Tossing the coin of ESBL: Prevalence of ESBL-producing Klebsiella pneumoniae isolated from patients with sepsis.

  1. Beatrice Achan
  2. Tonny Luggya
  3. Robert Innocent Ebwongu
  4. Simon Sekyanzi
  5. Henry Kajumbula

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Abstract

Background. Klebsiella pneumoniae is part of the ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp) group of MDR pathogens. It is the second leading cause of nosocomial bloodstream infections, and it has a propensity to be drug resistant. Therefore, it was aimed to determine the antibiotic resistance patterns of K. pneumoniae isolated from blood cultures of patients with features of sepsis at Mulago National Referral Hospital, Uganda. Methods The cross-sectional study on patients with features of sepsis utilised K. pneumoniae (N= 30) isolated from positive blood culture specimens. The antibiotic resistance profile was determined by the Clinical and Laboratory Standards Institute’s Kirby Bauer disk diffusion method, which was used to classify the isolates as susceptible, intermediate, and resistant. K. pneumoniae isolates that were resistant to third generation cephalosporins were subjected to extended spectrum b-lactamase (ESBL) screening and confirmation using the double-disk synergy test using cefotaxime, ceftazidime, ceftriaxone, cefotaxime-clavulanic acid, and ceftazidime-clavulanic acid. The results were analysed for frequencies. Results. K. pneumoniae isolates showed minimum resistance to imipenem 13% (4/30) followed by amikacin 17% (5/30). There was intermediate resistance to gentamycin 60% (18/30). However, K. pneumoniae showed the highest resistance to piperacillin; 100% (30/30) followed by sulphamethoxazole-trimethoprim and cefepime both showing a percentage of 97% (29/30). Up to 16/30 (53.3%) of K. pneumoniae were positive for ESBL production while 14/30 (46.7%) were negative. Conclusion. There was a high prevalence of antibiotic resistant ESBL-producing K pneumoniae isolates from bloodstream infection of patients with features of sepsis in Uganda’s Mulago National Referral Hospital.

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  1. Access Microbiology

    Thank you very much for submitting your revised manuscript to Access Microbiology and for introducing the corrections suggested by the reviewers. I am pleased to let you know that your manuscript has been accepted for publication. Congratulations to all authors!

  2. Version published to 10.1099/acmi.0.000962.v2 on Access Microbiology
  3. Version published to 10.1099/acmi.0.000962.v3 on Access Microbiology
  4. Access Microbiology

    Thank you very much for submitting your manuscript to Access Microbiology. It has now been reviewed by two experts in the field whose comment are attached at the bottom of this email. They both agree that this study is of great interest and it has been performed rigorously. However, they have provided a number of comments and suggestions that need to be corrected in a revised version. I would also recommend that you consider changing the title of the manuscript, shortening it and pinpointing the specific results/conclusions of the study. Please provide a revised version of the manuscript (including a tracked-changes version) along with a point-by-point response to the reviewer comments within 1 month.

  5. Access Microbiology

    Comments to Author

    Thank you very much for associating me with the analysis of this study. I have read with great interest this manuscript entitled: "Tossing the coin of ESBL: 50% prevalence of ESBL- producing Klebsiella pneumoniae isolated from bloodstream infections of patients with features of sepsis at a national referral and teaching hospital of a low-income setting". The aim of the study was to determine the rate of antibiotic resistance in Klebsiella pneumoniae strains isolated from blood cultures. It revealed that a high proportion (30%) of these strains produce extended-spectrum beta-lactamases, making them resistant to third-generation cephalosporins. The study's highlights are as follows: - The research methodology used is appropriate - Good Klebsiella pneumoniae strain identification, susceptibility testing and ESBL phenotypic detection techniques. - Well-written text However, this study has one major weakness: - the absence of a molecular study, which would have made it possible to distinguish the different types of ESBL genes, essential for monitoring these resistances. Let me finish with a question: On line 129: why did you cultivate K. pneumoniae in a 5% CO2-rich atmosphere, when it's an enterobacteria that grows well in aerobic conditions?

    Please rate the manuscript for methodological rigour

    Good

    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

  6. Access Microbiology

    Comments to Author

    In this short communication, Achan, Luggya, and Kajambula investigated the antibiotic resistance profiles of Klebsiella pneumoniae isolated from the blood cultures of patients with sepsis at a national referral and teaching hospital in Uganda. They found that most K. pneumoniae isolates (26/30; 87%) were susceptible to imipenem, but all isolates were clinically resistant to piperacillin, and most were resistant to 2nd, 3rd and 4th generation cephalosporins. Using a double disk synergy assay, they found that ~50% of the isolates were ESBL-positive. This study is methodologically rigorous, and I have no major comments. General comments: In a previous study at the same hospital (https://doi.org/10.1371/journal.pone.0286955), the authors found that blaCTX-M is the ideal gene for tracking ESBL-mediated resistance at Mulago. Is there a reason why this was not attempted for the current study? The authors should also discuss their findings in the context of further similar studies conducted in Uganda: https://wwwnc.cdc.gov/eid/article/30/14/24-0370_article https://www.mdpi.com/2076-0817/12/11/1334 https://aricjournal.biomedcentral.com/articles/10.1186/s13756-023-01229-9 Minor comments: Line 91: ESBL-k.p should be changed to ESBL-K.p Line 99: Please provide a reference for the criteria used for sepsis. Line 104: Please provide a reference for the use of Kish-Leslie formula. Line 129: Remove the extra 'in' Line 133: Please provide a reference for the biochemical test of Klebsiella pneumoniae Table 1 has two table legends. Please remove one of them. Line 203: (Fig. 1) is unnecessary if Figure 1 is referred to directly in the text. Figure 1: Please use standardised abbreviations for the names of antibiotics and define the abbreviations in the figure legend. Line 253: Please provide a reference to support this statement. Line 259: K. pneumoniae needs to be italicised. The list of abbreviations is missing BSI, UTI, and ICU

    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

  7. Version published to 10.1099/acmi.0.000962.v1 on Access Microbiology