Displaying publications 1 - 20 of 87 in total

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  1. Hussin Z, Lim VKE
    Med J Malaysia, 1982 Jun;37(2):104-7.
    PMID: 7132829
    Gentamicin is an aminoglycoside antibiotic which is commonly used in the treatment of serious Gram-negative infections. However, gentamicin like other aminoglycosides, has a narrow therapeutic index and is potentially ototoxic and nephrotoxic. Blood levels following administration of gentamicin has been shown to be highly unpredictable and monitoring of gentamicin levels is necessary to ensure effective therapeutic levels as well as to avoid toxicity. The Department of Microbiology, Universiti Kebangsaan Malaysia offers such a monitoring service. This paper analyses the results of 135 such estimations performed between August 1979 and May 1981. It is shown that a significant proportion of patients were receiving either too much or too little gentamicin. Empirical determinations of dosages is unsatisfactory and as the microbiological assay method of determining gentamicin levels is both easy to perform and inexpensive, such a service should be offered by all general hospitals in Malaysia.
    Matched MeSH terms: Gentamicins/blood*
  2. Ng JML, Ngeow YF, Saw SH, Ng HF, Zin T
    J Med Microbiol, 2022 Dec;71(12).
    PMID: 36748567 DOI: 10.1099/jmm.0.001618
    Introduction Listeriosis, a foodborne infection caused by Listeria monocytogenes, could lead to febrile listerial gastroenteritis and a more invasive form which is often associated with a high mortality and hospitalisation rate. Gentamicin, used as an adjunct therapy with ampicillin, remains the treatment of choice for this life-threatening and invasive infection.Gap statement Nevertheless, there is little data on gentamicin resistance determinants in L. monocytogenes.Aim In this study, we selected and characterised B2b, a gentamicin-resistant mutant derived from L. monocytogenes ATCC 19115 to determine the target(s) of resistance in L. monocytogenes after exposure to gentamicin.Methodology Whole-genome sequencing was carried out to identify the mutation site(s) and possible mechanism(s) of resistance. The mutant was characterised using antimicrobial susceptibility testing and PCR. For biological verifications, complementation and allelic exchange mutagenesis were carried out.Results We found that the gentamicin resistance in B2b was caused by a 10 bp deletion in atpG2 which encodes a gamma subunit of the ATP synthase in L. monocytogenes. Using atpG2 PCR, various other mutations were identified in other gentamicin resistant mutants derived from ATCC 19115. In addition, the mutation from B2b, when introduced into L. ivanovii, also caused gentamicin resistance in this Listeria species.Conclusion Hence, atpG2 mutations appear to be important determinants of gentamicin resistance not only in L. monocytogenes but possibly also in other Listeria species.
    Matched MeSH terms: Gentamicins/pharmacology
  3. Hussin A, Nathan S, Shahidan MA, Nor Rahim MY, Zainun MY, Khairuddin NAN, et al.
    Mol Genet Genomics, 2024 Feb 21;299(1):12.
    PMID: 38381232 DOI: 10.1007/s00438-024-02105-w
    The bacterium Burkholderia pseudomallei is typically resistant to gentamicin but rare susceptible strains have been isolated in certain regions, such as Thailand and Sarawak, Malaysia. Recently, several amino acid substitutions have been reported in the amrB gene (a subunit of the amrAB-oprA efflux pump gene) that confer gentamicin susceptibility. However, information regarding the mechanism of the substitutions conferring the susceptibility is lacking. To understand the mechanism of amino acid substitution that confers susceptibility, this study identifies the corresponding mutations in clinical gentamicin-susceptible B. pseudomallei isolates from the Malaysian Borneo (n = 46; Sarawak: 5; Sabah: 41). Three phenotypically confirmed gentamicin-susceptible (GENs) strains from Sarawak, Malaysia, were screened for mutations in the amrB gene using gene sequences of gentamicin-resistant (GENr) strains (QEH 56, QEH 57, QEH20, and QEH26) and publicly available sequences (AF072887.1 and BX571965.1) as the comparator. The effect of missense mutations on the stability of the AmrB protein was determined by calculating the average energy change value (ΔΔG). Mutagenesis analysis identified a polymorphism-associated mutation, g.1056 T > G, a possible susceptible-associated in-frame deletion, Delta V412, and a previously confirmed susceptible-associated amino acid substitution, T368R, in each of the three GENs isolates. The contribution of Delta V412 needs further confirmation by experimental mutagenesis analysis. The mechanism by which T368R confers susceptibility, as elucidated by in silico mutagenesis analysis using AmrB-modeled protein structures, is proposed to be due to the location of T368R in a highly conserved region, rather than destabilization of the AmrB protein structure.
    Matched MeSH terms: Gentamicins/pharmacology
  4. Ismail R, Sarriff A, Abdul Rahman AF
    Med J Malaysia, 1990 Mar;45(1):57-64.
    PMID: 2152070
    We evaluated the usefulness of therapeutic drug monitoring (TDM) for gentamicin and the use of a two-point peak and trough pair concentration method to adjust its dose. Of the 194 patients included, initial concentrations were appropriate in only sixty nine. In the seventy one cases of dosage adjustments using this method, those attaining therapeutic levels increased overall from 38% to 67%. It is concluded that TDM for gentamicin with dosage adjustment using this simple pharmacokinetic approach is useful and adequate in monitoring for gentamicin therapy.
    Matched MeSH terms: Gentamicins/administration & dosage*; Gentamicins/blood; Gentamicins/therapeutic use
  5. Ahmed Abdelrahim HE, Ab Rahman AF, Mohamed Ibrahim MI
    Eurasian J Med, 2012 Apr;44(1):1-5.
    PMID: 25610196 DOI: 10.5152/eajm.2012.01
    In Malaysia, therapeutic drug monitoring (TDM) service started in the late 1980s. Serum concentration measurements depend on commercially available drug assays, which are costly. In the present study, we attempted to document the impact of TDM service on cost and patient outcomes.
    Matched MeSH terms: Gentamicins*
  6. Farizaturradiah O, Mohamed Z, Sim SM, Lim CT
    JUMMEC, 1997;2:35-38.
    Matched MeSH terms: Gentamicins
  7. Ismail R, Haq AH, Azman M, Rahman AF
    J Clin Pharm Ther, 1997 Feb;22(1):21-5.
    PMID: 9292398
    In 1984 a therapeutic drug monitoring (TDM) service was established in Hospital Universiti Sains Malaysia (HUSM) and gentamicin concentrations were measured and used to design optimal regimens for the antibiotic. In this study we report on a 6-year follow-up audit since our first assessment of the service.
    Matched MeSH terms: Gentamicins/administration & dosage; Gentamicins/adverse effects; Gentamicins/blood; Gentamicins/therapeutic use*
  8. Gendeh BS, Said H, Gibb AG, Aziz NS, Zahir ZM
    J Laryngol Otol, 1991 Dec;105(12):999-1001.
    PMID: 1787382
    In a prospective study on 47 patients, 16 mg of gentamicin per two litres dialysate was administered intraperitoneally at every cycle of intermittent peritoneal dialysis, carried out over the course of several days. Serum gentamicin sampling, pure tone audiometry and caloric tests were performed before and during the treatment. The gentamicin levels reached at the end of the thirtieth cycle were observed to be low. In view of this, the risk of acute ototoxicity was considered to be minimal. This was confirmed by the absence of clinical audiometric or vestibulometric evidence of toxicity.
    Matched MeSH terms: Gentamicins/administration & dosage; Gentamicins/adverse effects*; Gentamicins/blood; Gentamicins/therapeutic use
  9. Podin Y, Sarovich DS, Price EP, Kaestli M, Mayo M, Hii K, et al.
    Antimicrob Agents Chemother, 2014;58(1):162-6.
    PMID: 24145517 DOI: 10.1128/AAC.01842-13
    Melioidosis is a potentially fatal disease caused by the saprophytic bacterium Burkholderia pseudomallei. Resistance to gentamicin is generally a hallmark of B. pseudomallei, and gentamicin is a selective agent in media used for diagnosis of melioidosis. In this study, we determined the prevalence and mechanism of gentamicin susceptibility found in B. pseudomallei isolates from Sarawak, Malaysian Borneo. We performed multilocus sequence typing and antibiotic susceptibility testing on 44 B. pseudomallei clinical isolates from melioidosis patients in Sarawak district hospitals. Whole-genome sequencing was used to identify the mechanism of gentamicin susceptibility. A novel allelic-specific PCR was designed to differentiate gentamicin-sensitive isolates from wild-type B. pseudomallei. A reversion assay was performed to confirm the involvement of this mechanism in gentamicin susceptibility. A substantial proportion (86%) of B. pseudomallei clinical isolates in Sarawak, Malaysian Borneo, were found to be susceptible to the aminoglycoside gentamicin, a rare occurrence in other regions where B. pseudomallei is endemic. Gentamicin sensitivity was restricted to genetically related strains belonging to sequence type 881 or its single-locus variant, sequence type 997. Whole-genome sequencing identified a novel nonsynonymous mutation within amrB, encoding an essential component of the AmrAB-OprA multidrug efflux pump. We confirmed the role of this mutation in conferring aminoglycoside and macrolide sensitivity by reversion of this mutation to the wild-type sequence. Our study demonstrates that alternative B. pseudomallei selective media without gentamicin are needed for accurate melioidosis laboratory diagnosis in Sarawak. This finding may also have implications for environmental sampling of other locations to test for B. pseudomallei endemicity.
    Matched MeSH terms: Gentamicins/pharmacology
  10. Mathews A, Bailie GR
    J Clin Pharm Ther, 1987 Oct;12(5):273-91.
    PMID: 3119606
    This article reviews the clinical pharmacokinetics, clinical toxicity and cost-effectiveness analysis of aminoglycosides and of dosing services for aminoglycosides. The reader is referred elsewhere for a review of the pharmacology, antimicrobial spectrum of activity and clinical use of these drugs. A critique of the more commonly used methods of aminoglycoside dosage determinations is included, based on the inter-individual variation in aminoglycoside disposition parameters. The advantages and disadvantages of arbitrary, predictive, and pharmacokinetic methods of dosing determination are summarized. Justification for the routine determination of serum aminoglycoside concentrations is reviewed. We review the lack of standardization of definitions for aminoglycoside-associated nephrotoxicity in published studies, and studies which illustrate these differences are highlighted. Evidence for the association between serum aminoglycoside concentrations and nephrotoxicity is examined. Ototoxicity is similarly reviewed. The concept of cost-effectiveness analysis is examined extensively in this review. We discuss the literature concerning the cost benefit analysis of drug dosing services.
    Matched MeSH terms: Gentamicins/administration & dosage; Gentamicins/adverse effects; Gentamicins/pharmacokinetics
  11. Abu Zarrin, A.M., Nor Munirah, M.A., Mohammad Izwan, E.O., Abdullah, A.S., Hanani, A.Y.
    Medicine & Health, 2020;15(1):166-176.
    MyJurnal
    Staphylococcus epidermidis (S. epidermidis) menjadi salah satu keprihatinan utama dalam pengurusan hospital berikutan kebolehannya menyebabkan jangkitan perolehan hospital terutamanya daripada alatan perubatan yang tercemar. Pengurusan jangkitan S. epidermidis semakin mencabar dengan peningkatan kes kerintangan terhadap antibiotik sejak kebelakangan ini. Laporan terhad mengenai kerintangan terhadap antibiotik oleh S. epidermidis di kalangan kumpulan komuniti yang sihat meninggalkan satu persoalan mengenai tahap penyebaran bakteria rintang antibiotik di kalangan komuniti. Oleh itu, kajian ini bertujuan untuk mengenalpasti corak rentan antibiotik oleh S. epidermidis yang dipencilkan daripada pelajar-pelajar sihat di salah satu kampus kesihatan di universiti awam. Sebanyak 96 sampel sapuan telapak tangan telah diambil dan melalui beberapa ujikaji termasuk ujian pengenalpastian secara mikroskopik, biokimia dan juga ujian rentan antiobiotik untuk eryhtromycin, oxacillin, gentamicin, penicillin dan tetracycline menerusi ujian Kirby Bauer. Sejumlah 43 sampel menunjukkan kehadiran S. epidermidis (44.8%), di mana 72.1% daripada jumlah pencilan bakteria ini menunjukkan kerintangan terhadap sekurang-kurangnya satu jenis antibiotik. Tahap kerintangan tertinggi dan terendah masing-masing didapati pada penicillin dan gentamicin. Walaupun tiada perbezaan yang signifikan antara corak rentan antibiotik antara kumpulan jantina, tahap kerintangan antibiotik yang tinggi di kalangan komuniti sihat menunjukkan terdapat keperluan terhadap kajian lanjut kerana penyebaran strain bakteria rintang antibiotik boleh berlaku kepada populasi komuniti lain dengan lebih meluas dan tanpa disedari.
    Matched MeSH terms: Gentamicins
  12. Ab Rahman AF, Md Sahak N, Ali AM
    Int J Pharm Pract, 2017 Feb;25(1):75-80.
    PMID: 28097717 DOI: 10.1111/ijpp.12336
    OBJECTIVES: Published nomograms to monitor extended-interval dosing (EID) gentamicin therapy were based on a fixed dose of 5 or 7 mg/kg. However, the average dose used for EID gentamicin regimen in our setting was about 3 mg/kg per day. We developed a new method of monitoring based on the duration of drug-free period (DFP) in a 24-h dosing interval.

    METHODS: Hospitalised adult patients on EID gentamicin were selected. We considered a DFP of between 2 and 8 h as appropriate. Data from two blood samples (2 and 6 h postdose) from each patient were used to estimate the duration of DFP (i.e. DFP method 1). DFP was also calculated for the same patient using an empirically estimated elimination rate constant (Ke ) and the same 6 h postdose concentration value (DFP method 2). Correlation between the two methods was made. An alternative graphical method to estimate DFP was attempted.

    KEY FINDINGS: Correlation between Ke and age was favourable (r = -0.453; P = 0.001). Ke derived from this empirical relationship was used to estimate DFP method 2. DFP method 1 correlated well with DFP method 2 (r = 0.742; P 

    Matched MeSH terms: Gentamicins/administration & dosage*; Gentamicins/blood; Gentamicins/pharmacokinetics*
  13. Jeyamalar R, Sivanesaratnam V
    Aust N Z J Obstet Gynaecol, 1991 May;31(2):123-4.
    PMID: 1930032
    Matched MeSH terms: Gentamicins/administration & dosage; Gentamicins/therapeutic use*
  14. Lee WX, Basri DF, Ghazali AR
    Molecules, 2017 Mar 17;22(3).
    PMID: 28304328 DOI: 10.3390/molecules22030463
    The antibacterial activity of pterostilbene in combination with gentamicin against six strains of Gram-positive and Gram-negative bacteria were investigated. The minimum inhibitory concentration and minimum bactericidal concentration of pterostilbene were determined using microdilution technique whereas the synergistic antibacterial activities of pterostilbene in combination with gentamicin were assessed using checkerboard assay and time-kill kinetic study. Results of the present study showed that the combination effects of pterostilbene with gentamicin were synergistic (FIC index < 0.5) against three susceptible bacteria strains: Staphylococcus aureus ATCC 25923, Escherichia coli O157 and Pseudomonas aeruginosa 15442. However, the time-kill study showed that the interaction was indifference which did not significantly differ from the gentamicin treatment. Furthermore, time-kill study showed that the growth of the tested bacteria was completely attenuated with 2 to 8 h treatment with 0.5 × MIC of pterostilbene and gentamicin. The identified combinations could be of effective therapeutic value against bacterial infections. These findings have potential implications in delaying the development of bacterial resistance as the antibacterial effect was achieved with the lower concentrations of antibacterial agents.
    Matched MeSH terms: Gentamicins/pharmacology*; Gentamicins/chemistry
  15. Gendeh BS, Said H, Gibb AG, Aziz NS, Kong N, Zahir ZM
    J Laryngol Otol, 1993 Aug;107(8):681-5.
    PMID: 8409715 DOI: 10.1017/s0022215100124132
    A prospective study was undertaken of 10 chronic renal failure patients on Continuous Ambulatory Peritoneal Dialysis (CAPD) complicated by repeated bouts of peritonitis treated with gentamicin. Each 10-day treatment course consisted of a 120 mg loading dose, followed by 16 mg in 21 of peritoneal dialysate, given four times a day. Serum gentamicin analysed by enzyme immunoassay showed a mean level of 5.2 micrograms/ml, (range 3.7 to 6.6 mg/ml) four hours after the loading dose. Similar levels, well within the therapeutic range, were maintained on the 3rd, 5th, 7th and 9th days of intraperitoneal gentamicin therapy, suggesting no accumulation of gentamicin in the serum. Pure tone audiometry, electronystagmography and clinical assessment were performed during each course of treatment. Although no evidence of ototoxicity was found during the first two courses of gentamicin, but disequilibrium and bobbing oscillopsia were present during the third and fourth courses of gentamicin. These findings could be explained by cumulative injury to the vestibular apparatus caused by repeated therapeutic insults.
    Matched MeSH terms: Gentamicins/adverse effects*; Gentamicins/blood; Gentamicins/therapeutic use
  16. Leong CL, Buising K, Richards M, Robertson M, Street A
    Intern Med J, 2006 Jan;36(1):37-42.
    PMID: 16409311
    BACKGROUND: Aminoglycoside antibiotics are commonly prescribed for the treatment of Gram-negative infections. Appropriate dosing and therapeutic monitoring of aminoglycosides are important because these agents have a narrow therapeutic index.
    AIM: To audit gentamicin use at our hospital, focusing on selection of the initial dose and therapeutic monitoring practices, and to compare the results against recommendations in the existing hospital aminoglycoside guidelines, which had recently been promoted to doctors.
    METHODS: This audit included all inpatients receiving gentamicin at The Royal Melbourne Hospital from 1 February to 12 March 2004. The principal researcher checked the drug charts of all inpatients to identify those receiving gentamicin and collected data from the medical records and the pathology database. Doses were considered 'concordant' if the dose given was within the recommended dosing range +/-20 mg.
    RESULTS: A total of 132 courses of gentamicin was included in the study. Gentamicin was prescribed for prophylaxis in 31.1% of courses. Thirty-six per cent of patients prescribed gentamicin were more than 65 years of age. Eighty-two per cent of the gentamicin used therapeutically was given as a single daily dose. Sixty-six per cent of gentamicin initial dosing was not in accordance with existing hospital guidelines. Seventy-seven per cent of gentamicin courses requiring therapeutic drug monitoring received such monitoring; however, in only 8.8% of these was the monitoring conducted according to guidelines.
    CONCLUSION: Aminoglycoside prescribing practices at our hospital are suboptimal, despite ready access to prescribing guidelines. Provision of a guideline and education sessions with doctors do not necessarily lead to widespread adoption of recommended practices. We suggest that changes to hospital systems related to prescribing and monitoring of aminoglycosides are required.
    Matched MeSH terms: Gentamicins/administration & dosage; Gentamicins/blood; Gentamicins/therapeutic use*
  17. Lee, K.H., Ng, A.B.Y., Tan, T.B., Mossinac, K., To, B.C. Se
    Malays Orthop J, 2008;2(2):11-15.
    MyJurnal
    Gentamicin, whether administered either intravenously, incorporated into bone cement or for local intra-operative irrigation, is a commonly used antibiotic in orthopaedic practice. The former two have been well studied, however the literature on the therapeutic efficacy and safety of gentamicin irrigation is sparse. The objective of this study was to assess systemic absorption of gentamicin irrigation in joint replacement surgery. This was a non-randomised, prospective study. Ninety-eight patients (group A) who underwent total joint replacement and 40 patients (group B) who underwent hemi-arthroplasty were treated traoperatively with gentamicin irrigation. Serum gentamicin levels were assayed at 4 hours and 24 hours post-surgery. Sixteen of 98 patients in group A (16%) and 12 out of 40 patients in group B (30%) were found to have serum gentamicin level above 2mcg/ml at 4 hours post-surgery. We conclude that intra-articular gentamicin irrigation is systemically absorbed at substantial levels.
    Matched MeSH terms: Gentamicins
  18. Haryani, Y., Tunung, R., Chai, L.C., Lee, H.Y., Tang, S.Y., Son, R.
    MyJurnal
    A total of 78 samples comprising different types of street foods, sold in different locations in Malaysia, were examined for the presence of Enterobacter cloacae. E. cloacae contamination was recorded in 9% of the samples examined. Tests for susceptibility to 12 different antibiotics showed that all were resistant to six or more antibiotics, but susceptible to chloramphenicol and gentamicin. Plasmids of four different sizes were detected from the three plasmid positive isolates. RAPD analysis using four primers yielded completely different banding patterns for all E. cloacae studied. In Malaysia, no published information on street foods in the epidemiological investigation of E.cloacae related disease is available. However, their occurrences have provided compelling evidence that the risk of disease transmission caused by E. cloacae through street foods is moderate.
    Matched MeSH terms: Gentamicins
  19. Noradilah Samseh Abdullah, Mohamed Kamel Abd Ghani, Anisah Nordin, Yusof Suboh, Noraina Ab Rahim
    MyJurnal
    Acanthamoeba keratitis is a serious ocular problem and can cause blindness if not treated. This study was therefore performed to evaluate the effectiveness of eyedrop antibiotics on eight Acanthamoeba spp. isolates, of which four
    were clinical isolates and the remaining four from the environment. Three different eyedrop antibiotics (neomycin, ciprofloxacin and gentamicin) currently available in the market and ready for use were tested. Cyst suspension from all strains were tested against eyedrop antibiotics, respectively. After 48 hours of incubation period, the solutions were filtered and the filtered membranes were put onto non-nutrient agar lawn with E. coli. The plates were examined daily for Acanthamoeba trophozoites under inverted microscope until day 14. Neomycin, ciprofloxacin and gentamicin were found
    to be effective against Acanthamoeba spp. cysts for all test strains.
    Key words: Acanthamoeba Keratitis, Eyedrop Antibiotics, Effectiveness
    Matched MeSH terms: Gentamicins
  20. Abdul Khodir WKW, Abdul Razak AH, Ng MH, Guarino V, Susanti D
    J Funct Biomater, 2018 May 18;9(2).
    PMID: 29783681 DOI: 10.3390/jfb9020036
    In the current practice, the clinical use of conventional skin substitutes such as autogenous skin grafts have shown several problems, mainly with respect to limited sources and donor site morbidity. In order to overcome these limitations, the use of smart synthetic biomaterials is tremendously diffusing as skin substitutes. Indeed, engineered skin grafts or analogues frequently play an important role in the treatment of chronic skin wounds, by supporting the regeneration of newly formed tissue, and at the same time preventing infections during the long-term treatment. In this context, natural proteins such as collagen-natively present in the skin tissue-embedded in synthetic polymers (i.e., PCL) allow the development of micro-structured matrices able to mimic the functions and to structure of the surrounding extracellular matrix. Moreover, the encapsulation of drugs, such as gentamicin sulfate, also improves the bioactivity of nanofibers, due to the efficient loading and a controlled drug release towards the site of interest. Herein, we have done a preliminary investigation on the capability of gentamicin sulfate, loaded into collagen-added nanofibers, for the controlled release in local infection treatments. Experimental studies have demonstrated that collagen added fibers can be efficaciously used to administrate gentamicin for 72 h without any toxic in vitro response, thus emerging as a valid candidate for the therapeutic treatment of infected wounds.
    Matched MeSH terms: Gentamicins
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