Displaying publications 1 - 20 of 68 in total

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  1. Feld R
    Int J Antimicrob Agents, 2008 Nov;32 Suppl 1:S30-3.
    PMID: 18778919 DOI: 10.1016/j.ijantimicag.2008.06.017
    Bloodstream infections (bacteraemia) account for approximately 25-30% of febrile episodes in patients with febrile neutropenia (FN). In developed countries, Gram-positive pathogens predominate. Mortality is higher in Gram-negative bacteraemia. A recent study involving 2142 patients with FN was reviewed, including 168 patients with Gram-negative bacteraemia (mortality 18%), 283 patients with Gram-positive bacteraemia (mortality 5%) and 48 patients with polymicrobial bacteraemia (mortality 13%). Among patients who received prophylactic antibiotics, Gram-positive bacteraemia was far more common than Gram-negative bacteraemia (75% vs. 25%), compared with approximately 50% of each in patients without prophylactic antibiotics. Patients with a Multinational Association for Supportive Care in Cancer (MASCC) score <15 had a 36% mortality compared with 3% if the MASCC score was >21. The MASCC score may help risk stratification of patients with FN and bacteraemia, although these data require confirmation. In two series of patients from developing countries (Lebanon and Malaysia), Gram-negative bacteraemia was more common and mortality was higher. In developing countries, Gram-negative bacteraemia may be more frequent due to less use of prophylactic antibiotics and central lines. Laboratory markers may have predictive and prognostic value for bacteraemia in patients at the onset of FN, including mannose-binding lectin, interleukin (IL)-6, IL-8 and procalcitonin, but further studies are required before they can be recommended. New therapies are required to lower the mortality in patients with FN with a high risk for bacteraemia.
    Matched MeSH terms: Gram-Negative Bacterial Infections/drug therapy; Gram-Positive Bacterial Infections/drug therapy
  2. Azmi F, Elliott AG, Marasini N, Ramu S, Ziora Z, Kavanagh AM, et al.
    Bioorg Med Chem, 2016 05 15;24(10):2235-41.
    PMID: 27048775 DOI: 10.1016/j.bmc.2016.03.053
    The spread of drug-resistant bacteria has imparted a sense of urgency in the search for new antibiotics. In an effort to develop a new generation of antibacterial agents, we have designed de novo charged lipopeptides inspired by natural antimicrobial peptides. These short lipopeptides are composed of cationic lysine and hydrophobic lipoamino acids that replicate the amphiphilic properties of natural antimicrobial peptides. The resultant lipopeptides were found to self-assemble into nanoparticles. Some were effective against a variety of Gram-positive bacteria, including strains resistant to methicillin, daptomycin and/or vancomycin. The lipopeptides were not toxic to human kidney and liver cell lines and were highly resistant to tryptic degradation. Transmission electron microscopy analysis of bacteria cells treated with lipopeptide showed membrane-damage and lysis with extrusion of cytosolic contents. With such properties in mind, these lipopeptides have the potential to be developed as new antibacterial agents against drug-resistant Gram-positive bacteria.
    Matched MeSH terms: Gram-Positive Bacterial Infections/drug therapy
  3. Selvakumar M, Srivastava P, Pawar HS, Francis NK, Das B, Sathishkumar G, et al.
    ACS Appl Mater Interfaces, 2016 Feb 17;8(6):4086-100.
    PMID: 26799576 DOI: 10.1021/acsami.5b11723
    Guided bone regeneration (GBR) scaffolds are futile in many clinical applications due to infection problems. In this work, we fabricated GBR with an anti-infective scaffold by ornamenting 2D single crystalline bismuth-doped nanohydroxyapatite (Bi-nHA) rods onto segmented polyurethane (SPU). Bi-nHA with high aspect ratio was prepared without any templates. Subsequently, it was introduced into an unprecedented synthesized SPU matrix based on dual soft segments (PCL-b-PDMS) of poly(ε-caprolactone) (PCL) and poly(dimethylsiloxane) (PDMS), by an in situ technique followed by electrospinning to fabricate scaffolds. For comparison, undoped pristine nHA rods were also ornamented into it. The enzymatic ring-opening polymerization technique was adapted to synthesize soft segments of PCL-b-PDMS copolymers of SPU. Structure elucidation of the synthesized polymers is done by nuclear magnetic resonance spectroscopy. Sparingly, Bi-nHA ornamented scaffolds exhibit tremendous improvement (155%) in the mechanical properties with excellent antimicrobial activity against various human pathogens. After confirmation of high osteoconductivity, improved biodegradation, and excellent biocompatibility against osteoblast cells (in vitro), the scaffolds were implanted in rabbits by subcutaneous and intraosseous (tibial) sites. Various histological sections reveal the signatures of early cartilage formation, endochondral ossification, and rapid bone healing at 4 weeks of the critical defects filled with ornamented scaffold compared to SPU scaffold. This implies osteogenic potential and ability to provide an adequate biomimetic microenvironment for mineralization for GBR of the scaffolds. Organ toxicity studies further confirm that no tissue architecture abnormalities were observed in hepatic, cardiac, and renal tissue sections. This finding manifests the feasibility of fabricating a mechanically adequate nanofibrous SPU scaffold by a biomimetic strategy and the advantages of Bi-nHA ornamentation in promoting osteoblast phenotype progression with microbial protection (on-demand) for GBR applications.
    Matched MeSH terms: Bacterial Infections/drug therapy*
  4. Lim VK, Cheong YM
    Malays J Pathol, 1995 Dec;17(2):73-6.
    PMID: 8935129
    Beta-lactamase production is one of the major mechanisms of resistance amongst bacteria especially the enteric bacilli. The purpose of this study is to assess the in-vitro activity of Sulperazon, a combination of cefoperazone and an irreversible beta-lactamase inhibitor, sulbactam, against the cefoperazone resistant isolates of aerobic gram-negative bacilli. A total of 92 such strains were tested. It was found that at a concentration of < or = 8 mg/l of sulbactam added to cefoperazone 82% of Klebsiella spp, 100% of E. coli, 100% of Enterobacter spp, 33% of Pseudomonas aeruginosa, 67% of Pseudomonas spp and 62% of Acinetobacter spp that were resistant to cefoperazone alone were susceptible to the combination. Hence it is concluded that the addition of sulbactam to cefoperazone does expand the spectrum of the in-vitro activity of cefoperazone.

    Study site: General Hospital Kuala Lumpur
    Matched MeSH terms: Gram-Negative Bacterial Infections/drug therapy*
  5. Pierce J, Apisarnthanarak A, Schellack N, Cornistein W, Maani AA, Adnan S, et al.
    Int J Infect Dis, 2020 Jul;96:621-629.
    PMID: 32505875 DOI: 10.1016/j.ijid.2020.05.126
    Antimicrobial resistance is a global public health crisis. Antimicrobial Stewardship involves adopting systematic measures to optimize antimicrobial use, decrease unnecessary antimicrobial exposure and to decrease the emergence and spread of resistance. Low- and middle-income countries (LMICs) face a disproportionate burden of antimicrobial resistance and also face challenges related to resource availability. Although challenges exist, the World Health Organization has created a practical toolkit for developing Antimicrobial Stewardship Programs (ASPs) that will be summarized in this article.
    Matched MeSH terms: Bacterial Infections/drug therapy*
  6. Lee WS
    J Pediatr Gastroenterol Nutr, 2000 Mar;30(3):241-5.
    PMID: 10749405
    Matched MeSH terms: Bacterial Infections/drug therapy
  7. Lau HJ, Lim CH, Foo SC, Tan HS
    Curr Genet, 2021 Jun;67(3):421-429.
    PMID: 33585980 DOI: 10.1007/s00294-021-01156-5
    Antimicrobial resistance (AMR) in bacteria is a global health crisis due to the rapid emergence of multidrug-resistant bacteria and the lengthy development of new antimicrobials. In light of this, artificial intelligence in the form of machine learning has been viewed as a potential counter to delay the spread of AMR. With the aid of AI, there are possibilities to predict and identify AMR in bacteria efficiently. Furthermore, a combination of machine learning algorithms and lab testing can help to accelerate the process of discovering new antimicrobials. To date, many machine learning algorithms for antimicrobial-resistance discovery had been created and vigorously validated. Most of these algorithms produced accurate results and outperformed the traditional methods which relied on sequence comparison within a database. This mini-review will provide an updated overview of antimicrobial design workflow using the latest machine-learning antimicrobial discovery algorithms in the last 5 years. With this review, we hope to improve upon the current AMR identification and antimicrobial development techniques by introducing the use of AI into the mix, including how the algorithms could be made more effective.
    Matched MeSH terms: Bacterial Infections/drug therapy*
  8. Chang CY, Chan KG
    J Infect, 2020 Sep;81(3):e29-e30.
    PMID: 32628960 DOI: 10.1016/j.jinf.2020.06.077
    Matched MeSH terms: Bacterial Infections/drug therapy
  9. Lee CC, Kwa ALH, Apisarnthanarak A, Feng JY, Gluck EH, Ito A, et al.
    Clin Chem Lab Med, 2020 11 26;58(12):1983-1991.
    PMID: 31926074 DOI: 10.1515/cclm-2019-1122
    Introduction Recently, an expert consensus on optimal use of procalcitonin (PCT)-guided antibiotic stewardship was published focusing mainly on Europe and the United States. However, for Asia-Pacific countries, recommendations may need adaptation due to differences in types of infections, available resources and standard of clinical care. Methods Practical experience with PCT-guided antibiotic stewardship was discussed among experts from different countries, reflecting on the applicability of the proposed Berlin consensus algorithms for Asia-Pacific. Using a Delphi process, the group reached consensus on two PCT algorithms for the critically ill and the non-critically ill patient populations. Results The group agreed that the existing evidence for PCT-guided antibiotic stewardship in patients with acute respiratory infections and sepsis is generally valid also for Asia-Pacific countries, in regard to proposed PCT cut-offs, emphasis on diagnosis, prognosis and antibiotic stewardship, overruling criteria and inevitable adaptations to clinical settings. However, the group noted an insufficient database on patients with tropical diseases currently limiting the clinical utility in these patients. Also, due to lower resource availabilities, biomarker levels may be measured less frequently and only when changes in treatment are highly likely. Conclusions Use of PCT to guide antibiotic stewardship in conjunction with continuous education and regular feedback to all stakeholders has high potential to improve the utilization of antibiotic treatment also in Asia-Pacific countries. However, there is need for adaptations of existing algorithms due to differences in types of infections and routine clinical care. Further research is needed to understand the optimal use of PCT in patients with tropical diseases.
    Matched MeSH terms: Bacterial Infections/drug therapy
  10. Jia Y, Zhao L
    Eur J Med Chem, 2021 Nov 15;224:113741.
    PMID: 34365130 DOI: 10.1016/j.ejmech.2021.113741
    Bacterial infection is amongst the most common diseases in community and hospital settings. Fluoroquinolones, exerting the antibacterial activity through binding to type II bacterial topoisomerase enzymes, DNA gyrase and topoisomerase IV, are mainstays of chemotherapy. At present, fluoroquinolones are the most valuable antibacterial agents used popularly. However, the emergence of more virulent and resistant pathogens by the development of either mutated DNA-binding proteins or efflux pump mechanism for fluoroquinolones results in an urgent demand to develop new fluoroquinolones to withstand the drug resistance and to obtain a broader spectrum of activity. This review aims to outline the recent advances of fluoroquinolone derivatives with antibacterial potential and to summarize the structure-activity relationship (SAR) so as to provide an insight for rational design of more active candidates, covering articles published between January 2018 and June 2021.
    Matched MeSH terms: Bacterial Infections/drug therapy*
  11. Chung PY
    Curr Drug Targets, 2018;19(7):832-840.
    PMID: 28891454 DOI: 10.2174/1389450118666170911114604
    BACKGROUND: Bacterial resistance to antibiotics is one of the most serious challenge to global public health. The introduction of new antibiotics in clinical settings, i.e. agents that belong to a new class of antibacterials, act on new targets or has a novel mechanisms of action, may not be sufficient to cope with the emergence of multidrug-resistant pathogens such as Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii and Escherichia coli, which are increasingly prevalent in healthcare settings in Europe, the USA and Asia. Hence, coordinated efforts in minimizing the risk of spread of resistant bacteria and renewing research efforts in the search for novel antibacterial agents are urgently needed to manage this global crisis.

    OBJECTIVE: This review highlights the challenges and potential in using current technologies in the discovery and development of novel antibacterial agents to keep up with the constantly evolving resistance in bacteria.

    CONCLUSION: With the explosion of bacterial genomic data and rapid development of new sequencing technologies, the understanding of bacterial pathogenesis and identification of novel antibiotic targets have significantly improved.

    Matched MeSH terms: Bacterial Infections/drug therapy*
  12. Henriksson PJ, Troell M, Rico A
    Proc Natl Acad Sci U S A, 2015 Jun 30;112(26):E3317.
    PMID: 26045495 DOI: 10.1073/pnas.1508952112
    Matched MeSH terms: Bacterial Infections/drug therapy*
  13. Ngu-Schwemlein M, Chin SF, Hileman R, Drozdowski C, Upchurch C, Hargrove A
    Bioorg Med Chem Lett, 2016 Apr 01;26(7):1745-9.
    PMID: 26923697 DOI: 10.1016/j.bmcl.2016.02.047
    We report the potential of carbon nanodots (CNDs) as a molecular scaffold for enhancing the antimicrobial activities of small dendritic poly(amidoamines) (PAMAM). Carbon nanodots prepared from sago starch are readily functionalized with PAMAM by using N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS). Electron microscopy images of these polyaminated CNDs show that they are approximately 30-60nm in diameter. Infrared and fluorescence spectroscopy analyses of the water-soluble material established the presence of the polyamidoaminated moiety and the intrinsic fluorescence of the nanodots. The polyaminated nanodots (CND-PAM1 and CND-PAM2) exhibit in vitro antimicrobial properties, not only to non-multidrug resistant bacteria but also to the corresponding Gram-negative multidrug bacteria. Their minimum inhibitory concentration (MIC) ranges from 8 to 64μg/mL, which is much lower than that of PAMAM G1 or the non-active PAMAM G0 and CNDs. Additionally, they show synergistic effect in combination with tetracycline or colistin. These preliminary results imply that CNDs can serve as a promising scaffold for facilitating the rational design of antimicrobial materials for combating the ever-increasing threat of antibiotic resistance. Moreover, their fluorescence could be pertinent to unraveling their mode of action for imaging or diagnostic applications.
    Matched MeSH terms: Bacterial Infections/drug therapy
  14. Kamaruzzaman NF, Kendall S, Good L
    Br J Pharmacol, 2017 Jul;174(14):2225-2236.
    PMID: 27925153 DOI: 10.1111/bph.13664
    Infectious diseases continue to threaten human and animal health and welfare globally, impacting millions of lives and causing substantial economic loss. The use of antibacterials has been only partially successful in reducing disease impact. Bacterial cells are inherently resilient, and the therapy challenge is increased by the development of antibacterial resistance, the formation of biofilms and the ability of certain clinically important pathogens to invade and localize within host cells. Invasion into host cells provides protection from both antibacterials and the host immune system. Poor delivery of antibacterials into host cells causes inadequate bacterial clearance, resulting in chronic and unresolved infections. In this review, we discuss the challenges associated with existing antibacterial therapies with a focus on intracellular pathogens. We consider the requirements for successful treatment of intracellular infections and novel platforms currently under development. Finally, we discuss novel strategies to improve drug penetration into host cells. As an example, we discuss our recent demonstration that the cell penetrating cationic polymer polyhexamethylene biguanide has antibacterial activity against intracellular Staphylococcus aureus.

    LINKED ARTICLES: This article is part of a themed section on Drug Metabolism and Antibiotic Resistance in Micro-organisms. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.14/issuetoc.

    Matched MeSH terms: Bacterial Infections/drug therapy*
  15. Darah I, Tong WY, Nor-Afifah S, Nurul-Aili Z, Lim SH
    Eur Rev Med Pharmacol Sci, 2014;18(2):171-8.
    PMID: 24488904
    Caulerpa (C.) sertularioides has many therapeutic uses in the practice of traditional medicine in Malaysia. Crude methanolic, diethyl ether extract, ethyl acetate extract and butanolic extract from C. sertularioides were subjected to antimicrobial screening including the three Gram-positive and three Gram-negative diarrhea-caused bacteria.
    Matched MeSH terms: Gram-Negative Bacterial Infections/drug therapy; Gram-Positive Bacterial Infections/drug therapy
  16. Sheikhlar A, Alimon AR, Daud H, Saad CR, Webster CD, Meng GY, et al.
    ScientificWorldJournal, 2014;2014:592709.
    PMID: 25574488 DOI: 10.1155/2014/592709
    Two experiments were simultaneously conducted with Morus alba (white mulberry) foliage extract (MFE) as a growth promoter and treatment of Aeromonas hydrophila infection in separate 60 and 30 days trail (Experiments 1 and 2, resp.) in African catfish (Clarias gariepinus). In Experiment 1, four diets, control and control supplemented with 2, 5, or 7 g MFE/kg dry matter (DM) of diet, were used. In Experiment 2, fish were intraperitoneally infected with Aeromonas hydrophila and fed the same diets as experiment 1 plus additional two diets with or without antibiotic. Results of experiment 1 showed that growth was unaffected by dietary levels of MFE. Treatments with the inclusion of MFE at the levels of 5 and 7 g/Kg DM had no mortality. Red blood cells (RBC), albumin, and total protein were all higher for the treatments fed MFE (5 and 7 g/Kg DM). Results of experiment 2 showed RBC, hemoglobin, hematocrit, globulin, albumin, and total protein improved with the increase in MFE in the infected fish. The dietary MFE at the level of 7 g/kg DM reduced mortality rate. In conclusion, MFE at the level of 7 g/kg DM could be a valuable dietary supplement to cure the infected fish.
    Matched MeSH terms: Gram-Negative Bacterial Infections/drug therapy*
  17. Chandrakantha B, Isloor AM, Shetty P, Fun HK, Hegde G
    Eur J Med Chem, 2014 Jan;71:316-23.
    PMID: 24321835 DOI: 10.1016/j.ejmech.2013.10.056
    A new series of N-[5-(4-(alkyl/aryl)-3-nitro-phenyl)-[1,3,4-thiadiazol-2-yl]-2,2-dimethyl-propionamide 4 (a-l) and 6-(4-Methoxy-phenyl)-2-(4-alkyl/aryl)-3-nitro-phenyl)-Imidazo [2,1-b] [1,3,4] thiadiazole 6 (a-l) were synthesized starting from 5-(4-Fluoro-3-nitro-phenyl)-[1,3,4] thiadiazole-2-ylamine. The synthesized compounds were characterized by IR, NMR, mass spectral and elemental analysis. All the compounds were tested for antibacterial and antifungal activities. The antimicrobial activities of the compounds were assessed by well plate method (zone of inhibition). Compounds 4a, 4c and 6e, 6g displayed appreciable activity at the concentration 0.5-1.0 mg/mL.
    Matched MeSH terms: Bacterial Infections/drug therapy
  18. Akter SF, Heller RD, Smith AJ, Milly AF
    J Infect Dev Ctries, 2009 Jul 01;3(6):447-51.
    PMID: 19762958
    BACKGROUND: Antimicrobials are often used inappropriately in paediatric wards of medical college hospitals in Bangladesh. Most of the antimicrobials are prescribed based on clinical grounds-signs and symptoms. This intervention study assessed the effectiveness of a training intervention on antimicrobials prescribing by physicians in paediatric wards of tertiary care level hospitals.

    METHODOLOGY: This study was conducted at medical college hospitals in Bangladesh during the period from 1998 through 2000. The pre-intervention survey of antimicrobial use was conducted during 1998 in five hospitals. The post-intervention survey was conducted after the interactive training during the succeeding year in three of the original five hospitals, of which one was the intervention hospital and two control hospitals. A total of 3,466 admitted paediatric patients' treatment charts (2,171 in the pre-intervention and 1,295 in the post-intervention surveys) were reviewed.

    RESULTS: The most commonly used antimicrobials were ampicillin, gentamicin, amoxicillin, cloxacillin and ceftriaxone. Appropriate antimicrobial therapy for the most common infectious diseases, pneumonia and diarrhoea, increased by 16.4% and 56.8% respectively in the intervention hospital compared with the two control hospitals and these improvements were significant (p = < 0.001 and p = 0.002, for pneumonia and diarrhoea respectively).

    CONCLUSIONS: An interactive, focussed educational intervention, targeted at physicians, appears to have been effective in improving appropriate antimicrobial prescribing for the most common paediatric infectious diseases in a medical college hospital in Bangladesh.

    Matched MeSH terms: Bacterial Infections/drug therapy
  19. Chang CY, Lee YT, Liu KS, Wang YL, Tsao SM
    J Microbiol Immunol Infect, 2007 Jun;40(3):272-5.
    PMID: 17639170
    Chromobacterium violaceum is a facultative anaerobic, Gram-negative bacillus which inhabits stagnant water in tropical and subtropical regions. We describe the case of an 80-year-old female patient with C. violaceum bacteremia due to traumatic wound infected by contaminated water and soil. She had persistent fever, hypotension and neutrophilic leukocytosis on admission. Two sets of blood cultures yielded C. violaceum. The patient was successfully treated with levofloxacin. Since the first case from Malaysia in 1927, about 150 cases have been reported in the world literature. To our knowledge, six other cases have been reported previously from Taiwan, including two children and four adults. Of the total of seven patients from Taiwan, four had a fatal outcome within several days, while the three survivors were apparently free of vital organ involvement. Although human infections caused by C. violaceum are rare, clinicians should be aware of this potentially fatal infection as part of the differential diagnosis of sepsis associated with a history of exposure to stagnant water.
    Matched MeSH terms: Gram-Negative Bacterial Infections/drug therapy
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