Article

Unmet medical needs in antibacterial therapy

Louis Stokes Cleveland VA Medical Center and Case Western Reserve University, Medical Service 111(W), 10701 East Blvd., Cleveland, OH 44106, USA.
Biochemical Pharmacology (Impact Factor: 5.01). 04/2006; 71(7):991-5. DOI: 10.1016/j.bcp.2005.09.018
Source: PubMed

ABSTRACT

The innate and evolutionary resourcefulness of bacterial pathogens virtually guarantees that there will always be important areas in which antimicrobial therapy can be improved. Current areas of need, or ones that are anticipated to be problematic in the near future include nosocomial infections caused by multi-resistant Gram-negative bacteria, where the variety and prevalence of multidrug efflux pumps provides a particular challenge to the designers of new drugs. In the community setting, the current prevalence of ampicillin and trimethoprim-sulfamethoxazole resistance, and the growing prevalence of fluoroquinolone resistance in Escherichia coli portend a need for new classes of oral agents to address this important need. On the Gram-positive side, the rapid increase in virulent community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections as a cause of pneumonia emphasizes the importance of developing more agents that are active against MRSA and that are effective for treating pneumonia. Finally, the importance of indwelling devices as a nidus for nosocomial infections emphasizes the need for effective agents for treating biofilm-associated device infection both inside and outside of the hospital.

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    • "Clinically, the continuous emergence of Gram-negative MDR bacteria drastically reduces the efficacy of the antibiotic arsenal and, consequently, increases the frequency of therapeutic failure (Rice, 2006). Approximately 60% of world's population still relies on medicinal plants for their primary healthcare (WHO, 2010). "
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    ABSTRACT: Fagara tessmannii is a shrub of the African rainforests used to treat bacterial infections, cancers, swellings and inflammation. In the present study, the methanol extract from the leaves (FTL), bark (FTB), and roots (FTR) of this plant as well as fractions (FTR1-5) and compounds isolated from FTR namely β-sitosterol-3-O-β-D-glucopyranoside (1), nitidine chloride (2) and buesgenine (3), were tested for their antimicrobial activities against a panel of Gram-negative bacteria including multidrug resistant (MDR) phenotypes. The broth microdilution method was used to determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of the above samples; Column chromatography was used for the fractionation and purification of the roots extract whilst the chemical structures of compounds were determined using spectroscopic techniques. Results of the MIC determinations indicated that the crude extracts from the roots as well as fraction FTRa4 were active on all the 26 tested bacterial strains. MIC values below 100µg/mL were obtained with roots, leaves and bark extract respectively against 30.8%, 15.4% and 11.5% tested bacteria. The lowest MIC value below of 8µg/mL was obtained with extract from the roots against Escherichia coli MC100 strain. The lowest MIC value of 4µg/mL was also obtained with compound 3 against Escherichia coli AG102 and Klebsiella pneumoniae ATCC11296 CONCLUSIONS: The present study demonstrates that Fagara tessmannii is a potential source of antimicrobial drugs to fight against MDR bacteria. Benzophenanthrine alkaloids 2 and 3 are the main antibacterial consituents of the roots of the plant. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Full-text · Article · Apr 2015 · Journal of ethnopharmacology
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    • "The continuous emergence of Gram-negative MDR bacteria drastically reduces the efficacy of our antibiotic armory and, consequently, increases the frequency of therapeutic failure [1]. On the other hand, the World Health Organization (WHO) estimates that there are nine million cases of tuberculosis (TB) currently, with 1.3 million reported deaths every year, 55 and 30% of the TB burden being shared by Asian and African countries respectively [2]. "
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    ABSTRACT: Dioscorea bulbifera is an African medicinal plant used to treat microbial infections. In the present study, the methanol extract, fractions (DBB1 and DBB2) and six compounds isolated from the bulbils of D. bulbifera, namely bafoudiosbulbins A (1), B (2), C (3), F (4), G (5) and 2,7-dihydroxy-4-methoxyphenanthrene (6), were tested for their antimicrobial activities against Mycobacteria and Gram-negative bacteria involving multidrug resistant (MDR) phenotypes expressing active efflux pumps. The microplate alamar blue assay (MABA) and the broth microdilution methods were used to determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of the above samples. The results of the MIC determinations indicated that when tested alone, the crude extract, fractions DBB1 and DBB2 as well as compounds 2 to 5 were able to prevent the growth of all the fifteen studied microorganisms, within the concentration range of 8 to 256 μg/mL. The lowest MIC value for the methanol extract and fractions (16 μg/mL) was obtained with DBB1 and DBB2 on E, coli AG100A and DBB2 on Mycobacterium tuberculosis MTCS2. The lowest value for individual compounds (8 μg/mL) was recorded with compound 3 on M. smegmatis and M. tuberculosis ATCC and MTCS2 strains respectively. The activity of the samples on many MDR bacteria such as Enterobacter aerogenes EA289, CM64, Klebsiella pneumoniae KP63 and Pseudomonas aeruginosa PA124 was better than that of chloramphenicol. When tested in the presence of the efflux pump inhibitor against MDR Gram-negative bacteria, the activity of most of the samples increased. MBC values not greater than 512 μg/mL were recorded on all studied microorganisms with fraction DBB2 and compounds 2 to 5. The overall results of the present investigation provided evidence that the crude extract D. bulbifera as well as some of the compounds and mostly compounds 3 could be considered as potential antimicrobial drugs to fight against MDR bacteria.
    Full-text · Article · Nov 2012 · BMC Complementary and Alternative Medicine
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    • "This proves that the killing effects of many tested samples could be expected on the sensitive strains [22]. The continuous emergence of multidrug-resistant (MDR) bacteria drastically reduces the efficacy of our antibiotic armory and, consequently, increases the frequency of therapeutic failure [23]. MDR Enterobacteriaceae, including K. pneumoniae, E. aerogenes and E. coli have also been classified as antimicrobial-resistant organisms of concern in healthcare facilities [24]. "
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    ABSTRACT: Dorstenia mannii (Moraceae) is a medicinal herb used traditionally for the treatment of many diseases. In the present study, the methanol extract of D. mannii and nine of its isolated compounds, namely dorsmanin A (1), B (2), C (3), D (4), E (6), F (7), G (8) dorsmanin I (9) and 6,8-diprenyleriodictyol (5), were tested for their antimicrobial activities against yeast, Mycobacteria and Gram-negative bacteria. The microplate alamar blue assay (MABA) and the broth microdilution method were used to determine the minimal inhibitory concentration (MIC) and minimal microbicidal concentration (MMC) of the above extract and compounds on a panel of bacterial species. The results of the MIC determinations demonstrated that the methanol extract as well as compounds 3 and 8 were able to prevent the growth of all the fourteen studied microorganisms within the concentration range of 4 to 1024 μg/ml. The lowest MIC value for the methanol extract (64 μg/ml) was obtained on Candida albicans. The lowest value for individual compounds (4 μg/ml) was recorded with compounds 3 on Pseudomonas aeruginosa PA01 and 7 on Eschericia coli ATCC strain. The MIC values recorded with compounds 3 on P. aeruginosa PA01, 6 on C. albicans,7 on P. aeruginosa PA01 and K. pneumoniae ATCC strain and C. albicans,and 8 on P. aeruginosa PA01, PA124, P. stuartii, M. tuberculosis MTCS1 were lower than or equal to those of the reference drugs. MMC values not greater than 1024 μg/ml were recorded on all studied microorganisms with compounds 3 and 8. The overall results of the present investigation provided evidence that the crude extract of D. mannii as well as some of its compounds such compounds 3 and 8 could be a potential source of natural antimicrobial products.
    Full-text · Article · Jun 2012 · BMC Complementary and Alternative Medicine
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