A Situation Analysis of Diagnostic and Management Strategies for Gestational Urinary Tract Infections (UTIs) in Kisumu County, Kenya: Maternal Health Implications and Opportunities for Diagnostic Improvement

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The manuscript addresses a clinically relevant gap: how gestational UTIs are diagnosed and managed in an LMIC setting, with implications for AMS and WHO AWaRe adherence. Key findings are impactful and policy-relevant: very high dipstick-based presumptive UTI positivity (57.9%), extremely low microbiological confirmation (1.4%), and antibiotic use split between AWaRe Access (60%) and Watch (40%).

 

I do have the following comments:

1. The inclusion criteria state that participants “presented with symptomatic UTI infections,” yet the Results and Discussion repeatedly frame the 57.9% as asymptomatic. This is contradictory and may affect interpretation. Check this and then align the prevalence language accordingly.
2. Treating dipstick positivity (nitrite/leucocyte esterase/bacteriuria on strip) as “UTI prevalence” likely overestimates true infection and conflates screening yield with confirmed disease. Given only 1.4% were culture-confirmed, the headline should be carefully re-phrased (something like “dipstick-positive screen rate”) and the limitations expanded. Explicitly state the dipstick criteria considered positive (e.g., nitrite and/or leukocyte esterase and/or any “bacteriuria” field) and whether symptoms were required for classification in any analysis.
3. Records were obtained via purposive sampling rather than consecutive sampling which may lead to selection bias. Please justify this approach and discuss how it affects generalizability. If feasible, describe the source population and the proportion of all eligible ANC attendees captured in the period.
4. Some information seems to be missing or limited. Please address this as a potential limitation.
5. The study window overlaps pandemic-related service disruptions, which may also be viewed as a potential limitation. 
6. You report 60% Access vs 40% Watch, but the manuscript doesn’t show the denominators by drug nor how each drug was mapped to AWaRe at the time of use. Provide a table listing each antibiotic, count/%, route, trimester of exposure (when known), AWaRe category, and standard pregnancy safety considerations. This will make the stewardship message more actionable.
7. A flow diagram for eligibility would improve readability.
8. Justify covariate selection a priori (Directed Acyclic Graph or literature-based rationale) and specify how gestational age, parity, gravidae, age, and ANC visits could confound the UTI–anemia relationship.
9. The instrument collects variables (religion, education) not analyzed. Either include them in descriptive tables or explain exclusion to avoid perceived selective reporting.
10. For the logistic regression, provide full model output (OR, 95% CI, p) and model fit metrics; address the extreme AOR (204.431) with non-significant p-value.
11. Consider adding a new table listing antibiotics prescribed, frequency/%, AWaRe category, and indication, if available, otherwise discuss this as a potential limitation.
12. With cross-sectional, record-based data and very low culture confirmation, keep conclusions cautious. Also, make sure to standardize terminology.
13. Regarding existing limitations, you list missing Hb and dipstick-based diagnosis. Please also add:

    • Non-probability sampling; selection bias.

    • Sparse data issues in regression (leading to unstable AORs).

    • Potential misclassification (dipstick false positives/negatives; undocumented antibiotic use before ANC).

    • Lack of organism-level data precludes stewardship-ready empiric guidance.

Author Response

Author's comments to Reviewer 1

Thank you for the exceptionally thorough appraisal. Each concern raised has informed a substantial revision. Below, you will find our carefully considered responses to each concern.

1. The inclusion criteria state that participants “presented with symptomatic UTI infections,” yet the Results and Discussion repeatedly frame the 57.9% as asymptomatic. This is contradictory and may affect interpretation. Check this and then align the prevalence language accordingly.

 

Response and location in the revised manuscript:

The inclusion criteria now specify ‘records of pregnant women presenting with dipstick-positive presumptive UTI’ removing the contradiction (methods section 2.5)

 

1. Treating dipstick positivity (nitrite/leucocyte esterase/bacteriuria on strip) as “UTI prevalence” likely overestimates true infection and conflates screening yield with confirmed disease. Given only 1.4% were culture-confirmed, the headline should be carefully re-phrased (something like “dipstick-positive screen rate”) and the limitations expanded. Explicitly state the dipstick criteria considered positive (e.g., nitrite and/or leukocyte esterase and/or any “bacteriuria” field) and whether symptoms were required for classification in any analysis.

 

Response and location in the revised manuscript

This is clarified as ‘presumptive dipstick-positive screen rate’ expanded limitations (results section 3.3; limitations)

 

1. Records were obtained via purposive sampling rather than consecutive sampling which may lead to selection bias. Please justify this approach and discuss how it affects generalizability. If feasible, describe the source population and the proportion of all eligible ANC attendees captured in the period.

 

Response and location in the revised manuscript

Justified given the retrospective record nature, generalizability caveat added (section 2.6; limitations)

 

1. Some information seems to be missing or limited. Please address this as a potential limitation.

 

1. The study window overlaps pandemic-related service disruptions, which may also be viewed as a potential limitation. 

Response and location in the revised manuscript

Added acknowledgement under limitations

 

1. You report 60% Access vs 40% Watch, but the manuscript doesn’t show the denominators by drug nor how each drug was mapped to AWaRe at the time of use. Provide a table listing each antibiotic, count/%, route, trimester of exposure (when known), AWaRe category, and standard pregnancy safety considerations. This will make the stewardship message more actionable.

 

Response

It was difficult to extract the information required in the study setting as this information/data was captured. This was acknowledged as part of the limitation.

Discussion of stewardship implications has been expanded under Section 4.4 Regulated Access to Antibiotic Prescriptions).

 

.

 

1. A flow diagram for eligibility would improve readability.

 

Response and location in the revised manuscript

The Methods (Section 2.5–2.6) have been revised for clarity. The sampling strategy is now justified as purposive, given the retrospective, record-based nature of ANC datasets, with an explicit statement on generalizability limitations in the Limitations section). The phrasing has been standardized to “dipstick-positive presumptive UTI cases” rather than “asymptomatic infections.”

 

 

1. Justify covariate selection a priori (Directed Acyclic Graph or literature-based rationale) and specify how gestational age, parity, gravidae, age, and ANC visits could confound the UTI–anemia relationship.

 

Response and location in the revised manuscript

Explained a priori variable choice (gestation, parity, ANC visits, etc) as biological plausible confounders (methods section 2.7)

 

1. The instrument collects variables (religion, education) not analysed. Either include them in descriptive tables or explain exclusion to avoid perceived selective reporting.

 

1. For the logistic regression, provide full model output (OR, 95% CI, p) and model fit metrics; address the extreme AOR (204.431) with non-significant p-value.

 

Response and location in the revised manuscript

Full model with OR (95% CI, p) + fit metrics retained (Table 3; Table 4)

 

1. Consider adding a new table listing antibiotics prescribed, frequency/%, AWaRe category, and indication, if available, otherwise discuss this as a potential limitation.

Addressed in the revised manuscript.

 

1. With cross-sectional, record-based data and very low culture confirmation, keep conclusions cautious. Also, make sure to standardise terminology.

 

Response: This is well addressed.

 

 

Reviewer 2 Report

Comments and Suggestions for Authors

I have read your manuscript carefully, and I find the topic of gestational urinary tract infections in LMICs to be of great interest, particularly due to its relevance for maternal health and antimicrobial resistance stewardship. Your work highlights important challenges in diagnostic practices and clinical management that deserve attention.

That said, I must also point out some significant limitations that affect the suitability of this manuscript for Microbiology Research:

• The study does not provide microbiological data (isolates, resistance profiles) that would allow correlating the clinical findings with the infectious etiology. In similar studies, this type of analysis is considered the minimum standard for research in urinary tract infections.

• The diagnostic method relies almost exclusively on urine dipsticks, which have limited sensitivity and specificity. Without correlation with urine sediment analysis or, most importantly, urine culture, the true prevalence of UTI in your population is likely either over- or underestimated.

• Clinical information such as anemia, and other patient characteristics, are presented as isolated data points, without statistical association or deeper discussion of their connection to UTI. This weakens the interpretability of the findings.

While I acknowledge the value of the clinical and epidemiological data you provide, the absence of microbiological results prevents a more robust discussion of the infectious disease and reduces the contribution of the study in the field of microbiology. For this reason, I believe your manuscript may be better suited for a journal with a clinical or epidemiological focus.

Author Response

Comments to reviewer 2;

We appreciate your emphasis on microbiological robustness and disciplinary fit.

• The study does not provide microbiological data (isolates, resistance profiles) that would allow correlating the clinical findings with the infectious etiology. In similar studies, this type of analysis is considered the minimum standard for research in urinary tract infections.

Response and location in the revised manuscript

We acknowledge this constraint explicitly (limitation page 9), and justify it as a programmatic situational-analysis within a broader mixed-methods project whose microbiological component will be reported separately.

• The diagnostic method relies almost exclusively on urine dipsticks, which have limited sensitivity and specificity. Without correlation with urine sediment analysis or, most importantly, urine culture, the true prevalence of UTI in your population is likely either over- or underestimated.

Response and location in the revised manuscript

This is clarified as presumptive screening, contrasted with culture standards (results section 3.3, page 5-6; Discussion section 4.2, page 7)

• Clinical information such as anemia, and other patient characteristics, are presented as isolated data points, without statistical association or deeper discussion of their connection to UTI. This weakens the interpretability of the findings.

Response and location in the revised manuscript

We have added correlation and regression commentary linking anaemia with possible chronic infection pathways (Discussion section 4.3)

While I acknowledge the value of the clinical and epidemiological data you provide, the absence of microbiological results prevents a more robust discussion of the infectious disease and reduces the contribution of the study in the field of microbiology. For this reason, I believe your manuscript may be better suited for a journal with a clinical or epidemiological focus.

Response and location in the revised manuscript

We respectfully note that Microbiology Research increasingly features translational and stewardship-focused public-health microbiology papers; our expanded AWaRe and diagnostic-stewardship framing now better aligns with this scope (Discussion section 4.4)

 

We believe that these revisions now delineate methodological limits while strengthening the paper’s microbiological policy contribution. We thank you for these clarifications, which have greatly improved the manuscript’s integrity and positioning.

Reviewer 3 Report

Comments and Suggestions for Authors

COMMENTS TO 3841336

 

The article is valuable because it addresses the following important aspects of urinary tract infections in pregnant women:

1. Bacteriuria is very common.
2. It should be treated to avoid complications during pregnancy and delivery.
3. Any bacteriuria or urinary tract infection should be investigated in pregnant women using cultures, not dipstick.
4. The use of empirical antibiotics can lead to increased resistance.

For all these reasons, the article is very interesting. It also emphasizes the need to improve healthcare for these women.

It's worth noting that strategies for controlling bacterial resistance are being implemented globally, because if countries have individual strategies, it won't be possible to combat the emergence of multidrug-resistant bacteria.

 

Although the retrospective design may seem lesser quality, it is sufficient and well thought out.

Author Response

Response to reviewer 3 comments;

We are indeed grateful for your recognition of the manuscript’s public-health importance and for reinforcing key clinical principles.

 

The need for culture-based confirmatory diagnosis has been reiterated throughout the discussion section 4.2 and in conclusions page 9; future work will incorporate culture and molecular assays.

 

The risk of empirical therapy and AMR had been highlighted, a paragraph is added detailing empirical use of broad-spectrum antibiotics and its AMR consequences (section 4.4)

 

A statement on global coordination on resistance control is integrated referencing the WHO Global Action Plan and harmonised AWaRe strategies (section 4.4).

 

The need for better healthcare for pregnant women has been strongly emphasized by strengthening the public-health conclusion advocating diagnostic capacity building within ANC services (conclusions)

 

Overall, we again thank the guest Editor and all the three reviewers for their meticulous evaluations. Every major and minor suggestion has been integrated with line-specific revisions and page annotations. The revised manuscript now presents a balanced evidence-based, and policy-responsive account of gestational UTI diagnosis and management in Kenya, reinforcing the importance of diagnostic and antimicrobial stewardship.

 

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Thank you for addressing some of the concerns. Still some comments still need to be further examined: 

1. The inclusion criteria in Section 2.5 still require revision for consistency with the study’s methodology. Please replace the phrase “presented with symptomatic UTI infections” with the following wording to reflect the dipstick-based case definition: records of pregnant women with dipstick-positive presumptive UTI (nitrite and/or leukocyte esterase and/or bacteriuria field positive) during Feb 2020–Feb 2021.
2. Terminology and reporting in Figure 3/4 and Section 3.3 should be updated to align with the dipstick-based approach and avoid implying culture-confirmed disease. Wherever the manuscript currently states “UTI prevalence,” please change this to “dipstick-positive presumptive UTI (screen-positive) proportion,” ensuring consistent use of this terminology throughout the text and figures.
3. I continue to recommend adding a one-page eligibility flow diagram summarizing record identification, exclusions (with reasons), and the final analytic sample (and the Hb subsample used for anemia analyses). Even an approximate flow based on best-available counts would substantially improve clarity.

 

Author Response

We sincerely thank you and the reviewer for the constructive feedback provided on our manuscript. We have carefully revised the paper to address all comments as summarised below;

1. Inclusion Criteria (section 2.5): This section has been updated to reflect a dipstick-based case definition (records of pregnant women with dipstick-positive presumptive UTI - nitrite and/or leukocyte esterase and/or bacteriuria field positive - during February 2020 – February 2021.)
2. Terminology and Reporting (Section 3.3; Figure 3-4): All references to ‘UTI prevalence’ have been changed to ’dipstick-positive presumptive UTI (Screen-positive) proportion’ for terminology accuracy.
3. Flow Diagram: A one-page eligibility flow chart has been added to improve methodological clarity and transparency.
4. References: Reviewed and refined to ensure relevance to the dipstick-based screening context and gestational UTI epidemiology. All the citations used are relevant to the content presented in the manuscript.

All changes are highlighted in the revised manuscript for ease of review.