Antibiotic treatment and stewardship in the era of microbiota-oriented diagnostics

Bogaert, Debby; Belkum, Alex van

doi:10.1007/s10096-018-3198-6

Cited by 4 publications

(4 citation statements)

References 26 publications

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“…30 If the cost of such technology decreases further and becomes available for paediatric use, use of broadspectrum antibiotics could be avoided more often, and the most abundant or overgrowing species could be targeted with narrow-spectrum drugs. 31 Although our microbiota-based approach has to be validated in independent cohorts, the similar performance of the genus-level model suggests potential for future development of universal or country-based or region-based models for the prediction of severity and duration of disease by combined microbiota and host character istics. Such a model would potentially allow physicians to increase or decrease the threshold for antimicrobial treatment depending on the predicted outcome.…”

Section: (N=108) D (N=171) E (N=100) F (N=78)mentioning

confidence: 98%

Bacterial and viral respiratory tract microbiota and host characteristics in children with lower respiratory tract infections: a matched case-control study

Man

Houten

Mérelle

et al. 2019

The Lancet Respiratory Medicine

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154

149

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Background Lower respiratory tract infections (LRTIs) are a leading cause of childhood morbidity and mortality. Potentially pathogenic organisms are present in the respiratory tract in both symptomatic and asymptomatic children, but their presence does not necessarily indicate disease. We aimed to assess the concordance between upper and lower respiratory tract microbiota during LRTIs and the use of nasopharyngeal microbiota to discriminate LRTIs from health.Methods First, we did a prospective study of children aged between 4 weeks and 5 years who were admitted to the paediatric intensive care unit (PICU) at Wilhelmina Children's Hospital (Utrecht, Netherlands) for a WHO-defined LRTI requiring mechanical ventilation. We obtained paired nasopharyngeal swabs and deep endotracheal aspirates from these participants (the so-called PICU cohort) between Sept 10, 2013, and Sept 4, 2016. We also did a matched case-control study (1:2) with the same inclusion criteria in children with LRTIs at three Dutch teaching hospitals and in age-matched, sex-matched, and time-matched healthy children recruited from the community. Nasopharyngeal samples were obtained at admission for cases and during home visits for controls. Data for child characteristics were obtained by questionnaires and from pharmacy printouts and medical charts. We used quantitative PCR and 16S rRNA-based sequencing to establish viral and bacterial microbiota profiles, respectively. We did sparse random forest classifier analyses on the bacterial data, viral data, metadata, and the combination of all three datasets to distinguish cases from controls.Findings 29 patients were enrolled in the PICU cohort. Intra-individual concordance in terms of viral microbiota profiles (96% agreement [95% CI 93-99]) and bacterial microbiota profiles (58 taxa with a median Pearson's r 0·93 [IQR 0·62-0·99]; p<0·05 for all 58 taxa) was high between nasopharyngeal and endotracheal aspirate samples, supporting the use of nasopharyngeal samples as proxy for lung microbiota during LRTIs. 154 cases and 307 matched controls were prospectively recruited to our case-control cohort. Individually, bacterial microbiota (area under the curve 0·77), viral microbiota (0·70), and child characteristics (0·80) poorly distinguished health from disease. However, a classification model based on combined bacterial and viral microbiota plus child characteristics distinguished children with LRTIs from their matched controls with a high degree of accuracy (area under the curve 0·92).Interpretation Our data suggest that the nasopharyngeal microbiota can serve as a valid proxy for lower respiratory tract microbiota in childhood LRTIs, that clinical LRTIs in children result from the interplay between microbiota and host characteristics, rather than a single microorganism, and that microbiota-based diagnostics could improve future diagnostic and treatment protocols.

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Section: (N=108) D (N=171) E (N=100) F (N=78)mentioning

confidence: 98%

Bacterial and viral respiratory tract microbiota and host characteristics in children with lower respiratory tract infections: a matched case-control study

Man

Houten

Mérelle

et al. 2019

The Lancet Respiratory Medicine

Self Cite

154

149

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“…As sequencing technologies and bioinformatic analyses continue to improve in efficiency and accessibility, more nuanced research quantifying microbiotoxicity is within reach, and even clinical diagnostic tests based on a patient's microbiome may be on the horizon [43]. Looking ahead, microbiome-based therapies are being investigated to mitigate antibiotic-induced microbial perturbation.…”

Section: Association Causation and Future Directionsmentioning

confidence: 99%

Microbiotoxicity: antibiotic usage and its unintended harm to the microbiome

Theodosiou

Jones

Read

et al. 2023

Current Opinion in Infectious Diseases

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Purpose of review Antibiotic use is associated with development of antimicrobial resistance and dysregulation of the microbiome (the overall host microbial community). These changes have in turn been associated with downstream adverse health outcomes. This review analyses recent important publications in a rapidly evolving field, contextualizing the available evidence to assist clinicians weighing the potential risks of antibiotics on a patient's microbiome. Recent finding Although the majority of microbiome research is observational, we highlight recent interventional studies probing the associations between antibiotic use, microbiome disruption, and ill-health. These studies include germ-free mouse models, antibiotic challenge in healthy human volunteers, and a phase III study of the world's first approved microbiome-based medicine. Summary The growing body of relevant clinical and experimental evidence for antibiotic-mediated microbiome perturbation is concerning, although further causal evidence is required. Within the limits of this evidence, we propose the novel term ‘microbiotoxicity’ to describe the unintended harms of antibiotics on a patient's microbiome. We suggest a framework for prescribers to weigh microbiotoxic effects against the intended benefits of antibiotic use.

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“…18 19 Moreover, optimising antibiotic use by minimising exposure, fine-tuning dosage and reducing superfluous therapy and focusing treatment to the likely culprit pathogens is a strategy that boosts patient safety 20 and ultimately safeguards against antibiotic resistance. 21 JustIfICAtIon Antibiotic resistance is a major health challenge globally. Studies in Kenya have shown rising antibiotic resistance over the last three decades.…”

Section: Open Accessmentioning

confidence: 99%

Combating antibiotic resistance using guidelines and enhanced stewardship in Kenya: a protocol for an implementation science approach

et al. 2020

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IntroductionAntimicrobial 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 in this area and provide critical data as well as practical experiences when using antibiotic guidelines and stewardship programmes in the public health sector. This will provide evidence of ASP performance and potentially contribute to the county, national and regional policies on antibiotics use.Methods and analysisThe study will be conducted in three geographically diverse regions, each represented by two hospitals. A baseline study on antibiotic usage, resistance and de-escalation, duration of hospital stay, rates of readmission and costs will be carried out in the preimplementation phase. The intervention, that is, the use of antibiotic guidelines and ASPs will be instituted for 18 months using a stepwise implementation strategy that will facilitate learning and continuous improvement of stewardship activities and updating of guidelines to reflect the evolving antibiotic needs.Ethics and disseminationApprovals to carry out the study have been obtained from the National Commission for Science, Technology and Innovation and the Mount Kenya University Ethics Review Committee. The approvals from the two institutions were used to obtain permission to conduct the study at each of the participating hospitals. Study findings will be presented to policy stakeholders and published in peer-reviewed scientific journals. It is anticipated that the findings will inform the appropriate antibiotic use guidelines within our local context.

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Antibiotic treatment and stewardship in the era of microbiota-oriented diagnostics

Cited by 4 publications

References 26 publications

Bacterial and viral respiratory tract microbiota and host characteristics in children with lower respiratory tract infections: a matched case-control study

Bacterial and viral respiratory tract microbiota and host characteristics in children with lower respiratory tract infections: a matched case-control study

Microbiotoxicity: antibiotic usage and its unintended harm to the microbiome

Combating antibiotic resistance using guidelines and enhanced stewardship in Kenya: a protocol for an implementation science approach

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