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

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). ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by Emory University SOM research grant. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: 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. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors