive CONS, Enterococcus faecalis, Klebsiela species, Kleb pneumoniae ESBL and Candida parapsilosis). Further phytochemical investigation of the water fraction of the crude ethanol extract of leaves afforded compound 7 (hyperin) and compound 8 (cynaroside) that had bactericidal activity against tested bacterial species (MIC 50 μg/ml and 100 μg/ml). The two compounds were isolated from this genus for the first time.
CONCLUSIONS: These results may provide a rational support for the traditional use of Canarium patentinervium Miq. in infections and wound healing, since the antimicrobial compounds isolated were also present in the leaves extract.
Antifungal susceptibility of molecularly confirmed Aspergillus species from clinical samples

Tzar MN, Mustakim S, Yusoff H, Tap RM

Malays J Pathol, 2024 Apr;46(1):71-78.
PMID: 38682846

Invasive aspergillosis is the second most common invasive human mycosis but susceptibility data of Aspergillus species is limited. Antifungal treatment of aspergillosis is often done empirically without knowing the true susceptibility. Therefore, we aimed to determine antifungal susceptibility of Aspergillus species isolated from various clinical specimens over a 1-year period. We identified 28 Aspergillus isolates by sequencing the internal transcribed spacer (ITS) and β-tubulin genes and performed antifungal susceptibility testing on these isolates using Sensititre YeastOne. The isolates were identified as Aspergillus niger (60.7%), A. fumigatus (21.4%), A. flavus (10.7%), A. chevalieri (3.6%) and A. tubingensis (3.6%). Based on the European Committee on Antimicrobial Susceptibility Testing (EUCAST) Antifungal Clinical Breakpoint for Aspergillus spp., 16/17 (94.1%) A. niger isolates were susceptible to amphotericin B, all six isolates (100%) of A. fumigatus were susceptible to amphotericin B, itraconazole and voriconazole, but only 5/6 (83.3%) A. fumigatus were susceptible to posaconazole. Meanwhile, all three (100%) A. flavus isolates were susceptible to itraconazole. There are no other breakpoints established by the EUCAST for other antifungal-species combinations. In conclusions, Aspergillus niger remains the most commonly isolated species from clinical specimens and Aspergillus isolates at our centre are still largely susceptible to amphotericin B, echinocandins and most azoles. This information is valuable in guiding antifungal therapy in the treatment of aspergillosis.
Fulltext A systematic review of the outcomes of osteoporotic fracture patients after hospital discharge: morbidity, subsequent fractures, and mortality

Nazrun AS, Tzar MN, Mokhtar SA, Mohamed IN

Ther Clin Risk Manag, 2014;10:937-48.
PMID: 25429224 DOI: 10.2147/TCRM.S72456

PURPOSE:
Osteoporotic fracture is the main complication of osteoporosis. The current management is to discharge patients as early as possible so they can get back to their daily activities. Once discharged, there are three main issues relating to morbidity, mortality, and risk of a subsequent fracture that need to be addressed and discussed. Therefore, the aim of this systematic review was to summarize and evaluate the evidence from published literature, to determine the outcome of osteoporotic fracture patients after their hospital discharge.

METHODS:
The MEDLINE and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases were searched, using the terms "osteoporosis", "fracture", "osteoporotic fracture", "hip fracture", and "vertebral fracture". We included only human studies published in English between 2004 and 2014. The reference lists of included studies were thoroughly reviewed in search for other relevant studies.

RESULTS:
A total of 18 studies met the selection criteria. Most were observational and cohort studies. Out of all the studies, five studies looked into the morbidity, six studies looked into the risk of subsequent fractures, and seven studies looked into mortality. Vertebral fracture caused the greatest health burden, but hip fracture patients were the main users of informal care after hospital discharge. There was an increased risk of a subsequent fracture after a primary fracture compared with the control group, a cohort comparison, or the general population. Osteoporotic fractures, especially hip fractures, are associated with higher mortality rate despite the advances in the management of osteoporotic fracture cases.

CONCLUSION:
There is strong evidence to show that after hospital discharge, osteoporotic fracture patients are faced with higher morbidity, subsequent fractures, and mortality.

KEYWORDS:
hip fracture; osteoporosis; vertebral fracture
A case of mycotic aneurysm due to Burkholderia pseudomallei

Ding CH, Hussin S, Tzar MN, Rahman MM, Ramli SR

Pak J Med Sci, 2013 Apr;29(2):666-8.
PMID: 24353601

Burkholderia pseudomallei is an free-living gram-negative bacterium causing melioidosis and is endemic in Southeast Asia. A 56-year-old diabetic construction worker with a 1-month history of abdominal pain and 1-day history of high-grade fever was found to have a left non-dissecting infrarenal mycotic aortic aneurysm by abdominal computerized tomography scan. Bacteriological examination of his blood yielded Burkholderia pseudomallei. The patient was treated with right axillo-bifemoral bypass with excision of aneurysm and high-dose intravenous ceftazidime for two weeks, followed by oral trimethoprim/sulfamethoxazole and oral doxycycline for a minimum of five months.
Fulltext Prevalence of toenail onychomycosis among diabetics at a primary care facility in Malaysia

Muthupalaniappen L, Azimah MN, Kharuddin NF, Tzar MN

Southeast Asian J. Trop. Med. Public Health, 2013 May;44(3):479-83.
PMID: 24050080

Onychomycosis increases the risk of developing secondary bacterial infection and cellulitis if left untreated. The aim of this study was to determine the prevalence of onychomycosis among diabetics and its associated factors. A cross sectional study using universal sampling of all type 1 and 2 diabetic patients attending a primary care facility of the Universiti Kebangsaan Malaysia (UKM) from January to March 2011 was conducted. Samples were taken from clinically abnormal nails and from the first right toenail in the absence of nail abnormalities and cultured for fungal elements. A total of 151 diabetics participated in the study. The mean patient age was 60.7 +/- 9.1 years. A total of 123 nail samples (81.5%) were culture positive for fungal elements. A positive correlation was found between onychomycosis and increasing age (p = 0.011) and clinically abnormal nails (p < 0.05). There were no significant correlations with gender, ethnic group, duration of diabetes, types of diabetes or glycemic control. The prevalence of onychomycosis among diabetics in our study was high.
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.
Bullous cellulitis as an extraordinary manifestation of a Vibrio cholerae O1 Ogawa infection

Ummu SF, Ding CH, Wahab AA, Tzar MN

Trop Biomed, 2023 Jun 01;40(2):170-173.
PMID: 37650403 DOI: 10.47665/tb.40.2.007

Vibrio cholerae is a gram-negative bacterium synonymous with its namesake disease, cholera. Thus, gastrointestinal symptoms are the norm and V. cholerae is very rarely associated with skin and soft tissue infections. We describe a case of a 63-year-old Chinese woman with multiple medical comorbidities on corticosteroid therapy who developed fever and a painful swelling on her left leg after being pricked by a branch while gardening. There was no abdominal pain, vomiting or diarrhea. A diagnosis of bullous cellulitis was made clinically, and blood was sent for bacteriological culture. A beta-hemolytic commashaped gram-negative bacillus was isolated from the blood. It was also oxidase-positive and produced an acid/alkaline (A/K) reaction on triple sugar iron agar. It was identified biochemically as Vibrio cholerae. After additional testing, it was found to be of the O1 serogroup and Ogawa serotype. The infection resolved following a 10-day course of high-dose co-trimoxazole therapy.
Campylobacter jejuni bacteremia in a leukemic child: a nearly missed diagnosis

Ding CH, Wahab AA, Tzar MN, Mokhtar MN, Arunasalam V

Trop Biomed, 2024 Jun 01;41(2):206-208.
PMID: 39154274 DOI: 10.47665/tb.41.2.011

Globally, Campylobacter spp. are responsible for most cases of bacterial gastrointestinal infections in humans and although rare, extraintestinal Campylobacter infections have been described. A 2-yearold neutropenic girl with underlying precursor B-cell acute lymphoblastic leukemia presented with a 3-day history of diarrhea. Her stool culture yielded no enteric bacterial pathogens. However, when her blood culture was flagged as positive for bacterial growth, no colonies could be observed on routine bacteriological isolation media. Nonetheless, gram-negative bacilli with seagull and spiral morphologies were seen when the surface of the isolation media used to subculture her blood was Gram-stained. Bacterial colonies were only visible when a subculture was attempted on a Campylobacter blood-free selective agar medium. The organism was identified as Campylobacter jejuni by matrix-assisted laser desorption ionization-time of flight mass spectrometry. Since the organism was erythromycin-resistant and the patient's age precluded the use of tetracycline and ciprofloxacin, an antibiotic regimen consisting of piperacillin-tazobactam and gentamicin was commenced. Her C. jejuni bacteremia resolved following eight days of antibiotic therapy.
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.
Fulltext Cryptococcal osteomyelitis of the femur: a case report and review of literature

Zainal AI, Wong SL, Pan KL, Wong OL, Tzar MN

Trop Biomed, 2011 Aug;28(2):444-9.
PMID: 22041767 MyJurnal

Fungal osteomyelitis is a rare opportunistic infection. It exhibits some clinical and radiological similarities to several other bone pathologies. A diagnostic delay may result in significant increase in morbidity. We report a case of a 37-year-old man with underlying hypogammaglobulinaemia presented with isolated cryptococcal osteomyelitis of the femur.
Fulltext An approach to develop clinical prediction rule for candidemia in critically ill patients: A retrospective observational study

Jameran AS, Cheah SK, Tzar MN, Musthafa QA, Low HJ, Maaya M, et al.

J Crit Care, 2021 10;65:216-220.
PMID: 34252648 DOI: 10.1016/j.jcrc.2021.06.018

PURPOSE: Early detection of candidemia in critically ill patients is important for preemptive antifungal treatment. Our study aimed to identify the independent risk factors for the development of a new candidemia prediction score.
METHODS: This single-centre retrospective observational study evaluated 2479 intensive care unit (ICU) cases from January 2016 to December 2018. A total of 76 identified candidemia cases and 76 matched control cases were analyzed. The patients' demographic characteristics and illness severity were analyzed, and possible risk factors for candidemia were investigated.
RESULTS: Multivariate logistic regression analysis identified renal replacement therapy (RRT) (odds ratio [OR]: 52.83; 95% confidence interval [CI]: 7.82-356.92; P < 0.0001), multifocal Candida colonization (OR: 23.55; 95% CI: 4.23-131.05; P < 0.0001), parenteral nutrition (PN) (OR: 63.67; 95% CI: 4.56-889.77; P = 0.002), and acute kidney injury (AKI) (OR: 7.67; 95% CI: 1.24-47.30; P = 0.028) as independent risk factors. A new prediction score with a cut-off value of 5.0 (80.3% sensitivity and 77.3% specificity) was formulated from the logit model equation.
CONCLUSIONS: Renal replacement therapy, AKI, PN, and multifocal Candida colonization were the independent risk factors for the new candidemia prediction score with high discriminatory performance and predictive accuracy.
Fulltext Exophiala dermatitidis, 'the real black fungus' fungemia in a patient with COVID-19

Tzar MN, Meor Jamaludin WHB, Abdul Wahab A, Ding CH

IDCases, 2022;27:e01428.
PMID: 35127454 DOI: 10.1016/j.idcr.2022.e01428

The second wave of the COVID-19 pandemic in India had brought with it a surge of 'black fungus' co-infection, which is a misnomer for mucormycosis. The present case illustrates the 'real black fungus' infection in a 50-year old male patient with COVID-19 pneumonia, who otherwise had no significant previous medical history. He was admitted on day 8 of COVID-19 illness and was intubated due to persistently low oxygen saturation. Blood cultures were positive for flask-shaped dematiaceous budding yeasts with pseudohyphae formation, which grew as brown-black fuzzy colonies on Sabouraud dextrose agar. The isolate was identified as Exophiala dermatitidis based on phenotypic characterization. Despite antifungal therapy with amphotericin B and itraconazole, the patient deteriorated rapidly and succumbed to acute respiratory distress syndrome and multiorgan failure. A review of reported cases of Exophiala dermatitidis fungemia over the last 5-years is discussed.
Fulltext Isolation of an obscure fungus, Parengyodontium album, from the blood of a severely neutropenic patient: The first reported case from Malaysia

Mohamed N, Ding CH, Wahab AA, Tzar MN, Hassan M

J Infect Dev Ctries, 2022 Oct 31;16(10):1668-1670.
PMID: 36332225 DOI: 10.3855/jidc.17016

Parengyodontium album is a very rarely encountered opportunistic fungal pathogen. A severely neutropenic 11-year-old boy with acute T-cell lymphoblastic leukemia/lymphoma was febrile and lethargic during his admission for elective chemotherapy. No cutaneous lesion or obvious source of infection was noted, and clinical examination was otherwise unremarkable. A blood specimen was sent for culture and fungal elements were visualized. Amphotericin B was administered empirically while awaiting fungal identification. Morphologically, a hyaline mould with thin septate hyphae plus smooth-walled conidiophores and conidiogenous cells arranged in whorls of up to four was cultured. Internal transcribed spacer region sequencing identified the fungus conclusively as P. album. Repeat blood culture was also positive for the same fungus. Following a two-week course of amphotericin B, fungemia clearance was attained.
Antifungal susceptibility profile and biofilm-producing capability of Candida tropicalis isolates in a tertiary medical centre

Navarathinam SD, Neoh HM, Tan TL, Wahab AA, Mohd Nizam Tzar MN, Ding CH

Malays J Pathol, 2023 Dec;45(3):417-424.
PMID: 38155383

BACKGROUND: Candida tropicalis is a globally distributed yeast that has been popping up in the medical literature lately, albeit for unenviable reasons. C. tropicalis is associated with substantial morbidity, mortality as well as drug resistance. The aims of this study were to ascertain the antifungal susceptibility profile and the biofilm-producing capability of this notorious yeast in our centre.
METHODS: C. tropicalis isolates from sterile specimens were collected over a 12-month period. Conclusive identification was achieved biochemically with the ID 32 C kit. Susceptibility to nine antifungal agents was carried out using the colourimetric broth microdilution kit Sensititre YeastOne YO10. Biofilm-producing capability was evaluated by quantifying biomass formation spectrophotometrically following staining with crystal violet.
RESULTS: Twenty-four non-repetitive isolates of C. tropicalis were collected. The resistance rates to the triazole agents were 29.2% for fluconazole, 16.7% for itraconazole, 20.8% for voriconazole and 8.3% for posaconazole-the pan-azole resistance rate was identical to that of posaconazole. No resistance was recorded for amphotericin B, flucysosine or any of the echinocandins tested. A total of 16/24 (66.7%) isolates were categorized as high biomass producers and 8/24 (33.3%) were moderate biomass producers. None of our isolates were low biomass producers.
CONCLUSION: The C. tropicalis isolates from our centre were resistant only to triazole agents, with the highest resistance rate being recorded for fluconazole and the lowest for posaconazole. While this is not by itself alarming, the fact that our isolates were prolific biofilm producers means that even azole-susceptible isolates can be paradoxically refractory to antifungal therapy.
Fulltext Successful Treatment of Sternal Osteomyelitis and Mediastinitis Caused by Rhizopus Following Cardiac Surgery

Tiew TC, Md Ali NA, Ismail MI, Abdul Rahman MR, Ding CH, Tzar MN

Cureus, 2024 Jun;16(6):e62312.
PMID: 39006712 DOI: 10.7759/cureus.62312

Sternal osteomyelitis and mediastinitis are rare yet severe complications post-cardiac surgery, often associated with significant morbidity and mortality. Fungal etiologies, particularly those caused by Rhizopus spp., are infrequent but can lead to aggressive infections. Here, we present the case of a 68-year-old male who developed sternal osteomyelitis and mediastinitis caused by Rhizopus spp. two weeks following coronary artery bypass grafting surgery. Debridement and pectoralis flap reconstruction were performed following clinical identification and confirmation with microbiological examinations and a CT scan. Prompt recognition, aggressive surgical intervention, and targeted antifungal therapy were crucial for successful management. This case underscores the importance of considering fungal pathogens, such as Rhizopus, in the differential diagnosis of post-cardiac surgery infections, as well as aggressive treatment to improve outcomes for affected patients.
In Vitro Antifungal Susceptibility of Neoscytalidium dimidiatum Clinical Isolates from Malaysia

James JE, Santhanam J, Lee MC, Wong CX, Sabaratnam P, Yusoff H, et al.

Mycopathologia, 2017 Apr;182(3-4):305-313.
PMID: 27815659 DOI: 10.1007/s11046-016-0085-5

Neoscytalidium dimidiatum is an opportunistic fungus causing cutaneous infections mostly, which are difficult to treat due to antifungal resistance. In Malaysia, N. dimidiatum is associated with skin and nail infections, especially in the elderly. These infections may be mistaken for dermatophyte infections due to similar clinical appearance. In this study, Neoscytalidium isolates from cutaneous specimens, identified using morphological and molecular methods (28 Neoscytalidium dimidiatum and 1 Neoscytalidium sp.), were evaluated for susceptibility towards antifungal agents using the CLSI broth microdilution (M38-A2) and Etest methods. Amphotericin B, voriconazole, miconazole and clotrimazole showed high in vitro activity against all isolates with MIC ranging from 0.0313 to 1 µg/mL. Susceptibility towards fluconazole and itraconazole was noted in up to 10% of isolates, while ketoconazole was inactive against all isolates. Clinical breakpoints for antifungal drugs are not yet available for most filamentous fungi, including Neoscytalidium species. However, the results indicate that clinical isolates of N. dimidiatum in Malaysia were sensitive towards miconazole, clotrimazole, voriconazole and amphotericin B, in vitro.

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