Carbapenem-resistant Klebsiella pneumoniae in university-affiliated hospitals: risk factors for isolation among hospitalized patients and molecular subtyping

  1. Ketevan Kobaidze
  2. Jesse Jacob
  3. Traci Leong
  4. W. Dana Flanders

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Abstract

Background

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an important healthcare-associated pathogen. This study aimed to identify factors associated with CRKP isolation among hospitalized patients, describe molecular epidemiology, and mortality associated with CRKP isolation.

Methods

We performed a retrospective case-control study at the two university-affiliated teaching hospitals. 150 patients were included (30 cases and 120 controls) in this study.

Each patient with CRKP, a case-patient, was matched with four controls by admission facility, age, and sex. Controls, patients without CRKP were randomly selected from a computerized list of inpatients whose admission date was the same as that of the case, within 48 hours of the date of the initial positive culture. We calculated the risk of in-hospital death as the number of deaths divided by the number of cases and evaluated the risk of mortality associated with the site of positive culture. Molecular epidemiology investigation using comparison of restricted DNA patterns of CRKP by pulsed-field gel electrophoresis (PFGE) was conducted.

Results

A greater proportion of cases than controls had undergone an invasive procedure, including use of a central vein catheter (p=0.007, OR, 3.4, 95% CI, 1.4-8.7), and mechanical ventilation (p=0.002, OR, 3.6, 95% CI, 1.6-8.1), nutrition by tube feeding (p=0.001, OR, 4.2, 95% CI, 1.8 −10).

Pre-admission treatment within two months with the following antibiotic classes was associated with CRKP isolation: carbapenems (p=0.001, OR, 24.4, 95% CI, 2.73-217.96), fluoroquinolones (p<0.0001, OR, 6.17, 95% CI, 2.4 – 15.83), anti-pseudomonal penicillin (p = 0.02; OR, 6.03; 95% CI, 1.98 −18.32), and cephalosporins (p=0.001, OR, 5.36, 95% CI, 2.07 −13.87).

The molecular analysis detected that over 90% of isolates shared similar PFGE patterns.

CRKP isolation was associated with significantly higher In-hospital mortality (36.7% vs 3.3%) in comparison to controls (p<.0001).

Positive cultures from sites other than urine were associated with substantially higher mortality than was a positive urine culture (RR= 4.0).

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  1. PeerRef

    Peer review report

    Reviewer: Wei Zhang Institution: The First Affiliated Hospital of Hebei North University, Hebei Province, China. email: 15369318318@163.com

    Section 1 – Serious concerns

    • Do you have any serious concerns about the manuscript such as fraud, plagiarism, unethical or unsafe practices? No
    • Have authors’ provided the necessary ethics approval (from authors’ institution or an ethics committee)? *Yes

    Section 2 – Language quality

    • How would you rate the English language quality? High quality

    Section 3 – validity and reproducibility

    • Does the work cite relevant and sufficient literature? Yes
    • Is the study design appropriate and are the methods used valid? Yes
    • Are the methods documented and analysis provided so that the study can be replicated? Yes
    • Is the source data that underlies the result available so that the study can be replicated? not applicable
    • Is the statistical analysis and its interpretation appropriate? Yes
    • Is quality of the figures and tables satisfactory? No
    • Are the conclusions adequately supported by the results? not applicable
    • Are there any objective errors or fundamental flaws that make the research invalid?

    Table 1 - The number of people in the gender section is wrong.

    Section 4 – Suggestions

    • Based on your answers in section 3 how could the author improve the study?

    （1）There is no "conclusion" in the abstract.

    （2）In order to make the study group comparable with the control group, should the patients in the control group be CSKP infected patients? Or the control group should at least be patients with bacterial infection.

    （3）The font in Table 2 is inconsistent with the original text.

    （4）The table format should be "three line table".

    （5）The number "0" can be added before some decimal points in Table 2.

    （6）The references are generally too old. It is suggested to increase the proportion of references published within 5 years.

    （7）It is suggested to write more specific experimental methods for amplifying KPC gene, such as primers, PCR reaction conditions and reaction system of KPC gene.

    （8）Have you done the drug sensitivity test of Klebsiella pneumoniae? If so, it is recommended to write the results in the article.

    Section 5 – Decision

    Verified with reservations: The content is scientifically sound but has shortcomings that could be improved by minor revisions.

  2. PeerRef

    SciScore rigor report

    Sciscore is an AI platform that assesses the rigor of the methods used in the manuscript. SciScore assists expert referees by finding and presenting information scattered throughout a manuscript in a simple format.

    Not required = Field is not applicable to this study

    Not detected = Field is applicable to this study, but not included.

    Ethics

    IRB: This study was approved by the Institutional Review Board of the Emory University School of Medicine.

    Consent: IRB of Emory University School of Medicine gave ethical approval for this work I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

    Inclusion and Exclusion Criteria

    not detected.

    Attrition

    The first case was identified in September of 2006 , 13 cases were detected in 2007 , and 16 cases in 2008 across these two hospitals ( total of 30 with 120 matched controls) .

    Sex as a biological variable

    Mean Median 60 62 ( range from 27 to 90 ) Sex Female Male 25 ( 52 ) 23 ( 48 ) Site of isolation Urine

    Subject Demographics

    Age: not detected. Weight: not detected.

    Randomization

    Controls, patients without CRKP were randomly selected from a computerized list of inpatients who matched the case age (+/- 5 years), sex, and facility and whose admission date was within 48 hours of the date of the initial, positive culture.

    Blinding

    not detected.

    Power Analysis

    not detected.

    Replication

    not required.

    Data Information

    Availability: The comparison of clinical characteristics between cases and controls was made using Chi-Square (or It is made available under a CC-BY-NC-ND 4.0 International license .

    Identifiers: medRxiv preprint doi: https:// doi.org/10.1101/2022.02.08.22269570; this version posted February 9 , 2022 . https://doi.org/10.1101/2022.02.08.22269570

  3. Version published to 10.1101/2022.02.08.22269570v1 on medRxiv