Evidence map›Paper›PMID 35264582›Full record

ArticleNature communications2022

Rapid expansion and extinction of antibiotic resistance mutations during treatment of acute bacterial respiratory infections.

Hattie Chung, Christina Merakou, Matthew M Schaefers, Kelly B Flett, Sarah Martini, Roger Lu, Jennifer A Blumenthal, Shanice S Webster, Ashley R Cross, Roy Al Ahmar and 13 more

Abstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Article
  6. Phage-antibiotic synergy attenuatesFrontiers in cellular and infection microbiology · 2026
    Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. Article
  17. Review
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors.

Hattie ChungDepartment of Systems Biology, Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-8417-5606
Christina MerakouDepartment of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, MA, USA.ORCID 0000-0002-2098-599X
Matthew M SchaefersDepartment of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, MA, USA.ORCID 0000-0001-7454-4180
Kelly B FlettDepartment of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, MA, USA.
Sarah MartiniDepartment of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, MA, USA.
Roger LuDepartment of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, MA, USA.
Jennifer A BlumenthalDepartment of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, MA, USA.
Shanice S WebsterDepartment of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
Ashley R CrossDivision of Pulmonary, Allergy & Immunology, Cystic Fibrosis and Sleep, Emory Children's Center for Cystic Fibrosis and Airway Disease Research, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
Roy Al AhmarDepartment of Biomedical Science, Joan C. Edwards School of Medicine at Marshall University, Huntington, WV, USA.
Erin HalpinDepartment of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, MA, USA.
Michelle AndersonDepartment of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, MA, USA.
Nicholas S MooreHarvard Medical School, Boston, MA, USA.ORCID 0000-0002-0079-7035
Eric C SnesrudWalter Reed Army Institute of Research, Silver Spring, MD, USA.
Hongwei D YuDepartment of Biomedical Science, Joan C. Edwards School of Medicine at Marshall University, Huntington, WV, USA.
Joanna B GoldbergDivision of Pulmonary, Allergy & Immunology, Cystic Fibrosis and Sleep, Emory Children's Center for Cystic Fibrosis and Airway Disease Research, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
George A O'TooleDepartment of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
Patrick McGannWalter Reed Army Institute of Research, Silver Spring, MD, USA.
Jason A StamWalter Reed Army Institute of Research, Silver Spring, MD, USA.
Mary HinkleWalter Reed Army Institute of Research, Silver Spring, MD, USA.
Alexander J McAdamDepartment of Laboratory Medicine, Boston Children's Hospital, Boston, MA, USA.
Roy KishonyDepartment of Systems Biology, Harvard Medical School, Boston, MA, USA. rkishony@technion.ac.il.ORCID 0000-0002-5013-5072
Gregory P PriebeDepartment of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, MA, USA. gregory.priebe@childrens.harvard.edu.ORCID 0000-0001-9831-0354

Funding

cdiGMP regulation of Biofilm FormationR37AI083256 · NIAID · DARTMOUTH COLLEGE · PI O'TOOLE, GEORGE A. · 2014 to 2023
$4.7M
The population genetics of antibiotic resistance in multi-drug environmentsR01GM081617 · NIGMS · TECHNION-ISRAEL INSTITUTE OF TECHNOLOGY · PI KISHONY, ROY · 2007 to 2018
$3.7M
NIAID NIH HHS R37 AI083256NIGMS NIH HHS R01 GM081617
6 · The paper itself

Abstract

Acute bacterial infections are often treated empirically, with the choice of antibiotic therapy updated during treatment. The effects of such rapid antibiotic switching on the evolution of antibiotic resistance in individual patients are poorly understood. Here we find that low-frequency antibiotic resistance mutations emerge, contract, and even go to extinction within days of changes in therapy. We analyzed Pseudomonas aeruginosa populations in sputum samples collected serially from 7 mechanically ventilated patients at the onset of respiratory infection. Combining short- and long-read sequencing and resistance phenotyping of 420 isolates revealed that while new infections are near-clonal, reflecting a recent colonization bottleneck, resistance mutations could emerge at low frequencies within days of therapy. We then measured the in vivo frequencies of select resistance mutations in intact sputum samples with resistance-targeted deep amplicon sequencing (RETRA-Seq), which revealed that rare resistance mutations not detected by clinically used culture-based methods can increase by nearly 40-fold over 5-12 days in response to antibiotic changes. Conversely, mutations conferring resistance to antibiotics not administered diminish and even go to extinction. Our results underscore how therapy choice shapes the dynamics of low-frequency resistance mutations at short time scales, and the findings provide a possibility for driving resistance mutations to extinction during early stages of infection by designing patient-specific antibiotic cycling strategies informed by deep genomic surveillance.

Indexed as

Bacterial InfectionsCystic FibrosisPseudomonas InfectionsRespiratory Tract InfectionsAnti-Bacterial AgentsDrug Resistance, BacterialDrug Resistance, MicrobialHumansMutationPseudomonas aeruginosaAnti-Bacterial Agents

Identifiers

PMID35264582
PMCPMC8907320

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.