Subacute Bartonella Endocarditis with Glomerulonephritis: A Diagnostic and Therapeutic Challenge in Blood Culture–Negative Infective Endocarditis

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Abstract

Background: Bartonella species are increasingly recognized as a significant cause of blood culture–negative infective endocarditis (BCNIE). Their diagnosis is often challenging, leading to delays and suboptimal treatment outcomes. Case report: This report includes a concise literature review and a case involving a 77-year-old male with a history of bovine aortic valve replacement. The patient presented with lethargy, fever, unintentional weight loss, and acute kidney injury. Despite repeated blood cultures and extensive diagnostic evaluations yielding negative results, the definitive diagnosis was achieved post-surgery when valve PCR identified Bartonella species, likely linked to cat exposure. The patient was successfully treated with an extended course of doxycycline and rifampicin, leading to clinical resolution. Conclusion: This case highlights the diagnostic complexities of Bartonella endocarditis, including negative blood cultures, subacute clinical presentation and its ability to mimic autoimmune glomerulonephritis, leading to unnecessary immunosuppressive therapy. It underscores the need for improved diagnostic approaches and clinician awareness to identify at-risk populations, such as those with cat exposure or poor hygiene, ensuring the correct diagnostic investigation for an early antibiotic intervention.

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  1. Comments to Author

    When discussing the common causes of BCNIE it is worth mentioning that one of the most common causes are organisms that would have been detected in blood culture ie Staph/Strep but the patient was administered antibiotics prior to blood culture collection. Organism names should be italicized which is done very inconsistently in the current draft. Generic organism group terms like "fungi" should not be italicized. Also, organism genera should always be capitalized. It is noted in line 64 that the sensitivity of blood culture for Bartonella is "as low as 20%" - it is actually far lower than this in routine practice. The Raoult paper cited was performed at a large reference lab that specializes in atypical bacterial culture and performed methods that virtually no hospital lab would perform (cell line culture, and direct plating of blood to agar). The primary issue is that Bartonella are slow and do not generate enough CO2 in blood culture bottle media which is used in the detection and flagging of blood cultures - so if the lab is not informed of the suspicion of Bartonella then the sensitivity is essentially 0%. If special methods are available it might be as high as 20%. Hospital labs can be asked to hold blood cultures longer, and terminal subculture etc to try to detect it, but this is still slow and insensitive. Blood PCR is better, sensitivity still only about 60% but much better than culture and faster. I think the authors should clarify what was included in "broad investigations for culture-negative endocarditis (including screening for Legionella, group A Streptococcus, Aspergillus, and Coxiella)" - what tests specifically were used? It seems a bit odd not to have included Bartonella serology at least at this phase, and why single out group A Streptococcus among streptococci? The authors state that "C. burnetii is the most reported cause of culture-negative endocarditis, followed by Bartonella spp", however it should be noted that this is highly variable regionally. In some parts of the world there is more Bartonella than Coxiella. The following sentence should be re-worded "One study found that combining a positive PCR result from blood, an IFA titer ≥1:800, and a positive Western blot provided 100% sensitivity for detecting Bartonella in 102 patients, proposing these metrics as potential major criteria for diagnosing Bartonella endocarditis in blood culture-negative endocarditis (BCNE)." What do you mean combining POSITIVE results? Especially in the case of PCR if positive you don't need any of the other results. I think you mean performing all three and if any are positive considering the diagnosis confirmed, given that for each modality sensitivity is more of an issue than specificity.

    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

  2. Comments to Author

    In this article you present an interesting case of a Blood culture-negative infective endocarditis caused by Bartonella henselae and perform a thorough literature revision. I found it certainly of special interest as these cases are uncommon enough to not to suspect them initially but not rare enough to forget about them. And how important it is to perform an extensive questioning to the patient (cat ownership) in order to have a clear clinical suspicion. I have however some questions and concerns: 1) You should revise the microbial nomenclature through all the manuscript as capitalization and italization of the species names is not very correct or consistent in your manuscript (e.g line 49: "coxiella burnetii; (Q fever), ;bartonella spp., tropheryma whipplei, fungi, mycobacteria" should be like this instead: "Coxiella burnetti; (Q fever), Bartonella spp., Tropheryma whipplei , fungi and mycobacteria". Genus name should be capitalized and spp. shouldn't be italicized as common names shouldn't be either. What I mentioned is only an example in a certain line, but there are many more. 2) You speak about detection of B. henselae by PCR (abstract) and then about nanopore sequencing, I asume that what you performed was a targeted 16S rRNA PCR and then nanopore sequencing, but it would be nice to describe it better in the manuscript. 3) Bartonella serology wasn't performed to the patient?

    Please rate the quality of the presentation and structure of the manuscript

    Good

    To what extent are the conclusions supported by the data?

    Partially 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