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Colonization, Infection, and the Accessory Genome of Klebsiella pneumoniae 2023 Apr;30(2):42-54. doi: 10.21315/mjms2023.30.2.4. Published by Oxford University Press for the Infectious Diseases Society of America. Evolution and Epidemiology of Multidrug-Resistant. (A), Unrooted tree of all isolates, revealing three distinct species that are typically identified as K. pneumoniae in diagnostic laboratories. Timelines for all lineages detected in multiple patients that show any inter-patient pairwise genetic distance between isolates of 25 SNPs per 5 Mbp. Duchne Federal government websites often end in .gov or .mil. Klebsiella pneumoniae is an opportunistic pathogen and leading cause of hospital-associated infections. The average distance between lineages within each species was 0.5% nucleotide divergence, representing thousands of years of evolutionary separation based on molecular clock estimates for K. pneumoniae [17]. Follow-up swabs were repeated each 57 days after baseline for the duration of ICU stay and up to 4 days following transfer to another ward. Safety profile of subdural and depth electrode implantations in invasive EEG exploration of drug-resistant focal epilepsy. We estimated a 5.9% CA rate for culture-positive GI carriage of K. pneumoniae, similar to the 3.9% estimated among healthy individuals in the Human Microbiome Project based on 16S rRNA amplicon sequencing of stool samples [7]. There is likely a significant false negative rate. A 1971 study found 18.5% of patients admitted to various wards in the Denver Veterans Administration Hospital were culture-positive for rectal carriage of K. pneumoniae, and carriage was significantly associated with risk of subsequent HA infection (45% vs 11%) [11]. Notably, similar culture-positive rates were observed for swabs collected on day 0, 1, or 2 of admission (Supplementary Table 2), so it is unlikely that this had a significant impact on CA colonization results. For the last 3 months a universal surveillance study for multidrug resistant organisms was conducted for which consent was waived; samples and data from this period were also included in KASPAH (see Supplementary Methods and Supplementary Figure 1). Bethesda, MD 20894, Web Policies 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. Most Klebsiella lineages (n = 69/85, 81%) were identified in just 1 patient, and 60% of patients (n = 64) had their own unique lineage not observed in any other patients (Figure 2, Supplementary Table 3). Most Klebsiella lineages (n = 69/85, 81%) were identified in just 1 patient, and 60% of patients (n = 64) had their own unique lineage not observed in any other patients (Figure 2, Supplementary Table 3). Before Hypervirulent Klebsiella pneumoniae; healthy people; human gut; reservoir Introduction Klebsiella pneumoniae is a member of the family Enterobacteriaceae that is best known for its capa-city to cause infections, including healthcare- associated infections and community-acquired infections (CAIs). Clipboard, Search History, and several other advanced features are temporarily unavailable. The .gov means its official. Outbreak of NDM-1-producing Klebsiella pneumoniae in a Dutch Hospital, with interspecies transfer of the resistance plasmid and unexpected occurrence in unrelated health care centers. Bonomo (C), Midpoint rooted species tree for K. pneumoniae sensu stricto isolates. 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. Inclusion in an NLM database does not imply endorsement of, or agreement with, Klebsiella pneumoniae can cause different types of health care-associated infections, including pneumonia, bloodstream infections, wound or surgical site infections, and meningitis, the CDC states Klebsiella pneumoniae is part of the healthy human microbiome, providing a potential reservoir for infection. Potential conflict of interest. One third of the participants in the ICU screening study (n = 170) contributed 1 or more follow-up screening swabs (Table 1). A 2016 study at the University of Michigan Health System tertiary care hospital reported similar colonization rates (23%) and increased risk of infection following colonization (5.2% in colonized vs 1.3% in noncolonized) [12]. Thank you for submitting a comment on this article. Pujol Of all ICU patients who developed K. pneumoniae infections and contributed baseline screening swabs, 48% (n = 13/27) tested positive for K. pneumoniae GI carriage at baseline (including 8 who were screened >2 days prior to developing the infection). Using culture-free methods, K. pneumoniae was detected in approximately 10% of Human Microbiome Project samples from the mouth, nares, and skin, and 3.8% of stool samples [7]. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author. Abstract. Klebsiella pneumoniae - ScienceDirect These included 2 episodes of pneumonia, 2 wound infections, and 2 UTIs, one of which disseminated to cause bacteremia with sepsis (Table 2, Supplementary Table 3). Abbreviations: GI, gastrointestinal; ICU, intensive care unit; MDR, multidrug-resistant; UTI, urinary tract infection. Melhus 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. Dao Additionally, we investigated whether colonization on admission enhances risk of subsequent K. pneumoniae infection among ICU patients and the relative contribution of patients own gut microbiota and intra-hospital transmission to the burden of K. pneumoniae carriage and infection in the ICU. Gaynes Cheesman MJ, Shivashekaregowda NKH, Cock IE. 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. . Weinstein RA, Gaynes R, Edwards JR; National Nosocomial Infections Surveillance System, Overview of nosocomial infections caused by gram-negative bacilli, Mathai D, Jones RN, Pfaller MA; SENTRY Participant Group North America, Epidemiology and frequency of resistance among pathogens causing urinary tract infections in 1510 hospitalized patients: a report from the SENTRY Antimicrobial Surveillance Program (North America), Species-level analysis of DNA sequence data from the NIH Human Microbiome Project, Gastrointestinal colonization by KPC-producing. Background: Klebsiella pneumoniae is an opportunistic pathogen and leading cause of hospital-associated infections. The main limitations of the study arise from the swabbing procedure to identify K. pneumoniae colonization on admission. Expression of MDR phenotypes elaborated by these bacteria is due to the nature of various plasmids carrying antimicrobial resistance (AMR)-encoding genes, and is a challenge to animal, environmental, and human health alike. A WC FOIA KbvR mutant of Klebsiella pneumoniae affects the synthesis of type 1 fimbriae and provides protection to mice as a live attenuated vaccine. and transmitted securely. et al. et al. . Ultimately, we find that host-to-host spread of K. pneumoniae occurs principally from its intestinal reservoir, and that commensal-colonization-factor-producing Bacteroidetes are sufficient to . C Y RN All trees are maximum likelihood trees inferred from core genome SNP alignments. The overall GI carriage rate at follow-up was 15.3% (n = 26/170), similar to the HA GI carriage rate of 19% (OR = 1.3; 95% CI, 0.712.38). V A total of 143 high-quality whole genome sequences were obtained from 106 patients, including 56 clinical, 80 GI carriage, and 7 throat carriage isolates. The authors gratefully acknowledge the contribution and support of Janine Roney, Mellissa Bryant, Jennifer Williams, Iain Abbott and Noelene Browne at the Alfred Hospital, and the sequencing team at the Wellcome Trust Sanger Institute. Certain environmental niches, e.g. Phylogenetic lineages to which more than one ICU isolate belongs are highlighted and labeled with their corresponding multi-locus sequence type (ST) and the total number of SNPs identified between isolates in the lineage; darker shading indicates multiple patients contributed isolates in that cluster, as per inset legend. Segre Ricart Yet although the majority of K. pneumoniae HA infections are not ESBL or CP [5, 6], there are little data on the frequency and clinical relevance of colonization with K. pneumoniae more generally. JV Frontiers | Exploring Klebsiella pneumoniae in Healthy Poultry Reveals official website and that any information you provide is encrypted A Screening for colonization on admission could limit risk of infection in the colonized patient and others. All statistical analyses were conducted using R (v3.3.1) (details in Supplementary Methods). et al. Cimon A total of 700 milk samples from symptomatic mastitic cows were screened for MDR K. Pneumoniae. Klebsiella pneumoniae; Raman spectroscopy; antimicrobial resistance; foodborne pathogen; infection; pathogenicity; prevalence; virulence. (A), Unrooted tree of all isolates, revealing three distinct species that are typically identified as K. pneumoniae in diagnostic laboratories. Received 2017 Jan 5; Accepted 2017 Mar 21. Although the recruitment rate was low (33%) during the consent-based recruitment period, the demographic features and K. pneumoniae colonization rate in this group were not significantly different from those recruited under the universal surveillance protocol (75% recruitment; Supplementary Figure 1); hence, there is no evidence of significant selection bias. Canbck Whole genome sequencing of Klebsiella pneumoniae clinical - PLOS Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. In this Review, Wyres, Lam and Holt discuss how genomics. For the other 11 lineages that were detected in more than 1 ICU patient, between-patient SNP distances exceeded 80 SNPs per 5 Mbp and ICU admissions were generally nonoverlapping (Supplementary Figure 4). A It is a common opportunistic hospital-associated pathogen, accounting for about one third of all Gram-negative infections overall. Correspondence: K. E. Holt, Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria, Australia (. Huynh BT, Passet V, Rakotondrasoa A, Diallo T, Kerleguer A, Hennart M, Lauzanne A, Herindrainy P, Seck A, Bercion R, Borand L, Pardos de la Gandara M, Delarocque-Astagneau E, Guillemot D, Vray M, Garin B, Collard JM, Rodrigues C, Brisse S. Gut Microbes. Klebsiella pneumoniae: Prevalence, Reservoirs, Antimicrobial Resistance G Klebsiella pneumoniae is a leading cause of hospital-associated (HA) infections. AB Severin Follow-up swabs were repeated each 57 days after baseline for the duration of ICU stay and up to 4 days following transfer to another ward. Lau A total of 49 patients (1.8% of all adult ICU admissions) who spent time in the ICU during their hospital stay were identified as having K. pneumoniae infections (11 ESBL, of which 3 were also CP). DNA was extracted from overnight cultures using a phenol:chloroform protocol and phase lock gel tubes and sequenced via Illumina HiSeq to generate 125 bp paired-end reads (see Supplementary Methods). Highly conserved composite transposon harbouring aerobactin . Isolates falling within the same lineage were further investigated to identify pairwise SNPs via assembly and read mapping; full details of genomic analyses are given in Supplementary Methods. The main limitations of the study arise from the swabbing procedure to identify K. pneumoniae colonization on admission. Critical asthma exacerbations in children are associated with a distinct inflammatory profile. (C), Midpoint rooted species tree for K. pneumoniae sensu stricto isolates. R Type of infection and source of infection outlined (position/presence in transmission chain, prior colonization, unknown). Laurent C, Rodriguez-Villalobos H, Rost F, et al. . Scale bars indicate average number of substitutions per site across the genome. We found strong evidence that a large proportion of ICU K. pneumoniae infections are attributable to patients own GI microbiota: (i) of all 49 K. pneumoniae infections diagnosed in ICU patients during the study period, 49% were associated with K. pneumoniae lineages unique to the patient; and (ii) of the 27 K. pneumoniae infections diagnosed in ICU patients from whom screening swabs were obtained, 48% occurred in patients who tested positive for prior GI colonization with K. pneumoniae. Resistance mechanisms, epidemiology, and approaches to screening for vancomycin-resistant enterococcus in the health care setting. Carrier rates of K. pneumoniae in the community range from 5 to 38 percent in stool samples and 1 to 6 percent in the nasopharynx; Klebsiella species are rarely carried on the skin . However, the frequency of gut colonization and its contribution to infections are not well characterized. HA carriage among ICU patients was estimated to be much higher at 19%, with 12% of patients converting from culture-negative at baseline to culture-positive on follow-up. S HHS Vulnerability Disclosure, Help Population genomics of Klebsiella pneumoniae - Nature Supplementary materials are available at Clinical Infectious Diseases online. Gastrointestinal Carriage Is a Major Reservoir of Klebsiella pneumoniae Klebsiella pneumoniae: Prevalence, Reservoirs, Antimicrobial Resistance, Pathogenicity, and Infection: A Hitherto Unrecognized Zoonotic Bacterium | Request PDF. Federal government websites often end in .gov or .mil. official website and that any information you provide is encrypted Most of the infections associated with transmission were MDR (3/4 donors and 3/6 recipients), yielding a strong association between MDR infections and transmission in the ICU (OR = 13.6, P = .002). Von Gottberg Nosocomial klebsiella infections: intestinal colonization as a reservoir, Molecular Epidemiology of colonizing and infecting isolates of, FastTree: computing large minimum evolution trees with profiles instead of a distance matrix, FastTree 2approximately maximum-likelihood trees for large alignments. Using 25 and 10 SNPs per 5 Mbp as cut-offs to indicate likely and very likely strain sharing between patients, we identified 5 groups of ICU patients that likely shared Klebsiella strains. MA Wertheim Raz-Pasteur Note that unknown source also includes one patient who had a wound infection diagnosed as K. pneumoniae but genome sequencing found the subcultured isolate to be dominated by A. baumannii DNA; this is consistent with mixed infection or contamination, and prevents reliable comparative analysis with other K. pneumoniae strains. A . Key strengths of this study are the prospective cohort design and the use of WGS to confirm species identification and strain relatedness for all K. pneumoniae isolated from ICU patients, regardless of antimicrobial susceptibility. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. N Hence our study probably underestimates the rate of colonization in the community and the contribution of colonisation to subsequent infection. JA Lundberg Clinical Epidemiology, Risk Factors, and Control Strategies of Our data demonstrate that K. pneumoniae is a fairly common component of the human GI microbiome (5.9%) and of clinical significance in the ICU setting, as: (i) K. pneumoniae carriage on admission to ICU was significantly associated with subsequent K. pneumoniae infection (OR = 6.9, P = .0003), consistent with the results reported from the 1970s Denver study (OR = 4.0, P = .0009 [11]) and the 2016 Michigan study (OR = 4.1, P = .00002 [12]); and (ii) the WGS data confirmed a direct link between colonizing and infecting strains in 13 patients (80% of those with paired isolates available for testing), also consistent with the Michigan study [12]. Dehal Microbiology Unit, Alfred Health, Melbourne, Victoria, Australia; 4 Using bacteriological culture, a 2010 study detected nasopharyngeal carriage in 15% of Indonesian adults and 7% of children [8], whereas a 2014 study detected nasopharyngeal carriage in 2.7% of Vietnamese adults and throat carriage in 14% [9]. Oxford University Press is a department of the University of Oxford. S Fifty-four patients (10.8%) tested positive at baseline screening (50 GI carriage only, 2 throat carriage only, 2 both). MR Klebsiella pneumoniae is part of the healthy human microbiome, providing a potential reservoir for infection. RM Patients With Infection(s) and Time in the ICU. Circles indicate K. pneumoniae infection isolates (red, belonging to the lineage; black, other lineage); triangles indicate rectal screening swabs (red, K. pneumoniae belonging to the lineage; black, K. pneumoniae of another lineage; unfilled, negative for K. pneumoniae). Of the 4 donors in the transmission chains, 3 had pneumonia and 1 had a wound infection. Klebsiella pneumonia is a gram-negative bacteria that . Individuals referred to the Alfred Hospital ICU by the trauma ward of another hospital were assumed to be emergency admissions from the community and were assigned to the CA/Day 02 or HA/Day 3+ screening groups according to the day of first swab relative to their Alfred Hospital admission. Unknown source includes those infections for which there is no genetic or epidemiological evidence to indicate whether the infection has arisen from a patients own carriage strains or through transmission from another source; numbers in brackets indicate the number of such infections associated with a lineage that was unique to that patient. Pneumonia was the most frequent form of K. pneumoniae infection in ICU patients (60%), followed by wound infections (15%), nondisseminated urinary tract infection (UTI) (10%), and bacteremia with sepsis (8%). This suggests that although measures to reduce cross-contamination between patients are necessary, they are not sufficient to eliminate K. pneumoniae infections in hospitalized patients, and measures to minimize the risk of infection with the patients own microbiome deserves significant attention [2123]. Glick SB, Samson DJ, Huang ES, Vats V, Aronson N, Weber SG. Lineages are boxed and labeled with their multi-locus sequence type (ST). et al. A major reservoir in the patient population could not be unveiled. Scale bars indicate average number of substitutions per site across the genome. Open Access Peer-reviewed Research Article Whole genome sequencing of Klebsiella pneumoniae clinical isolates sequence type 627 isolated from Egyptian patients Shymaa Enany , Samira Zakeer, Aya A. Diab, Usama Bakry, Ahmed A. Sayed Whole genome sequencing of Klebsiella pneumoniae clinical isolates sequence type 627 isolated from Egyptian patients K. pneumoniae is the major species within this complex. D The .gov means its official. Patient groups: ICU CA/Day 02, rectal screening swab obtained on day 0, 1, or 2 of admission to Alfred Hospital and not referred from another hospital (except from trauma unit); ICU HA/Day 3+, rectal screening swab obtained on day 3 or later of admission to Alfred Hospital or referred from another hospital. 2018 Jan 22;8:4. doi: 10.3389/fcimb.2018.00004. Epub 2023 Apr 18. . National Library of Medicine Note the log10 scale which excludes display of 1 strain pair that was separated by 0 SNPs. A similar study introduced screening for ESBL K. pneumoniae in order to limit and prevent current and future outbreaks [29]. Carriage was detected at the same frequency in males and females (11.0% vs 10.4%; P = .9), and the median age of carriers was moderately higher than that of carriage-negative participants (67 vs 58 years, Supplementary Figure 2; P = .06, Wilcoxon rank-sum test). *Possible mixed isolate (0.020.1 het/hom SNP ratio, excluded from pairwise SNP analysis in Figure 3). Clinical epidemiology of the global expansion of, Genomic analysis of diversity, population structure, virulence, and antimicrobial resistance in. Individuals referred to the Alfred Hospital ICU by the trauma ward of another hospital were assumed to be emergency admissions from the community and were assigned to the CA/Day 02 or HA/Day 3+ screening groups according to the day of first swab relative to their Alfred Hospital admission. The Author 2017. Klebsiella pneumoniae : an increasing threat to public health Weber FOIA Abbreviations: GI, gastrointestinal; ICU, intensive care unit; MDR, multidrug-resistant. Klebsiella pneumoniae bacterial outbreak at Seattle hospital: 9 deaths Gardam . Here, we assessed the prevalence of K. pneumoniae colonization in an at-risk cohort in an intensive care unit (ICU) within a modern, well-equipped, and well-managed tertiary teaching hospital in Australia. H Klebsiella pneumoniae : when a colonizer turns bad - Nature Six infection episodes (n = 6/49, 12%) were attributable to these intra-hospital transmission chains (n = 4 ST681 [K. variicola], n = 1 ST323, n = 1 ST231; Figure 4).

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