Effect of a widespread reduction in treatment duration for group A streptococcal pharyngitis on outcomes and household transmission

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1. 

   PREreview

   Oct 30, 2024

   This Zenodo record is a permanently preserved version of a Structured PREreview. You can view the complete PREreview at https://prereview.org/reviews/14010561.

   Does the introduction explain the objective of the research presented in the preprint? Yes The introduction clearly explains the objective of the paper by providing a background of group A streptococcus and the current treatment procedure. The introduction then explains existing literature on shorter course antibiotic treatments and the impact of treatment length on antimicrobial resistance. Additionally, it provides context of the experiment taking place in New Zealand.

   Are the methods well-suited for this research? …

   This Zenodo record is a permanently preserved version of a Structured PREreview. You can view the complete PREreview at https://prereview.org/reviews/14010561.

   Does the introduction explain the objective of the research presented in the preprint? Yes The introduction clearly explains the objective of the paper by providing a background of group A streptococcus and the current treatment procedure. The introduction then explains existing literature on shorter course antibiotic treatments and the impact of treatment length on antimicrobial resistance. Additionally, it provides context of the experiment taking place in New Zealand.

   Are the methods well-suited for this research? Highly appropriate Matched analysis in this setting is the best use of available data. The study was technically an observational cohort study as the authors were able to identify a window where a subset of a population was subjected to a reduced antibiotic prescription duration with a demographically equivalent 'control', which can be compared to a non-randomized pseudo-experimental study. The methods that they used to approach matching was thorough, accounting for clinically appropriate exclusion groups (e.g. Maori population who are at high risk of developing ARF, or those who received antibiotics that were irrelevant to treatment of pharyngitis).

   Are the conclusions supported by the data? Highly supported The authors' main conclusion is that shorter antibiotic treatment durations did not result in any changes for GAS-P outcomes. They also claim that household transmissions and hospitalization rates showed no significant difference across treatment groups. The authors acknowledge the observational nature of their study made it difficult to account for confounding factors and unmeasured patient factors (milder vs more severe symptoms) which might have impacted treatment durations. They recognize their choice to only examine patients not on antibiotics at the time of TSC results could have led to their study population containing those with less severe symptoms. Finally, they recognize their choice to only perform the study in a certain region of New Zealand impacts the generalizability of their results. Importantly, they also discuss that groups with a higher baseline risk of clinically adverse events (e.g. Maori/Pacific Islander population) were excluded from this study, which provides additional clinical contexts as to when a shortened antibiotic duration may be appropriate. Additionally, the authors clearly imply when their findings are applicable at the household level versus the individual level depending on which part of their study they are referencing. Overall, their results are consistent with their methodology and they don't make claims that go beyond the limits of their study and its findings.

   Are the data presentations, including visualizations, well-suited to represent the data? Somewhat appropriate and clear Figure 2 would benefit from p-value bars, particularly on the 0-days of treatment bar. Additional figures would be beneficial in illustrating the absence of significant difference in hospitalization rates, need for further abx treatment, and GAS in TSC within a follow-up period. Would suggest a bar graph similar to Figure 2 with confidence interval bars and p values included.

   How clearly do the authors discuss, explain, and interpret their findings and potential next steps for the research? Very clearly The paper clearly explains that the shorter course durations did not result in more poor patient outcomes or decreased transmission efficacy. Additionally, the study effectively highlights the strengths and limitations within the design and results. The authors noted that while there was a large sample size and examination of multiple differences, the study was observational in nature with potential confounding factors. Moreover, the authors describe their results as consistent with previous studies on shorter antibiotic treatment courses. However, their study is the first to examine the effect of shorter course therapy on real-world household transmission of GAS Improvements: More clear wording on the next steps (eg. If this should be tested with other antibiotics or implemented into practice) Add a part about New Zealand study's Maori/Pacific Island population that continues the discussion in the results and introduction section.

   Is the preprint likely to advance academic knowledge? Highly likely The preprint explores new approaches to the use of antibiotics for GAS-P ranging from shorter treatment windows or even skipping antibiotics as a treatment entirely. The novel finding in this preprint is that they saw no difference in household transmissions rates occurring even with a shortened duration of antibiotic treatment in those with GAS-P, and this is the first study to look at this outcome. Overall, the preprint can advance medical knowledge surrounding antibiotic treatment of GAS-P, giving reassurance that a shortened duration of therapy may be sufficient not only for individual clearance, but does not impact household transmission rates or adverse outcomes. This is important in the context of improving antimicrobial stewardship.

   Would it benefit from language editing? No

   Would you recommend this preprint to others? Yes, it's of high quality It has some minor limitations but study results are interesting and clinically relevant.

   Is it ready for attention from an editor, publisher or broader audience? Yes, as it is If authors are able to strengthen the evidence by presenting sub-population data (e.g. do they have subgroup analyses characterized by different age groups, particularly pediatric patients where GAS-P is most relevant, as the median age was ~18-20y but no clarity on age range that was included), or if there is availability of data regarding potential confounders (e.g. pre-existing medical status of patients), the evidence may become more relevant.

   Competing interests

   The authors declare that they have no competing interests.

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2. 

   Version published to 10.1101/2024.10.09.24315208v1 on medRxiv

   Oct 10, 2024