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13 results for “AmpC”
When does antimicrobial resistance increase bacterial fitness? Effects of dosing, social interactions and frequency dependence on the benefits of AmpC β-lactamases in broth, biofilms and a gut infection model.
<p><span>One of the longstanding puzzles of antimicrobial resistance is why the frequency of resistance persists at intermediate levels.<span> </span>Theoretical explanations for the lack of fixation of resistance include cryptic costs of resistance or negative frequency-dependence but are seldom explored experimentally. <span> </span><em>β</em>-lactamases, which detoxify penicillin-related antibiotics, have well-characterized frequency-dependent dynamics driven by cheating and cooperation.<span> </span>However, bacterial physiology determines whether <em>β</em>-lactamases are cooperative and we know little about the sociality or fitness of <em>β</em>-lactamase producers in infections.<span> </span>Moreover, media-based experiments constrain how we measure fitness, and ignore important parameters such as infectivity and transmission among hosts.<span> </span>Here, we investigated the fitness effects of broad-spectrum AmpC <em>β</em>-lactamases in <em>Enterobacter cloacae</em> in broth, biofilms and gut infections in a model insect. <span> </span>We quantified frequency- and dose-dependent fitness using cefotaxime, a third-generation cephalosporin.<span> </span>We predicted that infection dynamics would be similar to those observed in biofilms, with social protection extending over a wide dose range.<span> </span>We found evidence for the sociality of <em>β</em>-lactamases in all contexts with negative frequency-dependent selection ensuring the persistence of wild-type bacteria although cooperation was less prevalent in biofilms, contrary to predictions.<span> </span>While competitive fitness in gut infections and broth had similar dynamics, incorporating infectivity into measurements of fitness in infections<em> </em>significantly affected conclusions. <span> </span>Resistant bacteria had reduced infectivity which limited the fitness benefits of resistance to infections challenged with low antibiotic doses and having low initial frequencies of resistance. <span> </span>The fitness of resistant bacteria in more physiologically tolerant states (in biofilms, in infections) could be constrained by the presence of wild-type bacteria, high antibiotic doses and limited availability of <em>β</em>-lactamases.<span> </span>One conclusion is that increased tolerance of <em>β</em> -lactams does not necessarily increase selection pressure for resistance.<span> </span>Overall, both cryptic fitness costs and frequency-dependence curtailed the fitness benefits of resistance in this study.<span> </span></span></p> <p><span> </span></p>
Code and Additional Files for the Manuscript "The Impact of Farming Practices on Resistance to Critically Important Antimicrobials in ESBL or AmpC-producing Escherichia coli in Thailand"
<p>These scripts were used in the"The Impact of Farming Practices on Resistance to Critically Important Antimicrobials in ESBL or AmpC-producing Escherichia coli in Thailand" manuscript. The scripts are ordered for ease of use. It also contains intermediate files and files necessary for the mapping. Table S1 containing the metadata is available in the supplementary information of the manuscript.</p>
Efficacy of Temocillin in Urinary Tract Infection Due to ESBL Producing and AmpC Hyperproducing Enterobacteriaceae
ClinicalTrials.gov study NCT02681263. IPD Sharing: Not stated. Countries: 1. Publications: 5.
Ceftolozane-tazobactam Versus Meropenem for ESBL and AmpC-producing Enterobacterales Bloodstream Infection
ClinicalTrials.gov study NCT04238390. IPD Sharing: NO. Countries: 5. Publications: 1.
PipEracillin/Tazobactam Versus mERoPENem for Treatment of AmpC Producing Blood Stream Infections
ClinicalTrials.gov study NCT05355350. IPD Sharing: YES. Countries: 1. Publications: 0.
Cefazolin and Imipenem Enhance AmpC Expression and Resistance in NagZ-dependent manner in Enterobacter cloacae complex
GEO Series GSE207144. Enterobacter cloacae complex. 6 samples. Type: Expression profiling by high throughput sequencing.
Standard sequences of six groups of ampC β-lactamase genes
<p>Standard sequences of six groups of <em>ampC</em> β-lactamase genes, ACC, EBC, CIT, DHA, MOX and FOX, were selected from GenBank to synthesize genes and confirmed by sequencing.</p>
Clinical Comparison of Treatment Strategies in AmpC Beta-lactamase Producing Enterobacterales in a Swiss Tertiary Care Hospital
ClinicalTrials.gov study NCT04577989. IPD Sharing: Not stated. Countries: 1. Publications: 0.
Piperacillin/Tazobactam for Bacteremia With Organisms Producing Chromosomally-Encoded AmpC Beta-Lactamase
ClinicalTrials.gov study NCT00414193. IPD Sharing: Not stated. Countries: 1. Publications: 0.
Cefepime vs. Carbapenems for Treating AmpC β-lactamase-producing Enterobacteriaceae Bloodstream Infections
ClinicalTrials.gov study NCT05535751. IPD Sharing: Not stated. Countries: 1. Publications: 0.
The Effects of AMPC in the Treatments of Refractory or Relapsed AML
ClinicalTrials.gov study NCT03825146. IPD Sharing: UNDECIDED. Countries: 1. Publications: 0.
Pseudomonas aeruginosa Ceftolozane-Tazobactam Resistance Development Requires Multiple Mutations Leading to Overexpression and Structural Modification of AmpC.
GEO Series GSE58390. Pseudomonas aeruginosa PAO1. 16 samples. Type: Expression profiling by high throughput sequencing.
Clinical Significance and Optimal Treatment of Community-onset Urinary Tract Infections Caused by Extended-spectrum β-lactamase and/or AmpC β-lactamase Producing Enterobacteriaceae
ClinicalTrials.gov study NCT01138566. IPD Sharing: Not stated. Countries: 1. Publications: 0.
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