Displaying publications 41 - 60 of 129 in total

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  1. Lourdesamy Anthony AI, Muthukumaru U
    Respirology, 2014 Nov;19(8):1178-82.
    PMID: 25183304 DOI: 10.1111/resp.12375
    We evaluated the efficacy of a 12-week oral treatment with azithromycin in adult patients with bronchiectasis. The objectives were to demonstrate that this treatment reduces sputum volume, improves quality of life and to assess the lengths of effects after cessation of therapy.
    Matched MeSH terms: Anti-Bacterial Agents/administration & dosage
  2. Ling SS, Magosso E, Khan NA, Yuen KH, Barker SA
    Drug Dev Ind Pharm, 2006 Mar;32(3):335-45.
    PMID: 16556538
    A liposome system was evaluated for oral delivery of a poorly bioavailable hydrophilic drug. The system was prepared from proliposome, which consisted of negatively charged phosphatidylcholine, whereas cefotaxime was chosen as the model drug. An in vivo study was carried out on nine rats according to a three-way crossover design to compare the oral bioavailability of cefotaxime from the liposomal formulation with that of an aqueous drug solution and a physical mixture of cefotaxime with blank liposomes. The results indicated that the extent of bioavailability of cefotaxime was increased approximately 2.7 and 2.3 times compared with that of the aqueous solution and the physical mixture, respectively. In a separate study, simultaneous determination of cefotaxime in intestinal lymph (collected from the mesenteric lymph duct) and in plasma (collected from the tail vein) revealed that its concentration was consistently higher in the lymph than in the plasma when administered via the liposomal formulation, whereas the reverse was observed with the aqueous solution. Thus, the results indicated that the liposomes system has the potential of increasing the oral bioavailability of poorly bioavailable hydrophilic drugs and also promote their lymphatic transport in the intestinal lymph.
    Matched MeSH terms: Anti-Bacterial Agents/administration & dosage
  3. Hashim H, Azmin S, Razlan H, Yahya NW, Tan HJ, Manaf MR, et al.
    PLoS One, 2014;9(11):e112330.
    PMID: 25411976 DOI: 10.1371/journal.pone.0112330
    BACKGROUND: Previous studies have demonstrated a higher prevalence of Helicobacter pylori (H. pylori) infection in patients with Parkinson's disease (PD) compared to controls. H. pylori infection affects levodopa absorption and its eradication significantly improves clinical response to levodopa. Here, we studied the prevalence of H. pylori infection and its eradication effects among our PD patients.

    METHODS: A prospective study involving idiopathic PD patients on levodopa therapy. 13C-urea breath test (UBT) was used to detect H. pylori. UBT-positive patients were given standard eradication therapy and followed up at 6 and 12 weeks in an open label single arm design. Repeat UBT was performed at 12 weeks. The UPDRS, PD NMQ, PD NMSS and PDQ-39 were administered at baseline and post-eradication (6 and 12 weeks). Levodopa 'onset' time and ON-duration were recorded.

    RESULTS: Of 82 patients recruited, 27 (32.9%) had positive UBT. H. pylori-positive patients had significantly poorer total UPDRS (p = 0.005) and PDQ39 (p<0.0001) scores compared to H. pylori-negative patients. At 12 weeks post-eradication, the mean levodopa onset time shortened by 14 minutes (p = 0.011). The mean ON duration time increased by 56 minutes at week 6 (p = 0.041) and 38 minutes at week 12 (p = 0.035). The total UPDRS scores (p<0.0001), scores for parts II (p = 0.001), III (p<0.0001) and IV (p = 0.009) were significantly better. The total PDQ-39 scores (p = 0.001) and subdomains mobility (p = 0.002), ADL (p = 0.001), emotional well being (p = 0.026) and stigma (p = 0.034) significantly improved. The PD NMSQ did not show significant improvement.

    CONCLUSIONS: H. pylori eradication improved levodopa onset time, ON duration, motor severity and quality of life parameters. Screening and eradication of H. pylori is inexpensive and should be recommended in PD patients, particularly those with erratic response to levodopa.

    TRIAL REGISTRATION: ClinicalTrials.gov NCT02112812.

    Matched MeSH terms: Anti-Bacterial Agents/administration & dosage*
  4. 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: Anti-Bacterial Agents/administration & dosage
  5. Daud J, Ishak SR, Deris ZZ, Hitam WH
    Asian Pac J Trop Biomed, 2011 Oct;1(5):419-20.
    PMID: 23569805 DOI: 10.1016/S2221-1691(11)60092-0
    Infectious conjunctivitis is a very common presentation to medical professional and ophthalmologist all over the world. Although its typically self-limiting and treatable in almost all of the cases, but we need to be aware of the rare and potentially life threatening if the cause is not promptly identified and treated accordingly. In our case report, we highlighted the rare case of Neisseria meningitidis as a primary cause of keratoconjunctivitis. Neisseria meningitidis is a rare etiology of keratoconjunctivitis and its ocular presentations are quite similar with other bacterial or viral infection. The infection may potentially fatal if systemic invasion occurred, however with immediate and proper treatment the outcome is satisfactory. Early diagnosis and proper antibiotic treatment are critical to prevent systemic spread of the infection. Public health intervention is needed to prevent outbreak of the disease.
    Matched MeSH terms: Anti-Bacterial Agents/administration & dosage
  6. Mushahar L, Mei LW, Yusuf WS, Sivathasan S, Kamaruddin N, Idzham NJ
    Perit Dial Int, 2015 09 15;36(2):135-9.
    PMID: 26374836 DOI: 10.3747/pdi.2014.00195

    OBJECTIVE: Peritoneal dialysis (PD)-related infection is a common cause of catheter loss and the main reason for PD drop-out. Exit-site infection (ESI) is a pathway to developing tunnel infection and peritonitis, hence rigorous exit-site care has always been emphasized in PD therapy. The aim of this study was to evaluate the effect of exit-site dressing vs non-dressing on the rate of PD-related infection. ♦

    METHODS: A prospective randomized controlled study was conducted in prevalent PD patients at the Hospital Tuanku Jaafar Seremban, Negeri Sembilan, Malaysia, from April 2011 until April 2013. All patients were required to perform daily washing of the exit site with antibacterial soap during a shower. In the dressing group (n = 54), patients were required to clean their exit site using povidone-iodine after drying, followed by topical mupirocin antibiotic application to the exit site. The exit site was then covered with a sterile gauze dressing and the catheter immobilized with tape. In the non-dressing group (n = 54), patients were not required to do any further dressing after drying. They were only required to apply mupirocin cream to the exit site and then left the exit site uncovered. The catheter was immobilized with tape. The primary outcome was ESI. The secondary outcomes were evidence of tunnel infection or peritonitis. ♦

    RESULTS: A total of 97 patients completed the study. There were a total of 12 ESI episodes: 4 episodes in 4 patients in the dressing group vs 8 episodes in 4 patients in the non-dressing group. This corresponds to 1 episode per 241.3 patient-months vs 1 episode per 111.1 patient-months in the dressing and non-dressing groups respectively. Median time to first ESI episode was shorter in the non-dressing than in the dressing group, but not significant (p = 0.25). The incidence of gram-positive ESI in both groups was similar. There were no gram-negative ESI in the non-dressing group compared with 2 in the dressing group. The peritonitis rate was 1 per 37.1 patient-month in the dressing group and 1 per 44.4 patient-months in the non-dressing group. Median time to first peritonitis episode was significantly shorter in the dressing group compared to non-dressing (p = 0.03). There was no impact of dressing disruptions in the occurrence of major PD catheter-related infection. ♦

    CONCLUSION: Use of a non-dressing technique with only prophylactic topical mupirocin cream application is effective in preventing PD-related infection. The non-dressing technique is more cost-effective and convenient for PD patients, with fewer disposables.

    Matched MeSH terms: Anti-Bacterial Agents/administration & dosage
  7. Fatokun O
    Int J Clin Pharm, 2014 Jun;36(3):564-9.
    PMID: 24700341 DOI: 10.1007/s11096-014-9937-6
    BACKGROUND: In Malaysia, antibacterial agents are among the most utilized drugs. There has been an increase in their use in recent years, contributing to an increase of antimicrobial resistance (AMR).

    OBJECTIVES: This study explores the pattern of antibiotic use and practices in a Malaysian community and identifies the variables associated with a likelihood of non-compliance with a course of antibiotic treatment.

    SETTING: The study was conducted in Cheras, a community located to the south-east of Kuala Lumpur, the capital city of Malaysia.

    METHOD: A cross-sectional survey was conducted with 250 individuals, using an interviewer-administered questionnaire in Cheras, Kuala Lumpur, Malaysia.

    MAIN OUTCOME MEASURES: Frequency of antibiotic use, sources of antibiotics, use of antibiotics without prescription, discontinuation of antibiotic treatment, antibiotic resistance awareness, handling of unused antibiotics, and association between respondents characteristics and compliance with a course of antibiotic treatment.

    RESULTS: Approximately 36 % of the participants (n = 91) had taken antibiotics in the year of the study. The majority (66.8 %) obtained antibiotics from clinics. Almost 80 % of the participants had never obtained antibiotics without a doctor's prescription. Nearly 55 % discontinued the course of antibiotics once symptoms disappeared. The most common method of disposing leftover antibiotics was throwing them into the household rubbish bin (78.8 %). Only 6.4 % of participants returned leftover antibiotics to the pharmacist or doctor. Univariate analysis revealed that male gender (p = 0.04), lack of knowledge of antibiotic functions (p < 0.0001), and lack of awareness of antibiotic resistance (p < 0.0001) were all significantly associated with a greater likelihood of non-compliance with a full course of prescribed antibiotic treatment.

    CONCLUSION: Most individuals in the Malaysian community obtained antibiotics through prescription. Non-completion of a course of antibiotic treatment and improper disposal of unused antibiotics need to be addressed to prevent AMR. Male gender, lack of knowledge and awareness of antibiotics and resistance were significantly associated with a greater likelihood of non-compliance with a full course of prescribed antibiotic treatment. Therefore, patient education and counselling about antibiotics and antibacterial resistance is very important to enhance compliance to antibiotic therapy.

    Matched MeSH terms: Anti-Bacterial Agents/administration & dosage*
  8. Ong CY, Lim JL, Galang LD
    Pan Afr Med J, 2017;28:30.
    PMID: 29138666 DOI: 10.11604/pamj.2017.28.30.13544
    We report a case study on a patient who presented with low back and thigh pain of one month duration. He was eventually diagnosed with left thigh pyomyositis. Tissue from thigh grew Staphylococcus aureus. With commencement of antibiotics and surgical drainage, patient made recovery despite prolonged hospital stay. The underlying mechanism of the extensive abscess accompanied by lack of systemic symptoms; is related to relative immunocompromised state of having underlying diabetes mellitus.
    Matched MeSH terms: Anti-Bacterial Agents/administration & dosage
  9. Ahmad A, Khan MU, Balkrishnan R
    Lancet Glob Health, 2016 08;4(8):e521.
    PMID: 27443777 DOI: 10.1016/S2214-109X(16)30093-6
    Matched MeSH terms: Anti-Bacterial Agents/administration & dosage*
  10. Musa SH, Basri M, Masoumi HR, Karjiban RA, Malek EA, Basri H, et al.
    Colloids Surf B Biointerfaces, 2013 Dec 1;112:113-9.
    PMID: 23974000 DOI: 10.1016/j.colsurfb.2013.07.043
    Palm kernel oil esters nanoemulsion-loaded with chloramphenicol was optimized using response surface methodology (RSM), a multivariate statistical technique. Effect of independent variables (oil amount, lecithin amount and glycerol amount) toward response variables (particle size, polydispersity index, zeta potential and osmolality) were studied using central composite design (CCD). RSM analysis showed that the experimental data could be fitted into a second-order polynomial model. Chloramphenicol-loaded nanoemulsion was formulated by using high pressure homogenizer. The optimized chloramphenicol-loaded nanoemulsion response values for particle size, PDI, zeta potential and osmolality were 95.33nm, 0.238, -36.91mV, and 200mOsm/kg, respectively. The actual values of the formulated nanoemulsion were in good agreement with the predicted values obtained from RSM. The results showed that the optimized compositions have the potential to be used as a parenteral emulsion to cross blood-brain barrier (BBB) for meningitis treatment.
    Matched MeSH terms: Anti-Bacterial Agents/administration & dosage*
  11. Suleman Ismail Abdalla S, Katas H, Chan JY, Ganasan P, Azmi F, Fauzi MB
    Mol Pharm, 2021 05 03;18(5):1956-1969.
    PMID: 33822631 DOI: 10.1021/acs.molpharmaceut.0c01033
    Gelatin hydrogels are attractive for wound applications owing to their well-defined structural, physical, and chemical properties as well as good cell adhesion and biocompatibility. This study aimed to develop gelatin hydrogels incorporated with bio-nanosilver functionalized with lactoferrin (Ag-LTF) as a dual-antimicrobial action dressing, to be used in treating infected wounds. The hydrogels were cross-linked using genipin prior to loading with Ag-LTF and characterized for their physical and swelling properties, rheology, polymer and actives interactions, and in vitro release of the actives. The hydrogel's anti-biofilm and antibacterial performances against S. aureus and P. aeruginosa as well as their cytotoxicity effects were assessed in vitro, including primary wound healing gene expression of human dermal fibroblasts (HDFs). The formulated hydrogels showed adequate release of AgNPs and LTF, with promising antimicrobial effects against both bacterial strains. The Ag-LTF-loaded hydrogel did not significantly interfere with the normal cellular functions as no alteration was detected for cell viability, migration rate, and expression of the target genes, suggesting the nontoxicity of Ag-LTF as well as the hydrogels. In conclusion, Ag-LTF-loaded genipin-cross-linked gelatin hydrogel was successfully synthesized as a new approach for fighting biofilms in infected wounds, which may be applied to accelerate healing of chronic wounds.
    Matched MeSH terms: Anti-Bacterial Agents/administration & dosage*
  12. Shameli K, Ahmad MB, Yunus WM, Rustaiyan A, Ibrahim NA, Zargar M, et al.
    Int J Nanomedicine, 2010 Oct 22;5:875-87.
    PMID: 21116328 DOI: 10.2147/IJN.S13632
    In this study, silver nanoparticles (Ag-NPs) were synthesized using a green physical synthetic route into the lamellar space of montmorillonite (MMT)/chitosan (Cts) utilizing the ultraviolet (UV) irradiation reduction method in the absence of any reducing agent or heat treatment. Cts, MMT, and AgNO(3) were used as the natural polymeric stabilizer, solid support, and silver precursor, respectively. The properties of Ag/MMT/Cts bionanocomposites (BNCs) were studied as the function of UV irradiation times. UV irradiation disintegrated the Ag-NPs into smaller sizes until a relatively stable size and size distribution were achieved. Meanwhile, the crystalline structure and d-spacing of the MMT interlayer, average size and size distribution, surface morphology, elemental signal peaks, functional groups, and surface plasmon resonance of Ag/MMT/Cts BNCs were determined by powder X-ray diffraction, transmission electron microscopy, scanning electron microscopy, energy dispersive X-ray fluorescence, Fourier transform infrared, and UV-visible spectroscopy. The antibacterial activity of Ag-NPs in MMT/Cts was investigated against Gram-positive bacteria, ie, Staphylococcus aureus and methicillin-resistant S. aureus and Gram-negative bacteria (ie, Escherichia coli) by the disk diffusion method on Muller-Hinton Agar at different sizes of Ag-NPs. All of the synthesized Ag/MMT/Cts BNCs were found to have high antibacterial activity. These results show that Ag/MMT/Cts BNCs can be useful in different biologic research and biomedical applications, such as surgical devices and drug delivery vehicles.
    Matched MeSH terms: Anti-Bacterial Agents/administration & dosage*
  13. Mahachai V, Vilaichone RK, Pittayanon R, Rojborwonwitaya J, Leelakusolvong S, Maneerattanaporn M, et al.
    J Gastroenterol Hepatol, 2018 Jan;33(1):37-56.
    PMID: 28762251 DOI: 10.1111/jgh.13911
    Helicobacter pylori (H. pylori) infection remains to be the major cause of important upper gastrointestinal diseases such as chronic gastritis, peptic ulcer, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma. H. pylori management in ASEAN: the Bangkok consensus report gathered key opinion leaders for the region to review and evaluate clinical aspects of H. pylori infection and to develop consensus statements, rationales, and grades of recommendation for the management of H. pylori infection in clinical practice in ASEAN countries. This ASEAN Consensus consisted of 34 international experts from 10 ASEAN countries, Japan, Taiwan, and the United States. The meeting mainly focused on four issues: (i) epidemiology and disease association; (ii) diagnostic tests; (iii) management; and (iv) follow-up after eradication. The final results of each workshop were presented for consensus voting by all participants. Statements, rationale, and recommendations were developed from the available current evidence to help clinicians in the diagnosis and treatment of H. pylori and its clinical diseases.
    Matched MeSH terms: Anti-Bacterial Agents/administration & dosage
  14. Goh KL, Manikam J, Qua CS
    Aliment Pharmacol Ther, 2012 May;35(9):1097-102.
    PMID: 22404486 DOI: 10.1111/j.1365-2036.2012.05054.x
    BACKGROUND:
    H. pylori eradication failures are difficult to treat and rescue therapies often consist of complex treatment regimens.

    AIM:
    To determine an effective and practical rescue therapeutic strategy for H. pylori treatment failures using two consecutive regimens: first rescue therapy - rabeprazole 20 mg t.d.s. and amoxicillin 1 g t.d.s. for 2 weeks and for failures a further second rescue therapy - rabeprazole 20 mg b.d., levofloxacin 500 mg b.d., amoxicillin 1 g b.d. for a further 2 weeks.

    METHODS:
    Consecutive patients who failed the proton pump inhibitor (PPI) 1-week triple therapy were recruited for the study. H. pylori status was determined by a C(13) urea breath test.

    RESULTS:
    One hundred and forty-nine patients received the first rescue therapy. Seven were not compliant to medication/defaulted follow-up. Eradication success- first rescue therapy: per protocol (PP) analysis-107/142 (75.4%) (95% CI (68.3-82.4%) and intention to treat (ITT) analysis-107/149 (71.8%) 95% CI (64.6-79.0%). Thirty-one of 35 patients who failed the first rescue therapy received the second rescue therapy. All were compliant with medications. Eradication success- PP and ITT was 28/31 (90.3%) 95% CI (74.2-98.0%). The cumulative eradication rate using both rescue therapies: PP analysis- 135/138 (97.8%) 95% CI: (93.8-99.6%), ITT analysis- 135/149 (90.6%) 95% CI: (84.7-94.8%).

    CONCLUSIONS:
    A 2-week high dose PPI-amoxicillin dual therapy followed by a PPI-amoxicillin-levofloxacin triple therapy were highly successful in achieving eradication in H. pylori treatment failures.
    Matched MeSH terms: Anti-Bacterial Agents/administration & dosage
  15. Dhabaan GN, AbuBakar S, Cerqueira GM, Al-Haroni M, Pang SP, Hassan H
    Antimicrob Agents Chemother, 2015 Dec 14;60(3):1370-6.
    PMID: 26666943 DOI: 10.1128/AAC.01696-15
    Acinetobacter baumannii has emerged as a notorious multidrug-resistant pathogen, and development of novel control measures is of the utmost importance. Understanding the factors that play a role in drug resistance may contribute to the identification of novel therapeutic targets. Pili are essential for A. baumannii adherence to and biofilm formation on abiotic surfaces as well as virulence. In the present study, we found that biofilm formation was significantly induced in an imipenem-resistant (Imp(r)) strain treated with a subinhibitory concentration of antibiotic compared to that in an untreated control and an imipenem-susceptible (Imp(s)) isolate. Using microarray and quantitative PCR analyses, we observed that several genes responsible for the synthesis of type IV pili were significantly upregulated in the Imp(r) but not in the Imp(s) isolate. Notably, this finding is corroborated by an increase in the motility of the Imp(r) strain. Our results suggest that the ability to overproduce colonization factors in response to imipenem treatment confers biological advantage to A. baumannii and may contribute to clinical success.
    Matched MeSH terms: Anti-Bacterial Agents/administration & dosage
  16. Ramatillah DL, Gan SH, Pratiwy I, Syed Sulaiman SA, Jaber AAS, Jusnita N, et al.
    PLoS One, 2022;17(1):e0262438.
    PMID: 35077495 DOI: 10.1371/journal.pone.0262438
    BACKGROUND AND AIM: Coronavirus Disease 2019 (COVID-19) has become a worldwide pandemic and is a threat to global health. Patients who experienced cytokine storms tend to have a high mortality rate. However, to date, no study has investigated the impact of cytokine storms.

    MATERIALS AND METHODS: This retrospective cohort study included only COVID-19 positive patients hospitalized in a Private Hospital in West Jakarta between March and September 2020. All patients were not vaccinated during this period and treatment was based on the guidelines by the Ministry of Health Indonesia. A convenience sampling method was used and all patients who met the inclusion criteria were enrolled.

    RESULTS: The clinical outcome of COVID-19 patients following medical therapy was either cured (85.7%) or died (14.3%), with 14.3% patients reported to have cytokine storm, from which 23.1% led to fatalities. A plasma immunoglobulin (Gammaraas®) and/or tocilizumab (interleukin-6 receptor antagonist; Actemra®) injection was utilised to treat the cytokine storm while remdesivir and oseltamivir were administered to ameliorate COVID-19. Most (61.5%) patients who experienced the cytokine storm were male; mean age 60 years. Interestingly, all patients who experienced the cytokine storm had hypertension or/ and diabetes complication (100%). Fever, cough and shortness of breath were also the common symptoms (100.0%). Almost all (92.3%) patients with cytokine storm had to be treated in the intensive care unit (ICU). Most (76.9%) patients who had cytokine storm received hydroxychloroquine and all had antibiotics [1) azithromycin + levofloxacin or 2) meropenam for critically ill patients] and vitamins such as vitamins C and B-complex as well as mineral. Unfortunately, from this group, 23.1% patients died while the remaining 70% of patients recovered. A significant (p<0.05) correlation was established between cytokine storms and age, the presence of comorbidity, diabetes, hypertension, fever, shortness of breath, having oxygen saturation (SPO2) less than 93%, cold, fatigue, ward of admission, the severity of COVID-19 disease, duration of treatment as well as the use of remdesivir, Actemra® and Gammaraas®. Most patients recovered after receiving a combination treatment (oseltamivir + remdesivir + Antibiotics + Vitamin/Mineral) for approximately 11 days with a 90% survival rate. On the contrary, patients who received oseltamivir + hydroxychloroquine + Gammaraas® + antibiotics +Vitamin/Mineral, had a 83% survival rate after being admitted to the hospital for about ten days.

    CONCLUSION: Factors influencing the development of a cytokine storm include age, duration of treatment, comorbidity, symptoms, type of admission ward and severity of infection. Most patients (76.92%) with cytokine storm who received Gammaraas®/Actemra®, survived although they were in the severe and critical levels (87.17%). Overall, based on the treatment duration and survival rate, the most effective therapy was a combination of oseltamivir + favipiravir + hydroxychloroquine + antibiotics + vitamins/minerals.

    Matched MeSH terms: Anti-Bacterial Agents/administration & dosage
  17. Johari SA, Mohtar M, Syed Mohamad SA, Mohammat MF, Sahdan R, Mohamed A, et al.
    Biomed Res Int, 2017;2017:8032865.
    PMID: 28536702 DOI: 10.1155/2017/8032865
    Previously we have discovered a synthetically derived pyrrolidone alkaloid, MFM501, exhibiting good inhibitory activity against 53 MRSA and MSSA isolates with low cytotoxicity against three normal cell-lines with IC50 values at >625 µg/ml. Time-kill assay, scanning electron microscopy (SEM) analysis, in vivo oral acute toxicity test, and mice peritonitis model were carried out in this study. In the time-kill study, MFM501 showed a less than 3 log10 decrease in bacterial colony concentration value (CFU/ml) which represented a bacteriostatic action while displaying a time-dependent inhibitory mechanism. Following that, SEM analysis suggested that MFM501 may exert its inhibitory activity via cytoplasmic membrane disruption. Moreover, MFM501 showed no toxicity effect on treated mice at an estimated median acute lethal dose (LD50) value of more than 300 mg/kg and less than 2000 mg/kg. For the efficacy test, a mean effective dose (ED50) of 87.16 mg/kg was obtained via a single dose oral administration. Our data demonstrated that MFM501 has the potential to be developed further as a new, safe, and effective oral-delivered antibacterial agent against MRSA isolates.
    Matched MeSH terms: Anti-Bacterial Agents/administration & dosage
  18. Johari SA, Mohtar M, Mohammad SA, Sahdan R, Shaameri Z, Hamzah AS, et al.
    Biomed Res Int, 2015;2015:823829.
    PMID: 25710030 DOI: 10.1155/2015/823829
    28 new pyrrolidine types of compounds as analogues for natural polyhydroxy alkaloids of codonopsinine were evaluated for their anti-MRSA activity using MIC and MBC value determination assay against a panel of S. aureus isolates. One pyrrolidine compound, MFM 501, exhibited good inhibitory activity with MIC value of 15.6 to 31.3 μg/mL against 55 S. aureus isolates (43 MRSA and 12 MSSA isolates). The active compound also displayed MBC values between 250 and 500 μg/mL against 58 S. aureus isolates (45 MRSA and 13 MSSA isolates) implying that MFM 501 has a bacteriostatic rather than bactericidal effect against both MRSA and MSSA isolates. In addition, MFM 501 showed no apparent cytotoxicity activity towards three normal cell lines (WRL-68, Vero, and 3T3) with IC50 values of >625 µg/mL. Selectivity index (SI) of MFM 501 gave a value of >10 suggesting that MFM 501 is significant and suitable for further in vivo investigations. These results suggested that synthetically derived intermediate compounds based on natural products may play an important role in the discovery of new anti-infective agents against MRSA.
    Matched MeSH terms: Anti-Bacterial Agents/administration & dosage*
  19. Lulu GA, Karunanidhi A, Mohamad Yusof L, Abba Y, Mohd Fauzi F, Othman F
    Ann Clin Microbiol Antimicrob, 2018 Dec 28;17(1):46.
    PMID: 30593272 DOI: 10.1186/s12941-018-0296-3
    BACKGROUND: Osteomyelitis is an acute or chronic inflammatory process of the bone following infection with pyogenic organisms like Staphylococcus aureus. Tobramycin (TOB) is a promising aminoglycoside antibiotic used to treat various bacterial infections, including S. aureus. The aim of this study was to investigate the efficacy of tobramycin-loaded calcium phosphate beads (CPB) in a rabbit osteomyelitis model.

    METHODS: Tobramycin (30 mg/mL) was incorporated into CPB by dipping method and the efficacy of TOB-loaded CPB was studied in a rabbit osteomyelitis model. For juxtaposition, CPB with and without TOB were prepared. Twenty-five New Zealand white rabbits were grouped (n = 5) as sham (group 1), TOB-loaded CPB without S. aureus (group 2), S. aureus only (group 3), S. aureus + CPB (group 4), and S. aureus + TOB-loaded CPB (group 5). Groups infected with S. aureus followed by CPB implantation were immediately subjected to surgery at the mid-shaft of the tibia. After 28 days post-surgery, all rabbits were euthanized and the presence or absence of chronic osteomyelitis and the extent of architectural destruction of the bone were assessed by radiology, bacteriology and histological studies.

    RESULTS: Tobramycin-loaded CPB group potentially inhibited the growth of S. aureus causing 3.2 to 3.4 log10 reductions in CFU/g of bone tissue compared to the controls. Untreated groups infected with S. aureus showed signs of chronic osteomyelitis with abundant bacterial growth and alterations in bone architecture. The sham group and TOB-loaded CPB group showed no evidence of bacterial growth.

    CONCLUSIONS: TOB-incorporated into CPB for local bone administration was proven to be more successful in increasing the efficacy of TOB in this rabbit osteomyelitis model and hence could represent a good alternative to other formulations used in the treatment of osteomyelitis.

    Matched MeSH terms: Anti-Bacterial Agents/administration & dosage*
  20. Liu R, Tang AM, Tan YL, Limenta LM, Lee EJ
    Eur J Clin Pharmacol, 2009 Jan;65(1):65-70.
    PMID: 18766334 DOI: 10.1007/s00228-008-0488-4
    OBJECTIVES: The aims of this study were to characterize the population frequency of PEPT2 (SLC15A2) polymorphic variants in three Asian ethnic populations, namely Chinese, Malay and Asian Indian, and to investigate the associations of ethnicity (Chinese vs. Asian Indian), PEPT2 haplotype and cephalexin pharmacokinetics in healthy Asian subjects.

    METHODS: PEPT2 polymorphisms were screened from a cohort of 96 Chinese, 96 Malay and 96 Asian Indian subjects. Cephalexin (1000 mg, orally) pharmacokinetics was characterized in an additional 15 Chinese and 15 Asian Indian healthy subjects. These 30 subjects were subsequently genotyped for their PEPT2 polymorphisms.

    RESULTS: In total, ten common single nucleotide polymorphisms (SNPs) were detected in the three populations, forming two PEPT2 haplotypes. There were significant ethnic differences in PEPT2 haplotype distribution: the frequencies of the *1 and *2 alleles were 0.307 and 0.693 in the Chinese population, 0.495 and 0.505 in the Malay population and 0.729 and 0.271 in Asian Indian population, respectively. The C (max) of cephalexin was significantly lower in the Chinese (29.80 +/- 4.09 microg ml(-1)) population than in the Asian Indian one (33.29 +/- 4.97 microg ml(-1); P = 0.045). This difference could be explained by the higher average body weight of the Chinese population. There was no other significant difference in cephalexin pharmacokinetics between either ethnic or PEPT2 genotype groups.

    CONCLUSION: PEPT2 polymorphism distributions differ significantly between Chinese, Malay and Asian Indian populations. However, cephalexin pharmacokinetics is not meaningfully different between Chinese and Asian Indians. The association between the PEPT2 haplotype and cephalexin pharmacokinetics could not be confirmed, and future studies under better controlled conditions are needed.

    Matched MeSH terms: Anti-Bacterial Agents/administration & dosage
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