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Pharmaceuticals
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Antimicrobial Agents
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Antimicrobial Agents

A special issue of Pharmaceuticals (ISSN 1424-8247).

Deadline for manuscript submissions: closed (31 July 2013) | Viewed by 117085

Special Issue Editor

Dr. D. Andrew Knight

E-Mail Website
Guest Editor
Chemistry Department, Florida Institute of Technology, 150 West University Boulevard, Melbourne, FL 32901, USA
Interests: catalysis and organic synthesis; nanoscale and layered materials; medicinal chemistry; molecular biology; biodefense and green chemistry

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Published Papers (6 papers)

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Research

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206 KiB  
Article
Longitudinal Assessment of Antimicrobial Susceptibility among Gram-Negative and Gram-Positive Organisms Collected from Italy as Part of the Tigecycline Evaluation and Surveillance Trial between 2004 and 2011
by Stefania Stefani and Michael J. Dowzicky
Pharmaceuticals 2013, 6(11), 1381-1406; https://doi.org/10.3390/ph6111381 - 7 Nov 2013
Cited by 9 | Viewed by 6286
Abstract
The Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) was initiated in 2004 to longitudinally monitor the activity of the broad-spectrum glycylcycline antimicrobial tigecycline, and a suite of comparator agents, against an array of clinically important bacterial pathogens worldwide. In this report, we examine the [...] Read more.
The Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) was initiated in 2004 to longitudinally monitor the activity of the broad-spectrum glycylcycline antimicrobial tigecycline, and a suite of comparator agents, against an array of clinically important bacterial pathogens worldwide. In this report, we examine the activity of tigecycline and comparators against a collection of 13,245 clinical isolates, both Gram-positive (n = 4,078 and Gram-negative (n = 9,167), collected from 27 centres in Italy between 2004 and 2011. Susceptibility was established according to Clinical Laboratory Standards Institute guidelines. Tigecycline and linezolid exhibited very good activity against Gram-positive pathogens, with MIC90s ranging from 0.06 to 0.25 mg/L and 1–4 mg/L, respectively; vancomycin and the carbapenems also showed good activity against select Gram-positive pathogens. Tigecycline was the most active agent against Gram-negative pathogens (except P. aeruginosa), with MIC90s ranging from 0.25–2 mg/L (16 mg/L for P. aeruginosa). Amikacin and the carbapenems also possessed good activity against many Gram-negative pathogens here. ESBL-positive E. coli increased in prevalence from 2004 to 2011, while ESBL-positive Klebsiella spp., vancomycin-resistant enterococci and MRSA decreased in prevalence. Linezolid, tigecycline and vancomycin susceptibility were very stable over the course of this study, while susceptibility to ampicillin, piperacillin-tazobactam, ceftriaxone and levofloxacin varied over time according to pathogen; minocycline and cefepime susceptibility among several pathogens decreased during this study. Full article
(This article belongs to the Special Issue Antimicrobial Agents)
346 KiB  
Article
What Goes around Comes around-A Comparative Study of the Influence of Chemical Modifications on the Antimicrobial Properties of Small Cyclic Peptides
by Kathi Scheinpflug, Heike Nikolenko, Igor V. Komarov, Marina Rautenbach and Margitta Dathe
Pharmaceuticals 2013, 6(9), 1130-1144; https://doi.org/10.3390/ph6091130 - 6 Sep 2013
Cited by 12 | Viewed by 7497
Abstract
Tryptophan and arginine-rich cyclic hexapeptides of the type cyclo-RRRWFW combine high antibacterial activity with rapid cell killing kinetics, but show low toxicity in human cell lines. The peptides fulfil the structural requirements for membrane interaction such as high amphipathicity and cationic charge, but [...] Read more.
Tryptophan and arginine-rich cyclic hexapeptides of the type cyclo-RRRWFW combine high antibacterial activity with rapid cell killing kinetics, but show low toxicity in human cell lines. The peptides fulfil the structural requirements for membrane interaction such as high amphipathicity and cationic charge, but membrane permeabilisation, which is the most common mode of action of antimicrobial peptides (AMPs), could not be observed. Our current studies focus on elucidating a putative membrane translocation mechanism whereupon the peptides might interfere with intracellular processes. These investigations require particular analytical tools: fluorescent analogues and peptides bearing appropriate reactive groups were synthesized and characterized in order to be used in confocal laser scanning microscopy and HPLC analysis. We found that minimal changes in both the cationic and hydrophobic domain of the peptides in most cases led to significant reduction of antimicrobial activity and/or changes in the mode of action. However, we were able to identify two modified peptides which exhibited properties similar to those of the cyclic parent hexapeptide and are suitable for subsequent studies on membrane translocation and uptake into bacterial cells. Full article
(This article belongs to the Special Issue Antimicrobial Agents)
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428 KiB  
Article
Diamidines versus Monoamidines as Anti-Pneumocystis Agents: An in Vivo Study
by Dimitri Stanicki, Muriel Pottier, Nausicaa Gantois, Claire Pinçon, Delphine Forge, Isabelle Mahieu, Sébastien Boutry, Jean Jacques Vanden Eynde, Anna Martinez, Eduardo Dei-Cas and El-Moukhtar Aliouat
Pharmaceuticals 2013, 6(7), 837-850; https://doi.org/10.3390/ph6070837 - 1 Jul 2013
Cited by 4 | Viewed by 7919
Abstract
Some compounds articulated around a piperazine or an ethylenediamine linker have been evaluated in vitro to determine their activity in the presence of a 3T6 fibroblast cell line and an axenic culture of Pneumocystis carinii, respectively. The most efficient antifungal derivatives, namely [...] Read more.
Some compounds articulated around a piperazine or an ethylenediamine linker have been evaluated in vitro to determine their activity in the presence of a 3T6 fibroblast cell line and an axenic culture of Pneumocystis carinii, respectively. The most efficient antifungal derivatives, namely N,N′-bis(benzamidine-4-yl)ethane-1,2-diamine (compound 6, a diamidine) and N-(benzamidine-4-yl)-N′-phenylethane-1,2-diamine (compound 7, a monoamidine), exhibited no cytotoxicity and were evaluated in vivo in a rat model. Only the diamidine 6 emerged as a promising hit for further studies. Full article
(This article belongs to the Special Issue Antimicrobial Agents)
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Review

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252 KiB  
Review
Effect of Essential Oils on Pathogenic Bacteria
by Filomena Nazzaro, Florinda Fratianni, Laura De Martino, Raffaele Coppola and Vincenzo De Feo
Pharmaceuticals 2013, 6(12), 1451-1474; https://doi.org/10.3390/ph6121451 - 25 Nov 2013
Cited by 1439 | Viewed by 60506
Abstract
The increasing resistance of microorganisms to conventional chemicals and drugs is a serious and evident worldwide problem that has prompted research into the identification of new biocides with broad activity. Plants and their derivatives, such as essential oils, are often used in folk [...] Read more.
The increasing resistance of microorganisms to conventional chemicals and drugs is a serious and evident worldwide problem that has prompted research into the identification of new biocides with broad activity. Plants and their derivatives, such as essential oils, are often used in folk medicine. In nature, essential oils play an important role in the protection of plants. Essential oils contain a wide variety of secondary metabolites that are capable of inhibiting or slowing the growth of bacteria, yeasts and moulds. Essential oils and their components have activity against a variety of targets, particularly the membrane and cytoplasm, and in some cases, they completely change the morphology of the cells. This brief review describes the activity of essential oils against pathogenic bacteria. Full article
(This article belongs to the Special Issue Antimicrobial Agents)
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566 KiB  
Review
A Review of Ten Years of the Study for Monitoring Antimicrobial Resistance Trends (SMART) from 2002 to 2011
by Ian Morrissey, Meredith Hackel, Robert Badal, Sam Bouchillon, Stephen Hawser and Douglas Biedenbach
Pharmaceuticals 2013, 6(11), 1335-1346; https://doi.org/10.3390/ph6111335 - 1 Nov 2013
Cited by 199 | Viewed by 16708
Abstract
Surveillance of antimicrobial agent resistance provides important information to guide microbiologists and infectious disease specialists understanding of the control and the spread of resistance mechanisms within the local environment. Continued monitoring of antimicrobial resistance patterns in the community and in local hospital environments [...] Read more.
Surveillance of antimicrobial agent resistance provides important information to guide microbiologists and infectious disease specialists understanding of the control and the spread of resistance mechanisms within the local environment. Continued monitoring of antimicrobial resistance patterns in the community and in local hospital environments is essential to guide effective empiric therapy. The Study for Monitoring Antimicrobial Resistance Trends (SMART) has monitored the in vitro susceptibility patterns of clinical Gram-negative bacilli to antimicrobial agents collected worldwide from intra-abdominal infections since 2002 and urinary tract infections since 2009. Resistance trends, with a particular focus on carbapenem resistance and the rate of extended-spectrum β-lactamases (ESBLs), were analyzed. Isolates from intra-abdominal infections (n = 92,086) and urinary-tract infections (n = 24,705) were collected and tested using Clinical and Laboratory Standards Institute methods. This review presents carbapenem susceptibility and ESBL rates over ten years of SMART study analysis, including key publications during this period. The SMART study has proved to be a valuable resource in determining pathogen prevalence and antibiotic susceptibility over the last ten years and continues to provide evidence for regulatory susceptibility breakpoints and clinical decision making. Full article
(This article belongs to the Special Issue Antimicrobial Agents)
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1019 KiB  
Review
Characterization of Antimicrobial Peptides toward the Development of Novel Antibiotics
by Wataru Aoki and Mitsuyoshi Ueda
Pharmaceuticals 2013, 6(8), 1055-1081; https://doi.org/10.3390/ph6081055 - 21 Aug 2013
Cited by 214 | Viewed by 17019
Abstract
Antimicrobial agents have eradicated many infectious diseases and significantly improved our living environment. However, abuse of antimicrobial agents has accelerated the emergence of multidrug-resistant microorganisms, and there is an urgent need for novel antibiotics. Antimicrobial peptides (AMPs) have attracted attention as a novel [...] Read more.
Antimicrobial agents have eradicated many infectious diseases and significantly improved our living environment. However, abuse of antimicrobial agents has accelerated the emergence of multidrug-resistant microorganisms, and there is an urgent need for novel antibiotics. Antimicrobial peptides (AMPs) have attracted attention as a novel class of antimicrobial agents because AMPs efficiently kill a wide range of species, including bacteria, fungi, and viruses, via a novel mechanism of action. In addition, they are effective against pathogens that are resistant to almost all conventional antibiotics. AMPs have promising properties; they directly disrupt the functions of cellular membranes and nucleic acids, and the rate of appearance of AMP-resistant strains is very low. However, as pharmaceuticals, AMPs exhibit unfavorable properties, such as instability, hemolytic activity, high cost of production, salt sensitivity, and a broad spectrum of activity. Therefore, it is vital to improve these properties to develop novel AMP treatments. Here, we have reviewed the basic biochemical properties of AMPs and the recent strategies used to modulate these properties of AMPs to enhance their safety. Full article
(This article belongs to the Special Issue Antimicrobial Agents)
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