Carbapenemase-Producing Enterobacteriaceae (CPE) Newborn Colonization in a Portuguese Neonatal Intensive Care Unit (NICU): Epidemiology and Infection Prevention and Control Measures

Round 1

Reviewer 1 Report

The authors present a prospective, observational, cohort study of carbapenemase producing (CPE) enterobacteria in neonatal intensive care units in Lisabon hospital, Portugal. The time period was 9 months in 2019 and total of admitted neonates was 173, and in 4.8% was detected the CPE in rectal swab. Authors present interesting data and define some possible risk factors for CPE colonization in neonates. Authors give explanations for all questions and make adequate corrections in text. In this form is text prepared for publication. 

Author Response

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Reviewer 2 Report

Thanks for the revised manuscript. Much better.

Minor edits only:

Line 19 - omit 'the'

Line 23 - 'were' not was

Line 36 - omit 'the'

Line 48 - Carbapenem, not carbapenems

line 50 - Carbapenemase, not carbapenemases

Line 52 - 'the' Ambler classification

Line 63 - derived, not evolved

line 92 - during contact, not in the contact

line 125 - Statistical Package for Social Science, not all lower case

line 198 - neonatal units, however only a few ...

line 276 - the associated complications

Author Response

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Author Response File: Author Response.docx

This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.

Round 1

Reviewer 1 Report

The authors present a prospective, observational, cohort study of carbapenemase producing (CPE) enterobacteria in neonatal intensive care units in Lisabon hospital, Portugal. The time period was 9 months in 2019 and total of admitted neonates was 173, and in 4.8% was detected the CPE in rectal swab. Authors present interesting data and define some possible risk factors for CPE colonization in neonates. But there is also some problems of this study. First of all is that for the conclusion cohorts needs higher numbers of admitted neonates. And some other important unclearness was found in text:

• Line47 – authors wrote about non-enzymatic mechanism of carbapenem resistance and mentioned production AmpC with decreased membrane permeability for carbapenems. But more frequent bacteria associated with carbapenems resistance is Klebsiella pneumoniae and by this bacterium is in case of non-enzymatic resistance to carbapenem associated with extended spectrum beta lactamases (ESBL) than AmpC. Please rewrite.
• Lines 109-110 – authors defined the symptomatic CPE cases. The case definition is unclear, authors wrote about necessity of positive specimen, but because in methodology was mentioned the rectal swabs only. Did authors used also the positive rectal swab for prove of symptomatic cases? If yes, it is insufficient for association prove, for this the CPE positive sample from possible infected body compartment is needs. Please give an explanation.
• Did all mothers for CPE colonization screened as well? If not, authors are not able to define the risk factor for colonization. In lines 202-204 authors discussed that traveling into risk countries (e.g. India) was defined as risk factor. The authors determined the median for first positive sample 12.5 days (range 4-90 days). From this information is highly unprobeable that neonates were infected in utero or during birth, because in these cases the positiveness have to be earlier. The time association showed more probable   colonization from hospital environment or staff than to mother. Please give an explanation and rewrite.

 

In conclusion – the text give some interesting data, but before publication major revision is needed.

Author Response

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Reviewer 2 Report

Thank you; I read your paper with interest; CPE colonisation is an emerging problem in NICU's. The paper will be of interest to those with leadership responsibilities in neonatology, infection prevention and control, and antimicrobial stewardship. As there were no independent risk factors for CPE colonisation, one conclusion should be that efforts to identify risk factors need to look beyond the baby. Another discussion point might be screening of women delivering an infant who is likely to be admitted to the NICU for longer than a brief stay. This relates to known risks with international travel to endemic areas, and other health risk factors in the mother. Suggest mention whether or not your unit uses probiotics, and if any of the babies who were positive were receiving probiotics.

Your average day of CPE colonisation (typing error in table 1) was 12.5 days. The time taken to achieve identified colonisation  after transmission between mother and baby is not well known - an additional discussion point.

Also - You might suggest the suspected source hospital should be screening weekly for CPE. Other discussion points are searching for an environmental source, for example hospital sinks in NICU.

Minor comments on the text:

Dystocic and eutocic (line 137 and table 1) are not words used in English speaking hospitals. Usually classified as normal vaginal delivery, instrumental delivery, Caesarean delivery.

Line 68 - thus maintaining a high level of suspicion is crucial (no commas)

Line 85 - "using rectal swabs"

Line 189 - should read "KPC being the most frequently isolated"

Line 205 - "international travel to CPE....factor, raising concern about carbapenemase prevalence in the community"

Line 209 - morbidity and mortality

Line 214 - would say "cohorting of CPE colonized neonates" prevented "further cross-transmission and progression to infection"

Line 215 - the decreasing number.....

Line 239 - in the literature

Author Response

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Round 2

Reviewer 1 Report

The authors present a prospective, observational, cohort study of carbapenemase producing (CPE) enterobacteria in neonatal intensive care units in Lisabon hospital, Portugal. The time period was 9 months in 2019 and total of admitted neonates was 173, and in 4.8% was detected the CPE in rectal swab. Authors present interesting data and define some possible risk factors for CPE colonization in neonates. I still think that it is a pity, that data from mother screening was not included into study design. Authors give explanations for all questions and make adequate corrections in text. In this form is text prepared for publication.