Unveiling the role of sex as a predictor for KPC-Klebsiella pneumoniae and carbapenem-resistant Acinetobacter baumannii bacteremia in critically Ill colonized patients

BACKGROUND: Nosocomial infections caused by multidrug-resistant bacteria represent a major global public health threat. They occur most frequently in Intensive Care Units (ICUs), particularly due to Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-KP) and carbapenem-resistant Acinetobacter baumannii (CRAB). Only a limited number of studies have examined sex as a predictor of KPC-KP and CRAB infections. In this study, we investigated whether sex influences patterns of KPC-KP and CRAB colonization in ICU patients, as well as the risk and timing of bloodstream infection (BSI) development among colonized individuals. METHODS: We included critically ill patients who developed rectal colonization by CRAB or KPC-Kp during the ICU stay. The two-sided Mann-Whitney U test, the Student's t test, the χ2 test or the Fisher's exact test were applied to analyse the differences in age, colonising pathogens, comorbidities, rate of BSI and mortality between male and female patients. Two age categories were created: 0-54 and over 55 years. Cox regression analysis was conducted to identify independent risk factors for colonization and BSI outcomes. For mortality outcomes backward stepwise logistic regression models were applied. For survival analysis, the Kaplan-Meier method was used. RESULTS: A total of 273 patients, 185 men and 88 women, were included in the study. The prevalence of KPC-KP and CRAB BSI was 31.8%. Our results show that sex and age affected both the risk and timing of BSI onset after admission to ICU. In particular, we found that the overall risk of BSI irrespective of sex and age was higher in patients with KPC-KP colonization than in those with CRAB colonization (IRR=1.56; 95%CI 1.00-2.45). After stratifying for sex, this risk was statistically higher in men than in women (IRR=2.06; 95%CI 1.22-3.49). Women presented a lower rate (19% vs 31%) and later onset [median 35 days (15-56) days vs 16.5 days (10-24.5), p<0.05] of CRAB BSI in comparison to men. After stratifying for age in women over 55 years, the proportion of BSI was lower and the onset occurred later for both pathogens, while, for KPC-KP BSI, women in 0-54 years group had the highest proportion and earliest onset compared to men irrespective of age group and older women. CONCLUSIONS: Our data show that both the risk of developing systemic infections due to KPC-KP and CRAB, as well as the timing from colonization to BSI in critically ill patients colonized with KPC-KP and CRAB, are influenced by sex and age. We therefore propose that sex and age should be incorporated into risk stratification analyses aimed at identifying predictors of systemic infections in colonized critically ill patients.