Displaying publications 1 - 20 of 45 in total

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  1. Burkholderia pseudomallei: in vitro susceptibility to some new and old antimicrobials
    Karunakaran R, Puthucheary SD
    Scand. J. Infect. Dis., 2007;39(10):858-61.
    PMID: 17852912
    The treatment of melioidosis currently involves the use of antimicrobials such as ceftazidime, trimethoprim-sulfamethoxazole, amoxicillin-clavulanate and doxycycline. Evaluation of other antimicrobials with activity against the organism continues to be pursued, however, as the causative organism, B. pseudomallei, may not always be susceptible to the above antimicrobials. This study aimed to test the susceptibility of Malaysian isolates of B. pseudomallei against imipenem, meropenem, ertapenem, moxifloxacin and azithromycin. 80 previously stocked clinical isolates collected between 1978 and 2003 from the UMMC, Kuala Lumpur were tested for in vitro susceptibility to these antimicrobials using the E-test minimum inhibitory concentration method. 100% of isolates were sensitive to imipenem and meropenem, 97.5% were sensitive to trimethoprim-sulfamethozaxole, 37.5% to moxifloxacin, and only a minority was sensitive to ertapenem (7.5%). Using breakpoints for Staphylococcus and Haemophilus, 5.0%-6.3% of isolates were sensitive to azithromycin. In conclusion, our findings support the in vitro efficacy of imipenem, meropenem and trimethoprim-sulfamethoxazole against B. pseudomallei. Moxifloxacin, ertapenem and azithromycin cannot be recommended for the treatment of melioidosis; however, further studies are needed to test the efficacy of azithromycin in combination with quinolones.
  2. Mutations in gyrA and parC in ciprofloxacin-resistant Neisseria gonorrhoeae in Kuala Lumpur, Malaysia
    Karunakaran R, Sam IC
    J Antimicrob Chemother, 2007 Apr;59(4):803-4.
    PMID: 17329273
  3. A molecular dynamics approach to explore the structural characterization of cataract causing mutation R58H on human γD crystallin
    Karunakaran R, Srikumar PS
    Mol Cell Biochem, 2018 Dec;449(1-2):55-62.
    PMID: 29532225 DOI: 10.1007/s11010-018-3342-8
    The crystallins are a family of monomeric proteins present in the mammalian lens and mutations in these proteins cause various forms of cataracts. The aim of our current study is to emphasize the structural characterization of aggregation propensity of mutation R58H on γD crystallin using molecular dynamics (MD) approach. MD result revealed that difference in the sequence level display a wide variation in the backbone atomic position, and thus exhibits rigid conformational dynamics. Changes in the flexibility of residues favoured to increase the number of intra-molecular hydrogen bonds in mutant R58H. Moreover, notable changes in the hydrogen bonding interaction resulted to cause the misfolding of mutant R58H by introducing α-helix. Principal component analysis (PCA) result suggested that mutant R58H showed unusual conformational dynamics along the two principal components when compared to the wild-type (WT)-γD crystallin. In a nutshell, the increased surface hydrophobicity could be the cause of self-aggregation of mutant R58H leading to aculeiform cataract.
  4. Serotype distribution and antibiotic susceptibility of group B streptococci in pregnant women
    Dhanoa A, Karunakaran R, Puthucheary SD
    Epidemiol Infect, 2010 Jul;138(7):979-81.
    PMID: 19889253 DOI: 10.1017/S0950268809991105
    Group B streptococcus (GBS) is a leading cause of neonatal sepsis and is usually acquired via the woman's birth canal. GBS serotypes isolated from 200 pregnant women were determined. Serotypes V (19%) and VI (17%) were the most frequent followed by serotypes III (12%), Ia (11.5%) and IV (10%); 17% of the strains were non-typable. All isolates were susceptible to penicillin, 96% to erythromycin and 97.5% to clindamycin. The emergence of new GBS serotypes has important implications for vaccine prevention strategies.
  5. Isolation of Neissseria meningitidis from an unusual site
    Karunakaran R, Ngeow YF, Mashor M
    Malays J Pathol, 2002 Dec;24(2):103-5.
    PMID: 12887169
    A 59-year-old post-menopausal lady who had returned from a pilgrimage to Mecca about a month earlier presented with a three days' history of profuse vaginal discharge. Neissseria meningitidis was isolated from high vaginal swab specimens taken from her on 2 occasions, five days apart. Her symptoms disappeared without treatment after two weeks. We conclude that although the organism may have been a colonizer, it is possible that it was responsible for the self-limiting genital infection in this patient.
  6. Fulltext Structure-Activity Relationship Analysis of Benzimidazoles as Emerging Anti-Inflammatory Agents: An Overview
    Veerasamy R, Roy A, Karunakaran R, Rajak H
    Pharmaceuticals (Basel), 2021 Jul 11;14(7).
    PMID: 34358089 DOI: 10.3390/ph14070663
    A significant number of the anti-inflammatory drugs currently in use are becoming obsolete. These are exceptionally hazardous for long-term use because of their possible unfavourable impacts. Subsequently, in the ebb-and-flow decade, analysts and researchers are engaged in developing new anti-inflammatory drugs, and many such agents are in the later phases of clinical trials. Molecules with heterocyclic nuclei are similar to various natural antecedents, thus acquiring immense consideration from scientific experts and researchers. The arguably most adaptable heterocyclic cores are benzimidazoles containing nitrogen in a bicyclic scaffold. Numerous benzimidazole drugs are broadly used in the treatment of numerous diseases, showing promising therapeutic potential. Benzimidazole derivatives exert anti-inflammatory effects mainly by interacting with transient receptor potential vanilloid-1, cannabinoid receptors, bradykinin receptors, specific cytokines, 5-lipoxygenase activating protein and cyclooxygenase. Literature on structure-activity relationship (SAR) and investigations of benzimidazoles highlight that the substituent's tendency and position on the benzimidazole ring significantly contribute to the anti-inflammatory activity. Reported SAR analyses indicate that substitution at the N1, C2, C5 and C6 positions of the benzimidazole scaffold greatly influence the anti-inflammatory activity. For example, benzimidazole substituted with anacardic acid on C2 inhibits COX-2, and 5-carboxamide or sulfamoyl or sulfonyl benzimidazole antagonises the cannabinoid receptor, whereas the C2 diarylamine and C3 carboxamide substitution of the benzimidazole scaffold result in antagonism of the bradykinin receptor. In this review, we examine the insights regarding the SARs of anti-inflammatory benzimidazole compounds, which will be helpful for researchers in designing and developing potential anti-inflammatory drugs to target inflammation-promoting enzymes.
  7. Community-acquired vancomycin-resistant Enterococcus faecium: a case report from Malaysia
    Raja NS, Karunakaran R, Ngeow YF, Awang R
    J Med Microbiol, 2005 Sep;54(Pt 9):901-903.
    PMID: 16091445 DOI: 10.1099/jmm.0.46169-0
    Vancomycin-resistant enterococci (VRE) are formidable organisms renowned for their ability to cause infections with limited treatment options and their potential for transferring resistance genes to other Gram-positive bacteria. Usually associated with nosocomial infections, VRE are rarely reported as a cause of community-acquired infection. Presented here is a case of community-acquired infection due to vancomycin-resistant Enterococcus faecium. The patient had been applying herbal leaves topically to his cheek to treat a buccal space abscess, resulting in a burn of the overlying skin. From pus aspirated via the skin a pure culture of E. faecium was grown that was resistant to vancomycin with a MIC of >256 microg ml-1 by the E test and resistant to teicoplanin by disc diffusion, consistent with the VanA phenotype. The organism was suspected of contaminating the leaf and infecting the patient via the burnt skin. This case highlights the need for further studies on the community prevalence of VRE among humans and animals to define unrecognized silent reservoirs for VRE, which may pose a threat to public health.
  8. Imipenem-resistance in Klebsiella pneumoniae in Malaysia due to loss of OmpK36 outer membrane protein coupled with AmpC hyperproduction
    Palasubramaniam S, Karunakaran R, Gin GG, Muniandy S, Parasakthi N
    Int J Infect Dis, 2007 Sep;11(5):472-4.
    PMID: 17337225
  9. Etiology of blood culture isolates among patients in a multidisciplinary teaching hospital in Kuala Lumpur
    Karunakaran R, Raja NS, Ng KP, Navaratnam P
    J Microbiol Immunol Infect, 2007 Oct;40(5):432-7.
    PMID: 17932604
    Bloodstream infections are an important cause of morbidity and mortality among hospitalized patients and the surveillance of etiological agents in these infections is important for their prevention and treatment. Data on common organisms isolated from blood cultures from Malaysia are limited, and our aim was to identify the common bloodstream isolates in hospitalized patients at the University of Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia.
  10. Eikenella corrodens from a brain abscess
    Karunakaran R, Marret MJ, Hassan H, Puthucheary SD
    Malays J Pathol, 2004 Jun;26(1):49-52.
    PMID: 16190107
    A 2-year-old boy with underlying congenital cyanotic heart disease presented with seizures and fever and was found to have bilateral parietal cerebral abscesses. Drainage of the pus from the abscesses was done in stages; on the day of admission, four days after admission and 3 weeks after admission. Although the pus from the first drainage did not grow any organisms, the pus from the second drainage on the fourth day of admission yielded a mixed growth of Eikenella corrodens and Streptococcus milleri. Following the second drainage of pus, the child was noted to have mild weakness (grade 3/5) and increased tone in the left upper limb. Three weeks after admission, due to recurring fever, further neurological signs and findings of an enlarging right cerebral abscess on a repeat CT scan, a third drainage was carried out. However no growth was obtained from this specimen. This patient was managed both surgically and with appropriate antibiotics. Over the next four months, serial CT scans revealed gradual resolution of the abscesses with disappearance of the surrounding oedema. The child showed gradual recovery of his left sided weakness with resolution of tone and reflexes to normal.
  11. Fulltext Genotypic and Phenotypic Detection of AmpC β-lactamases in Enterobacter spp. Isolated from a Teaching Hospital in Malaysia
    Mohd Khari FI, Karunakaran R, Rosli R, Tee Tay S
    PLoS One, 2016;11(3):e0150643.
    PMID: 26963619 DOI: 10.1371/journal.pone.0150643
    OBJECTIVES: The objective of this study was to determine the occurrence of chromosomal and plasmid-mediated β-lactamases (AmpC) genes in a collection of Malaysian isolates of Enterobacter species. Several phenotypic tests for detection of AmpC production of Enterobacter spp. were evaluated and the agreements between tests were determined.

    METHODS: Antimicrobial susceptibility profiles for 117 Enterobacter clinical isolates obtained from the Medical Microbiology Diagnostic Laboratory, University Malaya Medical Centre, Malaysia, from November 2012-February 2014 were determined in accordance to CLSI guidelines. AmpC genes were detected using a multiplex PCR assay targeting the MIR/ACT gene (closely related to chromosomal EBC family gene) and other plasmid-mediated genes, including DHA, MOX, CMY, ACC, and FOX. The AmpC β-lactamase production of the isolates was assessed using cefoxitin disk screening test, D69C AmpC detection set, cefoxitin-cloxacillin double disk synergy test (CC-DDS) and AmpC induction test.

    RESULTS: Among the Enterobacter isolates in this study, 39.3% were resistant to cefotaxime and ceftriaxone and 23.9% were resistant to ceftazidime. Ten (8.5%) of the isolates were resistant to cefepime, and one isolate was resistant to meropenem. Chromosomal EBC family gene was amplified from 36 (47.4%) E. cloacae and three (25%) E. asburiae. A novel blaDHA type plasmid-mediated AmpC gene was identified for the first time from an E. cloacae isolate. AmpC β-lactamase production was detected in 99 (89.2%) of 111 potential AmpC β-lactamase producers (positive in cefoxitin disk screening) using D69C AmpC detection set. The detection rates were lower with CC-DDS (80.2%) and AmpC induction tests (50.5%). There was low agreement between the D69C AmpC detection set and the other two phenotypic tests. Of the 40 isolates with AmpC genes detected in this study, 87.5%, 77.5% and 50.0% of these isolates were positive by the D69C AmpC detection set, CC-DDS and AmpC induction tests, respectively.

    CONCLUSIONS: Besides MIR/ACT gene, a novel plasmid-mediated AmpC gene belonging to the DHA-type was identified in this study. Low agreement was noted between the D69C AmpC detection set and two other phenotypic tests for detection of AmpC production in Enterobacter spp. As plasmid-mediated genes may serve as the reservoir for the emergence of antibiotic resistance in a clinical setting, surveillance and infection control measures are necessary to limit the spread of these genes in the hospital.

  12. Fulltext A retrospective review of mucocutaneous infections by human herpesvirus 1 and 2 in an urban population in Malaysia
    Hooi PS, Chua BH, Karunakaran R, Lam SK, Chua KB
    Med J Malaysia, 2002 Mar;57(1):80-7.
    PMID: 14569722 MyJurnal
    This is a 10-year retrospective review of mucocutaneous infection by human herpesvirus 1 (HHV1) and human herpesvirus 2 (HHV2) carried out by the virus diagnostic unit of University Malaya Medical Centre (UMMC). A total of 504 specimens from UMMC and a private clinic in the same city (KLSC) were tested; 198 samples from patients with oral lesions and 306 from patients with genital lesions. HHV1 was found to be responsible for 98.4% of oral lesions whereas HHV2 was the cause of 83.6% of all genital lesions. Detailed analysis showed no statistical difference by age group, race or gender among the patients with oral and genital lesions. Two laboratory methods were used in this study. Of the total 504 specimens tested, 18.0% specimens were positive by direct immunofluorescence (IF), 55.0% by virus isolation and 56.5% when both methods were used in combination. Although IF can provide a more rapid diagnosis, it is, however, less sensitive and can be attributed partly to inadequate collection of specimens.
  13. Group B Streptococcus infection: epidemiology, serotypes, and antimicrobial susceptibility of selected isolates in the population beyond infancy (excluding females with genital tract- and pregnancy-related isolates) at the University Malaya Medical Centre, Kuala Lumpur
    Karunakaran R, Raja NS, Hafeez A, Puthucheary SD
    Jpn J Infect Dis, 2009 May;62(3):192-4.
    PMID: 19468178
    Group B Streptococcus (GBS) infection was studied in 49 patients collected at convenience (convenience sampling), excluding infants and women with genital tract- and pregnancy-related isolates, according to the availability of stocked isolates and easy accessibility to epidemiological data. The data were examined both prospectively and retrospectively from 2003-2005 at a tertiary-level multidisciplinary hospital in Kuala Lumpur, Malaysia. Skin and soft-tissue infections in 35 patients (71.4%) were the most common clinical presentation, while diabetes mellitus was the most common underlying condition (35 patients, 71.4%). All GBS isolates were sensitive to penicillin, and most isolates tested were sensitive to erythromycin (97.7%). Serotyping of 45 GBS isolates using a commercial serotyping kit revealed that the most common serotype was Ia (22.2%), followed by VI (17.8%), III and V (13.3% each). Others included Ib, II, IV, VIII, and VII; 13.3% were nontypeable. The findings of this pilot study are limited by the small sample size, the sampling method and the possibility that the cases are not wholly representative of the University Malaya Medical Centre population. Further studies from our hospital with larger numbers and using probabilistic sampling techniques are required to confirm the relatively high occurrence of serotype VI (the second most common serotype) in the population studied.
  14. Fulltext Transcriptome analysis during fruit developmental stages in durian (Durio zibethinus Murr.) var. D24
    Husin NA, Rahman S, Karunakaran R, Bhore SJ
    Genet Mol Biol, 2023;45(4):e20210379.
    PMID: 36622241 DOI: 10.1590/1678-4685-GMB-2021-0379
    Durian (Durio zibethinus Murr.) fruits are famous for their unique aroma. This study analysed the Durian fruit transcriptome to discover the expression patterns of genes and to understand their regulation. Three developmental stages of Durian fruit, namely, early [90 days post-anthesis (DPA)], mature (120 DPA), and ripen (127 DPA), were studied. The Illumina HiSeq platform was used for sequencing. The sequence data were analysed using four different mapping aligners and statistical methods: CLC Genomic Workbench, HISAT2+DESeq2, Tophat+Cufflinks, and HISAT2+edgeR. The analyses showed that over 110 million clean reads were mapped to the Durian genome, yielding 19,976, 11,394, 17,833, and 24,351 differentially expressed genes during 90-127 days post-anthesis. Many identified differentially expressed genes were linked to the fruit ripening processes. The data analysis suggests that most genes with increased expression at the ripening stage were primarily involved in the metabolism of cofactors and vitamins, nucleotide metabolism, and carbohydrate metabolism. Significantly expressed genes from the young to mature stage were mainly associated with carbohydrate metabolism, amino acid metabolism, and cofactor and vitamin metabolism. The transcriptome data will serve as a foundation for understanding Durian fruit development-specific genes and could be helpful in fruit's trait improvement.
  15. Fulltext A review on the nutritional, medicinal, molecular and genome attributes of Durian (Durio zibethinus L.), the King of fruits in Malaysia
    Husin NA, Rahman S, Karunakaran R, Bhore SJ
    Bioinformation, 2018;14(6):265-270.
    PMID: 30237671 DOI: 10.6026/97320630014265
    Durian (Durio zibethinus L.; Family Bombacaceae) is an iconic tropical fruit plant cultivated in Malaysia and the Southeast Asian countries. In Malaysia, durian is recognised as the King of fruits and well known as a rich source of volatile sulphur compounds that make it unique. Fruit pulp of this fruit is an excellent source of nutrients as it contains proteins, dietary fat, fibers, and carbohydrates. Durian leaf and root decoctions are known to have a febrifuge and anti-malarial properties. The understanding of this plant's molecular biology will help breeders to develop a strategy for its further improvements. Hence, there is a need to identify and understand the genes necessary for the quality improvement of the durian fruits. Its genome contains about 46,000 genes which is almost double that of humans (Homo sapiens). The understanding of durian genes will be useful not only in the molecular breeding but also in the microbial production of novel proteins and or enzymes. This review highlights nutritional and medicinal attributes of durian. The molecular studies including the importance of undertaking transcriptomics work and the insights from the most recently reported genome draft are also highlighted.
  16. Isolation of Aggregatibacter aphrophilus from a patient with acute appendicitis
    Aye AM, Law CW, Sabet NS, Karunakaran R, Hanifah YA, Jafar FL, et al.
    Eur Rev Med Pharmacol Sci, 2011 Jul;15(7):845-7.
    PMID: 21780555
    Acute appendicitis is a common surgical emergency. The etiology and pathophysiology of appendicitis have been well investigated. Aggregatibacter aphrophilus is a fastidious gram-negative coccobacilli. Detection of this organism in clinical samples and its differentiation from Haemophilus aphrophilus or from Aggregatibacter actinomycetemcomitans in routine microbiology settings could be difficult.
  17. Fulltext Tsukamurella tyrosinosolvens intravascular catheter-related bacteremia in a haematology patient: a case report
    Karunakaran R, Halim HA, Ng KP, Hanifah YA, Chin E, Jaafar FL, et al.
    Eur Rev Med Pharmacol Sci, 2011 Nov;15(11):1343-6.
    PMID: 22195371
    Tsukamurella spp. are a rare but important cause of intravascular catheter-related bacteremia in immunocompromised patients. The organism is an aerobic, Gram-positive, weakly acid-fast bacillus that is difficult to differentiate using standard laboratory methods from other aerobic actinomycetales such as Nocardia spp., Rhododoccus spp., Gordonia spp., and the rapid growing Mycobacterium spp. We report a case of Tsukamurella tyrosinosolvens catheter-related bacteremia in a 51-year-old haematology patient who responded to treatment with imipenem and subsequent line removal. 16srRNA sequencing allowed for the prompt identification of this organism.
  18. Fulltext Clinical features of Malaysian children hospitalized with community-acquired seasonal influenza
    Sam IC, Abdul-Murad A, Karunakaran R, Rampal S, Chan YF, Nathan AM, et al.
    Int J Infect Dis, 2010 Sep;14 Suppl 3:e36-40.
    PMID: 20153233 DOI: 10.1016/j.ijid.2009.10.005
    OBJECTIVES: The clinical impact of seasonal influenza is understudied in tropical countries. The aim of this study was to describe the clinical features and seasonal pattern of influenza in children hospitalized in Malaysia, and to identify predictors of severe disease.
    METHODS: Children hospitalized with community-acquired, laboratory-confirmed influenza at a teaching hospital in Kuala Lumpur, Malaysia during 2002-2007 were identified retrospectively. Clinical data were collected, and predictors of severe disease were identified by multivariate logistic regression. All influenza cases from 1982 to 2007 were also analyzed for seasonal patterns.
    RESULTS: A total of 132 children were included in the study, 48 (36.4%) of whom had underlying medical conditions. The mean age was 2.5 years and 116 (87.9%) were <5 years old. The most common presenting features were fever or history of fever, cough, rhinitis, vomiting, and pharyngitis. Severe influenza was seen in 16 patients (12.1%; nine previously healthy), including 12 (9.1%; eight previously healthy) requiring intensive care. There were three (2.3%) deaths. Severe disease was associated with age <12 months, female sex, and absence of rhinitis on admission. Influenza was seen year-round, with peaks in November-January and May-July.
    CONCLUSIONS: Seasonal influenza has a considerable impact on children hospitalized in Malaysia, in both the healthy and those with underlying medical conditions.

    Study site: University Malaya Medical Centre (UMMC)
  19. Evaluation of the routine use of the anaerobic bottle when using the BACTEC blood culture system
    Karunakaran R, Raja NS, Quek KF, Hoe VC, Navaratnam P
    J Microbiol Immunol Infect, 2007 Oct;40(5):445-9.
    PMID: 17932606
    The established practice of sending blood cultures in an aerobic-anaerobic pair of bottles has been questioned in recent years, and this study was conducted to evaluate the routine use of an anaerobic bottle in the BACTEC blood culture set at the University of Malaya Medical Centre, Kuala Lumpur, from January to December 2004. A total of 11,663 paired blood culture sets were received, of which 3326 were from pediatric patients and 8337 were from adult patients. The overall positive isolation rate was 15%; the positive isolation rate on excluding the anaerobic bottles was 13%. Overall, there were significantly more organisms isolated from the aerobic bottle (p<0.05); however, the best yield was obtained on using the paired aerobic-anaerobic bottles. Among the positive blood culture sets, organisms were isolated from the anaerobic bottle alone in 15.2% of the pediatric sets and in 18.1% of the adult sets. Organisms that grew more frequently in the anaerobic bottle were anaerobes and some facultative anaerobes; however, the difference was not statistically significant except for anaerobes in the adult sets. We recommend that when culturing blood, an aerobic-anaerobic pair of bottles be used rather than an aerobic-aerobic pair, to optimize the recovery of a wider spectrum of organisms, including obligatory anaerobes.
  20. Rotavirus and other enteropathogens in childhood acute diarrhoea: a study of two centres in Malaysia
    Lee WS, Rajasekaran G, Pee S, Karunakaran R, Hassan HH, Puthucheary SD
    J Paediatr Child Health, 2006 Sep;42(9):509-14.
    PMID: 16925536
    To study the role of rotavirus in children hospitalised for acute gastroenteritis (AGE) in two urban hospitals in Malaysia.
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