Prosthetic valve endocarditis due to Candida parapsilosis – a rare case report
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Fungal endocarditis is a rare and fatal condition , most frequently caused by species of the genera Candida and Aspergillus . Fever and changing heart murmur are the most common clinical manifestations. The diagnosis of fungal endocarditis is challenging, with prosthetic valve endocarditis being extremely difficult to diagnose. The optimal management of the condition still remains debatable. We present a case of prosthetic valve endocarditis caused by Candida parapsilosis , managed empirically with liposomal amphotericin B, which was later shifted to combination therapy with high-dose echinocandin and fluconazole, but had a fatal outcome because the patient could not undergo timely surgical intervention. Treating C. parapsilosis endocarditis cases is difficult because of their biofilm production on native and prosthetic heart valves. A combined approach consisting of a high index of clinical suspicion, early diagnosis using serological markers followed by culture or PCR and prompt initiation of appropriate antifungals may aid in improving outcomes.
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The reviewers have highlighted major 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) 69 Rest of the systemic examinations were 70 normal. Comment: Should read "Other systemic examinations were normal." 75 showed Haemoglobin of 9.0 gm/dL, total leucocyte count of 4390/mm3 with 69% neutrophil, Comment: Should read haemoglobin (small "h") 2. Presentation of results None 3. How the style and organization of the paper communicates and represents key findings None 4. Literature analysis or discussion 188 Despite of the use of a combination of medical and 189 surgical therapy, the mortality rate of C. parapsilosis endocarditis remains as high as 40%. Comment: Should read "Despite the use of medical and surgical combination therapy, the mortality rate of C. parapsilosis endocarditis remains as high as 40%." However despite of the combined medical and …
Comments to Author
1. Description of the case(s) 69 Rest of the systemic examinations were 70 normal. Comment: Should read "Other systemic examinations were normal." 75 showed Haemoglobin of 9.0 gm/dL, total leucocyte count of 4390/mm3 with 69% neutrophil, Comment: Should read haemoglobin (small "h") 2. Presentation of results None 3. How the style and organization of the paper communicates and represents key findings None 4. Literature analysis or discussion 188 Despite of the use of a combination of medical and 189 surgical therapy, the mortality rate of C. parapsilosis endocarditis remains as high as 40%. Comment: Should read "Despite the use of medical and surgical combination therapy, the mortality rate of C. parapsilosis endocarditis remains as high as 40%." However despite of the combined medical and surgical 199 approach, the mortality due to Candida endocarditis still remains high, which emphasizes the 200 need of combined approach of high index of clinical suspicion, early diagnosis by serological 201 markers like BDG followed by culture or PCR and prompt initiation of appropriate 202 antifungals to improve the outcome. Comment: This sentence is too complex and will need to be broken into 2 different sentences. For example, "However, despite the use of combined medical and surgical approach, the mortality due to Candida endocarditis still remains high. This emphasizes the need for combined approach using high index of clinical suspicion, early diagnosis by serological markers like BDG, followed by culture or PCR and prompt initiation of appropriate antifungals to improve the outcome." 5. Any other relevant comments None
Please rate the quality of the presentation and structure of the manuscript
Very 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
1. Description of the case(s): the description gives a clear picture of the case and its progress. in L57: complains of fever and weight loss over past five months. With similar complains, he was to be corrected as : complaints of fever & weight loss over past five months. With similar complaints, he was 2. Presentation of results : The results are presented well. 3. How the style and organization of the paper communicates and represents key findings, the style & organization of paper communicates about the key findings, 4. Literature analysis or discussion: literature has been analysed well. L185-L186: the patient passed away before he could undergo valve L 186 replacement due to cardiac failure. The sentence should be rephrased as , "the patient passed away due to cardiac failure before he …
Comments to Author
1. Description of the case(s): the description gives a clear picture of the case and its progress. in L57: complains of fever and weight loss over past five months. With similar complains, he was to be corrected as : complaints of fever & weight loss over past five months. With similar complaints, he was 2. Presentation of results : The results are presented well. 3. How the style and organization of the paper communicates and represents key findings, the style & organization of paper communicates about the key findings, 4. Literature analysis or discussion: literature has been analysed well. L185-L186: the patient passed away before he could undergo valve L 186 replacement due to cardiac failure. The sentence should be rephrased as , "the patient passed away due to cardiac failure before he could undergo valve replacement. " 5. Any other relevant comments: nil
Please rate the quality of the presentation and structure of the manuscript
Very 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
Thank you for adapting the manuscript in line with the previous review comments. I am happy with the manuscript to recommend for publication
Please rate the quality of the presentation and structure of the manuscript
Very 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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The reviewers have highlighted major concerns with the work presented. Please ensure that you address their comments.
-
Comments to Author
1. Description of the case(s) The article is well written and of an appropriate length, however I have noted the following corrections and input. 84 After this, ceftriaxone, vancomycin and amphotericin B were stopped and high dose caspofungin 85 (150 mg i.v. OD) and fluconazole (400 mg i.v. OD) were added to the treatment regimen. Correction/input: Having stopped the ongoing antimicrobial regimen, the statement should state that the new regime was started or commenced but not added since we're not informed of other non-antimicrobial treatment. 94 CECT brain angiography was also performed which showed multiple right frontal, occipital-temporal gyrus and right cerebellar sub-acute embolic 95 infarcts. Correction/input: Is there any effect of the multiple infarcts found in the brain, since the lower …
Comments to Author
1. Description of the case(s) The article is well written and of an appropriate length, however I have noted the following corrections and input. 84 After this, ceftriaxone, vancomycin and amphotericin B were stopped and high dose caspofungin 85 (150 mg i.v. OD) and fluconazole (400 mg i.v. OD) were added to the treatment regimen. Correction/input: Having stopped the ongoing antimicrobial regimen, the statement should state that the new regime was started or commenced but not added since we're not informed of other non-antimicrobial treatment. 94 CECT brain angiography was also performed which showed multiple right frontal, occipital-temporal gyrus and right cerebellar sub-acute embolic 95 infarcts. Correction/input: Is there any effect of the multiple infarcts found in the brain, since the lower limb pain can be justifiably attributed to the embolic found by Doppler scan of the lower limb. 104 But unfortunately, the patient expired before the prosthetic valve replacement and vegetation removal could be performed. Correction/input: I suppose that the word "expired" meant that the patient had died. I do not know if this is an acceptable formal way to describe the situation. 117 Candida PVE (prosthetic valve endocarditis) is more commonly left-sided and occurs most of the times at the aortic valve and is often missed by TTE (Trans-thoracic ECHO). Correction/input: Is there any reason why TTE (Trans-thoracic ECHO) is unable to regularly visualize left-sided vegetation? Reasons such as anatomical locations and relation. 125 reported to occur within one year of surgery. However, our patient gave a negative history of 126 any previous episodes of candidemia. Correction/input: Should read, there were no previous history of symptoms necessitating hospitalization and possible isolation of candida. 156 Even though lifelong fluconazole therapy has shown survival benefits in the patients with Candida PVE who are unfit for surgery 157 , our patient expired before he could undergo valve replacement 158 due to pulmonary embolism. Correction/input: I do not think using the word "expired" to describe the passing of away of a patient is respectful and empathic. 2. Presentation of results The findings are significant and represent an advance in knowledge and understanding? The results and conclusions are adequate and well discussed in relation to published literature. 3. How the style and organization of the paper communicates and represents key findings The article is well written and of an appropriate length, however I have noted the above corrections and input. 4. Literature analysis or discussion This is adequate. 5. Any other relevant comments None
Please rate the quality of the presentation and structure of the manuscript
Very 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
-
Comments to Author
1. Description of the case(s) - History of severe Mitral stenosis ( line 54-55), operated for mitral valve regurgitation (line 56), No mention of history or status of diabetes, cancer or any other condition, causing immunocompromised state- HIV, Cancer etc. History and examination findings to rule out any respiratory disease is not mentioned. Investigations mentioned does not comment on other investigations viz. Blood sugar, Hba1c, DLC, chest xray, and other tests for work up of case of fever with weight loss over 5 months., and their findings. Treatment history over last 5 months is also not mentioned to establish/rule out Antibiotic pressure. Follow up investigations done during the hospital stay are not mentioned in the description to establish persistent thrombocytopenia, Liver enzymes. …
Comments to Author
1. Description of the case(s) - History of severe Mitral stenosis ( line 54-55), operated for mitral valve regurgitation (line 56), No mention of history or status of diabetes, cancer or any other condition, causing immunocompromised state- HIV, Cancer etc. History and examination findings to rule out any respiratory disease is not mentioned. Investigations mentioned does not comment on other investigations viz. Blood sugar, Hba1c, DLC, chest xray, and other tests for work up of case of fever with weight loss over 5 months., and their findings. Treatment history over last 5 months is also not mentioned to establish/rule out Antibiotic pressure. Follow up investigations done during the hospital stay are not mentioned in the description to establish persistent thrombocytopenia, Liver enzymes. Indication for Brain angiography not mentioned. Doppler study of other areas abdomen, chest is not mentioned after VTE event Management of VTE viz Anticoagulant given for prevention of thromboembolic events after diagnosis of Fungal endocarditis is not mentioned. 2. Presentation of results : Other Relevant history, examination, investigations and their results are not mentioned as described above. 3. How the style and organization of the paper communicates and represents key findings description of the case: the paper communicates about the key findings, however other relevant information to be included as mentioned before. 4. Literature analysis or discussion: literature has been analysed well. Discussion to include other relevant information of this case with respect to the literature. Death due to pulmonary embolism is mentioned in discussion but no mention in the description of the case. 5. Any other relevant comments: conclusion does not mention/comment about surgical management Serological marker 1, 3 beta d glucan is discussed based on literature but whether done in this case is not mentioned.
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?
No: Fungal endocarditis cases are prone for thromboembolic episodes as per the literature and discussion. However as per the description of the case, there is no mention of prevention or management of VTE events , other investigations, doppler studies of other areas including chest. Post discharge Follow up details not mentioned. Review after fortnight is a long gap for follow up esp. when the mortality in such cases is high and early surgical procedure was to be planned.
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Comments to Author
1. Description of the case(s) Clear and detailed 2. Presentation of results Use of normal ranges would be beneficial for non-clinical reading audience. 3. How the style and organization of the paper communicates and represents key findings Key findings are relatively clear, 4. Literature analysis or discussion Discussion links well with previous research and cases, and highlights the importance or invasive fungal infections, particularly re: cardiac infection 5. Any other relevant comments L103/104: Patient expiration information would be useful here - is it due to the fungal infection or other factors? Particularly as patient was discharged. I see this now in line 158 - pelase add into the above section. Minor comments L35: rephrase to 'species of the genera Candida and Aspergillus' L39: …
Comments to Author
1. Description of the case(s) Clear and detailed 2. Presentation of results Use of normal ranges would be beneficial for non-clinical reading audience. 3. How the style and organization of the paper communicates and represents key findings Key findings are relatively clear, 4. Literature analysis or discussion Discussion links well with previous research and cases, and highlights the importance or invasive fungal infections, particularly re: cardiac infection 5. Any other relevant comments L103/104: Patient expiration information would be useful here - is it due to the fungal infection or other factors? Particularly as patient was discharged. I see this now in line 158 - pelase add into the above section. Minor comments L35: rephrase to 'species of the genera Candida and Aspergillus' L39: English language review of this sentence L54: Not sure of the significance of 'businessman' in this sentence. Specify gender. L54/55: 'severe mitral stenosis ten years prior'
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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