ArticlePloS one2013
Designing antibiotic cycling strategies by determining and understanding local adaptive landscapes.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The Effect of Antibiotic-Cycling Strategy on Antibiotic-Resistant Bacterial Infections or Colonization in Intensive Care Units: A Systematic Review and Meta-Analysis.Worldviews on evidence-based nursing · 2020Pooled it
- Cryptic phenotypic variation emerges rapidly during the adaptive evolution of a carbapenemase.Nature ecology & evolution · 2026Article
- Computational framework for streamlining the success of sequential antibiotic therapy.npj antimicrobials and resistance · 2025Article
- Fitness seascapes are necessary for realistic modeling of the evolutionary response to drug therapy.Science advances · 2025Article
- Decalogue for the selection of oral antibiotics for lower respiratory tract infections.Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia · 2022Review
- Adaptive Processes Change as Multiple Functions Evolve.Antimicrobial agents and chemotherapy · 2021Article
- A two-step PCR assembly for construction of gene variants across large mutational distances.Biology methods & protocols · 2021Article
- Antimicrobial Stewardship Program in Critical Care-Need of the Hour.Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine · 2020Review
- Article
- Article
- Model genotype-phenotype mappings and the algorithmic structure of evolution.Journal of the Royal Society, Interface · 2019Article
- Evolving generalists in switching rugged landscapes.PLoS computational biology · 2019Article
- Article
- Selecting among three basic fitness landscape models: Additive, multiplicative and stickbreaking.Theoretical population biology · 2018Article
- Multiplexed deactivated CRISPR-Cas9 gene expression perturbations deter bacterial adaptation by inducing negative epistasis.Communications biology · 2018Article
- Article
- Strategies to avoid treatment-induced lineage crisis in advanced prostate cancer.Nature reviews. Clinical oncology · 2017Review
- Effect of Host Species on Topography of the Fitness Landscape for a Plant RNA Virus.Journal of virology · 2016Article
- A pivot mutation impedes reverse evolution across an adaptive landscape for drug resistance in Plasmodium vivax.Malaria journal · 2016Article
- Adaptive Landscape by Environment Interactions Dictate Evolutionary Dynamics in Models of Drug Resistance.PLoS computational biology · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
Abstract
The evolution of antibiotic resistance among bacteria threatens our continued ability to treat infectious diseases. The need for sustainable strategies to cure bacterial infections has never been greater. So far, all attempts to restore susceptibility after resistance has arisen have been unsuccessful, including restrictions on prescribing [1] and antibiotic cycling [2], [3]. Part of the problem may be that those efforts have implemented different classes of unrelated antibiotics, and relied on removal of resistance by random loss of resistance genes from bacterial populations (drift). Here, we show that alternating structurally similar antibiotics can restore susceptibility to antibiotics after resistance has evolved. We found that the resistance phenotypes conferred by variant alleles of the resistance gene encoding the TEM β-lactamase (bla(TEM)) varied greatly among 15 different β-lactam antibiotics. We captured those differences by characterizing complete adaptive landscapes for the resistance alleles bla(TEM-50) and bla(TEM-85), each of which differs from its ancestor bla(TEM-1) by four mutations. We identified pathways through those landscapes where selection for increased resistance moved in a repeating cycle among a limited set of alleles as antibiotics were alternated. Our results showed that susceptibility to antibiotics can be sustainably renewed by cycling structurally similar antibiotics. We anticipate that these results may provide a conceptual framework for managing antibiotic resistance. This approach may also guide sustainable cycling of the drugs used to treat malaria and HIV.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.