Clinical predictors of mortality in patients with pseudomonas aeruginosa infection

Jim Abi Frem; George Doumat; Jamil Kazma; Amal Gharamti; Souha S. Kanj; Antoine G. Abou Fayad; Ghassan M. Matar; Zeina A. Kanafani

doi:10.1371/journal.pone.0282276

Peer Review History

Original SubmissionDecember 7, 2022
2 Jan 2023 Decision Letter - Benjamin M. Liu, Editor PONE-D-22-33603CLINICAL PREDICTORS OF MORTALITY IN PATIENTS WITH PSEUDOMONAS AERUGINOSA INFECTIONPLOS ONE Dear Dr. Kanafani, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by Jan 31 2023. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. 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Please ensure that you have an ORCID iD and that it is validated in Editorial Manager. To do this, go to ‘Update my Information’ (in the upper left-hand corner of the main menu), and click on the Fetch/Validate link next to the ORCID field. This will take you to the ORCID site and allow you to create a new iD or authenticate a pre-existing iD in Editorial Manager. Please see the following video for instructions on linking an ORCID iD to your Editorial Manager account: https://www.youtube.com/watch?v=_xcclfuvtxQ Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ****** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: The overall manuscript is very well written, detailed and well explained. The data is presented well, the literature review is lucid, and the figures are very clear. However, I would like to recommend minor revisions for the manuscript. 1. Abstract --" Pseudomonas aeroginosa" should be in italics. 2. Introduction --" Intra-abdominal" should be hyphenated. 3. Materials and Methods -- Please remove the term " Definitions". Also P. aeroginosa should be in italics. Reviewer #2: Pseudomonas aeruginosa is a relevant microorganism associated with severe infections, mostly in hospitalized persons. The manuscript is about predictors of mortality in patients with P aeruginosa infections in Lebanon. The study has an understandable designed but I miss information concerning methodology and data The study was a cross-sectional one, involving 196 patients from 2017 to 2020 with positive cultures for P aeruginosa who developed an infection. I wonder how infections were diagnosed as the differential diagnosis between infection and colonization is not always easy. And how many patients with a first colonization became infected? The authors enroled in the same study patients in hospitalization (50%), outpatients (25%) and health care associated (25%) patients. In the later group, the infection was treated where? I wonder if this heterogeneity of the group cannot give be responsible for differences from other studies in the literature, concerning for instance prevalence of MDR isolates I would like to have more information about the type of clinical infection, as this is a clinical study. What about the health-care infections for instance? In 24% of cases P aeruginosa was not isolated from the blood, respiratory specimes or urine. From where the strains were isolated? At what kind of infections were they associated? ICU acquired infections were more severe than the others? And how many patients were in the need of IcU admission? What were the criteria for a dual antipseudomonal therapy? Finally some remarks a) Abstract “Pseudomonas aeruginosa (PSA) is difficult to treat microorganism..”- in spite of “the infection caused by PSA is difficult to treat..” b) Page 16 - “Similar findings were reported in.” need to be finished the sentence ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No Reviewer #2: No ******** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". 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Revision 1
11 Jan 2023 Author Response Response to Reviewers Reviewer #1: The overall manuscript is very well written, detailed and well explained. The data is presented well, the literature review is lucid, and the figures are very clear. However, I would like to recommend minor revisions for the manuscript. 1. Abstract --" Pseudomonas aeruginosa" should be in italics. 2. Introduction --" Intra-abdominal" should be hyphenated. 3. Materials and Methods -- Please remove the term " Definitions". Also P. aeruginosa should be in italics. Thank you for your comments. We have made all the proposed edits. Reviewer #2: Pseudomonas aeruginosa is a relevant microorganism associated with severe infections, mostly in hospitalized persons. The manuscript is about predictors of mortality in patients with P aeruginosa infections in Lebanon. The study has an understandable design but I miss information concerning methodology and data The study was a cross-sectional one, involving 196 patients from 2017 to 2020 with positive cultures for P aeruginosa who developed an infection. I wonder how infections were diagnosed as the differential diagnosis between infection and colonization is not always easy. And how many patients with a first colonization became infected? Thank you for pointing this out. There was an official Infectious Diseases consultation on all patients. We relied on the assessment of the ID consult service in determining infection vs. colonization. In general, patients were considered infected if they displayed typical infection symptoms, such as fever, and symptoms related to the infection site. In case of any uncertainty, another study researcher would have reassessed the eligibility of the patient. Unfortunately, we did not collect information about colonization status prior to the index infection. Hence, we cannot tell how many colonized patients later became infected. The authors enrolled in the same study patients in hospitalization (50%), outpatients (25%) and health care associated (25%) patients. In the later group, the infection was treated where? I wonder if this heterogeneity of the group cannot give be responsible for differences from other studies in the literature, concerning for instance prevalence of MDR isolates Thank you for your response. To clarify, our patient population consisted only of hospitalized patients. However, we classified these hospitalized based on where the infection was acquired (community-acquired, hospital-acquired, or healthcare-associated). We have clarified this in the Methods section. I would like to have more information about the type of clinical infection, as this is a clinical study. What about the health-care infections for instance? The sites of clinical infection are mentioned in the Results section (48% respiratory, 20.3% urine, 7.7% blood, 24% other). In healthcare-associated infections, 10 were from urine, 23 from respiratory specimens, 3 from blood, and 12 from other sources. We did not find any statistical difference in the distribution of sites of infection by place of acquisition (hospital, healthcare, or community). We have added this information to the text. In 24% of cases P aeruginosa was not isolated from the blood, respiratory specimens or urine. From where the strains were isolated? At what kind of infections were they associated? Various other sites of infection included wounds, abdominal fluid, CSF, skin abscess. This was added to the Results. ICU acquired infections were more severe than the others? And how many patients were in the need of ICU admission? On bivariable analysis (Table 4), we found that ICU admission was associated with higher mortality. However, this relationship was no longer significant when we adjusted for coufounders as evidenced by the regression analysis. We have added this information to the text. A total of 53/196 (27%) patients required ICU admission, which is mentioned in the complications paragraph. What were the criteria for a dual antipseudomonal therapy? Thank you for your comment. Since this is a retrospective study, the decision on treatment resided solely with the treating physician. Based on our hospital care practices, however, patients are generally treated with dual anti-pseudomonal therapy if the organism in multidrug-resistant, and in the setting of severe sepsis, neutropenia with bacteremia, and severe pneumonia in ICU. Finally some remarks a) Abstract “Pseudomonas aeruginosa (PSA) is difficult to treat microorganism..”- in spite of “the infection caused by PSA is difficult to treat..” Thank you. We modified it. b) Page 16 - “Similar findings were reported in.” need to be finished the sentence Thank you. We removed the sentence because it’s a duplicate. Attachments Attachment Submitted filename: Comments to the Author.docx https://doi.org/10.1371/journal.pone.0282276.r002
23 Jan 2023 Decision Letter - Benjamin M. Liu, Editor PONE-D-22-33603R1CLINICAL PREDICTORS OF MORTALITY IN PATIENTS WITH PSEUDOMONAS AERUGINOSA INFECTIONPLOS ONE Dear Dr. Kanafani, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by Feb 22 2023. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. 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The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: (No Response) Reviewer #2: Methods Please explain "healthcare-associated" infections in the text as hospital adquired infections are also health care associated - you did it out of the paper, please see answers to reviers Please note that the place of isolation is not the same of type of infection - we may have a pielonephritis or a simple ITU from a positive urine culture, this should be clear, in all the results I wonder from the 24 samples out of the most common places of isolation how may cases from cerebrospinal samples were positive, and what was the course of the disease - this is a quite rare situation would be important to detail Please answer the question about infections acquired in ICU - were they different? Please correct in line 79 -cut "Written consents taken" line 149 ("in" in spite of "is") and 164 (confounders "4") ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No Reviewer #2: No ******** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0282276.r003
Revision 2
8 Feb 2023 Author Response Reviewer #2: Please explain "healthcare-associated" infections in the text as hospital acquired infections are also health care associated - you did it out of the paper, please see answers to reviewers. Thank you for pointing this out. We added the following definitions: Infections were considered community-acquired if they manifested outside the hospital or were diagnosed within 48 hours of admission without any healthcare encounter in the past 30 days. Hospital-acquired infection was defined as an infection that manifested 48 hours or more after hospital admission or within 7 days of discharge. Healthcare-associated infection was defined as an infection occurring in patients receiving home and/or ambulatory intravenous therapy, chemotherapy, hemodialysis, wound care, specialized nursing care, or who had attended a hospital clinic within the last 30 days; patients hospitalized in an acute care hospital for ≥ 2 days within the last 90 days; and those residing in a nursing home or long-term care facility. 2.Please note that the place of isolation is not the same of type of infection - we may have a pyelonephritis or a simple ITU from a positive urine culture, this should be clear, in all the results Thank you, we replaced the “site of infection” phrase with “type of infection” throughout the text. 3.I wonder from the 24 samples out of the most common places of isolation how many cases from cerebrospinal samples were positive, and what was the course of the disease - this is a quite rare situation would be important to detail. Thank you for your comment. We had one CSF sample from a lymphoma patient who had a good outcome. We will be happy to add more details to the text if so required. 4.Please answer the question about infections acquired in ICU - were they different? ICU acquired infections were more severe than the others? And how many patients were in the need of ICU admission? Thank you for your comments. On bivariable analysis, we found that ICU admission was associated with a worse outcome (mortality). However, this relationship was no longer significant when we adjusted for confounders as evidenced by the regression analysis in Table 4. A total of 53/196 (27%) patients required ICU admission. With a p-value of 0.011, ICU mortality was 17/55 (30.9%) and non-ICU mortality was 21/196 (17.5%). We have added this information to the text. Please correct in line 79 -cut "Written consents taken" done line 149 ("in" in spite of "is") ?? done and 164 (confounders "4") done Attachments Attachment Submitted filename: Response to Reviewers 2.docx https://doi.org/10.1371/journal.pone.0282276.r004
13 Feb 2023 Decision Letter - Benjamin M. Liu, Editor CLINICAL PREDICTORS OF MORTALITY IN PATIENTS WITH PSEUDOMONAS AERUGINOSA INFECTION PONE-D-22-33603R2 Dear Dr. Kanafani, We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Benjamin M. Liu, MBBS, PhD, D(ABMM), MB(ASCP) Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation. Reviewer #2: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #2: (No Response) ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #2: (No Response) ****** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #2: (No Response) ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #2: (No Response) ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #2: (No Response) ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #2: No ******** https://doi.org/10.1371/journal.pone.0282276.r005
Formally Accepted
20 Apr 2023 Acceptance Letter - Benjamin M. Liu, Editor PONE-D-22-33603R2 Clinical predictors of mortality in patients with pseudomonas aeruginosa infection Dear Dr. Kanafani: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Benjamin M. Liu Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0282276.r006

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