Dataset Information

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

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.

SUBMITTER: Chung H

PROVIDER: S-EPMC8907320 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Chung Hattie H Merakou Christina C Schaefers Matthew M MM Flett Kelly B KB Martini Sarah S Lu Roger R Blumenthal Jennifer A JA Webster Shanice S SS Cross Ashley R AR Al Ahmar Roy R Halpin Erin E Anderson Michelle M Moore Nicholas S NS Snesrud Eric C EC Yu Hongwei D HD Goldberg Joanna B JB O'Toole George A GA McGann Patrick P Stam Jason A JA Hinkle Mary M McAdam Alexander J AJ Kishony Roy R Priebe Gregory P GP

Nature communications 20220309 1

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 mechanica ...[more]

PMID: 35264582

Similar Datasets

Project description:BackgroundAcute respiratory infections are the most common symptomatic reason for seeking care among patients in the US, and account for the majority of all antibiotic prescribing, yet a large fraction of antibiotic prescriptions are inappropriate.ObjectiveWe sought to identify the underlying factors driving variation in antibiotic prescribing across clinicians and settings.Design, participantsUsing electronic health data for adult ambulatory visits for acute respiratory infections to a retail clinic chain and primary care practices from an integrated healthcare system, we identified a random sample of clinicians for survey.Main measuresWe evaluated independent predictors of overall prescribing and imperfect antibiotic prescribing, controlling for clinician and site of care. We defined imperfect antibiotic prescribing as prescribing for non-antibiotic-appropriate diagnoses, failure to prescribe for an antibiotic-appropriate diagnosis, or prescribing a non-guideline-concordant antibiotic.Key resultsResponse rates were 34 % for retail clinics and 24 % for physicians' offices (N = 187). Clinicians in physicians' offices prescribed antibiotics less often than those in retail clinics (53 % versus 67 %; p < 0.01), but had a higher imperfect antibiotic prescribing rate (65 % versus 31 %; p < 0.01). Feeling rushed was associated with higher antibiotic prescribing (OR 1.34; 95 % CI 1.03, 1.75). Antibiotic prescribing was also associated with clinician disagreement that antibiotics are overused (OR 1.60, 95 % CI, 1.16, 2.20). Imperfect antibiotic prescribing was associated with receiving antibiotic prescribing feedback (OR 1.35, 95 % CI 1.04, 1.75) and disagreement that patient demand was a problem (OR 1.66, 95 % CI 1.00, 2.73). Imperfect antibiotic prescribing was less common with clinicians who perceived that they prescribed antibiotics less often than their peers (OR 0.63, 95 % CI 0.46, 0.87).ConclusionsPoor-quality antibiotic prescribing was associated with feeling rushed, believing less strongly that antibiotics were overused, and believing that patient demand was not an issue, factors that can be assessed and addressed in future interventions.

Project description:ImportanceAcute respiratory infections (ARIs) are the syndrome for which antibiotics are most commonly prescribed; viruses for which antibiotics are ineffective cause most ARIs.ObjectivesTo characterize antibiotic prescribing among outpatients with ARI during influenza season and to identify targets for reducing inappropriate antibiotic prescribing for common ARI diagnoses, including among outpatients with laboratory-confirmed influenza.Design, setting, and participantsCohort study enrolling outpatients aged 6 months or older with ARI evaluated at outpatient clinics associated with 5 US Influenza Vaccine Effectiveness Network sites during the 2013-2014 and 2014-2015 influenza seasons. All patients received influenza testing by real-time reverse transcriptase-polymerase chain reaction for research purposes only. Antibiotic prescriptions, medical history, and International Classification of Diseases, Ninth Revision diagnosis codes were collected from medical and pharmacy records, as were group A streptococcal (GAS) testing results in a patient subset.ExposureVisit for ARI, defined by a new cough of 7 days' duration or less.Main outcomes and measuresAntibiotic prescription within 7 days of enrollment. Appropriateness of antibiotic prescribing was based on diagnosis codes, clinical information, and influenza and GAS testing results.ResultsOf 14 987 patients with ARI (mean [SD] age, 32 [24] years; 8638 [58%] women; 11 892 [80%] white), 6136 (41%) were prescribed an antibiotic. Among these 6136 patients, 2522 (41%) had diagnoses for which antibiotics are not indicated; 2106 (84%) of these patients were diagnosed as having a viral upper respiratory tract infection or bronchitis (acute or not otherwise specified). Among the 3306 patients (22%) not diagnosed as having pneumonia and who had laboratory-confirmed influenza, 945 (29%) were prescribed an antibiotic, accounting for 17% of all antibiotic prescriptions among patients with nonpneumonia ARI. Among 1248 patients with pharyngitis, 1137 (91%) had GAS testing; 440 of the 1248 patients (35%) were prescribed antibiotics, among whom 168 (38%) had negative results on GAS testing. Of 1200 patients with sinusitis and no other indication for antibiotic treatment who received an antibiotic, 454 (38%) had symptoms for 3 days or less prior to the outpatient visit, suggesting acute viral sinusitis not requiring antibiotics.Conclusions and relevanceAntibiotic overuse remains widespread in the treatment of outpatient ARIs, including among patients with laboratory-confirmed influenza, although study sites may not be representative of other outpatient settings. Identified targets for improved outpatient antibiotic stewardship include eliminating antibiotic treatment of viral upper respiratory tract infections and bronchitis and improving adherence to prescribing guidelines for pharyngitis and sinusitis. Increased access to sensitive and timely virus diagnostic tests, particularly for influenza, may reduce unnecessary antibiotic use for these syndromes.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets