Bloodstream infections in cancer patients in central India: pathogens and trends of antimicrobial resistance over a 5-year period

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Abstract

Introduction. Bloodstream infection (BSI) is a common complication with a high fatality rate in cancer patients. There are notable variations in the epidemiology of BSI over time and among different countries. Infections due to multidrug-resistant organisms (MDROs) such as extended-spectrum beta-lactamases (ESBLs) and carbapenem-resistant Enterobacteriaceae (CRE) are increasing. This may lead to inadequate empirical antibiotic therapy, increasing the antimicrobial resistance (AMR) problem and unfavourable outcomes in these immunocompromised patients. There is paucity of data pertaining to AMR in such vulnerable patients from developing countries such as India. The aim of this study was to investigate the distribution of the bacterial pathogens causing BSI and the AMR trend in cancer patients in central India.

Methodology. This single-centre retrospective observational study was conducted in a tertiary care cancer hospital. Patients with solid organ and haematological malignancies, both adults and paediatric, who had blood cultures sent to the microbiology laboratory from January 2018 to December 2022 were included. Blood cultures were processed using the BacT/ALERT 3D system (bioMérieux, France), and the identification of the bacteria and their antimicrobial susceptibility (AST) was performed using the Vitek 2 compact system (bioMérieux, France). Electronic medical records and microbiology lab records were used to retrieve the demographic and microbiological data. Microsoft Excel (RRID:SCR_016137) was used to enter and tabulate the data. Statistical analysis was performed using SPSS version 29 (RRID:SCR_002865).

Results. A total of 687 isolates from 524 patients were studied. Gram-negative bacteria (64%) were the commonest cause of BSI in the studied patients, followed by Gram-positive cocci (25%) and fungal isolates (9%). Ten cases were polymicrobial. Escherichia coli ( n =140) was the most common among the isolated pathogens, followed by Klebsiella species ( n =103), Pseudomonas species ( n =102), and coagulase-negative staphylococci (CONS) ( n =92). Among the 140 isolates of E. coli , 66% were extended-spectrum β-lactamase (ESBL) producers and 26% were resistant to carbapenem. Among the 103 isolated Klebsiella species, 50% were carbapenem resistant and 36% were ESBL producers. Among enterobacterales, the CRE rate was 34%. Carbapenem resistance was seen in 25% of Pseudomonas species and 53% of Acinetobacter species isolates. Klebsiella species were the most resistant pathogens isolated. CONS comprised 56% of all Gram-positive isolates, followed by Staphylococcus aureus (36%), enterococci species (11%), and streptococci species (3%). Methicillin resistance was 60% in CONS and 64% in S. aureus . One vancomycin-resistant enterococcus was isolated. Non- albicans Candida was the most common fungal pathogen. The sensitivity to fluconazole was 84% in non- albicans Candida species, while only one isolate of Candida albicans was resistant to fluconazole. The trend of pathogens was insignificant over 5 years, with Gram-negative bacteria being the commonest. Further, there was no significant change in the trend of ESBL and CRE resistance pattern over 5 years.

Conclusion. Gram-negative bacteria were the most common isolated pathogens from BSI with a higher antimicrobial resistance rate in cancer patients. The CRE rate of 34% is alarming, limiting the choices for empirical antibiotic therapy.

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  1. Many thanks for your contribution, and sincerest apologies for the delay with this decision. There are a very few grammatical and spellings oversights, but these should be polished through the Publication process on our end. You have collected a vast quantity of valuable surveillance information; and we look forward to further future submissions.

  2. Please rate the manuscript for methodological rigour

    Good

    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

  3. Comments to Author

    I would like to congratulate the authors on the amount of work they have put into generating this manuscript. However, there are some minor corrections that should be implemented. Abstract: the aim should be removed and written at the end of the introduction section in sentence case. Line 38: Klebsiella species isolated is said to be n=103 while in line 40, it is said to be n=130. This is also repeated in line 166. Line 80: 'toa' should be written as 'to a'. Method: Microbiological Processing (line 130)- what antibiotics susceptibility testing method was used? It should be stated. The antibiotics tested for can be represented in a table indicating their mode of action, antibiotic class and name (including the strength of the antibiotic discs, if this is what used). Also, the data collected about the patients, how were they recorded and stored for easy tracking? Definitions can be removed from the Method section. Result: Line 174- what agar was used to isolate the fungal species and how were they identified to species level. Table 1: 'N' and '%' written as the title of the second and third columns respectively should be written in words with the symbols 'N' and '%' written in brackets. Border lines and colours should be removed from all tables. Discussion: Line 246- the name of the developing country should be stated. Line 253-254: the first sentence should be rewritten. Reference list and citations should be written in Vancouver style.

    Please rate the manuscript for methodological rigour

    Good

    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

  4. Many thanks for your re-submission and for addressing previous concerns. I do think your study is of value as understanding antimicrobial resistance trends in vulnerable patient groups is so important in informing local policy and antimicrobial guidelines. However, while I appreciate you expanding your manuscript, I do believe that a fair bit of the information is repetitive and adds nothing more to your interesting work. Please summarise and proof-read thoroughly. There are a few grammatical errors throughout, spelling mistakes and please be careful about abbreviations. Your Results could be better developed. You have collected quite important data but it is lost in the current presentation. The text is not the easiest to follow and the figures are not the clearest. While line graphs are the best for displaying trends, because you report so many antimicrobials it is difficult to really get a sense of what we are seeing. Perhaps you can be more selective in which antimicrobials you want to report; which antimicrobials are actually of value clinically to report? You should also be more selective on which figures you want to use and which would be most impactful. Currently, I think you can revise a few. Putting a tabe and a graph to show the same data is unnecessary. Additionally, fungal infections were mentioned but no further details on those were provided; and it is stated that Spearman's Correlation was done to compare resistance trends but I cannot seem to find that result. Moreover, your Abstract needs to be significantly improved as this is what Reviewers would read prior to deciding on whether they want to review your manuscript. Consider doing a structured abstract because as it stands, no results or conclusions were included. You are presenting a study on tends of pathogens and antimicrobial resistance among a cohort of patients yet none of this data is reflected in your abstract. Please amend and consider re-submission once rectified.

  5. There is no clear hypothesis for this study. There is no clear reason for this study. The language used is poor, which can cause ambiguity at times. Please carefully rewrite it. We offer a discounted translation service, Editage (https://www.editage.com/; see https://www.microbiologyresearch.org/prepare-an-article#13 for more information). Please provide more detail in the Methods section and ensure that software is consistently cited and its version and parameters included. The paper is poorly structured and written, which has prevented a proper assessment of the research done.