Gastrointestinal Carriage Is a Major Reservoir of Klebsiella pneumoniae Infection in Intensive Care Patients.
ABSTRACT: Klebsiella pneumoniae is an opportunistic pathogen and leading cause of hospital-associated infections. Intensive care unit (ICU) patients are particularly at risk. Klebsiella pneumoniae is part of the healthy human microbiome, providing a potential reservoir for infection. However, the frequency of gut colonization and its contribution to infections are not well characterized.We conducted a 1-year prospective cohort study in which 498 ICU patients were screened for rectal and throat carriage of K. pneumoniae shortly after admission. Klebsiella pneumoniae isolated from screening swabs and clinical diagnostic samples were characterized using whole genome sequencing and combined with epidemiological data to identify likely transmission events.Klebsiella pneumoniae carriage frequencies were estimated at 6% (95% confidence interval [CI], 3%-8%) among ICU patients admitted direct from the community, and 19% (95% CI, 14%-51%) among those with recent healthcare contact. Gut colonization on admission was significantly associated with subsequent infection (infection risk 16% vs 3%, odds ratio [OR] = 6.9, P < .001), and genome data indicated matching carriage and infection isolates in 80% of isolate pairs. Five likely transmission chains were identified, responsible for 12% of K. pneumoniae infections in ICU. In sum, 49% of K. pneumoniae infections were caused by the patients' own unique strain, and 48% of screened patients with infections were positive for prior colonization.These data confirm K. pneumoniae colonization is a significant risk factor for infection in ICU, and indicate ~50% of K. pneumoniae infections result from patients' own microbiota. Screening for colonization on admission could limit risk of infection in the colonized patient and others.
Project description:PURPOSE:Loss of colonization resistance within the gastrointestinal microbiome facilitates the expansion of pathogens and has been associated with death and infection in select populations. We tested whether gut microbiome features at the time of intensive care unit (ICU) admission predict death or infection. METHODS:This was a prospective cohort study of medical ICU adults. Rectal surveillance swabs were performed at admission, selectively cultured for vancomycin-resistant Enterococcus (VRE), and assessed using 16S rRNA gene sequencing. Patients were followed for 30 days for death or culture-proven bacterial infection. RESULTS:Of 301 patients, 123 (41%) developed culture-proven infections and 76 (25%) died. Fecal biodiversity (Shannon index) did not differ based on death or infection (p?=?0.49). The presence of specific pathogens at ICU admission was associated with subsequent infection with the same organism for Escherichia coli, Pseudomonas spp., Klebsiella spp., and Clostridium difficile, and VRE at admission was associated with subsequent Enterococcus infection. In a multivariable model adjusting for severity of illness, VRE colonization and Enterococcus domination (??30% 16S reads) were both associated with death or all-cause infection (aHR 1.46, 95% CI 1.06-2.00 and aHR 1.47, 95% CI 1.00-2.19, respectively); among patients without VRE colonization, Enterococcus domination was associated with excess risk of death or infection (aHR 2.13, 95% CI 1.06-4.29). CONCLUSIONS:Enterococcus status at ICU admission was associated with risk for death or all-cause infection, and rectal carriage of common ICU pathogens predicted specific infections. The gastrointestinal microbiome may have a role in risk stratification and early diagnosis of ICU infections.
Project description:This study was conducted to investigate the prevalence of and risk factors for colonization and acquisition of carbapenem-resistant (CR) Gram-negative bacteria (GNB) among patients admitted to intensive care units (ICUs) in two tertiary care hospitals in northern Thailand. Screening of rectal swab specimens for CR-GNB was performed on patients at ICU admission and discharge. The phenotypes and genotypes of all isolates were determined. Risk factors were analyzed by logistic regression analysis. The overall carriage rate of CR-GNB at admission was 11.6% (32/275), with the most predominant species carried being Acinetobacter baumannii (n = 15), followed by Klebsiella pneumoniae (n = 9). The risk factor for CR-GNB colonization was hospitalization within the previous 6 months (P = 0.002). During the ICU stay, the rate of CR-GNB acquisition was 25.2% (52/206), with the most predominant species carried being A. baumannii (n = 28) and K. pneumoniae (n = 13). Risk factors associated with CR-GNB acquisition were the use of an enteral feeding tube (P = 0.008) and administration of third-generation cephalosporins (P = 0.032) and carbapenems (P = 0.045). The most common carbapenemase genes in A. baumannii and K. pneumoniae were blaOXA-23/51 and blaNDM, respectively. Patient-to-patient transmission was demonstrated in three cases, resulting in the acquisition of CR A. baumannii (2 cases) and K. pneumoniae (1 case) isolates from other patients who were admitted during the same period of time. This is the first Indochinese study screening patients, examining patients for the carriage of CR-GNB, and further demonstrating the transfer of CR-GNB isolates in ICUs. Our study suggests that effective infection control measures are required to limit the spread of CR-GNB within hospitals.
Project description:Objective:To investigate the prevalence of infections due to carbapenem-resistant Klebsiella pneumoniae (CRKP) among ICU admission patients in central China and develop a reliable prediction model. Methods:Five hundred and seven consecutive ICU admission patients with Klebsiella pneumoniae (KP) infection were enrolled in this retrospective multicenter case-control study from January 2014 to June 2018. The prevalence and antimicrobial susceptibility pattern were analyzed. Multivariate analysis was performed by logistic regression modeling to determine the risk factors. A prediction model was developed and verified using data from six hospitals in central China. Results:Of the total 507 isolates of KP, 244 (48.1%) strains were carbapenem resistant. The majority of these isolates were from sputum (30.9%) and blood (20.9%) samples. Tigecycline had good activity against CRKP (95.5%). The most common sequence type (ST) of CRKP was ST11 (84.4%), and 98.6% of them had the blaKPC-2 antimicrobial resistance gene. Thirteen variables were identified as independent risk factors for CRKP infection, including KP colonization or infection in the preceding year (OR=3.32, 95% CI 2.01-4.38), CD4/CD8 ratio <1 (OR=2.98, 95% CI 2.02-4.19), and parenteral nutrition ?48 h (OR=1.88, 95% CI 1.22-3.04). The model developed to predict CRKP infection was effective, with an area under the receiver-operating characteristic curve of 0.854 (95% CI 0.821-0.884, p<0.001). Conclusions:ST11 carrying the blaKPC-2 antimicrobial resistance gene was the most common type of CRKP among the ICU admission patients in central China. The model demonstrated excellent predictive performance and exhibited good discrimination.
Project description:Background:Klebsiella pneumoniae is a leading cause of extended-spectrum ?-lactamase (ESBL)-producing hospital-associated infections, for which elderly patients are at increased risk. Methods:We conducted a 1-year prospective cohort study, in which a third of patients admitted to 2 geriatric wards in a specialized hospital were recruited and screened for carriage of K. pneumoniae by microbiological culture. Clinical isolates were monitored via the hospital laboratory. Colonizing and clinical isolates were subjected to whole-genome sequencing and antimicrobial susceptibility testing. Results:K. pneumoniae throat carriage prevalence was 4.1%, rectal carriage 10.8%, and ESBL carriage 1.7%, and the incidence of K. pneumoniae infection was 1.2%. The isolates were diverse, and most patients were colonized or infected with a unique phylogenetic lineage, with no evidence of transmission in the wards. ESBL strains carried blaCTX-M-15 and belonged to clones associated with hospital-acquired ESBL infections in other countries (sequence type [ST] 29, ST323, and ST340). One also carried the carbapenemase blaIMP-26. Genomic and epidemiological data provided evidence that ESBL strains were acquired in the referring hospital. Nanopore sequencing also identified strain-to-strain transmission of a blaCTX-M-15 FIBK/FIIK plasmid in the referring hospital. Conclusions:The data suggest the major source of K. pneumoniae was the patient's own gut microbiome, but ESBL strains were acquired in the referring hospital. This highlights the importance of the wider hospital network to understanding K. pneumoniae risk and infection prevention. Rectal screening for ESBL organisms on admission to geriatric wards could help inform patient management and infection control in such facilities.
Project description:Background:Prior colonization by Klebsiella pneumoniae and vancomycin-resistant Enterococci (VRE) is associated with subsequent infection, particularly in intensive care unit (ICU) populations. Screening for VRE colonization, but not K. pneumoniae, is routinely performed in some health care systems. Identification of patient factors associated with K. pneumoniae colonization could enable infection prevention. Methods:ICU patients were screened for VRE and K. pneumoniae by rectal swab culture over 2 time periods: July-October 2014 (n?=?1209) and January-May 2016 (n?=?1243). Patient demographics, baseline laboratory data, comorbidities, and outcomes were analyzed. 16S rRNA gene-based analysis was performed on a subset of patients (n?=?248) to identify microbiota characteristics associated with VRE and K. pneumoniae colonization. Results:K. pneumoniae colonization (17.3% of patients in the 2014 cohort, 7.3% in 2016) was significantly associated with VRE colonization in multivariable analysis (P?=?.03 in 2016; P?=?.08 in 2014). VRE colonization was associated with poor underlying health, whereas K. pneumoniae colonization was associated with advanced age. The most prevalent operational taxonomic units were Escherichia coli /Shigella spp., Klebsiella, and Enterococcus, consistent with high rates of detectable K. pneumoniae and VRE by culture. Microbial community structure in noncolonized patients was significantly different from those with VRE, K. pneumoniae, or both, attributable to differences in the relative abundance of Klebsiella and Enterococcus. Conclusions:K. pneumoniae co-colonizes with VRE and is a predominant taxon in ICU patients, but colonization was not associated with significant comorbidities. Screening for K. pneumoniae and VRE simultaneously could be an efficient approach for novel infection prevention strategies.
Project description:Multidrug-resistant (MDR) Enterobacteriaceae infections are associated with increased morbidity. We describe a 20-year-old hematopoietic cell transplantation recipient with recurrent MDR Klebsiella pneumoniae infection, prolonged intestinal colonization, and subsequent intestinal decontamination. Further study should evaluate stool surveillance, molecular typing, and fecal microbiota transplantation for patients with intestinal MDR Enterobacteriaceae carriage.
Project description:Health care-acquired infections (HAIs) kill tens of thousands of people each year and add significantly to health care costs. Multidrug-resistant and epidemic strains are a large proportion of HAI agents, and multidrug-resistant strains of Klebsiella pneumoniae, a leading HAI agent, have caused an urgent public health crisis. In the health care environment, patient colonization by K. pneumoniae precedes infection, and transmission via colonization leads to outbreaks. Periodic patient screening for K. pneumoniae colonization has the potential to curb the number of HAIs. In this report, we describe the design and validation of KlebSeq, a highly informative screening tool that detects Klebsiella species and identifies clinically important strains and characteristics by using highly multiplexed amplicon sequencing without a live-culturing step. We demonstrate the utility of this tool on several complex specimen types, including urine, wound swabs and tissue, and several types of respiratory and fecal specimens, showing K. pneumoniae species and clonal group identification and antimicrobial resistance and virulence profiling, including capsule typing. Use of this amplicon sequencing tool to screen patients for Klebsiella carriage could inform health care staff of the risk of infection and outbreak potential. KlebSeq also serves as a model for next-generation molecular tools for public health and health care, as expansion of this tool can be used for several other HAI agents or applications.
Project description:OBJECTIVES:To identify transmission patterns of Carbapenem-resistant Klebsiella pneumoniae infection during an outbreak at a large, tertiary care hospital and to detect whether the outbreak organisms spread to other facilities in the integrated healthcare network. METHODS:We analyzed 71?K. pneumoniae whole genome sequences collected from clinical specimens before, during and after the outbreak and reviewed corresponding patient medical records. Sequence and patient data were used to model probable transmissions and assess factors associated with the outbreak. RESULTS:We identified close genetic relationships among carbapenem-resistant K. pneumoniae isolates sampled during the study period. Transmission tree analysis combined with patient records uncovered extended periods of silent colonization in many study patients and transmission routes that were likely the result of asymptomatic patients transitioning between facilities. CONCLUSIONS:Detecting how and where Carbapenem-resistant K. pneumoniae infections spread is challenging in an environment of rising prevalence, asymptomatic carriage and mobility of patients. Whole genome sequencing improved the precision of investigating inter-facility transmissions. Our results emphasize that containment of Carbapenem-resistant K. pneumoniae infections requires coordinated efforts between healthcare networks and settings of care that acknowledge and mitigate transmission risk conferred by undetected carriage and by patient transfers between facilities.
Project description:BACKGROUND: The burden and significance of vancomycin-resistant enterococci (VRE) colonization in the ICU is not clearly understood. METHODS: We searched PubMed and EMBASE up to May 2013 for studies reporting the prevalence of VRE upon admission to the ICU and performed a meta-analysis to assess rates and trends of VRE colonization. We calculated the prevalence of VRE on admission and the acquisition (colonization and/or infection) rates to estimate time trends and the impact of colonization on ensuing VRE infections. FINDINGS: Across 37 studies (62,959 patients at risk), the estimated prevalence of VRE on admission to the ICU was 8.8% (7.1-10.6). Estimates were more consistent when cultures were obtained within 24 hours from admission. The VRE acquisition rate was 8.8% (95% CI 6.9-11.0) across 26 evaluable studies (35,364 patients at risk). Across US studies, VRE acquisition rate was 10.2% (95% CI 7.7-13.0) and demonstrated significant decline in annual trends. We used the US estimate of colonization on admission [12.3% (10.5-14.3)] to evaluate the impact of VRE colonization on admission in overall VRE prevalence. We demonstrated that VRE colonization on admission is a major determinant of the overall VRE burden in the ICU. Importantly, among colonized patients (including admitted and/or acquired cases) the VRE infection rates vary widely from 0-45% (with the risk of VRE bacteremia being reported from 0-16%) and <2% among those without a proven colonization. CONCLUSION: In summary, up to 10.6% of patients admitted in the ICU are colonized with VRE on admission and a similar percentage will acquire VRE during their ICU stay. Importantly, colonization on admission is a major determinant of VRE dynamics in the ICU and the risk of VRE-related infections is close related to colonization.
Project description:The intestine is the main reservoir of bacterial pathogens in most organisms. Klebsiella pneumoniae is an important opportunistic pathogen associated with nosocomial bacterial infections. Intestinal colonization with K. pneumoniae has been shown to be associated with an increased risk of subsequent infections. However, not all K. pneumoniae strains in the intestine cause further infection, and the distinction of the difference among strains that cause infection after colonization and the ones causing only asymptomatic colonization is unclear. In this study, we report a case of a hospitalized patient from the ICU. We screened out two intestine colonization strains (FK4111, FK4758) to analyze the subsequent infection conditions. We set up infection models of zebrafish and Galleria mellonella to establish the differences in the potential for causing subsequent infection and the immunological specificities after K. pneumoniae intestine colonization. Sudan Black B and neutral red staining results indicated that FK4758 was more responsive to neutrophil recruitment and phagocytosis of macrophages than FK4111. The results of the assessment of the organ bacterial load revealed that FK4111 and FK4758 both had the highest bacterial loads in the zebrafish intestine compared to those in other organs. However, in the zebrafish spleen, liver, and heart, the FK4758 load was significantly higher than that of FK4111. The ST37 strain FK4111, which does not produce carbapenemase, did not cause infection after colonization, whereas the ST11 strain FK4758, which produces carbapenemase, caused infection after intestinal colonization. Our finding demonstrated that not all intestinal colonization of K. pneumoniae subsequently caused infections, and the infections of K. pneumoniae after colonization are different. Therefore, the infection models we established provided possibility for the estimation of host-microbial interactions.