PONE-D-24-20393

Reduction of misdiagnosis in urinary tract infections during pregnancy: the role of adjusted urine flow cytometry parameters

PLOS ONE

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PLOS ONE

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Reviewers' comments:

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Reviewer #1: Partly

Reviewer #2: Yes

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Reviewer #1: N/A

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

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Reviewer #1: The idea of the study is a very promising one. Indeed, there are a lot of false positive and false negative results. For the diagnosis of urinary tract infection both in pregnant woman and in the female population without this physiological stage.

The 2 study groups were correctly chosen. I appreciate the fact that the urine samples were examined double blind by people with special experience. However, despite the design of the study, the idea is at a very beginning because it does not elaborate a clear algorithm for a single person in the conditions of consultation for urinary infection, regardless of the person's pregnancy status or not.

For this I belive that a much larger, possibly multicenter study is necessary that includes a major cohort from both groups that allows for some relevant conclusions and the individualization for each individual of what is of interest to clinicians.

The bias in this study may also come from the fact that twice as many patients with diabetes are included in the cohort of pregnant women than in the other cohort.

Therefore, the study could be of interest in the conditions of a large cohort that can this externalize the minuses or the interpretation deficiency.

Even in these conditions, the clinician will decide on antibiotic therapy or not for each individual case, including in the clinical judgement several element, not only age and pregnancy status.

The problem being a particularly serious one and on the edge and on one side and the other of the problem in the conditions in which you make a mistake by excess antibiotic therapy when it is not needed or in the minus with the risk of sepsis with urinary entrance in the conditions of physiological immunosuppression during pregnancy.

Reviewer #2: This is a study conducted in one center from China and reporting on how to improve urine flow cytometry parameters for detecting leukocyturia in pregnancy. The data are important as they discuss potential erroneous findings that might lead to inappropriate treatment. However the current manuscript is limited by the insufficient description of participant selection and by the unclarities with regards to UTI versus leukocyturia. Specifically, the authors often describe the presence of leukocyturia as indicative for UTI which may not always be the case. The authors should also consider presenting the diagnostic performance of flow cytometry separately for those who have bacteriologically confirmed UTI and those who do not. Further, the discussion would benefit from a more in-depth reflection on the benefits of using this diagnostic test and the implications of misdiagnosis in this patient population. More specific comments below.

Introduction

- Paragraph 1: suggest leaving out the mortality due to preterm births as the contribution of UTIs to this is not that substantial. The authors could just leave the association with pregnancy complications

- Paragraph 2: I would not expect that pregnant women would have much more difficulties in collecting a urine sample than any young adult (I expect it would be much more difficult in the elderly) – consider rephrasing

Methods:

- Provide more details on how the study participants were selected. Given that they were evenly split into the two groups, I assume that they were not included consecutively

- If the study aims to evaluate diagnostic accuracy of UF (as suggested by calculating sensitivities and specificities), then UF should not be included in the definition of the condition (criterion #3)

- Microbiological assessment: please be more specific with regards to which bacteria had to be isolated – the bacteria would have to be a uropathogen and there would be one/few bacterial species growing on the plate (otherwise it would be considered contaminated)

- The subheading “microbiological examination” has a typographical error

- Statistics: would the authors be able to clarify in the methods how false positives and false negatives were defined

- Please clarify in the manuscript text how the different gain values were selected

Results

- The authors should explain why leukocyturia in the absence of bacterial growth in culture was considered as UTI. This should be rephrased, as leukocyturia in the absence of infection can occur in pregnancy. This comment also applies to the methods

- The variables should have complete names (e.g. instead of microscope WBC>… ). Also the top information should be filled (replace “+” and “-“ by description)

- “Parallel, urine bacterial culture, another gold standard diagnostic method for UTIs, exhibited no significant difference in positive rates between pregnant (17.92%) and non-pregnant women (16.09%) (P > 0.05)” consider removing as this is not clinically meaningful

- Define in the footnote of table 3 false positives and negatives

Discussion

- How do the authors explain the low proportion of positive urine cultures among the study participants given that in other settings bacterial cultures are often positive among patients with UTI symptoms. Please discuss

- Discuss in more detail the implications of incorrect UTI diagnosis

- Discuss the advantages and disadvantages of using flow cytometry over more conventional methods for diagnosing UTIs (high throughput vs cost)

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Reviewer #1: No

Reviewer #2: No

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Reduction of misdiagnosis in urinary tract infections during pregnancy: the role of adjusted urine flow cytometry parameters

PONE-D-24-20393R1

Dear Dr. Yang,

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Kind regards,

Seth Agyei Domfeh, PhD

Academic Editor

PLOS ONE