Correction: Optimal Drug Synergy in Antimicrobial Treatments
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PROVIDER: S-EPMC2909090 | biostudies-literature | 2010 Jul
REPOSITORIES: biostudies-literature
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Project description:The rapid proliferation of antibiotic-resistant pathogens has spurred the use of drug combinations to maintain clinical efficacy and combat the evolution of resistance. Drug pairs can interact synergistically or antagonistically, yielding inhibitory effects larger or smaller than expected from the drugs' individual potencies. Clinical strategies often favor synergistic interactions because they maximize the rate at which the infection is cleared from an individual, but it is unclear how such interactions affect the evolution of multi-drug resistance. We used a mathematical model of in vivo infection dynamics to determine the optimal treatment strategy for preventing the evolution of multi-drug resistance. We found that synergy has two conflicting effects: it clears the infection faster and thereby decreases the time during which resistant mutants can arise, but increases the selective advantage of these mutants over wild-type cells. When competition for resources is weak, the former effect is dominant and greater synergy more effectively prevents multi-drug resistance. However, under conditions of strong resource competition, a tradeoff emerges in which greater synergy increases the rate of infection clearance, but also increases the risk of multi-drug resistance. This tradeoff breaks down at a critical level of drug interaction, above which greater synergy has no effect on infection clearance, but still increases the risk of multi-drug resistance. These results suggest that the optimal strategy for suppressing multi-drug resistance is not always to maximize synergy, and that in some cases drug antagonism, despite its weaker efficacy, may better suppress the evolution of multi-drug resistance.
| S-EPMC2880566 | biostudies-literature
Project description:Therapeutic drug synergism intervened in cancer treatments has been demonstrated to be more effective than using a single effector. However, it remains inherently challenging, with a limited cell count from tumor samples, to achieve potent personalized drug cocktails. To address the issue above, we herein present a nanodroplet cell processing platform. The platform incorporates an automatic nanodroplet dispenser with cell array ParaStamp chips, which were fabricated by a new wax stamping approach derived from laser direct writing. Such approach enables not only the on-demand de-wetting with hydrophobic wax films on substrates but also the mask-less fabrication of non-planar microstructures (i.e. no photolithography process). The ParaStamp chip was pre-occupied with anti-cancer drugs and their associate mixtures, enabling for the spatially addressable screening of optimal drug combinations simultaneously. Each droplet with a critical volume of 200 nl containing with 100 cells was utilized. Results revealed that the optimal combination reduces approximate 28-folds of conducted doses compared with single drugs. Tumor inhibition with the optimally selected drug combination was further confirmed by using PC-3 tumor-bearing mouse models. Together, the nanodroplet cell processing platform could therefore offer new opportunities to power the personalized cancer medicine at early-stage drug screening and discovery.
| S-EPMC6625988 | biostudies-literature
Project description:Muscle redundancy allows the central nervous system (CNS) to choose a suitable combination of muscles from a number of options. This flexibility in muscle combinations allows for efficient behaviors to be generated in daily life. The computational mechanism of choosing muscle combinations, however, remains a long-standing challenge. One effective method of choosing muscle combinations is to create a set containing the muscle combinations of only efficient behaviors, and then to choose combinations from that set. The notion of muscle synergy, which was introduced to divide muscle activations into a lower-dimensional synergy space and time-dependent variables, is a suitable tool relevant to the discussion of this issue. The synergy space defines the suitable combinations of muscles, and time-dependent variables vary in lower-dimensional space to control behaviors. In this study, we investigated the mechanism the CNS may use to define the appropriate region and size of the synergy space when performing skilled behavior. Two indices were introduced in this study, one is the synergy stability index (SSI) that indicates the region of the synergy space, the other is the synergy coordination index (SCI) that indicates the size of the synergy space. The results on automatic posture response experiments show that SSI and SCI are positively correlated with the balance skill of the participants, and they are tunable by behavior training. These results suggest that the CNS has the ability to create optimal sets of efficient behaviors by optimizing the size of the synergy space at the appropriate region through interacting with the environment.
| S-EPMC3796759 | biostudies-literature
Project description:The unrestricted use of antibiotics has led to rapid development of antibiotic resistance (AR) and renewed calls to address this serious problem. This review summarizes the most common mechanisms of antibiotic action, and in turn antibiotic resistance, as well as pathways to mitigate the harm. Focus is then turned to emerging antibiotic strategies, including antimicrobial peptides (AMPs), with a discussion of their modes of action, biochemical features, and potential challenges for their use as antibiotics. The role of synergy in antimicrobials is also examined, with a focus on the synergy of AMPs and other emerging interactions with synergistic potential.
| S-EPMC9132191 | biostudies-literature
Project description:BackgroundBlue light therapy (BLT) is a Food and Drug Administration cleared modality used in dermatology as an effective treatment of acne. The primary purpose of this study is to determine if there are dose-dependent antimicrobial effects of BLT against Cutibacterium acnes (C. acnes).MethodsA known strain of C. acnes was grown on chocolate agar in a controlled laboratory environment under anaerobic conditions for 1 week. After 1 week, 2-3 colonies of C. acnes were isolated and transferred to broth medium to incubate for 2 or 7 days. Broth vials (treatment arm) then underwent 1 of 6 different blue light dosing treatment regimens and a duplicate broth vial served as a control left open to the same environment. The BLT regimens were a single treatment of 25 J/cm2, 50 J/cm2, 75 J/cm2, 100 J/cm2, 2 serial treatments of 50 J/cm2 separated by 24 hours, or 2 serial treatments of 75 J/cm2 separated by 24 hours. The Omnilux Blue device (415 nm wavelength) was used for all BLT treatments and delivered, on average, 1.68 ± 0.004 J/min. Following treatment, the control and treatment broth samples were plated on chocolate agar and allowed to grow for 7 days. After 7 days, plates were counted and colony forming units (CFUs) were calculated. Six trials were completed for each BLT dosing regimen based on an a priori power analysis of 6 individual 2-sided t-tests. Comparisons in the primary outcome were made via mixed-effects analysis of variance with replicate as a random effect.ResultsAll BLT treatment regimens resulted in significantly fewer CFUs than their aggregate control plate CFUs (P < .05 for all). Furthermore, in 2-way comparison of CFUs between BLT treatment groups, a single treatment of 75 J/cm2 did lead to significantly less growth than 25 J/cm2 (P = .017) and 50 J/cm2 (P = .017). There were no improved antimicrobial effects with serial treatments when comparing 2 doses of 50 J/cm2 with a single dose of 100J/cm2, nor were 2 doses of 75 J/cm2 more efficacious than 100 J/cm2. Using the Omnilux Blue device, it took 44.8 minutes to deliver a 75 J/cm2 dose.ConclusionBLT is an effective antimicrobial agent against this single virulent strain of C. acnes. Treatment dosing of 75 J/cm2 was identified to be the most effective dose per unit time. Serial treatments did not lead to superior antimicrobial effects over a single, high-dose treatment.
| S-EPMC10920142 | biostudies-literature
Project description:To compare the effects of curative surgery and curative definitive concurrent chemoradiotherapy (CCRT) on cervical adenocarcinoma (AC) by conducting a national cohort study with a large sample size, we enrolled women with cervical AC and categorized them into two groups according to treatment modality to compare treatment outcomes: group 1, comprising patients who received curative surgery, and group 2, comprising patients who received curative definitive CCRT. Data of 1,621 patients with cervical AC were extracted from the Taiwan Cancer Registry database. Univariate and multivariate Cox regression analysis results indicated that high American Society of Anesthesiologists scores, advanced American Joint Committee on Cancer (AJCC) clinical stage, and curative definitive CCRT were significant independent poor prognostic factors. The adjusted hazard ratio (aHR; 95% confidence interval [CI]) for overall mortality in early invasive clinical stages (IB-IIA) was 1.27 (0.77-2.69) in group 2 compared with group 1, whereas that for overall mortality at AJCC clinical stage IIB was 2.46 (1.34-4.53) in group 2 compared with group 1. The aHR (95% CI) for overall mortality at advanced clinical stages (III and IV) was 1.47 (1.09-1.97) in group 2 compared with group 1. Curative surgery improves survival in cervical AC at advanced clinical stages. Either curative surgery or definitive CCRT is an option in the early invasive clinical stages of cervical AC.
| S-EPMC6610057 | biostudies-literature
Project description:BackgroundGuidelines and evidence-based drug treatment recommendations are usually based on the results of clinical trials, which have limited generalisability in routine clinical settings due to their restrictive eligibility criteria. These trials are also conducted in ideal and rigorously controlled settings. N of 1 trials, which are single patient multiple crossover studies, offer a means of increasing the evidence base and individualising care for individuals in clinical practice. This systematic review of the N of 1 drug treatment trial aims to investigate its usefulness for achieving optimal individualised patient care.MethodsThe following databases will be searched for relevant articles: MEDLINE, EMBASE, PsycINFO (all via Ovid), AMED, CINAHAL (via EBSCO), The Cochrane Library (including CENTRAL, NHS EED, and DARE), and Web of Science (Thomson Reuters). Supplementary searches will include ongoing trial databases and organisational websites. All N of 1 trials in which patients have been treated with a drug will be considered. Outcomes will include information on the clinical usefulness of N of 1 trials-i.e. achievement of optimal individualised care, health-care utilisation of patients, frequently used practices, experiences of clinical care or participation in N of 1 trials, adherence to treatment plan, and unwanted effects of the treatment. Screening of included papers will be undertaken independently by two reviewers, while data extraction and the quality of reporting will be conducted by one reviewer and checked by another. Both quantitative and qualitative summaries will be reported using appropriate methods.DiscussionThis review will provide new insights into the clinical utility of N of 1 drug trials in helping participants find the most acceptable treatment as defined by patients and clinicians based on the selected outcome measures and the perspectives of participants involved in such trials. Findings from this review will inform the development of a stakeholder workshop and guidance to help physicians find the optimum therapy for their patients and will help guide future research on N of 1 trials.Systematic review registrationPROSPERO CRD42016032452.
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Project description:[This corrects the article DOI: 10.1371/journal.pone.0251948.].
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