Although Klebsiella pneumoniae bloodstream infections (KP-BSIs) have recently attracted attention due to an alarming raise in morbidity and mortality, there have been few reports on the epidemiology of KP-BSIs in mainland China. We sought to describe the epidemiological, microbiological, and clinical characteristics of KP-BSIs, focusing on the risk factors of carbapenem resistance and patient mortality. A retrospective analysis of WHONET data of KP-BSI patients admitted to a teaching hospital in Shanghai, China, between January 1, 2011 and December 31, 2015 was performed, and the annual percentage of patients with carbapenem-resistant K. pneumoniae (CRKP) was determined. Risk factors related to the carbapenem resistance and patient mortality were analyzed using binary logistic regression model. The genetic relatedness of CRKP strains isolated from intensive care unit (ICU) patients was determined by pulsed-field gel electrophoresis (PFGE). A total of 293 incidences of KP-BSIs were identified in a 5-year period, 22.18% of these (65/293) were CRKP strains, and the proportion of CRKP-BSI in ICU was 59.62% (31/52), equaling the levels observed in the epidemic regions. A number of KP-BSIs (114), obtained from January 1, 2014, to December 31, 2015, were further investigated. Skin and soft tissue infection source (odds ratio [OR] 26.63, 95% confidence interval [CI] 4.8–146.8) and ICU-acquired infection (OR 5.82, 95% CI 2.0–17.2) was shown to be powerful risk factors leading to the development of CRKP-BSI. The crude 28-day mortality rates of KP-BSI and CRKP-BSI patients were 22.8% and 33.3%, respectively. Lung as the probable source of infection (OR 4.23, 95% CI 1.0–17.3), and high Sequential Organ Failure Assessment (SOFA) score (OR 1.40, 95% CI 1.2–1.6) were strong prognostic factors determining crude 28-day KP-BSI mortality rates. PFGE analysis demonstrated that 10/11 random CRKP isolates in ICU belonged to the same clonal type. During the study period, we observed a significant increase in the occurrence of CRKP infections among the identified KP-BSIs in our hospital and especially in ICU, and we demonstrated that carbapenem resistance is associated with the increased mortality of KP-BSI patients.

To determine whether infection-prevention and control (IPC) interventions can reduce the colonisation and infection of intensive care unit (ICU)-acquired carbapenem-resistant Klebsiella pneumoniae (CRKP) in a general ICU ward in China. We used a quasi-experimental before-and-after study design. The study was conducted in 4 stages: baseline period, January 2013–June 2013; IPC interventions period including de-escalation and targeted bundle interventions, July 2013–June 2014; modified IPC interventions period, July 2014–June 2015; and follow-up period, July 2015–June 2016. We used modified de-escalation interventions according to patient-risk assessments to prevent the transmission of CRKP. A total of 629 patients were enrolled in study. The incidence of ICU-acquired CRKP colonisation/infection was 10.08 (4.43–16.43) per 1000 ICU patient-days during the baseline period, and significantly decreased early during the IPC interventions, but the colonisation/infections reappeared in April 2014. During the modified IPC intervention and follow-up periods, the incidence of ICU-acquired CRKP colonisations/infections reduced to 5.62 (0.69–6.34) and 2.84 (2.80–2.89), respectively, with ongoing admission of cases with previously acquired CRKP. The incidence of ICU-acquired CRKP catheter-related bloodstream infections decreased from 2.54 during the baseline period to 0.41 during the follow-up period. The incidence of ventilator-associated pneumonia and skin and soft tissue infections showed a downward trend from 2.84 to 0.41 and from 3.4 to 0.47, respectively, with slight fluctuations. Comprehensive IPC interventions including de-escalation and targeted bundle interventions showed a significant reduction in ICU-acquired CRKP colonisations/infections, despite ongoing admission of patients colonised/infected with CRKP.

Purpose We aimed to explore the prevalence and within-host evolution of resistance in polymyxin-heteroresistant carbapenem-resistant Klebsiella pneumoniae (PHR-CRKP) in critically ill patients. Methods We performed an epidemiological analysis of consecutive patients with PHR-CRKP from clinical cases. Our study investigated the within-host resistance evolution and its clinical significance during polymyxin exposure. Furthermore, we explored the mechanisms underlying the dynamic evolution of polymyxin resistance at both subpopulation and genetic levels, involved population analysis profile test, time-killing assays, competition experiments, and sanger sequencing. Additionally, comparative genomic analysis was performed on 713 carbapenemase-producing K. pneumoniae strains. Results We enrolled 109 consecutive patients, and PHR-CRKP was found in 69.7% of patients without previous polymyxin exposure. 38.1% of PHR-CRKP isolates exhibited polymyxin resistance and led to therapeutic failure in critically ill scenarios. An increased frequency of resistant subpopulations was detected during PHR-CRKP evolution, with rapid regrowth of resistant subpopulations under high polymyxin concentrations, and a fitness cost in an antibiotic-free environment. Mechanistic analysis revealed that diverse mgrB insertions and pmrB hypermutations contributed to the dynamic changes in polymyxin susceptibility in dominant resistant subpopulations during PHR evolution, which were validated by comparative genomic analysis. Several deleterious mutations (e.g. pmrB^Leu82Arg, pmrB^Ser85Arg) were firstly detected during PHR-CRKP evolution. Indeed, specific sequence types of K. pneumoniae demonstrated unique deletions and deleterious mutations. Conclusions Our study emphasizes the high prevalence of pre-existing heteroresistance in CRKP, which can lead to polymyxin resistance and fatal outcomes. Hence, it is essential to continuously monitor and observe the treatment response to polymyxins in appropriate critically ill scenarios. Graphical Abstract

Background: With the widespread spread of carbapenem-resistant gram-negative bacteria (CR-GNB) in medical facilities, the carriage of CR-GNB among critically ill patients has become a significant concern in intensive care units (ICU). This study aimed to develop a scoring system to identify CR-GNB carriers upon ICU admission. Methods: Consecutive critically ill patients admitted to the ICU of Shanghai Ruijin Hospital between January 2017 and December 2020 were included. The patients were then divided into training and testing datasets at a 7:3 ratio. Parameters associated with CR-GNB carriage were identified using least absolute shrinkage and selection operator regression analysis. Each parameter was assigned a numerical score ranging from 0 to 100 using logistic regression analysis. Subsequently, a four-tier risk-level system was developed based on the cumulative scores, and assessed using the area under the receiver operating characteristic curve (AUC). Results: Of the 1736 patients included in this study, the prevalence of CR-GNB carriage was 10.60%. The clinical scoring system including seven variables (neurological disease, high-risk department history, length of stay ≥ 14 days, ICU history, invasive mechanical ventilation, gastrointestinal tube placement, and carbapenem usage) exhibited promising predictive capabilities. Patients were then stratified using the scoring system, resulting in CR-GNB carriage rates of 2.4%, 12.0%, 36.1%, and 57.9% at the respective risk levels (P < 0.001). Furthermore, the AUC of the developed model in the training set was calculated to be 0.82 (95% CI, 0.78–0.86), while internal validation yielded an AUC of 0.83 (95% CI, 0.77–0.89). Conclusions: The ICU-CARB Score serves as a straightforward and precise tool that enables prompt evaluation of the risk of CR-GNB carriage at the time of ICU admission, thereby facilitating the timely implementation of targeted pre-emptive isolation.

Background: In recent years, septic shock remains a common fatal disease in the intensive care unit (ICU). After sufficient fluid resuscitation, some patients still experience tachycardia, which may lead to adverse effects on cardiac function. However, the use of β-blockers in the treatment of septic shock remains controversial. Thus, the purpose of this study is to evaluate the efficacy of β-blockers in the treatment of patients with septic shock and explore the most appropriate patient subgroups for this treatment.Methods: This retrospective observational study enrolled septic shock patients from the Medical Information Mart for Intensive Care (MIMIC)-IV and used propensity score matching (PSM) to balance some baseline differences between patients with and without β-blockers treatment. The primary outcome was the 28-day mortality. Length of stay (LOS) in the ICU and hospital, and the degree of support for organs such as circulatory, respiratory and renal systems were also assessed. Subgroup analysis and multivariate logistic regression were performed to determine the relationship between β-blockers therapy and 28-day mortality in different patient groups.Results: A total of 4,860 septic shock patients were enrolled in this study and 619 pairs were finally matched after PSM. Our analysis revealed that β-blocker therapy was associated with a significant improvement in 28-day mortality (21.5% vs. 27.1%; P = 0.020) and led to a prolonged LOS in both the ICU and hospital. Subgroup analysis indicated that there was an interaction between cardiovascular diseases and β-blocker therapy in patients with septic shock. Patients with pre-existing heart disease or atrial arrhythmias were more likely to derive benefits from β-blocker treatment.Conclusion: We found β-blockers therapy was effective to improve 28-day mortality in patients with septic shock. Patients in the subgroup with cardiovascular diseases were more likely to benefit from β-blockers in mortality.