Special Issue "Feature Paper 2013"

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A special issue of Antibiotics (ISSN 2079-6382).

Deadline for manuscript submissions: closed (31 October 2013)

Special Issue Editor

Guest Editor
Dr. Christopher C. Butler (Website)

Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, OX2 6GG, UK
Fax: +44 2920 687219
Interests: antibiotic use; common infections; antibiotic resistance; clinical trials; observational studies; qualitative research

Special Issue Information

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed Open Access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 300 CHF (Swiss Francs). English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.

Published Papers (6 papers)

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Research

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Open AccessArticle Experimental Simulation of the Effects of an Initial Antibiotic Treatment on a Subsequent Treatment after Initial Therapy Failure
Antibiotics 2014, 3(1), 49-63; doi:10.3390/antibiotics3010049
Received: 24 October 2013 / Revised: 23 January 2014 / Accepted: 29 January 2014 / Published: 17 February 2014
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Abstract
Therapy failure of empirical antibiotic treatments prescribed by primary care physicians occurs commonly. The effect of such a treatment on the susceptibility to second line antimicrobial drugs is unknown. Resistance to amoxicillin was rapidly induced or selected in E. coli at concentrations [...] Read more.
Therapy failure of empirical antibiotic treatments prescribed by primary care physicians occurs commonly. The effect of such a treatment on the susceptibility to second line antimicrobial drugs is unknown. Resistance to amoxicillin was rapidly induced or selected in E. coli at concentrations expected in the patient’s body. Strains with reduced susceptibility outcompeted the wild-type whenever antibiotics were present, even in low concentrations that did not affect the growth rates of both strains. Exposure of E. coli to amoxicillin caused moderate resistance to cefotaxime. The combined evidence suggests that initial treatment by amoxicillin has a negative effect on subsequent therapy with beta-lactam antibiotics. Full article
(This article belongs to the Special Issue Feature Paper 2013)
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Open AccessArticle Influence of Sterilized Human Fecal Extract on the Sensitivity of Salmonella enterica ATCC 13076 and Listeria monocytogenes ATCC 15313 to Enrofloxacin
Antibiotics 2013, 2(4), 485-499; doi:10.3390/antibiotics2040485
Received: 1 August 2013 / Revised: 14 November 2013 / Accepted: 20 November 2013 / Published: 2 December 2013
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Abstract
There is much debate on whether continuous exposure of commensal bacteria and potential pathogens residing in the human intestinal tract to low levels of antimicrobial agents from treated food animals pose a public health concern. To investigate antimicrobial effects on bacteria under [...] Read more.
There is much debate on whether continuous exposure of commensal bacteria and potential pathogens residing in the human intestinal tract to low levels of antimicrobial agents from treated food animals pose a public health concern. To investigate antimicrobial effects on bacteria under colonic conditions, we studied resistance development in Salmonella enterica and Listeria monocytogenes exposed to enrofloxacin in the presence of fecal extract. The bacteria were incubated at 37 °C in Mueller-Hinton broth, with and without 0.01~0.5 μg/mL enrofloxacin, in the presence and absence of sucrose, and with 1% or 2.5% filter-sterilized fecal extract, for three passages. In the second and third passages, only the bacteria incubated in the media containing sterilized fecal extract grew in 0.5 μg/mL of enrofloxacin. Fecal extract (1% and 2.5%) decreased the sensitivity of S. enterica to enrofloxacin in the medium containing the efflux pump inhibitors reserpine and carbonyl cyanide-m-chlorophenylhydrazone (CCCP) and affected the accumulation of ethidium bromide (EtBr) in this bacterium. Enrofloxacin (0.06 µg/mL) and fecal extract altered the composition of fatty acids in S. enterica and L. monocytogenes. We conclude that fecal extract decreased the susceptibilities of S. enterica and L. monocytogenes to concentrations of enrofloxacin higher than the MIC and resulted in rapid resistance selection. Full article
(This article belongs to the Special Issue Feature Paper 2013)
Open AccessArticle Low Request of Antibiotics from Patients with Respiratory Tract Infections in Six Countries: Results from the Happy Audit Study
Antibiotics 2013, 2(4), 477-484; doi:10.3390/antibiotics2040477
Received: 22 September 2013 / Revised: 13 November 2013 / Accepted: 13 November 2013 / Published: 19 November 2013
Cited by 1 | PDF Full-text (552 KB) | HTML Full-text | XML Full-text
Abstract
A total of 59,535 patients with respiratory tract infections were registered in the Happy Audit project, an audit-based, before-and-after study conducted in primary care centres of six countries (Argentina, Denmark, Lithuania, Russia, Spain, and Sweden) in 2008 and 2009. An antibiotic was [...] Read more.
A total of 59,535 patients with respiratory tract infections were registered in the Happy Audit project, an audit-based, before-and-after study conducted in primary care centres of six countries (Argentina, Denmark, Lithuania, Russia, Spain, and Sweden) in 2008 and 2009. An antibiotic was explicitly requested by the patient in 1,255 cases (2.1%), with a great variation across countries ranging from 0.4%–4.9%. Antibiotics were significantly more often prescribed to patients requesting them compared to those who did not (64% vs. 28%; p < 0.001). Patients with acute exacerbations of chronic bronchitis/chronic obstructive pulmonary disease were most likely to request antibiotics while those with common colds were least likely (3.9% vs. 1.2%, respectively). The presence of tonsillar exudates and dyspnoea were more commonly associated with a demand for antibiotics. Even though physicians very often perceive that patients demand an antibiotic, the results of this study clearly show that patients only request antibiotics in a low percentage of cases. Patients were most likely to request antibiotics when they had symptoms of lower respiratory tract infections and when they came with more severe symptoms. Furthermore, there were considerable differences between countries, suggesting that the different backgrounds and traditions largely explain this variability in patients’ requests for antibiotics. Full article
(This article belongs to the Special Issue Feature Paper 2013)
Open AccessArticle Public Beliefs about Antibiotics, Infection and Resistance: A Qualitative Study
Antibiotics 2013, 2(4), 465-476; doi:10.3390/antibiotics2040465
Received: 12 September 2013 / Revised: 17 October 2013 / Accepted: 31 October 2013 / Published: 5 November 2013
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Abstract
We aimed to gain an in-depth understanding of public views and ways of talking about antibiotics. Four focus groups were held with members of the public. In addition, 39 households were recruited and interviews, diaries of medicine taking, diaries of any contact [...] Read more.
We aimed to gain an in-depth understanding of public views and ways of talking about antibiotics. Four focus groups were held with members of the public. In addition, 39 households were recruited and interviews, diaries of medicine taking, diaries of any contact with medication were used to explore understanding and use of medication. Discussions related to antibiotics were identified and analyzed. Participants in this study were worried about adverse effects of antibiotics, particularly for recurrent infections. Some were concerned that antibiotics upset the body’s “balance”, and many used strategies to try to prevent and treat infections without antibiotics. They rarely used military metaphors about infection (e.g., describing bacteria as invading armies) but instead spoke of clearing infections. They had little understanding of the concept of antibiotic resistance but they thought that over-using antibiotics was unwise because it would reduce their future effectiveness. Previous studies tend to focus on problems such as lack of knowledge, or belief in the curative powers of antibiotics for viral illness, and neglect the concerns that people have about antibiotics, and the fact that many people try to avoid them. We suggest that these concerns about antibiotics form a resource for educating patients, for health promotion and social marketing strategies. Full article
(This article belongs to the Special Issue Feature Paper 2013)

Review

Jump to: Research

Open AccessReview Utility of the Biosynthetic Folate Pathway for Targets in Antimicrobial Discovery
Antibiotics 2014, 3(1), 1-28; doi:10.3390/antibiotics3010001
Received: 1 November 2013 / Revised: 8 January 2014 / Accepted: 9 January 2014 / Published: 21 January 2014
Cited by 4 | PDF Full-text (1822 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The need for new antimicrobials is great in face of a growing pool of resistant pathogenic organisms. This review will address the potential for antimicrobial therapy based on polypharmacological activities within the currently utilized bacterial biosynthetic folate pathway. The folate metabolic pathway [...] Read more.
The need for new antimicrobials is great in face of a growing pool of resistant pathogenic organisms. This review will address the potential for antimicrobial therapy based on polypharmacological activities within the currently utilized bacterial biosynthetic folate pathway. The folate metabolic pathway leads to synthesis of required precursors for cellular function and contains a critical node, dihydrofolate reductase (DHFR), which is shared between prokaryotes and eukaryotes. The DHFR enzyme is currently targeted by methotrexate in anti-cancer therapies, by trimethoprim for antibacterial uses, and by pyrimethamine for anti-protozoal applications. An additional anti-folate target is dihyropteroate synthase (DHPS), which is unique to prokaryotes as they cannot acquire folate through dietary means. It has been demonstrated as a primary target for the longest standing antibiotic class, the sulfonamides, which act synergistically with DHFR inhibitors. Investigations have revealed most DHPS enzymes possess the ability to utilize sulfa drugs metabolically, producing alternate products that presumably inhibit downstream enzymes requiring the produced dihydropteroate. Recent work has established an off-target effect of sulfonamide antibiotics on a eukaryotic enzyme, sepiapterin reductase, causing alterations in neurotransmitter synthesis. Given that inhibitors of both DHFR and DHPS are designed to mimic their cognate substrate, which contain shared substructures, it is reasonable to expect such “off-target” effects. These inhibitors are also likely to interact with the enzymatic neighbors in the folate pathway that bind products of the DHFR or DHPS enzymes and/or substrates of similar substructure. Computational studies designed to assess polypharmacology reiterate these conclusions. This leads to hypotheses exploring the vast utility of multiple members of the folate pathway for modulating cellular metabolism, and includes an appealing capacity for prokaryotic-specific polypharmacology for antimicrobial applications. Full article
(This article belongs to the Special Issue Feature Paper 2013)
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Open AccessReview Pipeline of Known Chemical Classes of Antibiotics
Antibiotics 2013, 2(4), 500-534; doi:10.3390/antibiotics2040500
Received: 13 September 2013 / Revised: 28 November 2013 / Accepted: 29 November 2013 / Published: 6 December 2013
Cited by 8 | PDF Full-text (895 KB) | HTML Full-text | XML Full-text
Abstract
Many approaches are used to discover new antibiotic compounds, one of the most widespread being the chemical modification of known antibiotics. This type of discovery has been so important in the development of new antibiotics that most antibiotics used today belong to [...] Read more.
Many approaches are used to discover new antibiotic compounds, one of the most widespread being the chemical modification of known antibiotics. This type of discovery has been so important in the development of new antibiotics that most antibiotics used today belong to the same chemical classes as antibiotics discovered in the 1950s and 1960s. Even though the discovery of new classes of antibiotics is urgently needed, the chemical modification of antibiotics in known classes is still widely used to discover new antibiotics, resulting in a great number of compounds in the discovery and clinical pipeline that belong to existing classes. In this scenario, the present article presents an overview of the R&D pipeline of new antibiotics in known classes of antibiotics, from discovery to clinical trial, in order to map out the technological trends in this type of antibiotic R&D, aiming to identify the chemical classes attracting most interest, their spectrum of activity, and the new subclasses under development. The result of the study shows that the new antibiotics in the pipeline belong to the following chemical classes: quinolones, aminoglycosides, macrolides, oxazolidinones, tetracyclines, pleuromutilins, beta-lactams, lipoglycopeptides, polymyxins and cyclic lipopeptides. Full article
(This article belongs to the Special Issue Feature Paper 2013)

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