Management of Pleural Infection: A Historical Review and Updates

Round 1

Reviewer 1 Report

Dear Authors, 

I have read a review about the management of pleural infections. I have several points that should be addressed:

1) Overall, the manuscript seems to be lacking major points of updated management in pleural infections. There is no new insight offered in this manuscript as compared to other published manuscripts. The topic should be focused on the management and more in-depth discussion about certain nuances should be brought up.

2) The authors also need to define clearly what constitutes pleural infection.

3) Please include some images of chest-radiography and the CT chest such as the split pleural sign.

4) What are the interpretations of pleural fluid in the management of pleural infection?

5) The authors compiled a list of other studies of intrapleural enzymatic therapy. Is there a specific reason for this?

6) There is a lack of conclusion here.

Some close brackets are missing (such as in line 114) and other spelling and punctuation errors persist everywhere. I suggest the authors double-check on these mistakes.

Author Response

See attached word document for author's reply to the reviewer. 

Author Response File: Author Response.pdf

Reviewer 2 Report

The topic is interesting and the review is quite well written. However, in my opinion, some parts need to be improved, I have some comments:

1) Abstract. Pleural infection, including empyema, continues to have a high morbidity. A deep understanding of the pathobiology and appropriate medical management is crucial to avoid complications and progression to the need for surgery. Over the last several decades we have learned much about the pathophysiology, microbiology, and epidemiology of pleural infections. Management has changed considerably over the years with more recent clinical practice favoring minimally invasive interventions over surgery. Here we discuss in detail the pathophysiology and microbiology of pleural infections and how this relates to their diagnosis and management. We review the literature dating back decades up to the most recent clinical trials on the use of intrapleural fibrinolytic therapy and give our recommendations for management based on this literature. Abstract might be beneficial to include a sentence  to summarizes the key findings of the review. This can provide readers with a quick overview of the research. 

2) Management of Pleural Infection: A Clinical Review and 2 Updates. I suggest to improve the title, undering the novelty of the paper, to increase the possible number of readers.

3) . Empyema, is a subcategory of complicated parapneumonic effusions 27 characterized by positive pleural fluid cultures or with overt purulent exudate within the 28 pleural cavity 2 . Empyema is usually a complication in up to 2-3% of cases of pneumonia, 29 and its incidence in the US has been increasing with about 32,000 case per year 3–5 . Empy- 30 ema can also been seen in cases with mediastinitis, spinal infections, bronchogenic carci- 31 noma, esophageal rupture, bronchopleural fistula, trauma, and post-surgical complica- 32 tions 5 . Please, add a brief description of the study aim.

4) 3. Management 153 The mainstay of treatment for empyema is antibiotic therapy and pleural fluid drain- 154 age using a chest tube. Additional strategies, such as intrapleural fibrinolytics and, if nec- 155 essary, surgical intervention, may also be considered 43. Please, improve this paragraph.

5) Table 2. This table lists both initial case reports/series with subsequent trials and studies through 269 the years evaluating the safety and effectiveness of intrapleural enzymatic therapy. Please, ameliorate the legend of this table.

6) 4. Prognosis 296 Among patients with pneumonia, the presence of parapneumonic effusions alone in- 297 creases the risk of 30-day mortality by 2-fold and are associated with a longer duration of 298 hospitalization. I suggest to include at the end of the paragraph a brief conclusions to summarise the novelty of the study and the possible clinical implications.

Minor changes of English language are required

Author Response

See attached word document for author's reply to the reviewer. 

Author Response File: Author Response.pdf

Reviewer 3 Report

I read this review with great interest. It is comprehensive and well-written.

The main question addressed by the research is how to effectively manage pleural infections, including empyema, to reduce morbidity by understanding the pathobiology and medical management and minimizing the need for surgical interventions.

The paper is particularly original and relevant. It fills the gap in understanding the optimal approach to managing pleural infections by integrating historical knowledge with recent clinical trials, especially regarding the use of intrapleural fibrinolytic therapy.

Compared to other published materials, this paper provides a comprehensive review of the literature from past decades to the most recent clinical trials, offering evidence-based recommendations for management.

The conclusions drawn from the review of literature appear consistent with the evidence presented. The references appear appropriate and comprehensive, covering a broad spectrum of studies and historical perspectives on the management of pleural infections.

The tables and figures provided are well-integrated into the discussion. I would only suggest to add a figure which summarizes the whole article "at a glance", like a graphical abstract. 

Author Response

See attached word document for author's reply to the reviewer. 

Author Response File: Author Response.pdf

Reviewer 4 Report

This is the comprehensive review paper concerning pleural infectious diseases including empyema.

The authors have discussed the pathophysiology and microbiology of pleural infections and how this relates to their diagnosis and management.

The management of pleural infection involves antibiotic therapy, chest drain insertion, intrapleural fibrinolytic therapy and surgery. Antibiotic therapy relies on empirical broad-spectrum antibiotics based on local policies, infection setting and resistance patterns.

However, the diagnostic development using thoracic ultrasound technique and pleural fluid biochemistry should be further discussed in the text,

Author Response

See attached word document for author's reply to the reviewer. 

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Dear Authors,

Thank you for the revision. I have several further questions:

1) If this review focuses on intrapleural enzymatic therapy, please mention so in the title section

2) The references suddenly ballooned up to more than 100. Is this number justified? If this is largely focused on intrapleural enzymatic therapy, it may be justified since the authors need to focus on IET. If not, I do not support the use of more than 100 references in this manuscript.

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Author Response

Reviewer one thank you for reviewing the revised manuscript. 

Comment 1:  If this review focuses on intrapleural enzymatic therapy, please mention so in the title section.

Response: We feel the intrapleural enzymatic therapy is a key component in the management of pleural infections. Our review intends to summarize the fibrinolytic data for context. However the review covers a wider scope than just enzymatic therapy and therefore we omitted naming that narrow focus in the title.

Comment 2: The references suddenly ballooned up to more than 100. Is this number justified? If this is largely focused on intrapleural enzymatic therapy, it may be justified since the authors need to focus on IET. If not, I do not support the use of more than 100 references in this manuscript

Response: The reference number has not changed. The other manuscript versions that have been submitted all have 101 references.  The authors do not see the relevance to arbitrarily removing one reference to make it an even 100 references.

Reviewer 2 Report

The manuscript has been improved. No further comments.

Minor changes of English language are required

Author Response

Thank you for your time and suggestions for the manuscript. 

Round 3

Reviewer 1 Report

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Author Response

Reviewer 1 Comments: [Blank]

Reply: We have made additional edits to the title and text based on prior reviewer 1 comments. There are now 100 references.