Correlation between blood group type and Catheter-associated urinary tract infections (CA-UTI) in critically ill patients: A Retrospective Cohort Study

Background: CA-UTI consider one of the most common hospital acquired infections. Several risk factors for CA-UTI have been identied. There is no enough evidence regard the impact of ABO type and the risk of CA-UTI acquisition. The aim of this study is to investigate the correlation between ABO types and the risk of having recurrent, reinfection CA-UTI, and MDR reinfection in critically ill. Methodology: A retrospective cohort study of adult ICU patients through 2018 in ICU at tertiary hospital who have conrmed CA-UTI to investigate the correlation between ABO type with the susceptibility of recurrent, reinfection and MDR reinfection CA-UTI in critically ill. 1730 patients were reviewed to screen patients for inclusion into the study,203 patients have conrmed CA-UTI using 2010 IDSA guideline denition.81patients meeting inclusion/exclusion criteria were enrolled. Patients were divided into two groups based on ABO type (O-group Vs. Non-O group). We considered a P value of < 0.05 as statistically signicant. Results: Among 81 patients, 37 patients (45.6%) had O blood group type. Patients with O blood group type were associated with lower rate of recurrent CA-UTI (OR 0.28, 95% CI 0.085-0.952, P = 0.0414), multidrug resistant (MDR) organisms (OR 0.05, 95% CI 0.003-0.752, P = 0.0304), shorter ICU LOS (Est (SE): -0.024 (0.045), P = <0.001) and mechanical ventilation duration (Est. (SE): -0.41 (0.066), P = <0.001) compared with non-O blood group type. On the other hand, neither CA-UTI reinfection (OR 1.47, 95% CI 0.357-6.054, P = 0.5538) nor ICU mortality (OR 0.70, 95% CI 0.219-2.257, P = 0.5538) were statistically signicant. Conclusion: Patients with non-O group type were statistically signicant associated with higher rate of recurrent CA-UTI and MDRO. These data conrm the need for randomized controlled trials with a larger sample size to clarify and conrm our study ndings. Our study is a retrospective cohort investigate the correlation between blood group type and catheter-associated urinary tract infection recurrent, reinfection, and the prevalence of the multidrug-resistant in reinfection cases in CA-UTI among adult critically ill patients as main endpoint. Although, we determine ICU 30 days’ mortality, length of stay as asecondary endpoints.

followed by Enterococcus species, Pseudomonas species, Klebsiella species & Staphylococcus aureus (Puri J et al. 2002, Weiner LM. et al. 2016. Several risk factors for CA-UTI acquisition have been identi ed, catheterization duration is one of the most important risk factors. Other risk factors include old age, female gender, colonization of the drainage bag with bacteria, and/or diabetes mellitus (Kunin CM. et al. 1966 ). There is no enough evidence regarding the impact of blood group type and the risk of CA-UTI acquisition. The aim of this is to investigate the correlation between blood group type (O-group Vs. Non-O group) and the risk of having recurrent CA-UTI, CA-UTI reinfection and MDR reinfection in critically ill patients with indwelling urinary catheter.

Study design
A retrospective cohort study of adult ICU patients over 12 months period in intensive care units at tertiary hospital who have con rmed Catheter-associated urinary tract infections (CA-UTI) between January 1st, 2018 to December 31st, 2018 to investigate the correlation between blood group type with recurrent, reinfection and MDR reinfection CA-UTI in critically ill patients with CA-UTI. Secondary endpoints to determine ICU mortality, ICU length of stay and the most common blood group type with high susceptibility to CA-UTI in Saudi populations. A total of 1730 patients were reviewed to screen patients for inclusion into the study, 203 patients have con rmed CA-UTI using IDSA guideline de nition (Hooton et al. 2010

Data collection
Demographic and clinical data including age, gender, weight, body mass index, associated comorbidities, laboratory baseline including but not limited to ABO and rhesus blood group type, urine output (UOP), and renal function within 24 hours of ICU admission. Additionally, Glasgow Coma Scale (GCS), Acute Physiology and Chronic Health Evaluation (APACHE II) score, Sequential Organ Failure Assessment (SOFA) score, and Nutrition Risk in Critically ill (NUTRIC) score were recorded for eligible patients on the rst day. Moreover, urinary culture (s), recurrent, reinfection and MDR reinfection CA-UTI, antibiotics dosing and duration, ICU admission date, ICU discharge date, ICU mortality with 30 days, mechanical ventilation duration and history of admission, surgery or dialysis within 3 months of ICU admission were reviewed and recorded. CA-UTI reinfection is de ned as UTI occurring more than 14 days after the original CA-UTI. While recurrence CA-UTI is de ned as infection by an organism different from that in the preceding infection.

Eligibility criteria
Patients were enrolled in the study if they were critically ill patients aged ≥ 16 y/o with known ABO group type and con rmed Catheter-associated urinary tract infections (CA-UTI) within ICU admission. Exclusion criteria included using immunosuppression medication(s)/ immunocompromised patient, inappropriate antibiotic (s) dosing and duration within 72 hours of positive culture (using Micromedex® database), previous admission or antibiotic use within 3 months of admission, repeated urinary catheter culture within 3 days is negative without any new addition of antibiotic (s). Also, patients with sampling from the catheter collection system (e.g., catheter bag), urine culture < 100000 CFU/MLS, or more than two species of microorganism isolated were excluded.

Outcomes
The primary outcome is to investigate the correlation between O-group types (O+ & O-) Vs. Non-O group types (A+, A-, B+, B-, AB+, AB-) and CA-UTI. In addition, the correlation of O-group types Vs. Non-O group types with the risk of having recurrent CA-UTI, CA-UTI reinfection and MDR reinfection in critically ill patients. Secondary outcomes were to determine the most common blood group type with high susceptibility to CA-UTI in critically ill patients, ICU length of stay (LOS), hospital LOS, Mechanical Ventilation (MV) duration and ICU mortality.

Data management and Statistical analysis
Collected data were entered in Microsoft Excel 2010 after being coded. There were two arms considered in this study, patients' O-group types Vs. Non-O group type. Multivariate binary and multinomial logistic regression were used to nd out the relationship between blood groups and different outcomes considered in this study, adjusting for patients' body mass index (BMI), Baseline APACHE II severity score, Acute Kidney Injury status within 24 hours of ICU admission, and status of previous surgery and/or dialysis with 3 months.
We summarized categorical variables as number (percentage) and numerical variables (continuous variables) as mean and standard deviation (SD). The normality assumptions were assessed for all numerical variables using statistical test (i.e. Shapiro-Wilk test) and using graphical representation (i.e. histograms and Q-Q plots). We compared categorical variables using the chi-square or Fisher exact test, normally distributed numerical variables with the t-test, and other quantitative variables with the Mann-Whitney U test. Baseline characteristics, baseline severity and outcome variables were compared between the two groups.
Generalized linear regression was also used to nd out the relationship between blood groups and the different outcomes considered in this study, adjusting for the same prognostic factors as used for logistic regressions. The odds ratios (OR) and estimates with the 95% con dence intervals (CI) were reported for the associations. We considered a P value of < 0.05 statistically signi cant and used SAS version 9.4 for all statistical analyses. of O and non-O blood group patients. Most of the baseline and clinical characteristics were found to be very similar between the two groups. Albumin was signi cantly high in patients with O blood group as compared to non-O blood groups (P = 0.0223).   Table 3 depicts the comparison of baseline severity illness between two blood groups. It was evident from this table that distributions of baseline severity illness scores were very similar between the two blood groups. Table 4 shows the most common CA-UTI organisms in O blood group type patients were E.
coli (61.9%) followed by Candida species (54.5%). Whereas, in non-O blood group patients, the common CA-UTI organisms were Candida 10 (45.5%) followed by E. coli 8 (38.1%).    Table 2 shows the outcome comparisons between two blood groups after adjusting for the patient's body mass index (BMI), baseline APACHE II score, the status of Acute Kidney Injury within 24 hours of ICU admission, the status of previous surgery and dialysis within 3 months of ICU admission.

Discussion:
Linking blood types to the occurrence of some diseases and infections is a new science that began to focus on recently (Minardi D. et al. 2011, Ziegler T. et al. 2004, Kinane D. et al. 1982. This connection came from many theories proven the carbohydrate located on RBCs surface plays a crucial role as a receptor for germs, and the attractiveness of these receptors to bacteria, parasites, and viruses varies with the different blood types (Hooton T. et al. 2001, Haylen B. et al. 2009, Hawn T. et al. 2009). Our study is a retrospective cohort investigate the correlation between blood group type and catheter-associated urinary tract infection recurrent, reinfection, and the prevalence of the multidrug-resistant in reinfection cases in CA-UTI among adult critically ill patients as main endpoint. Although, we determine ICU 30 days' mortality, ICU length of stay as asecondary endpoints.
The prevalence of UTI recurrent episodes are remarkably higher in non-O group types (17.1% vs. 33.3%) (p = 0.0414), where the reinfection episodes not differ between the two groups (11.4% vs. 7.1%) (P = 0.5928). Our data also reveal that O-blood group types have a lower incidence of multi-drug resistant gram-negative bacteria compared with non-O group types (P = 0.0304). A study by Rocha D and colleagues include a total of 307 patients, found that type A blood group patients have a higher predisposition to get urinary tract infections compared with other groups (Rocha D. et al. 2015). Another study by Sheinfeld J and colleagues observing the correlation between the Lewis blood-group phenotype and recurrent urinary tract infections among women, this study has shown a relationship between recurrent UTI among Lewis blood-group non-secretor (Le(a + b-)) and recessive (Le(a-b-)) phenotypes (Sheinfeld J. et al. 1989). Comparatively, optimal antibiotic choice, dosing, and duration directly affects treatment success and improve patients' outcomes (Cotta M. et al. 2015). Therefore, we excluded the patients who received sub-optimal antibiotics doses. . Also, in our study we did not correlate the latex rubber catheters with the incidence of urinary tract infections either the rst episode or recurrent as it's prone to cause infections.
Lack of large and well-conducted studies connecting the prevalence of infections, reinfection, and infection severity with human papulation blood group types is one of the serious limitations for this study. Although the patients' data collected retrospectively which is give us no chance to interfere with the patient's therapeutic plane or even observing the patients directly. However, our research population is all critically ill patients, and the length of ICU stay, MDRO incidence or reinfection could have affected by many other factors not speci cally related to blood group types. Conversely, our study is the rst of its kind to examine the relationship between CA-UTI recurrent, reinfection, and MDRO prevalence and blood group type among ICU patients. Further researches with a larger sample size should be done to investigate the relationship between blood groups and infections tendency.

Declarations Ethical consideration
The study was approved by King Abdullah International Medical Research Center Institutional Review Board, Riyadh, Saudi Arabia. Participants' con dentiality was strictly observed throughout the study by using the anonymous unique serial numbers for each subject and restricting data only to the investigators. Informed consent was not required due to the research's method as per the policy of the governmental and local research center. The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Author contributions
All authors contributed to data collections, analysis, drafted, revised and approved the nal version of the manuscript.
Compliance with Ethical standards: Funding: None Disclosure: No author has a con ict of interest in this study.
Availability of data and material: Data are available on request due to privacy and ethical restrictions.