<xhtml:span xmlns:xhtml="http://www.w3.org/1999/xhtml" xml:lang="en">FEBRILE SEPSIS:  FIRST REPORT OF HUMAN DISEASE DUE TO <em>PAENIBACILLUS SILVAE</em> </xhtml:span>
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ABSTRACT Introduction. Paenibacillus species are saprophytes widely distributed in nature and rarely associated with overt human infection. Most of cases have been described in people with important comorbidities and/or immunodepression. We report here what is, to the best of our knowledge, the first documented case of human disease due to P. silvae, so far considered an exclusively environmental micro-organism. Case presentation. A 57-year-old female patient was referred to our Unit after a 2-month history of remittent fever. Upon admission, septic state and bacteraemia was revealed; P. sylvae was speciated by 16S-rRNA gene amplification and sequencing MALDI-TOF. The patient became afebrile after 9 days of antibiotic treatment and was completely cured after a 2-week regimen with I.V. amoxicillin-clavulanate plus oral doxycycline. Conclusion. The patient did not report any episode of infection occurred previously. Most of the well-known risk factors to Paenibacillus bacteraemia, i.e., invasive procedures, use of intravenous drugs, and foreign bodies could be revealed, although her immune system was probably impaired due to obesity and heavy smoking. We suggest that the isolation of bacteria belonging to the Paenibacillus genus should not be disregarded, since there is accumulating evidence that these organisms may cause disease even in immunocompetent subjects.
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This study would be a valuable contribution to the existing literature. The reviewers have highlighted minor concerns with the work presented. Please ensure that you address their comments.
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Comments to Author
1. Description of the case(s) Thank you for your report of the first case of P. silvae infection. I found the description of the case clear and concise, however would like to ask for some further detail or clarification on a few points: i) I don't know when it was updated but the bacterio.net link from line 54 currently shows 292 child taxa with valid published names. ii) On lines 91-92 a 2-month history of fever is reported. Are there further details regarding the nature of the fevers, e.g. times between peaks, periods without pyrexia etc.? (I note that you have said the fever settled after the courses of antibiotics.) iii) On line 93 you describe 'two weekly antibiotic courses' - does this mean two courses of one week duration (one of amoxicillin and one of levofloxacin), or was she receiving two …
Comments to Author
1. Description of the case(s) Thank you for your report of the first case of P. silvae infection. I found the description of the case clear and concise, however would like to ask for some further detail or clarification on a few points: i) I don't know when it was updated but the bacterio.net link from line 54 currently shows 292 child taxa with valid published names. ii) On lines 91-92 a 2-month history of fever is reported. Are there further details regarding the nature of the fevers, e.g. times between peaks, periods without pyrexia etc.? (I note that you have said the fever settled after the courses of antibiotics.) iii) On line 93 you describe 'two weekly antibiotic courses' - does this mean two courses of one week duration (one of amoxicillin and one of levofloxacin), or was she receiving two week courses of antibiotics during the two month period? What period was there between the antibiotic courses? How long did it take for her pyrexia to reoccur after completing the antibiotic courses? iv) On lines 98-100 her admission blood results are reported. Were there any earlier results from the community (e.g. had her WBC or CRP been elevated before her initial antibiotic treatments?)? Are there additional results during treatment to show for example how long it took the procalcitonin to return to normal? v) Line 112 tells us the results from the MALDI-TOF. Was the test performed once only or were there other potential identifications from other attempts which might therefore show the possible mis-identifications in the laboratory? vi) The susceptibilities are reported on lines 112-114. What susceptibility method was used? (EUCAST does not have a specific Paenibacillus interpretation, and not all the agents listed have Bacillus or PK/PD breakpoints in the current version. Not all the agents reported are in CLSI M45 v3 for Bacillus and related genera.) 2. Presentation of results I thought the report was well presented, clear and easy to follow. 3. How the style and organization of the paper communicates and represents key findings I thought the case description presented the chronology and results well. 4. Literature analysis or discussion The literature review and discussion appear to be thorough and have briefly covered the clinical presentations of known Paenibacillus infections. 5. Any other relevant comments Lines 174-176 ask about consent for publication. The authors have not stated that the patient has consented to the case report.
Please rate the quality of the presentation and structure of the manuscript
Good
To what extent are the conclusions supported by the data?
Strongly support
Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?
No
Is there a potential financial or other conflict of interest between yourself and the author(s)?
No
If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?
Yes
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Comments to Author
This manuscript presents a case report of a novel human pathogen in a purportedly immunocompetent host, along with a topical review of human infections by this genus. It is well-written, methodologically sound, and offers an important contribution to the literature. COMMENTS AND SUGGESTIONS (by line number) 31 Consider including the method of identification (i.e. 16S rRNA) in the ABSTRACT 53 Consider citing URLs as websites in the bibliography rather than including them in the text. 59 For clarification, consider rephrasing as "… with overt human infection. Those so associated are more frequently isolated from elderly patients whose immune systems are generally weak, or are considered to be culture contaminants." 74 Cf. comment on 53 86 Although the authors include "immunocompetent" in the TITLE …
Comments to Author
This manuscript presents a case report of a novel human pathogen in a purportedly immunocompetent host, along with a topical review of human infections by this genus. It is well-written, methodologically sound, and offers an important contribution to the literature. COMMENTS AND SUGGESTIONS (by line number) 31 Consider including the method of identification (i.e. 16S rRNA) in the ABSTRACT 53 Consider citing URLs as websites in the bibliography rather than including them in the text. 59 For clarification, consider rephrasing as "… with overt human infection. Those so associated are more frequently isolated from elderly patients whose immune systems are generally weak, or are considered to be culture contaminants." 74 Cf. comment on 53 86 Although the authors include "immunocompetent" in the TITLE and elsewhere throughout the manuscript, they make a strong case that the patient does NOT have an intact immune system. A 120 pack/year smoking history alters the immune system (Qiu F, Liang CL, Liu H, Zeng YQ, Hou S, Huang S, Lai X, Dai Z. Impacts of cigarette smoking on immune responsiveness: Up and down or upside down? Oncotarget. 2017 Jan 3;8(1):268-284. doi: 10.18632/oncotarget.13613. PMID: 27902485; PMCID: PMC5352117.) as does morbid obesity (de Heredia FP, Gómez-Martínez S, Marcos A. Obesity, inflammation and the immune system. Proc Nutr Soc. 2012 May;71(2):332-8. doi: 10.1017/S0029665112000092. Epub 2012 Mar 20. PMID: 22429824.) and probably the patient's evident poor oral hygiene (Taubman MA, Han X, Larosa KB, Socransky SS, Smith DJ. Periodontal bacterial DNA suppresses the immune response to mutans streptococcal glucosyltransferase. Infect Immun. 2007 Aug;75(8):4088-96. doi: 10.1128/IAI.00623-07. Epub 2007 May 21. PMID: 17517867; PMCID: PMC1952018.). The manuscript, including TITLE and ABSTRACT, should be revised to point out that this patient, like other human cases of Paenibacillus spp. infection, occurred in a patient with an IMPAIRED immune system. 90 "Frequent exposure to soil" sounds very odd, and not out of the ordinary experience of most human beings. Either delete this phrase or explain how it is unique. 106 Excellent and appropriate use of identification techniques! 121 PET-CT and colonoscopy are not typical components of bacteremia workup in many countries, especially in patients responding to antibiotic therapy. Please expand to explain if this is the standard of care in Italy or what the extenuating circumstances where that prompted this extensive (and expensive) work-up. 152 Please provide a citation for sentence (or is it references 26-27? It isn't clear if those citations refer to this sentence as well as the preceding one). 161 This is an important point; in many places 16S rRNA and MOLDI-TOF is not routinely employed in the clinical setting. Consider offering some guidance on when the more accurate methods should be requested by the clinician. REFERENCES This section needs to be carefully reviewed and edited; it appears some artifacts may have been introduced by the bibliographic software. A couple of examples (not comprehensive) include citation 6 which has no journal title and citation 16 which doesn't follow the title abbreviation format used elsewhere in the section.
Please rate the quality of the presentation and structure of the manuscript
Good
To what extent are the conclusions supported by the data?
Strongly support
Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?
No
Is there a potential financial or other conflict of interest between yourself and the author(s)?
No
If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?
Yes
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