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antibiotic resistance

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161. Radial Expansion Facilitates the Maintenance of Double Antibiotic Resistances. (Abstract)

Radial Expansion Facilitates the Maintenance of Double Antibiotic Resistances. Most microbes live in spatially confined subpopulations. Under spatial structure conditions, the efficacy of natural selection is often reduced (relative to homogeneous conditions) due to the increased importance of genetic drift and local competition. Additionally, under spatial structure conditions, the fittest genotype may not always be the one with better access to the heterogeneous distribution of nutrients (...) . The effect of radial expansion may be particularly relevant for the elimination of antibiotic resistance mutations, as their dynamics within bacterial populations are strongly dependent on their growth rate. Here, we use Escherichia coli to systematically compare the allele frequency of streptomycin, rifampin, and fluoroquinolone single and double resistance mutants after 24 h of coexistence with a susceptible strain under radial expansion (local competition) and homogeneous (global competition

2020 Antimicrobial Agents and Chemotherapy

162. Complex Response of the CpxAR Two-Component System to β-Lactams on Antibiotic Resistance and Envelope Homeostasis in <i>Enterobacteriaceae</i>. Full Text available with Trip Pro

Complex Response of the CpxAR Two-Component System to β-Lactams on Antibiotic Resistance and Envelope Homeostasis in Enterobacteriaceae. The Cpx stress response is widespread among Enterobacteriaceae We previously reported a mutation in cpxA in a multidrug-resistant strain of Klebsiella aerogenes isolated from a patient treated with imipenem. This mutation yields a single-amino-acid substitution (Y144N) located in the periplasmic sensor domain of CpxA. In this work, we sought (...) to characterize this mutation in Escherichia coli by using genetic and biochemical approaches. Here, we show that cpxAY144N is an activated allele that confers resistance to β-lactams and aminoglycosides in a CpxR-dependent manner, by regulating the expression of the OmpF porin and the AcrD efflux pump, respectively. We also demonstrate the effect of the intimate interconnection between the Cpx system and peptidoglycan integrity on the expression of an exogenous AmpC β-lactamase by using imipenem as a cell

2020 Antimicrobial Agents and Chemotherapy

163. Strong Environment-Genotype Interactions Determine the Fitness Costs of Antibiotic Resistance <i>In Vitro</i> and in an Insect Model of Infection. (Abstract)

Strong Environment-Genotype Interactions Determine the Fitness Costs of Antibiotic Resistance In Vitro and in an Insect Model of Infection. The acquisition of antibiotic resistance commonly imposes fitness costs, a reduction in the fitness of bacteria in the absence of drugs. These costs have been quantified primarily using in vitro experiments and a small number of in vivo studies in mice, and it is commonly assumed that these diverse methods are consistent. Here, we used an insect (...) model of infection to compare the fitness costs of antibiotic resistance in vivo to those in vitro Experiments explored diverse mechanisms of resistance in a Gram-positive pathogen, Bacillus thuringiensis, and a Gram-negative intestinal symbiont, Enterobacter cloacae Rifampin resistance in B. thuringiensis showed fitness costs that were typically elevated in vivo, although these were modulated by genotype-environment interactions. In contrast, resistance to cefotaxime via derepression of AmpC β

2020 Antimicrobial Agents and Chemotherapy

164. Scarless Removal of Large Resistance Island AbaR Results in Antibiotic Susceptibility and Increased Natural Transformability in Acinetobacter baumannii. Full Text available with Trip Pro

Scarless Removal of Large Resistance Island AbaR Results in Antibiotic Susceptibility and Increased Natural Transformability in Acinetobacter baumannii. With a great diversity in gene composition, including multiple putative antibiotic resistance genes, AbaR islands are potential contributors to multidrug resistance in Acinetobacter baumannii However, the effective contribution of AbaR to antibiotic resistance and bacterial physiology remains elusive. To address this, we sought to accurately (...) of the open reading frame (ORF) of this island, the antibiotic resistance profiles were identical between the wild type and the AbaR11-cured AB5075 strains. In contrast, AbaR1 carries 25 ORFs, with predicted resistance to several classes of antibiotics, and the AYE AbaR1-cured derivative showed restored susceptibility to multiple classes of antibiotics. Moreover, curing of AbaRs restored high levels of natural transformability. Indeed, most AbaR islands are inserted into the comM gene involved in natural

2020 Antimicrobial Agents and Chemotherapy

165. Genomic Analysis Reveals Antibiotic-Susceptible Clones and Emerging Resistance in Neisseria gonorrhoeae in Saskatchewan, Canada. (Abstract)

Genomic Analysis Reveals Antibiotic-Susceptible Clones and Emerging Resistance in Neisseria gonorrhoeae in Saskatchewan, Canada. Whole-genome sequencing was used to identify mutations in antibiotic resistance-conferring genes to compare susceptibility predictions with MICs and to ascertain strain types in 99 isolates of Neisseria gonorrhoeae Genotypes associated with susceptibility, as well as MIC creep or emerging resistance, were noted. Phylogenomic analysis revealed three distinctive clades (...) and putative gonococcal transmission linkages involving a tetracycline-resistant N. gonorrhoeae outbreak and the clonal spread of susceptible isolates in men.Copyright © 2020 American Society for Microbiology.

2020 Antimicrobial Agents and Chemotherapy

166. Helcococcus kunzii methyltransferase Erm(47) responsible for MLSB resistance is induced by diverse ribosome-targeting antibiotics. Full Text available with Trip Pro

Helcococcus kunzii methyltransferase Erm(47) responsible for MLSB resistance is induced by diverse ribosome-targeting antibiotics. To determine the mechanism of induction of erm(47) and its atypical expression in the Gram-positive opportunistic pathogen Helcococcus kunzii, where it confers resistance to a subset of clinically important macrolide, lincosamide and streptogramin B (MLSB) antibiotics.The resistant H. kunzii clinical isolate UCN99 was challenged with subinhibitory concentrations (...) and linezolid antibiotics, all of which target the 50S ribosomal subunit. No induction was detected with spectinomycin, which targets the 30S subunit.The structure of the erm(47) leader sequence functions as a hair trigger for the induction mechanism that expresses resistance. Consequently, translation of the erm(47) mRNA is tripped by MLSB compounds and also by drugs that target the 50S ribosomal subunit outside the MLSB site. Expression of erm(47) thus extends previous assumptions about how erm genes can

2020 Journal of Antimicrobial Chemotherapy

167. Ribosome-mediated attenuation of <i>vga(A</i>) expression is shaped by the antibiotic resistance specificity of Vga(A) protein variants. (Abstract)

Ribosome-mediated attenuation of vga(A) expression is shaped by the antibiotic resistance specificity of Vga(A) protein variants. Vga(A) protein variants confer different levels of resistance to lincosamides, streptogramins A and pleuromutilins (LSAP) by displacing antibiotics from the ribosome. Here we show that expression of vga(A) variants from Staphylococcus haemolyticus is regulated by cis-regulatory RNA in response to the LSAP antibiotics by the mechanism of ribosome-mediated (...) attenuation. The specificity of induction depends on the Vga(A)-mediated resistance rather than on the sequence of the riboregulator. Fine-tuning between Vga(A) activity and its expression in response to the antibiotics may contribute to the selection of more potent Vga(A) variants because newly acquired mutation can be immediately phenotypically manifested.Copyright © 2020 American Society for Microbiology.

2020 Antimicrobial Agents and Chemotherapy

168. Epidemiological, and Clinical Characteristics of International Travelers with Enteric Fever and Antibiotic Resistance Profiles of their Isolates: A GeoSentinel Analysis. (Abstract)

Epidemiological, and Clinical Characteristics of International Travelers with Enteric Fever and Antibiotic Resistance Profiles of their Isolates: A GeoSentinel Analysis. Background. Enteric fever, caused by Salmonella enterica serovar Typhi (S. Typhi) and Paratyphi (S. Paratyphi), is a common travel-related illness. Limited data are available on their antimicrobial resistance (AMR) patterns among travelers. Methods. Records with a culture-confirmed diagnosis seen during or after travel from (...) January 2007 to December 2018 were obtained from GeoSentinel. Traveler demographics and antimicrobial susceptibility data were analyzed. Isolates were classified as 'non-susceptible' if intermediate or resistant, or 'susceptible' in accordance with participating site's national guidelines. Results. A total of 889 travelers (S. Typhi, n=474; S. Paratyphi, n=414; co-infection, n=1) were included; 114 (13%) were children <18 years. Most (41%) traveled to visit friends and relatives (VFRs) and acquired

2020 Antimicrobial Agents and Chemotherapy

169. Application of combined genomic and transfer analyses to identify factors mediating regional spread of antibiotic resistant bacterial lineages. Full Text available with Trip Pro

Application of combined genomic and transfer analyses to identify factors mediating regional spread of antibiotic resistant bacterial lineages. Patients entering nursing facilities (NFs) are frequently colonized with antibiotic resistant organisms (AROs). To understand the determinants of ARO colonization on NF admission we applied whole-genome sequencing to track the spread of four ARO species across regional NFs and evaluated patient-level characteristics and transfer acute-care hospitals (...) (ACHs) as risk factors for colonization.584 patients from six NFs were surveyed for methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecalis/faecium (VREfc/VREfm) and ciprofloxacin-resistant Escherichia coli (CipREc) colonization. Genomic analysis was performed to quantify ARO spread between NFs and compared to patient-transfer networks. The association between admission colonization and patient-level variables and recent ACH exposures was examined using

2020 Clinical Infectious Diseases

170. Assessment of data supporting the efficacy of new antibiotics for treating infections caused by multidrug resistant bacteria. (Abstract)

Assessment of data supporting the efficacy of new antibiotics for treating infections caused by multidrug resistant bacteria. Infections caused by multidrug resistant (MDR) bacteria are major public health threat. We aimed to assess the data supporting US Food and Drug (FDA) approval of new agents aimed to treat MDR bacterial infections, and the data provided by post-marketing studies.We identified all drugs with in-vitro activity against MDR bacteria initially approved by FDA between January (...) 2010- December 2018. Characteristics of trials supporting approval and regulatory pathways were collected from Drugs@FDA. Characteristics of post-marketing studies were extracted from drug labels and ClinicalTrials.gov entries effective on June 1, 2019.Initial approval of 11 newly approved antibiotics with anti-MDR activity was supported by 20 trials, all with non-inferiority design. All initially approved indications were for common infections, mostly acute bacterial skin and skin-structure

2020 Clinical Infectious Diseases

171. Gut microbiota features on nursing home admission are associated with subsequent acquisition of antibiotic resistant organism colonization. Full Text available with Trip Pro

Gut microbiota features on nursing home admission are associated with subsequent acquisition of antibiotic resistant organism colonization. Nursing home (NH) patients often acquire colonization with antibiotic-resistant organisms (AROs). We show that patients exposed to broad-spectrum antibiotics during previous hospitalizations have elevated enterococcal relative abundances on NH admission and higher risk of subsequent ARO acquisition. Our findings suggest that interventions preventing ARO

2020 Clinical Infectious Diseases

172. Effect of Pediatric Influenza Vaccination on Antibiotic Resistance, England and Wales. Full Text available with Trip Pro

Effect of Pediatric Influenza Vaccination on Antibiotic Resistance, England and Wales. Vaccines against viral infections have been proposed to reduce prescribing of antibiotics and thereby help control resistant bacterial infections. However, by combining published data sources, we predict that pediatric live attenuated influenza vaccination in England and Wales will not substantially reduce antibiotic consumption or adverse health outcomes associated with antibiotic resistance.

2020 Emerging Infectious Diseases

173. Exebacase Demonstrates <i>In Vitro</i> Synergy with a Broad Range of Antibiotics against both Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus. Full Text available with Trip Pro

Exebacase Demonstrates In Vitro Synergy with a Broad Range of Antibiotics against both Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus. In vitro synergy between an antimicrobial protein lysin (cell wall hydrolase) called exebacase and each of 12 different antibiotics was examined against Staphylococcus aureus isolates using a nonstandard medium approved for exebacase susceptibility testing by the Clinical and Laboratory Standards Institute. In the checkerboard

2020 Antimicrobial Agents and Chemotherapy

174. Considerations for Empiric Antimicrobial Therapy in Sepsis and Septic Shock in an Era of Antimicrobial Resistance. Full Text available with Trip Pro

Considerations for Empiric Antimicrobial Therapy in Sepsis and Septic Shock in an Era of Antimicrobial Resistance. Patients with sepsis present across a spectrum of infection sites and severity of illnesses requiring complex decision making at the bedside as to when prompt antibiotics are indicated and which regimen is warranted. Many hemodynamically stable patients with sepsis and low acuity of illness may benefit from further work up before initiating therapy, whereas patients with septic (...) shock warrant emergent broad-spectrum antibiotics. The precise empiric regimen is determined by assessing patient and epidemiological risk factors, likely source of infection based on presenting signs and symptoms, and severity of illness. Hospitals should implement quality improvement measures to aid in the rapid and accurate diagnosis of septic patients and to ensure antibiotics are given to patients in an expedited fashion after antibiotic order.Published by Oxford University Press

2020 Journal of Infectious Diseases

175. US Immigration Is Associated With Rapid and Persistent Acquisition of Antibiotic Resistance Genes in the Gut. (Abstract)

US Immigration Is Associated With Rapid and Persistent Acquisition of Antibiotic Resistance Genes in the Gut. Little is known about the effect of human migration on gut microbiome antibiotic resistance gene (ARG) carriage. Using deep shotgun stool metagenomics analysis, we found a rapid increase in gut microbiome ARG richness and abundance in women from 2 independent ethnic groups relocating from Thailand to the United States.© The Author(s) 2019. Published by Oxford University Press

2020 Clinical Infectious Diseases

176. Combating antibiotic resistance using guidelines and enhanced stewardship in Kenya: a protocol for an implementation science approach. Full Text available with Trip Pro

Combating antibiotic resistance using guidelines and enhanced stewardship in Kenya: a protocol for an implementation science approach. Antimicrobial resistance (AMR) is a growing problem globally especially in Sub-Saharan Africa including Kenya. Without any intervention, lower/middle-income countries (LMICs) will be most affected due to already higher AMR levels compared with higher income countries and due to the far higher burden of diseases in the LMICs. Studies have consistently shown (...) that inappropriate use of antimicrobials is the major driver of AMR. To address this challenge, hospitals are now implementing antibiotic stewardship programmes (ASPs), which have been shown to achieve reduced antibiotic usage, to decrease the prevalence of resistance and lead to significant economic benefits. However, the implementation of the guideline is highly dependent on the settings in which they are rolled out. This study, employing an implementation science approach, aims to address the knowledge gap

2020 BMJ open

177. Antibiotic Resistance in Acne: Mechanisms, Complications and Management. (Abstract)

, homeostasis of the skin microbiota, and the mechanisms of antibiotic resistance would be useful in the selection of narrow-spectrum or species-specific antimicrobials, as well as the non-antimicrobial, anti-inflammatory treatment of acne. A number of novel treatments awaiting clinical proof may include the use of bacteriophages, natural or synthetic antimicrobial peptides, probiotics, and biofilm-targeting agents, as well as the reassessment of phototherapy. (...) Antibiotic Resistance in Acne: Mechanisms, Complications and Management. Antibiotic resistance in acne was first observed in the 1970s, and since the 1980s has become a major concern in dermatologic daily practice. The mechanisms for this type of resistance include biofilm formation that promotes virulence and the transmission of resistant bacterial strains. Genetic mutations with modification of ribosomal RNA, alteration in efflux pumps, and enzymatic inactivation are able to create resistance

2020 American journal of clinical dermatology

178. Faecal microbiota transplant to ERadicate gastrointestinal carriage of Antibiotic Resistant Organisms (FERARO): a prospective, randomised placebo-controlled feasibility trial. Full Text available with Trip Pro

Faecal microbiota transplant to ERadicate gastrointestinal carriage of Antibiotic Resistant Organisms (FERARO): a prospective, randomised placebo-controlled feasibility trial. Antimicrobial resistance is rising, largely due to the indiscriminate use of antimicrobials. The human gut is the largest reservoir of antibiotic resistant bacteria (ARB). Individuals colonised with ARB have the potential to spread these organisms both in the community and hospital settings. Infections with ARB

2020 BMJ open

179. Quantifying the economic cost of antibiotic resistance and the impact of related interventions: rapid methodological review, conceptual framework and recommendations for future studies. Full Text available with Trip Pro

Quantifying the economic cost of antibiotic resistance and the impact of related interventions: rapid methodological review, conceptual framework and recommendations for future studies. Antibiotic resistance (ABR) poses a major threat to health and economic wellbeing worldwide. Reducing ABR will require government interventions to incentivise antibiotic development, prudent antibiotic use, infection control and deployment of partial substitutes such as rapid diagnostics and vaccines. The scale (...) in hospitals (95/110), used a healthcare provider or payer perspective (97/110), and used matched cohort approaches to compare costs of patients with antibiotic-resistant infections and antibiotic-susceptible infections (or no infection) (87/110). Better use of methods to correct biases and confounding when making this comparison is needed. Findings also need to be extended beyond their limitations in (1) time (projecting present costs into the future), (2) perspective (from the healthcare sector to entire

2020 BMC Medicine

180. Outcomes of Empirical Antimicrobial Therapy for Pediatric Community-onset Febrile Urinary Tract Infection in the Era of Increasing Antimicrobial Resistance. (Abstract)

Outcomes of Empirical Antimicrobial Therapy for Pediatric Community-onset Febrile Urinary Tract Infection in the Era of Increasing Antimicrobial Resistance. Urinary tract infection (UTI) is a common cause of fever in children. Despite the increasing numbers of extended-spectrum beta-lactamase-producing organisms in the community, the empirical therapy of choice is still third-generation cephalosporins. This study was performed to investigate whether inappropriate empirical therapy (IAT (...) (5.00-11.25) days, respectively; P = 0.000].No significant difference in treatment outcomes was found between pediatric patients receiving AT and IAT for the treatment of UTI. In the era of increasing antimicrobial resistance, third-generation cephalosporins may still be a good choice as an empirical antimicrobial for children diagnosed with community-onset UTI.

2020 Pediatric Infectious Dsease Journal

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