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Antibiotics, Volume 4, Issue 4 (December 2015) – 16 articles , Pages 411-674

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921 KiB  
Article
Implementation of a Clinical Decision Support Alert for the Management of Clostridium difficile Infection
by Sara Revolinski
Antibiotics 2015, 4(4), 667-674; https://doi.org/10.3390/antibiotics4040667 - 21 Dec 2015
Cited by 14 | Viewed by 5536
Abstract
Clostridium difficile infections are common in hospitalized patients and can result in significant morbidity and mortality. It is imperative to optimize the management of C. difficile infections to help minimize disease complications. Antimicrobial stewardship techniques including guidelines, order sets and other clinical decision [...] Read more.
Clostridium difficile infections are common in hospitalized patients and can result in significant morbidity and mortality. It is imperative to optimize the management of C. difficile infections to help minimize disease complications. Antimicrobial stewardship techniques including guidelines, order sets and other clinical decision support functionalities may be utilized to assist with therapy optimization. We implemented a novel alert within our electronic medical record to direct providers to the C. difficile order set in order to assist with initiating therapy consistent with institutional guideline recommendations. The alert succeeded in significantly increasing order set utilization, but guideline compliance was unchanged. Full article
(This article belongs to the Special Issue Antimicrobial Stewardship)
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Review
Examining the Clinical Effectiveness of Non-Carbapenem β-Lactams for the Treatment of Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae
by Allison M. Gibble, Alan E. Gross and Angela M. Huang
Antibiotics 2015, 4(4), 653-666; https://doi.org/10.3390/antibiotics4040653 - 15 Dec 2015
Cited by 2 | Viewed by 6088
Abstract
Treatment options for extended-spectrum β-lactamase-producing Enterobacteriaceae are limited. Piperacillin-tazobactam and cefepime represent potential alternative treatment options; however, large prospective studies are lacking. This review evaluates the current literature regarding use of piperacillin-tazobactam and cefepime for the treatment of extended-spectrum β-lactamase-producing Enterobacteriaceae. Antimicrobial stewardship [...] Read more.
Treatment options for extended-spectrum β-lactamase-producing Enterobacteriaceae are limited. Piperacillin-tazobactam and cefepime represent potential alternative treatment options; however, large prospective studies are lacking. This review evaluates the current literature regarding use of piperacillin-tazobactam and cefepime for the treatment of extended-spectrum β-lactamase-producing Enterobacteriaceae. Antimicrobial stewardship programs can play a key role in guiding the best practices for the management of these challenging infections. Full article
(This article belongs to the Special Issue Antimicrobial Stewardship)
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Article
Utilizing Monte Carlo Simulations to Optimize Institutional Empiric Antipseudomonal Therapy
by Sarah J. Tennant, Donna R. Burgess, Jeffrey M. Rybak, Craig A. Martin and David S. Burgess
Antibiotics 2015, 4(4), 643-652; https://doi.org/10.3390/antibiotics4040643 - 11 Dec 2015
Cited by 12 | Viewed by 6576
Abstract
Pseudomonas aeruginosa is a common pathogen implicated in nosocomial infections with increasing resistance to a limited arsenal of antibiotics. Monte Carlo simulation provides antimicrobial stewardship teams with an additional tool to guide empiric therapy. We modeled empiric therapies with antipseudomonal β-lactam antibiotic regimens [...] Read more.
Pseudomonas aeruginosa is a common pathogen implicated in nosocomial infections with increasing resistance to a limited arsenal of antibiotics. Monte Carlo simulation provides antimicrobial stewardship teams with an additional tool to guide empiric therapy. We modeled empiric therapies with antipseudomonal β-lactam antibiotic regimens to determine which were most likely to achieve probability of target attainment (PTA) of ≥90%. Microbiological data for P. aeruginosa was reviewed for 2012. Antibiotics modeled for intermittent and prolonged infusion were aztreonam, cefepime, meropenem, and piperacillin/tazobactam. Using minimum inhibitory concentrations (MICs) from institution-specific isolates, and pharmacokinetic and pharmacodynamic parameters from previously published studies, a 10,000-subject Monte Carlo simulation was performed for each regimen to determine PTA. MICs from 272 isolates were included in this analysis. No intermittent infusion regimens achieved PTA ≥90%. Prolonged infusions of cefepime 2000 mg Q8 h, meropenem 1000 mg Q8 h, and meropenem 2000 mg Q8 h demonstrated PTA of 93%, 92%, and 100%, respectively. Prolonged infusions of piperacillin/tazobactam 4.5 g Q6 h and aztreonam 2 g Q8 h failed to achieved PTA ≥90% but demonstrated PTA of 81% and 73%, respectively. Standard doses of β-lactam antibiotics as intermittent infusion did not achieve 90% PTA against P. aeruginosa isolated at our institution; however, some prolonged infusions were able to achieve these targets. Full article
(This article belongs to the Special Issue Antimicrobial Stewardship)
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Article
Genetic Screen Reveals the Role of Purine Metabolism in Staphylococcus aureus Persistence to Rifampicin
by Rebecca Yee, Peng Cui, Wanliang Shi, Jie Feng and Ying Zhang
Antibiotics 2015, 4(4), 627-642; https://doi.org/10.3390/antibiotics4040627 - 07 Dec 2015
Cited by 52 | Viewed by 8760
Abstract
Chronic infections with Staphylococcus aureus such as septicemia, osteomyelitis, endocarditis, and biofilm infections are difficult to treat because of persisters. Despite many efforts in understanding bacterial persistence, the mechanisms of persister formation in S. aureus remain elusive. Here, we performed a genome-wide screen [...] Read more.
Chronic infections with Staphylococcus aureus such as septicemia, osteomyelitis, endocarditis, and biofilm infections are difficult to treat because of persisters. Despite many efforts in understanding bacterial persistence, the mechanisms of persister formation in S. aureus remain elusive. Here, we performed a genome-wide screen of a transposon mutant library to study the molecular mechanisms involved in persistence of community-acquired S. aureus. Screening of the library for mutants defective in persistence or tolerance to rifampicin revealed many genes involved in metabolic pathways that are important for antibiotic persistence. In particular, the identified mutants belonged to metabolic pathways involved in carbohydrate, amino acid, lipid, vitamin and purine biosynthesis. Five mutants played a role in purine biosynthesis and two mutants, purB, an adenylosuccinate lyase, and purM, a phosphoribosylaminoimidazole synthetase, were selected for further confirmation. Mutants purB and purM showed defective persistence compared to the parental strain USA300 in multiple stress conditions including various antibiotics, low pH, and heat stress. The defect in persistence was restored by complementation with the wildtype purB and purM gene in the respective mutants. These findings provide new insights into the mechanisms of persistence in S. aureus and provide novel therapeutic targets for developing more effective treatment for persistent infections due to S. aureus. Full article
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Communication
Pharmacokinetic/Toxicity Properties of the New Anti-Staphylococcal Lead Compound SK-03-92
by William R. Schwan, Jill M. Kolesar, M. Shahjahan Kabir, Edmund J. Elder, Jeffrey B. Williams, Rachel Minerath, James M. Cook, Christopher M. Witzigmann, Aaron Monte and Tricia Flaherty
Antibiotics 2015, 4(4), 617-626; https://doi.org/10.3390/antibiotics4040617 - 24 Nov 2015
Cited by 2 | Viewed by 5061
Abstract
Because of the potential of a new anti-staphylococcal lead compound SK-03-92 as a topical antibiotic, a patch, or an orally active drug, we sought to determine its safety profile and oral bioavailability. SK-03-92 had a high IC50 (125 μg/mL) in vitro against [...] Read more.
Because of the potential of a new anti-staphylococcal lead compound SK-03-92 as a topical antibiotic, a patch, or an orally active drug, we sought to determine its safety profile and oral bioavailability. SK-03-92 had a high IC50 (125 μg/mL) in vitro against several mammalian cell lines, and mice injected intraperiteonally at the highest dose did not exhibit gross toxicity (e.g., altered gait, ungroomed, significant weight loss). Single dose (100 μg/g) pharmacokinetic (PK) analysis with formulated SK-03-92 showed that peak plasma concentration (1.64 μg/mL) was achieved at 20–30 min. Oral relative bioavailability was 8%, and the drug half-life was 20–30 min, demonstrating that SK-03-92 is likely not a candidate for oral delivery. Five-day and two-week PK analyses demonstrated that SK-03-92 plasma levels were low. Multi-dose analysis showed no gross adverse effects to the mice and a SK-03-92 peak plasma concentration of 2.12 μg/mL with the presence of significant concentrations of breakdown products 15 min after dosing. SK-03-92 appeared to be very safe based on tissue culture and mouse gross toxicity determinations, but the peak plasma concentration suggests that a pro-drug of SK-03-92 or preparation of analogs of SK-03-92 with greater bioavailability and longer half-lives are warranted. Full article
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Article
Remote Antimicrobial Stewardship in Community Hospitals
by Zachary H. Wood, Nicole C. Nicolsen, Nichole Allen and Paul P. Cook
Antibiotics 2015, 4(4), 605-616; https://doi.org/10.3390/antibiotics4040605 - 13 Nov 2015
Cited by 15 | Viewed by 5811
Abstract
Antimicrobial stewardship has become standard practice at university medical centers, but the practice is more difficult to implement in remote community hospitals that lack infectious diseases trained practitioners. Starting in 2011, six community hospitals within the Vidant Health system began an antimicrobial stewardship [...] Read more.
Antimicrobial stewardship has become standard practice at university medical centers, but the practice is more difficult to implement in remote community hospitals that lack infectious diseases trained practitioners. Starting in 2011, six community hospitals within the Vidant Health system began an antimicrobial stewardship program utilizing pharmacists who reviewed charts remotely from Vidant Medical Center. Pharmacists made recommendations within the electronic medical record (EMR) to streamline, discontinue, or switch antimicrobial agents. Totals of charts reviewed, recommendations made, recommendations accepted, and categories of intervention were recorded. Linear regression was utilized to measure changes in antimicrobial use over time. For the four larger hospitals, recommendations for changes were made in an average of 45 charts per month per hospital and physician acceptance of the pharmacists’ recommendations varied between 83% and 88%. There was no significant decrease in total antimicrobial use, but much of the use was outside of the stewardship program’s review. Quinolone use decreased by more than 50% in two of the four larger hospitals. Remote antimicrobial stewardship utilizing an EMR is feasible in community hospitals and is generally received favorably by physicians. As more community hospitals adopt EMRs, there is an opportunity to expand antimicrobial stewardship beyond the academic medical center. Full article
(This article belongs to the Special Issue Antimicrobial Stewardship)
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Review
Co-Selection of Resistance to Antibiotics, Biocides and Heavy Metals, and Its Relevance to Foodborne Pathogens
by Andrew D. Wales and Robert H. Davies
Antibiotics 2015, 4(4), 567-604; https://doi.org/10.3390/antibiotics4040567 - 13 Nov 2015
Cited by 263 | Viewed by 17765
Abstract
Concerns have been raised in recent years regarding co-selection for antibiotic resistance among bacteria exposed to biocides used as disinfectants, antiseptics and preservatives, and to heavy metals (particularly copper and zinc) used as growth promoters and therapeutic agents for some livestock species. There [...] Read more.
Concerns have been raised in recent years regarding co-selection for antibiotic resistance among bacteria exposed to biocides used as disinfectants, antiseptics and preservatives, and to heavy metals (particularly copper and zinc) used as growth promoters and therapeutic agents for some livestock species. There is indeed experimental and observational evidence that exposure to these non-antibiotic antimicrobial agents can induce or select for bacterial adaptations that result in decreased susceptibility to one or more antibiotics. This may occur via cellular mechanisms that are protective across multiple classes of antimicrobial agents or by selection of genetic determinants for resistance to non-antibiotic agents that are linked to genes for antibiotic resistance. There may also be relevant effects of these antimicrobial agents on bacterial community structure and via non-specific mechanisms such as mobilization of genetic elements or mutagenesis. Notably, some co-selective adaptations have adverse effects on fitness in the absence of a continued selective pressure. The present review examines the evidence for the significance of these phenomena, particularly in respect of bacterial zoonotic agents that commonly occur in livestock and that may be transmitted, directly or via the food chain, to human populations. Full article
(This article belongs to the Special Issue The Use of Antibiotics in Food-Producing Animals)
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Review
Focus on the Outer Membrane Factor OprM, the Forgotten Player from Efflux Pumps Assemblies
by Gilles Phan, Martin Picard and Isabelle Broutin
Antibiotics 2015, 4(4), 544-566; https://doi.org/10.3390/antibiotics4040544 - 12 Nov 2015
Cited by 14 | Viewed by 7279
Abstract
Antibiotics have been used extensively during several decades and we are now facing the emergence of multidrug resistant strains. It has become a major public concern, urging the need to discover new strategies to combat them. Among the different ways used by bacteria [...] Read more.
Antibiotics have been used extensively during several decades and we are now facing the emergence of multidrug resistant strains. It has become a major public concern, urging the need to discover new strategies to combat them. Among the different ways used by bacteria to resist antibiotics, the active efflux is one of the main mechanisms. In Gram-negative bacteria the efflux pumps are comprised of three components forming a long edifice crossing the complete cell wall from the inside to the outside of the cell. Blocking these pumps would permit the restoration of the effectiveness of the current antibiotherapy which is why it is important to increase our knowledge on the different proteins involved in these complexes. A tremendous number of experiments have been performed on the inner membrane protein AcrB from Escherichia coli and, to a lesser extent, the protein partners forming the AcrAB-TolC pump, but less information is available concerning the efflux pumps from other virulent Gram-negative bacteria. The present review will focus on the OprM outer membrane protein from the MexAB-OprM pump of Pseudomonas aeruginosa, highlighting similarities and differences compare to the archetypal AcrAB-TolC in terms of structure, function, and assembly properties. Full article
(This article belongs to the Special Issue Multi-drug Efflux and Drug Permeation)
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992 KiB  
Review
Livestock-Associated MRSA: The Impact on Humans
by Christiane Cuny, Lothar H. Wieler and Wolfgang Witte
Antibiotics 2015, 4(4), 521-543; https://doi.org/10.3390/antibiotics4040521 - 06 Nov 2015
Cited by 228 | Viewed by 16518
Abstract
During the past 25 years an increase in the prevalence of methicillin-resistant Staphylococcus aureus (HA-MRSA) was recorded worldwide. Additionally, MRSA infections may occur outside and independent of hospitals, caused by community associated MRSA (CA-MRSA). In Germany, we found that at least 10% of [...] Read more.
During the past 25 years an increase in the prevalence of methicillin-resistant Staphylococcus aureus (HA-MRSA) was recorded worldwide. Additionally, MRSA infections may occur outside and independent of hospitals, caused by community associated MRSA (CA-MRSA). In Germany, we found that at least 10% of these sporadic infections are due to livestock-associated MRSA (LA-MRSA), which is initially associated with livestock. The majority of these MRSA cases are attributed to clonal complex CC398. LA-MRSA CC398 colonizes the animals asymptomatically in about half of conventional pig farms. For about 77%–86% of humans with occupational exposure to pigs, nasal carriage has been reported; it can be lost when exposure is interrupted. Among family members living at the same farms, only 4%–5% are colonized. Spread beyond this group of people is less frequent. The prevalence of LA-MRSA in livestock seems to be influenced by farm size, farming systems, usage of disinfectants, and in-feed zinc. LA-MRSA CC398 is able to cause the same kind of infections in humans as S. aureus and MRSA in general. It can be introduced to hospitals and cause nosocomial infections such as postoperative surgical site infections, ventilator associated pneumonia, septicemia, and infections after joint replacement. For this reason, screening for MRSA colonization at hospital admittance is recommended for farmers and veterinarians with livestock contacts. Intrahospital dissemination, typical for HA-MRSA in the absence of sufficient hygiene, has only rarely been observed for LA-MRSA to date. The proportion of LA-MRSA among all MRSA from nosocomial infections is about 3% across Germany. In geographical areas with a comparatively high density of conventional farms, LA-MRSA accounts for up to 10% of MRSA from septicemia and 15% of MRSA from wound infections. As known from comparative genome analysis, LA-MRSA has evolved from human-adapted methicillin-susceptible S. aureus, and the jump to livestock was obviously associated with several genetic changes. Reversion of the genetic changes and readaptation to humans bears a potential health risk and requires tight surveillance. Although most LA-MRSA (>80%) is resistant to several antibiotics, there are still sufficient treatment options. Full article
(This article belongs to the Special Issue The Use of Antibiotics in Food-Producing Animals)
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Review
Core Steps of Membrane-Bound Peptidoglycan Biosynthesis: Recent Advances, Insight and Opportunities
by Alvin C. K. Teo and David I. Roper
Antibiotics 2015, 4(4), 495-520; https://doi.org/10.3390/antibiotics4040495 - 03 Nov 2015
Cited by 30 | Viewed by 13535
Abstract
We are entering an era where the efficacy of current antibiotics is declining, due to the development and widespread dispersion of antibiotic resistance mechanisms. These factors highlight the need for novel antimicrobial discovery. A large number of antimicrobial natural products elicit their effect [...] Read more.
We are entering an era where the efficacy of current antibiotics is declining, due to the development and widespread dispersion of antibiotic resistance mechanisms. These factors highlight the need for novel antimicrobial discovery. A large number of antimicrobial natural products elicit their effect by directly targeting discrete areas of peptidoglycan metabolism. Many such natural products bind directly to the essential cell wall precursor Lipid II and its metabolites, i.e., preventing the utlisation of vital substrates by direct binding rather than inhibiting the metabolising enzymes themselves. Concurrently, there has been an increase in the knowledge surrounding the proteins essential to the metabolism of Lipid II at and across the cytoplasmic membrane. In this review, we draw these elements together and look to future antimicrobial opportunities in this area. Full article
(This article belongs to the Special Issue Bacterial Cell Wall as Antimicrobial Target)
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Article
Induction of Antimicrobial Resistance in Escherichia coli and Non-Typhoidal Salmonella Strains after Adaptation to Disinfectant Commonly Used on Farms in Vietnam
by Nguyen T. Nhung, Cao T. Thuy, Nguyen V. Trung, James Campbell, Stephen Baker, Guy Thwaites, Ngo T. Hoa and Juan Carrique-Mas
Antibiotics 2015, 4(4), 480-494; https://doi.org/10.3390/antibiotics4040480 - 30 Oct 2015
Cited by 29 | Viewed by 7674
Abstract
In Vietnam, commercial disinfectants containing quaternary ammonium compounds (QACs) are commonly used in pig and poultry farms to maintain hygiene during production. We hypothesized that sustained exposure to sub-bactericidal concentrations of QAC-based disinfectants may result in increased levels of antimicrobial resistance (AMR) among [...] Read more.
In Vietnam, commercial disinfectants containing quaternary ammonium compounds (QACs) are commonly used in pig and poultry farms to maintain hygiene during production. We hypothesized that sustained exposure to sub-bactericidal concentrations of QAC-based disinfectants may result in increased levels of antimicrobial resistance (AMR) among Enterobacteriacea due to the increase of efflux pump expression. To test this hypothesis we exposed six antimicrobial-susceptible Escherichia coli (E. coli) and six antimicrobial-susceptible non-typhoidal Salmonella (NTS) isolates to increasing concentrations of a commonly used commercial disinfectant containing a mix of benzalkonium chloride and glutaraldehyde. Over the 12-day experiment, strains exhibited a significant change in their minimum inhibitory concentration (MIC) of the disinfectant product (mean increase of 31% (SD ± 40)) (p = 0.02, paired Wilcoxon test). Increases in MIC for the disinfectant product were strongly correlated with increases in MIC (or decreases in inhibition zone) for all antimicrobials (Pearson’s correlation coefficient 0.71–0.83, all p < 0.01). The greatest increases in MIC (or decreases in inhibition zone) were observed for ampicillin, tetracycline, ciprofloxacin, and chloramphenicol, and the smallest for gentamicin, trimethoprim/sulphamethoxazole. The treatment of 155 representative E. coli isolates from farmed and wild animals in the Mekong Delta (Vietnam) with phenyl-arginine beta-naphthylamide (PAβN), a generic efflux pump inhibitor, resulted in reductions in the prevalence of AMR ranging from 0.7% to 3.3% in these organisms, indicating a small contribution of efflux pumps on the observed prevalence of AMR on farms. These results suggest that the mass usage of commercial disinfectants, many of which contain QACs, is potentially a contributing factor on the generation and maintenance of AMR in animal production in Vietnam. Full article
(This article belongs to the Special Issue The Use of Antibiotics in Food-Producing Animals)
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912 KiB  
Review
Antibiotic Stewardship Initiatives as Part of the UK 5-Year Antimicrobial Resistance Strategy
by Alan P. Johnson, Diane Ashiru-Oredope and Elizabeth Beech
Antibiotics 2015, 4(4), 467-479; https://doi.org/10.3390/antibiotics4040467 - 30 Oct 2015
Cited by 16 | Viewed by 8733
Abstract
Antibiotic use is a major driver for the emergence and spread of antibiotic resistance. Antimicrobial stewardship programmes aim to improve antibiotic prescribing with the objectives of optimizing clinical outcomes while at the same time minimizing unintended consequences such as adverse effects and the [...] Read more.
Antibiotic use is a major driver for the emergence and spread of antibiotic resistance. Antimicrobial stewardship programmes aim to improve antibiotic prescribing with the objectives of optimizing clinical outcomes while at the same time minimizing unintended consequences such as adverse effects and the selection of antibiotic resistance. In 2013, a five-year national strategy for tackling antimicrobial resistance was published in the UK. The overarching goal of the strategy is to slow the development and spread of resistance and to this end it has three strategic aims, namely to improve knowledge and understanding of resistance, to conserve and steward the effectiveness of existing treatments and to stimulate the development of new antibiotics, diagnostics and novel therapies. This article reviews the antimicrobial stewardship activities included in the strategy and describes their implementation and evaluation. Full article
(This article belongs to the Special Issue Antimicrobial Stewardship)
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Article
Miniaturized Antimicrobial Susceptibility Test by Combining Concentration Gradient Generation and Rapid Cell Culturing
by Samuel C. Kim, Stefano Cestellos-Blanco, Keisuke Inoue and Richard N. Zare
Antibiotics 2015, 4(4), 455-466; https://doi.org/10.3390/antibiotics4040455 - 29 Oct 2015
Cited by 41 | Viewed by 8166
Abstract
Effective treatment of bacterial infection relies on timely diagnosis and proper prescription of antibiotic drugs. The antimicrobial susceptibility test (AST) is one of the most crucial experimental procedures, providing the baseline information for choosing effective antibiotic agents and their dosages. Conventional methods, however, [...] Read more.
Effective treatment of bacterial infection relies on timely diagnosis and proper prescription of antibiotic drugs. The antimicrobial susceptibility test (AST) is one of the most crucial experimental procedures, providing the baseline information for choosing effective antibiotic agents and their dosages. Conventional methods, however, require long incubation times or significant instrumentation costs to obtain test results. We propose a lab-on-a-chip approach to perform AST in a simple, economic, and rapid manner. Our assay platform miniaturizes the standard broth microdilution method on a microfluidic device (20 × 20 mm) that generates an antibiotic concentration gradient and delivers antibiotic-containing culture media to eight 30-nL chambers for cell culture. When tested with 20 μL samples of a model bacterial strain (E. coli ATCC 25922) treated with ampicillin or streptomycin, our method allows for the determination of minimum inhibitory concentrations consistent with the microdilution test in three hours, which is almost a factor of ten more rapid than the standard method. Full article
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Article
Learning Processes and Trajectories for the Reduction of Antibiotic Use in Pig Farming: A Qualitative Approach
by Nicolas Fortané, Florence Bonnet-Beaugrand, Anne Hémonic, Carole Samedi, Arnaud Savy and Catherine Belloc
Antibiotics 2015, 4(4), 435-454; https://doi.org/10.3390/antibiotics4040435 - 22 Oct 2015
Cited by 20 | Viewed by 5746
Abstract
Since 2011, French public policy has been encouraging a reduction in the use of antibiotics in animal farming. The aim of this article is to look at how some farms have already managed to lower their consumption of antibiotics, and to highlight the [...] Read more.
Since 2011, French public policy has been encouraging a reduction in the use of antibiotics in animal farming. The aim of this article is to look at how some farms have already managed to lower their consumption of antibiotics, and to highlight the levers of change in farming health practices. Our research uses a qualitative study based on 21 semi-structured interviews with farmers and veterinarians in the French pig-farming sector. We use the notion of “trajectory of change” to examine, over time, the intersection of the technical, economic, social and organisational determinants which affect the reduced use of antibiotics. The “learning process” concept makes it possible to take account of the way in which the actors assimilate, appropriate and implement new health practices. We have identified three interdependent levels of learning: technical learning, cognitive learning and organisational learning. Full article
(This article belongs to the Special Issue The Use of Antibiotics in Food-Producing Animals)
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Article
An FDA-Drug Library Screen for Compounds with Bioactivities against Meticillin-Resistant Staphylococcus aureus (MRSA)
by Qiu Ying Lau, Yoke Yan Fion Tan, Vanessa Chai Yin Goh, David Jing Qin Lee, Fui Mee Ng, Esther H. Q. Ong, Jeffrey Hill and Cheng San Brian Chia
Antibiotics 2015, 4(4), 424-434; https://doi.org/10.3390/antibiotics4040424 - 09 Oct 2015
Cited by 16 | Viewed by 11136
Abstract
The lack of new antibacterial drugs entering the market and their misuse have resulted in the emergence of drug-resistant bacteria, posing a major health crisis worldwide. In particular, meticillin-resistant Staphylococcus aureus (MRSA), a pathogen responsible for numerous human infections, has become endemic in [...] Read more.
The lack of new antibacterial drugs entering the market and their misuse have resulted in the emergence of drug-resistant bacteria, posing a major health crisis worldwide. In particular, meticillin-resistant Staphylococcus aureus (MRSA), a pathogen responsible for numerous human infections, has become endemic in hospitals worldwide. Drug repurposing, the finding of new therapeutic indications for approved drugs, is deemed a plausible solution to accelerate drug discovery and development in this area. Towards this end, we screened 1163 drugs approved by the Food and Drug Administration (FDA) for bioactivities against MRSA in a 10 μM single-point assay. After excluding known antibiotics and antiseptics, six compounds were identified and their MICs were determined against a panel of clinical MRSA strains. A toxicity assay using human keratinocytes was also conducted to gauge their potential for repurposing as topical agents for treating MRSA skin infections. Full article
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Review
A Review of Management of Clostridium difficile Infection: Primary and Recurrence
by Yasmeen Vincent, Arif Manji, Kathleen Gregory-Miller and Christine Lee
Antibiotics 2015, 4(4), 411-423; https://doi.org/10.3390/antibiotics4040411 - 24 Sep 2015
Cited by 9 | Viewed by 6285
Abstract
Clostridium difficile infection (CDI) is a potentially fatal illness, especially in the elderly and hospitalized individuals. The recurrence and rates of CDI are increasing. In addition, some cases of CDI are refractory to the currently available antibiotics. The search for improved modalities for [...] Read more.
Clostridium difficile infection (CDI) is a potentially fatal illness, especially in the elderly and hospitalized individuals. The recurrence and rates of CDI are increasing. In addition, some cases of CDI are refractory to the currently available antibiotics. The search for improved modalities for the management of primary and recurrent CDI is underway. This review discusses the current antibiotics, fecal microbiota transplantation (FMT) and other options such as immunotherapy and administration of non-toxigenic Clostridium difficile (CD) for the management of both primary and recurrent CDI. Full article
(This article belongs to the Special Issue Clostridium difficile Infection)
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