Adverse Outcomes of Patients with Non-Ventilator-Associated Hospital-Acquired Pneumonia (nvHAP)—A Single Centre Cohort Study

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Enrica et al., studies detail study of non-ventilator HAP. I found details description and presentation of the study. I recommond revise reference section. Else manuscript is well written. 

Author Response

We appreciate the reviewer for providing overall positive feedback. However, it is unclear to us what specific revisions the reviewer suggests for the manuscript. We would greatly appreciate a more detailed comment, and we will be happy to make the necessary amendments accordingly.

Please see attached the updated version of the manuscript based on the other reviewers comments, we believe it helped to improve the manuscript.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

Thank you for the opportunity to review this paper.

The aim of this retrospective single-center cohort study is to evaluate the nvHAP-related adverse outcomes and to identify the patient and the pneumonia specific factors related to the nvHAP adverse outcomes.

According to the results of this study, the lower BMI and the lower haemoglobin levels at admission were associated with adverse outcome, higher ICU admission rate and higher mortality nv-HAP related. Even if there were not specific comorbidities related with adverse outcomes, the author have mentioned "the mirroring multimorbidity", frailty and older age of the patients with adverse outcomes (lines 215-219). Plese extent the comments connecting these patients with the lower haemoglobin at admission. The patients with stage IIi and IV of congestive heart failure, cardiorenal and the patients with moderate to severe renal failure have anaemia (recieving specific therapy -erythropoietin and iron iv), please extent your comment about this group of patients. The Table 1 show that this is a small group, but it is related with high morbidity and mortality. The presence of coronary artery disease only (i.e myocardial infarction) is not a high risk factor.

Because according to the bibliography(12,37-39) there is a high percent (30-70%) of  preventable nvHAP ,please extend the discussion about the above group of patients.

This is a study from a tertiary university medical center, and according to the supplementary file, the study population include patients from all the departments of this hospital, add please a comment (or available supplimentary data) about the distribution of this patients acoording with the departments, in relation with the future prvention guidelines.

In terms of the follow-up, add pleas some comment about the in-hospital course of these patients after the ICU-discharge, (length of hospital stay, etc), these is in part related to the morbidity and mortality after discharge 

Author Response

Note: Reviewer comments are numbered. Our responses are given in the bullet points and italic font below. Passages amended in the text are in normal font, new text passages are underlined.

1. According to the results of this study, the lower BMI and the lower haemoglobin levels at admission were associated with adverse outcome, higher ICU admission rate and higher mortality nv-HAP related. Even if there were not specific comorbidities related with adverse outcomes, the author have mentioned "the mirroring multimorbidity", frailty and older age of the patients with adverse outcomes (lines 215-219).
   Plese extent the comments connecting these patients with the lower haemoglobin at admission. The patients with stage IIi and IV of congestive heart failure, cardiorenal and the patients with moderate to severe renal failure have anaemia (recieving specific therapy -erythropoietin and iron iv), please extent your comment about this group of patients. The Table 1 show that this is a small group, but it is related with high morbidity and mortality. The presence of coronary artery disease only (i.e myocardial infarction) is not a high risk factor.

We thank the reviewer for bringing up this point. While we acknowledge that severe renal disease and congestive heart failure can be associated with anemia, our additional statistical analyses revealed no correlation between either of these underlying conditions with anemia in our patient cohort. This lack of correlation may be influenced by the common use of erythropoietin in patients with renal diseases. Also, it's essential to note that our patient cohort was relatively small, limiting a comprehensive understanding of all factors relevant to adverse events in nvHAP. Rather than expanding on specific comorbidities in the discussion section, which may be speculative given our cohort's size, we have added a relevant limitation to the limitation section (lines 264-265).
“Third, in this retrospective study, some potential risk factors were not assessable due to inconsistent documentation (e.g. smoking, drug use, dental status, and oral hygiene) and the study population was relatively small, which might have prevented a more comprehensive analysis.”

2. Because according to the bibliography(12,37-39) there is a high percent (30-70%) of  preventable nvHAP ,please extend the discussion about the above group of patients.

We thank the reviewer for this suggestion, we extended lines 246-255 as follows:

Recent studies found a high preventable proportion of nvHAP (30-70%) in broad patient populations [12,37,38]: one study including patients from medical and surgical departments with above average nvHAP rates found a 31% reduction of nvHAP incidence rate [12], one study found a reduction of nvHAP rates from 5.92 to 1.79 per 1,000 admissions in all hospitalized patients [37], and one study in patients with enteral feeding showed a reduction of nvHAP from 5.71 to 3.77 per 1,000 admissions [38]. As no study has been conducted on a group of patients at the highest risk for adverse nvHAP outcomes, one cannot rule out the possibility that the effectiveness of prevention bundles might be lower in this population. Nonetheless, we maintain the assumption that some nvHAP, or a fraction of nvHAP-related mortality, may still be preventable in this cohort.

3. This is a study from a tertiary university medical center, and according to the supplementary file, the study population include patients from all the departments of this hospital, add please a comment (or available supplimentary data) about the distribution of this patients acoording with the departments, in relation with the future prvention guidelines.

We thank the reviewer for this comment. We added the additional information in the results section (lines 108-111):

A total of 80 patients were affiliated to internal medicine and subspecialties, 42 to oncology and hematology, 27 to neurology and neurosurgery, 89 to other surgical departments (cardiac, thoracic, visceral, urogenital, or plastic surgery, and traumatology), and six patient to other departments. 

4. In terms of the follow-up, add pleas some comment about the in-hospital course of these patients after the ICU-discharge, (length of hospital stay, etc), these is in part related to the morbidity and mortality after discharge.

Thank you for raising this request: We compared the median length of stay of patients who needed ICU-admission because of nvHAP and other patient. As expected, the median length of stay was longer in ICU-admitted patient (32.5 vs. 24 days). We included this information in the manuscript (lines 113-114)

“The median total length of hospital stay was 26 days (IQR: 16-39.5) (data not shown), longer for patients with (32.5 (IQR 19-57) than without ICU admission (24 (IQR 16.-37)).”

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

Dear Authors,

Thank you very much for your well-written manuscript, dealing with an important health-care issue, which is the prevalence, risk factors and clinical impact of non-ventilator associated hospital-acquired pneumonia (nvHAP). Please find below my comments and questions, pertaining to your manuscript:

1.      Lines 59-61: The cohort you used for your study has been already described in a paper by Wolfensberger et al., and comprised patients admitted to the hospital before the start of a large nvHAP prevention initiative in 2018. Please become more specific. This means that, for the current study, you included patients who were admitted to the hospital between the years 2017 and 2018. Is that right?

2.      Lines 59-61: Then please describe which were the preventive measurements initiated in 2018 and if you have already observed a reduction of nvHAP since then. What is the reason for the current study if you have already taken measures to prevent nvHAP after that? A comparison before and after the implication of measurements would be much more insightful.

3.      Line 86: Please add the abbreviation EMR (included in the abbreviation list at the end).

4.      Table 1: Please modify the columns of the table, so that the numbers and percentages referring to a variable are presented in the same line (for example the number 162 and the percentage 66.4% for the Male, sex).

5.      Table 3: Please present the diagnostic methods to detect the causative pathogens of pneumonia (CT scan characteristics, BAL and/or bronchial samples, culture and/or multiplex PCR).

Best Regards

Author Response

Note: Reviewer comments are numbered. Our responses are given in the bullet points and italic font below. Passages amended in the text are in normal font, new text passages are underlined.

1. Lines 59-61: The cohort you used for your study has been already described in a paper by Wolfensberger et al., and comprised patients admitted to the hospital before the start of a large nvHAP prevention initiative in 2018. Please become more specific. This means that, for the current study, you included patients who were admitted to the hospital between the years 2017 and 2018. Is that right?

 

We thank the reviewer for bringing up this point. It is correct that we included all patients from a one year period, i.e. the year 2017, with some exceptions. We specified this by extending the following sentence (line 62) new parts are underlined):

“All patients from the year 2017 with nvHAP were included with the exemption of patients who developed first symptoms after discharge (due to missing data).”

Together with the following unchanged sentence in the same paragraph, we hope this provides clarity to the readers: “All 255 patients with nvHAP from the year 2017 identified by retrospective, semi-automated nvHAP surveillance applying the European Centre for Disease Prevention and Control (ECDC) criteria were eligible [4,11].”

 

2. Lines 59-61: Then please describe which were the preventive measurements initiated in 2018 and if you have already observed a reduction of nvHAP since then. What is the reason for the current study if you have already taken measures to prevent nvHAP after that? A comparison before and after the implication of measurements would be much more insightful.
   
   We thank the reviewer for this comment. The prevention initiative that started in 2018 was successful (reduction of nvHAP by 31%) and was recently published in Lancet ID (reference No. 12). To not lengthen the manuscript, we would prefer to refrain from describing the prevention initiative in more detail - it consisted of a 5-element prevention bundle (oral care, dysphagia screening and management, mobilization, stopping non-indicated proton pump inhibitors and respiratory therapy) – but we leave this decision to the discretion of the editor.

We opted to incorporate the one-year patient cohort before the intervention due to the larger number of patients with nvHAP, our assumption that the patient cohort with nvHAP would differ from the post-initiative cohort, and that this 'before-cohort' would better represent patient cohorts in other hospitals. We agree that a comparison of patient cohorts before and after the prevention initiative would be very interesting, and this could be a next research project.

We amended the following sentence (lines 61-62, new passages are underlined):

 

“This cohort was described in a paper by Wolfensberger et al. [4], and comprised patients admitted to the hospital before the start of a large and successful nvHAP prevention initiative in 2018 [12], which we assumed to have an impact on characteristics of the remaining nvHAP patients.”

 

 

3. Line 86: Please add the abbreviation EMR (included in the abbreviation list at the end).

 

We thank the reviewer for this comment and the careful reading. We included the abbreviation EMR accordingly (line 88).

 

4. Table 1: Please modify the columns of the table, so that the numbers and percentages referring to a variable are presented in the same line (for example the number 162 and the percentage 66.4% for the Male, sex).

 

As requested, we amended the table in the manuscript.

 

5. Table 3: Please present the diagnostic methods to detect the causative pathogens of pneumonia (CT scan characteristics, BAL and/or bronchial samples, culture and/or multiplex PCR).
   
   

We thank the reviewer for this comment. To detect the causative pathogens, a respiratory specimen of sputum, tracheal aspirate, endobronchial aspirate, bronchoalveolar lavage, or tissue sample was cultured or examined by multiplex of species-specific PCR. We included an asterisk (*) in table 1 and added the following footnote: 

 

“ * Respiratory sample = bacterial cultures or PCR from sputum, tracheal aspirate, endobronchial aspirate, bronchoalveolar lavage, or tissue sample”

Author Response File: Author Response.pdf

Round 2

Reviewer 3 Report

Comments and Suggestions for Authors

Dear Authors,

thank you for providing comprehensive and convincing answers to the questions and queries, expressed by me and the other reviewers, and made changes that have contributed to quality improvement and increased the publishing potential of your work. I have no further points to denote.

Best Regards