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Antibiotics, Volume 4, Issue 2 (June 2015) – 6 articles , Pages 136-229

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Review
Doxycycline and Tigecycline: Two Friendly Drugs with a Low Association with Clostridium Difficile Infection
Antibiotics 2015, 4(2), 216-229; https://doi.org/10.3390/antibiotics4020216 - 19 Jun 2015
Cited by 14 | Viewed by 4322
Abstract
Clostridium difficile infection (CDI) is known to be associated with prior exposure to many classes of antibiotics. Standard therapy for CDI (i.e., metronidazole and vancomycin) is associated with high recurrence rates. Although tetracycline derivatives such as tetracycline, doxycycline or tigecycline are [...] Read more.
Clostridium difficile infection (CDI) is known to be associated with prior exposure to many classes of antibiotics. Standard therapy for CDI (i.e., metronidazole and vancomycin) is associated with high recurrence rates. Although tetracycline derivatives such as tetracycline, doxycycline or tigecycline are not the standard therapeutic choices for CDI, they may serve as an alternative or a component of combination therapy. Previous tetracycline or doxycycline usage had been shown to have less association with CDI development. Tigecycline, a broad-spectrum glycylcycline with potency against many gram-positive or gram-negative pathogens, had been successfully used to treat severe or refractory CDI. The in vitro susceptibility of C. difficile clinical isolates to tigecycline in many studies showed low minimal inhibitory concentrations. Tigecycline can suppress in vitro toxin production in both historical and hypervirulent C. difficile strains and reduce spore production in a dose-dependent manner. Tetracycline compounds such as doxycycline, minocycline, and tigecycline possess anti-inflammatory properties that are independent of their antibiotic activity and may contribute to their therapeutic effect for CDI. Although clinical data are limited, doxycycline is less likely to induce CDI, and tigecycline can be considered one of the therapeutic choices for severe or refractory CDI. Full article
(This article belongs to the Special Issue Clostridium difficile Infection)
Review
The Antimicrobial Stewardship Approach to Combating Clostridium Difficile
Antibiotics 2015, 4(2), 198-215; https://doi.org/10.3390/antibiotics4020198 - 17 Jun 2015
Cited by 11 | Viewed by 4446
Abstract
Clostridium difficile remains a major public health threat and continues to contribute to excess morbidity, mortality and healthcare costs. Antimicrobial stewardship programs have demonstrated success in combating C. difficile, primarily through antibiotic restrictive strategies. As the incidence and prevalence of C. difficile [...] Read more.
Clostridium difficile remains a major public health threat and continues to contribute to excess morbidity, mortality and healthcare costs. Antimicrobial stewardship programs have demonstrated success in combating C. difficile, primarily through antibiotic restrictive strategies. As the incidence and prevalence of C. difficile associate disease continues to increase both in the hospital and community setting, additional stewardship approaches are needed. This manuscript reviews stewardship interventions that have been successful against C. difficile associated disease and proposes future tactics that antimicrobial stewardship programs may employ to develop a more global approach to combat this difficult pathogen. Full article
(This article belongs to the Special Issue Clostridium difficile Infection)
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Article
The Transcriptional Repressor, MtrR, of the mtrCDE Efflux Pump Operon of Neisseria gonorrhoeae Can Also Serve as an Activator of “off Target” Gene (glnE) Expression
Antibiotics 2015, 4(2), 188-197; https://doi.org/10.3390/antibiotics4020188 - 03 Jun 2015
Cited by 6 | Viewed by 3133
Abstract
MtrR is a well-characterized repressor of the Neisseria gonorrhoeae mtrCDE efflux pump operon. However, results from a previous transcriptional profiling study suggested that MtrR also represses or activates expression of at least sixty genes outside of the mtr locus. Evidence that MtrR can [...] Read more.
MtrR is a well-characterized repressor of the Neisseria gonorrhoeae mtrCDE efflux pump operon. However, results from a previous transcriptional profiling study suggested that MtrR also represses or activates expression of at least sixty genes outside of the mtr locus. Evidence that MtrR can directly repress so-called “off target” genes has previously been reported; in particular, MtrR was shown to directly repress glnA, which encodes glutamine synthetase. In contrast, evidence for the ability of MtrR to directly activate expression of gonococcal genes has been lacking; herein, we provide such evidence. We now report that MtrR has the ability to directly activate expression of glnE, which encodes the dual functional adenyltransferase/deadenylase enzyme GlnE that modifies GlnA resulting in regulation of its role in glutamine biosynthesis. With its capacity to repress expression of glnA, the results presented herein emphasize the diverse and often opposing regulatory properties of MtrR that likely contributes to the overall physiology and metabolism of N. gonorrhoeae. Full article
(This article belongs to the Special Issue Multi-drug Efflux and Drug Permeation)
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Article
Identification of Anti-Persister Activity against Uropathogenic Escherichia coli from a Clinical Drug Library
Antibiotics 2015, 4(2), 179-187; https://doi.org/10.3390/antibiotics4020179 - 12 May 2015
Cited by 16 | Viewed by 3670
Abstract
Uropathogenic E. coli is a major cause of urinary tract infections (UTIs), but current antibiotics do not always effectively clear the persistent infection. To identify drugs that eliminate uropathogenic E. coli persisters, we screened a clinical drug library consisting of 1524 compounds using [...] Read more.
Uropathogenic E. coli is a major cause of urinary tract infections (UTIs), but current antibiotics do not always effectively clear the persistent infection. To identify drugs that eliminate uropathogenic E. coli persisters, we screened a clinical drug library consisting of 1524 compounds using high throughput drug exposure assay in 96-well plates. Bacterial survival was assessed by growth on LB plates. We identified 14 drug candidates (tosufloxacin, colistin, sparfloxacin, moxifloxacin and gatifloxacin, enrofloxacin and sarafloxacin, octodrine, clofoctol, dibekacin, cephalosporin C, pazufloxacin, streptomycin and neomycin), which had high anti-persister activity. Among them, tosufloxacin and colistin had the highest anti-persister activity and could completely eradicate E. coli persisters in 3 days in vitro while the current UTI antibiotics failed to do so. Our findings may have implications for the development of a more effective treatment for UTIs. Full article
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Review
Probiotics for the Primary and Secondary Prevention of C. difficile Infections: A Meta-analysis and Systematic Review
Antibiotics 2015, 4(2), 160-178; https://doi.org/10.3390/antibiotics4020160 - 13 Apr 2015
Cited by 61 | Viewed by 8621
Abstract
Clostridium difficile infections are a global clinical concern and are one of the leading causes of nosocomial outbreaks. Preventing these infections has benefited from multidisciplinary infection control strategies and new antibiotics, but the problem persists. Probiotics are effective in preventing antibiotic-associated diarrhea and [...] Read more.
Clostridium difficile infections are a global clinical concern and are one of the leading causes of nosocomial outbreaks. Preventing these infections has benefited from multidisciplinary infection control strategies and new antibiotics, but the problem persists. Probiotics are effective in preventing antibiotic-associated diarrhea and may also be a beneficial strategy for C. difficile infections, but randomized controlled trials are scarce. This meta-analysis pools 21 randomized, controlled trials for primary prevention of C. difficile infections (CDI) and four trials for secondary prevention of C. difficile recurrences and assesses the efficacy of specific probiotic strains. Four probiotics significantly improved primary CDI prevention: (Saccharomyces boulardii, Lactobacillus casei DN114001, a mixture of L. acidophilus and Bifidobacterium bifidum, and a mixture of L. acidophilus, L. casei and L. rhamnosus). None of the tested probiotics significantly improved secondary prevention of CDI. More confirmatory randomized trials are needed to establish if probiotics are useful for preventing C. difficile infections. v Full article
(This article belongs to the Special Issue Clostridium difficile Infection)
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Review
Host Defense Peptides from Asian Frogs as Potential Clinical Therapies
Antibiotics 2015, 4(2), 136-159; https://doi.org/10.3390/antibiotics4020136 - 30 Mar 2015
Cited by 18 | Viewed by 3701
Abstract
Host defense peptides (HDPs) are currently major focal points of medical research as infectious microbes are gaining resistance to existing drugs. They are effective against multi-drug resistant pathogens due to their unique primary target, biological membranes, and their peculiar mode of action. Even [...] Read more.
Host defense peptides (HDPs) are currently major focal points of medical research as infectious microbes are gaining resistance to existing drugs. They are effective against multi-drug resistant pathogens due to their unique primary target, biological membranes, and their peculiar mode of action. Even though HDPs from 60 Asian frog species belonging to 15 genera have been characterized, research into these peptides is at a very early stage. The purpose of this review is to showcase the status of peptide research in Asia. Here we provide a summary of HDPs from Asian frogs. Full article
(This article belongs to the Special Issue Antimicrobial Peptides)
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