ABSTRACT
Group B Streptococcus (GBS) is a major human and animal pathogen that threatens public health and food security. Spill-over and spill-back between host species is possible due to adaptation and amplification of GBS in new niches but the evolutionary and functional mechanisms underpinning those phenomena are poorly known. Based on analysis of 1,254 curated genomes from all major GBS host species and six continents, we found that the global GBS population comprises host-generalist, host-adapted and host-restricted sublineages, which are found across host groups, preferentially within one host group, or exclusively within one host group, respectively, and show distinct levels of recombination. Strikingly, the association of GBS genomes with the three major host groups (humans, cattle, fish) is driven by a single accessory gene cluster per host, regardless of sublineage or the breadth of host spectrum. Moreover, those gene clusters are shared with other streptococcal species occupying the same niche and are functionally relevant for host tropism. Our findings demonstrate (1) the heterogeneity of genome plasticity within a bacterial species of public health importance, enabling the identification of high-risk clones; (2) the contribution of inter-species gene transmission to the evolution of GBS; and (3) the importance of considering the role of animal hosts, and the accessory gene pool associated with their microbiota, in the evolution of multi-host bacterial pathogens. Collectively, these phenomena may explain the adaptation and clonal expansion of GBS in animal reservoirs and the risk of spill-over and spill-back between animals and humans.
ABSTRACT
Sortase-assembled pili contribute to virulence in many Gram-positive bacteria. In Enterococcus faecalis, the endocarditis and biofilm-associated pilus (Ebp) is polymerized on the membrane by sortase C (SrtC) and attached to the cell wall by sortase A (SrtA). In the absence of SrtA, polymerized pili remain anchored to the membrane (i.e. off-pathway). Here we show that the high temperature requirement A (HtrA) bifunctional chaperone/protease of E. faecalis is a quality control system that clears aberrant off-pathway pili from the cell membrane. In the absence of HtrA and SrtA, accumulation of membrane-bound pili leads to cell envelope stress and partially induces the regulon of the ceftriaxone resistance-associated CroRS two-component system, which in turn causes hyper-piliation and cell morphology alterations. Inactivation of croR in the OG1RF ΔsrtAΔhtrA background partially restores the observed defects of the ΔsrtAΔhtrA strain, supporting a role for CroRS in the response to membrane perturbations. Moreover, absence of SrtA and HtrA decreases basal resistance of E. faecalis against cephalosporins and daptomycin. The link between HtrA, pilus biogenesis and the CroRS two-component system provides new insights into the E. faecalis response to endogenous membrane perturbations.
Subject(s)
Aminoacyltransferases , Bacterial Proteins , Biofilms , Cysteine Endopeptidases , Enterococcus faecalis , Fimbriae, Bacterial , Molecular Chaperones , Fimbriae, Bacterial/genetics , Fimbriae, Bacterial/metabolism , Aminoacyltransferases/genetics , Aminoacyltransferases/metabolism , Enterococcus faecalis/genetics , Cysteine Endopeptidases/genetics , Cysteine Endopeptidases/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Molecular Chaperones/genetics , Molecular Chaperones/metabolism , Biofilms/growth & development , Cell Membrane/metabolism , Gene Expression Regulation, Bacterial , Virulence/genetics , Anti-Bacterial Agents/pharmacology , Ceftriaxone/pharmacologyABSTRACT
The tkt (transketolase) gene is one of the seven gene fragments used in the multilocus sequence typing (MLST) system for Streptococcus agalactiae. We discovered that the tkt_134 allele is derived from a homologous gene (which we designate tktX) that is not present in all S. agalactiae; all known strains that contain a match to the tkt_134 allele also contain a gene sequence that is much closer in sequence identity to the other non-tkt_134 alleles (i.e., the canonical tkt gene) in the database. Based on these data, the tkt_134 allele has been removed from the MLST database as of September 2021, and all sequence types containing tkt_134 have also been removed.IMPORTANCEMultilocus sequence typing (MLST) databases are a common good and remain important for research, medical, and epidemiological purposes. This remains true even in the context of widespread whole-genome sequencing. We discovered a contaminating allele of the tkt gene in the S. agalactiae MLST database that led to unstable, ambiguous, or erroneous MLST assignment. The allele has since been removed from the public database based on the results presented in this manuscript.
ABSTRACT
IMPORTANCE: Although E. faecalis is a common wound pathogen, its pathogenic mechanisms during wound infection are unexplored. Here, combining a mouse wound infection model with in vivo transposon and RNA sequencing approaches, we identified the E. faecalis purine biosynthetic pathway and galactose/mannose MptABCD phosphotransferase system as essential for E. faecalis acute replication and persistence during wound infection, respectively. The essentiality of purine biosynthesis and the MptABCD PTS is driven by the consumption of purine metabolites by E. faecalis during acute replication and changing carbohydrate availability during the course of wound infection. Overall, our findings reveal the importance of the wound microenvironment in E. faecalis wound pathogenesis and how these metabolic pathways can be targeted to better control wound infections.
Subject(s)
Urinary Tract Infections , Wound Infection , Animals , Mice , Enterococcus faecalis/genetics , Enterococcus faecalis/metabolism , Carbohydrates , PurinesABSTRACT
AIM: Fluoroquinolone (FQ) is a potent antibiotic class. However, resistance to this class emerges quickly which hinders its application. In this study, mechanisms leading to the emergence of multidrug-resistant (MDR) Staphylococcus aureus (S. aureus) strains under FQ exposure were investigated. METHODOLOGY: S. aureus ATCC 29213 was serially exposed to ciprofloxacin (CIP), ofloxacin (OFL), or levofloxacin (LEV) at sub-minimum inhibitory concentrations (sub-MICs) for 12 days to obtain S. aureus -1 strains and antibiotic-free cultured for another 10 days to obtain S. aureus-2 strains. The whole genome (WGS) and target sequencing were applied to analyze genomic alterations; and RT-qPCR was used to access the expressions of efflux-related genes, alternative sigma factors, and genes involved in FQ resistance. RESULTS: A strong and irreversible increase of MICs was observed in all applied FQs (32 to 128 times) in all S. aureus-1 and remained 16 to 32 times in all S. aureus-2. WGS indicated 10 noticeable mutations occurring in all FQ-exposed S. aureus including 2 insdel mutations in SACOL0573 and rimI; a synonymous mutation in hslO; and 7 missense mutations located in an untranslated region. GrlA, was found mutated (R570H) in all S. aureus-1 and -2. Genes encoding for efflux pumps and their regulator (norA, norB, norC, and mgrA); alternative sigma factors (sigB and sigS); acetyltransferase (rimI); methicillin resistance (fmtB); and hypothetical protein BJI72_0645 were overexpressed in FQ-exposed strains. CONCLUSION: The emergence of MDR S. aureus was associated with the mutations in the FQ-target sequences and the overexpression of efflux pump systems and their regulators.
Subject(s)
Staphylococcal Infections , Staphylococcus aureus , Humans , Staphylococcus aureus/genetics , Fluoroquinolones/pharmacology , Anti-Bacterial Agents/pharmacology , Ciprofloxacin/pharmacology , Microbial Sensitivity Tests , Genomics , Bacterial Proteins/geneticsABSTRACT
In South East Asia, Streptococcus agalactiae ST283 causes sepsis in healthy adults. Raw freshwater fish consumption is the only known risk factor. These two case reports are the first from Malaysia. Although they cluster with Singapore ST283, the epidemiology is complicated by the flow of people and fish across borders.
Subject(s)
Sepsis , Streptococcus agalactiae , Adult , Animals , Humans , Malaysia/epidemiology , Streptococcus agalactiae/genetics , Fresh Water , Risk FactorsABSTRACT
Group B Streptococcus (GBS) is a major pathogen of humans and aquatic species. Fish have recently been recognized as the source of severe invasive foodborne GBS disease, caused by sequence type (ST) 283, in otherwise healthy adults in Southeast Asia. Thailand and Vietnam are among the major aquaculture producers in Southeast Asia, with GBS disease reported in fish as well as frogs in both countries. Still, the distribution of potentially human-pathogenic GBS in aquaculture species is poorly known. Using 35 GBS isolates from aquatic species in Thailand collected from 2007 to 2019 and 43 isolates from tilapia collected in Vietnam in 2018 and 2019, we have demonstrated that the temporal, geographical, and host-species distribution of GBS ST283 is broader than previously known, whereas the distribution of ST7 and the poikilothermic lineage of GBS are geographically restricted. The gene encoding the human GBS virulence factor C5a peptidase, scpB, was detected in aquatic ST283 from Thailand but not in ST283 from Vietnam or in ST7 from either country, mirroring current reports of GBS strains associated with human sepsis. The observed distribution of strains and virulence genes is likely to reflect a combination of spill-over, host adaptation through the gain and loss of mobile genetic elements, and current biosecurity practices. The plastic nature of the GBS genome and its importance as a human, aquatic, and potentially foodborne pathogen suggests that active surveillance of GBS presence and its evolution in aquaculture systems may be justified.
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OBJECTIVES: Systemic strategies for combating antimicrobial resistance (AMR) currently focus on limiting antibiotic use and have been generally insufficient in preventing the rise of AMR. Additionally, they often generate other adverse incentives, such as discouraging pharmaceutical companies from investing in research and development of new antibiotics, further exacerbating the problem. This paper proposes a novel systemic strategy for tackling AMR, which we term 'antiresistics': any intervention (whether a small molecule, genetic element, phage, or whole organism) that reduces resistance rates in pathogen populations. A prime example of an antiresistic would be a small molecule that specifically disrupts the maintenance of antibiotic resistance plasmids. Of note, an antiresistic would be expected to have a population-level effect and not necessarily be useful on a time scale relevant to individual patients. METHODS: We developed a mathematical model to assess the effect of antiresistics on population resistance levels and calibrated it to longitudinal data available at the country level. We also estimated potential effects on idealised rates for the introduction of new antibiotics. RESULTS: The model shows that greater use of antiresistics allows for greater usage of existing antibiotics. This leads to an ability to maintain a constant overall rate of antibiotic efficacy with a slower rate of developing new antibiotics; subsequently, antiresistics have a positive benefit on the effective lifetime and thus profitability of antibiotics. CONCLUSIONS: By directly reducing resistance rates, antiresistics can provide clear qualitative benefits (which may be quantitatively large) in terms of existing antibiotic efficacy, longevity, and alignment of incentives.
Subject(s)
Anti-Bacterial Agents , Humans , Anti-Bacterial Agents/therapeutic use , Drug Resistance, MicrobialABSTRACT
The bacterial cell membrane is an interface for cell envelope synthesis, protein secretion, virulence factor assembly, and a target for host cationic antimicrobial peptides (CAMPs). To resist CAMP killing, several Gram-positive pathogens encode the multiple peptide resistance factor (MprF) enzyme that covalently attaches cationic amino acids to anionic phospholipids in the cell membrane. While E. faecalis encodes two mprF paralogs, MprF2 plays a dominant role in conferring resistance to killing by the CAMP human ß-defensin 2 (hBD-2) in E. faecalis strain OG1RF. The goal of the current study is to understand the broader lipidomic and functional roles of E. faecalis mprF. We analyzed the lipid profiles of parental wild-type and mprF mutant strains and show that while ΔmprF2 and ΔmprF1 ΔmprF2 mutants completely lacked cationic lysyl-phosphatidylglycerol (L-PG), the ΔmprF1 mutant synthesized ~70% of L-PG compared to the parent. Unexpectedly, we also observed a significant reduction of PG in ΔmprF2 and ΔmprF1 ΔmprF2. In the mprF mutants, particularly ΔmprF1 ΔmprF2, the decrease in L-PG and phosphatidylglycerol (PG) is compensated by an increase in a phosphorus-containing lipid, glycerophospho-diglucosyl-diacylglycerol (GPDGDAG), and D-ala-GPDGDAG. These changes were accompanied by a downregulation of de novo fatty acid biosynthesis and an accumulation of long-chain acyl-acyl carrier proteins (long-chain acyl-ACPs), suggesting that the suppression of fatty acid biosynthesis was mediated by the transcriptional repressor FabT. Growth in chemically defined media lacking fatty acids revealed severe growth defects in the ΔmprF1 ΔmprF2 mutant strain, but not the single mutants, which was partially rescued through supplementation with palmitic and stearic acids. Changes in lipid homeostasis correlated with lower membrane fluidity, impaired protein secretion, and increased biofilm formation in both ΔmprF2 and ΔmprF1 ΔmprF2, compared to the wild type and ΔmprF1. Collectively, our findings reveal a previously unappreciated role for mprF in global lipid regulation and cellular physiology, which could facilitate the development of novel therapeutics targeting MprF. IMPORTANCE The cell membrane plays a pivotal role in protecting bacteria against external threats, such as antibiotics. Cationic phospholipids such as lysyl-phosphatidyglycerol (L-PG) resist the action of cationic antimicrobial peptides through electrostatic repulsion. Here we demonstrate that L-PG depletion has several unexpected consequences in Enterococcus faecalis, including a reduction of phosphatidylglycerol (PG), enrichment of a phosphorus-containing lipid, reduced fatty acid synthesis accompanied by an accumulation of long-chain acyl-acyl carrier proteins (long chain acyl-ACPs), lower membrane fluidity, and impaired secretion. These changes are not deleterious to the organism as long as exogenous fatty acids are available for uptake from the culture medium. Our findings suggest an adaptive mechanism involving compensatory changes across the entire lipidome upon removal of a single phospholipid modification. Such adaptations must be considered when devising antimicrobial strategies that target membrane lipids.
Subject(s)
Anti-Bacterial Agents , Anti-Infective Agents , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/metabolism , Enterococcus faecalis/metabolism , Drug Resistance, Bacterial , Phospholipids/metabolism , Anti-Infective Agents/metabolism , Fatty Acids/metabolism , Phosphatidylglycerols/metabolism , Antimicrobial Cationic Peptides/pharmacology , Antimicrobial Cationic Peptides/metabolism , Cations/metabolism , Carrier Proteins/metabolism , Bacterial Proteins/metabolismABSTRACT
Background: Streptococcus agalactiae is a normal commensal of the human gastro-intestinal and female genital tracts. It causes serious disease in neonates and pregnant women, as well as non-pregnant adults. Food-borne outbreaks have also been described. A link between invasive Group B streptococcus (GBS) infection in humans caused by S. agalactiae serotype III-4, sequence type 283 (ST283) and the consumption of raw fresh-water fish was first described in Singapore in 2015. Case presentation: We report the simultaneous occurrence of acute fever and myalgia in two sisters who were visiting Laos. Both were found to have invasive GBS ST283 infection, confirmed by blood culture. Infection was temporally linked to fish consumption. They responded well to intravenous antibiotics within 48 hours. Conclusions: Food-borne transmission of Streptococcus agalactiae is an important and under-recognised source of serious human disease throughout Southeast Asia and possibly beyond.
ABSTRACT
Despite dramatic advances in genomics, connecting genotypes to phenotypes is still challenging. Sexual genetics combined with linkage analysis is a powerful solution to this problem but generally unavailable in bacteria. We build upon a strong negative selection system to invent mass allelic exchange (MAE), which enables hybridization of arbitrary (including pathogenic) strains of Escherichia coli. MAE reimplements the natural phenomenon of random cross-overs, enabling classical linkage analysis. We demonstrate the utility of MAE with virulence-related gain-of-function screens, discovering that transfer of a single operon from a uropathogenic strain is sufficient for enabling a commensal E. coli to form large intracellular bacterial collections within bladder epithelial cells. MAE thus enables assaying natural allelic variation in E. coli (and potentially other bacteria), complementing existing loss-of-function genomic techniques.
Subject(s)
Escherichia coli Infections , Escherichia coli Proteins , Urinary Tract Infections , Uropathogenic Escherichia coli , Humans , Uropathogenic Escherichia coli/genetics , Urinary Tract Infections/microbiology , Escherichia coli Infections/microbiology , Escherichia coli Proteins/genetics , Virulence/genetics , Virulence Factors/geneticsABSTRACT
Long-term colonization of the gut microbiome by carbapenemase-producing Enterobacteriaceae (CPE) is a growing area of public health concern as it can lead to community transmission and rapid increase in cases of life-threatening CPE infections. Here, leveraging the observation that many subjects are decolonized without interventions within a year, we used longitudinal shotgun metagenomics (up to 12 timepoints) for detailed characterization of ecological and evolutionary dynamics in the gut microbiome of a cohort of CPE-colonized subjects and family members (n = 46; 361 samples). Subjects who underwent decolonization exhibited a distinct ecological shift marked by recovery of microbial diversity, key commensals and anti-inflammatory pathways. In addition, colonization was marked by elevated but unstable Enterobacteriaceae abundances, which exhibited distinct strain-level dynamics for different species (Escherichia coli and Klebsiella pneumoniae). Finally, comparative analysis with whole-genome sequencing data from CPE isolates (n = 159) helped identify substrain variation in key functional genes and the presence of highly similar E. coli and K. pneumoniae strains with variable resistance profiles and plasmid sharing. These results provide an enhanced view into how colonization by multi-drug-resistant bacteria associates with altered gut ecology and can enable transfer of resistance genes, even in the absence of overt infection and antibiotic usage.
Subject(s)
Carbapenem-Resistant Enterobacteriaceae , Gastrointestinal Microbiome , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Carbapenem-Resistant Enterobacteriaceae/genetics , Escherichia coli/genetics , Humans , Klebsiella pneumoniae/genetics , beta-Lactamases/genetics , beta-Lactamases/metabolismABSTRACT
Salmonella Enteritidis is a major foodborne pathogen worldwide. In this study, a total of 276 S. enteritidis isolates, collected between 2016 and 2017 from human, food and farm/slaughterhouse samples, were studied to enhance the understanding of the epidemiology of human salmonellosis in Singapore. Results showed all 276 isolates belonged either to ST1925 (70.3%) or ST11 (29.7%), with ST11 being significantly more frequent in extra-intestinal isolates and chicken isolates. Food isolates, most of which were from poultry, showed the highest prevalence of resistance (33-37%) against beta-lactams or beta-lactams/beta-lactamase inhibitor combination (ampicillin, piperacillin and ampicillin/sulbactam). The analysis showed the detection of genes associated with resistance to aminoglycoside genes (99.6%), tetracycline (55.1%), and beta-lactams (14.9%) of all isolates. Nine types of plasmids were found in 266 isolates; the most common incompatibility group profiles were IncFIB(S)-IncFII(S)-IncX1 (72.2%) and IncFIB(S)-IncFII(S) (15.8%). Most plasmid harbouring isolates from chicken (63.6%, 14/22) and from human (73.8%, 175/237) shared the same plasmid profile (IncFIB(S)-IncFII(S)-IncX1). SNP analysis showed clustering of several isolates from poultry food products and human isolates, suggesting phylogenetic relatedness among these isolates. Lastly, this study provides important epidemiological insights on the application of phenotypic and next-generation sequencing (NGS) tools for improved food safety and public health surveillance and outbreak investigation of S.enteritidis.
Subject(s)
Chickens , Salmonella enteritidis , Ampicillin , Animals , Anti-Bacterial Agents/pharmacology , Humans , Microbial Sensitivity Tests , Phylogeny , Poultry , Salmonella enteritidis/genetics , Singapore/epidemiology , beta-LactamsABSTRACT
Circulating Ly6Chi monocytes often undergo cellular death upon exhaustion of their antibacterial effector functions, which limits their capacity for subsequent macrophage differentiation. This shrouds the understanding on how the host replaces the tissue-resident macrophage niche effectively during bacterial invasion to avert infection morbidity. Here, we show that proliferating transitional premonocytes (TpMos), an immediate precursor of mature Ly6Chi monocytes (MatMos), were mobilized into the periphery in response to acute bacterial infection and sepsis. TpMos were less susceptible to apoptosis and served as the main source of macrophage replenishment when MatMos were vulnerable toward bacteria-induced cellular death. Furthermore, TpMo and its derived macrophages contributed to host defense by balancing the proinflammatory cytokine response of MatMos. Consequently, adoptive transfer of TpMos improved the survival outcome of lethal sepsis. Our findings hence highlight a protective role for TpMos during bacterial infections and their contribution toward monocyte-derived macrophage heterogeneity in distinct disease outcomes.
Subject(s)
Bacterial Infections , Sepsis , Animals , Cytokines , Humans , Macrophages , Mice , Mice, Inbred C57BL , MonocytesABSTRACT
Group B Streptococcus (GBS; Streptococcus agalactiae) is the most common cause of neonatal meningitis and a rising cause of sepsis in adults. Recently, it has also been shown to cause foodborne disease. As with many other bacteria, the polysaccharide capsule of GBS is antigenic, enabling its use for strain serotyping. Recent advances in DNA sequencing have made sequence-based typing attractive (as has been implemented for several other bacteria, including Escherichia coli, Klebsiella pneumoniae species complex, Streptococcus pyogenes, and others). For GBS, existing WGS-based serotyping systems do not provide complete coverage of all known GBS serotypes (specifically including subtypes of serotype III), and none are simultaneously compatible with the two most common data types, raw short reads and assembled sequences. Here, we create a serotyping database (GBS-SBG, GBS Serotyping by Genome Sequencing), with associated scripts and running instructions, that can be used to call all currently described GBS serotypes, including subtypes of serotype III, using both direct short-read- and assembly-based typing. We achieved higher concordance using GBS-SBG on a previously reported data set of 790 strains. We further validated GBS-SBG on a new set of 572 strains, achieving 99.8% concordance with PCR-based molecular serotyping using either short-read- or assembly-based typing. The GBS-SBG package is publicly available and will hopefully accelerate and simplify serotyping by sequencing for GBS.
Subject(s)
Fishes/microbiology , Foodborne Diseases/microbiology , Streptococcus agalactiae/classification , Whole Genome Sequencing/methods , Animals , Databases, Genetic , Genome Size , Genome, Bacterial , High-Throughput Nucleotide Sequencing , Humans , Phylogeny , Serotyping , Streptococcus agalactiae/genetics , Streptococcus agalactiae/isolation & purificationABSTRACT
DNA methylation is a common epigenetic mark that influences transcriptional regulation, and therefore cellular phenotype, across all domains of life. In particular, both orphan methyltransferases and those from phasevariable restriction modification systems (RMSs) have been co-opted to regulate virulence epigenetically in many bacteria. We now show that three distinct non-phasevariable Type I RMSs in Escherichia coli have no measurable impact on gene expression, in vivo virulence, or any of 1190 in vitro growth phenotypes. We demonstrated this using both Type I RMS knockout mutants as well as heterologous installation of Type I RMSs into two E. coli strains. These data provide three clear and currently rare examples of restriction modification systems that have no impact on their host organism's gene regulation. This leads to the possibility that other such nonregulatory methylation systems may exist, broadening our view of the potential role that RMSs may play in bacterial evolution.
Subject(s)
DNA Methylation , DNA Restriction-Modification Enzymes , Escherichia coli/genetics , Animals , Escherichia coli/growth & development , Escherichia coli/metabolism , Escherichia coli Infections/microbiology , Gene Expression Regulation, Bacterial , Mice , Urinary Tract Infections/microbiology , Uropathogenic Escherichia coli/genetics , Uropathogenic Escherichia coli/growth & development , Uropathogenic Escherichia coli/metabolism , Uropathogenic Escherichia coli/pathogenicityABSTRACT
The draft genome sequences of 21 Salmonella isolates obtained from poultry production chains in Hat Yai City, Songkhla Province, Thailand, are reported in this study. Our study revealed that there was Salmonella environmental contamination along poultry production chains and cross-contamination among poultry through inanimate surfaces in the environment.
ABSTRACT
Movement of patients in a health care network poses challenges for the control of carbapenemase-producing Enterobacteriaceae (CPE). We aimed to identify intra- and interfacility transmission events and facility type-specific risk factors of CPE in an acute-care hospital (ACH) and its intermediate-term and long-term-care facilities (ILTCFs). Serial cross-sectional studies were conducted in June and July of 2014 to 2016 to screen for CPE. Whole-genome sequencing was done to identify strain relatedness and CPE genes (blaIMI, blaIMP-1, blaKPC-2, blaNDM-1, and blaOXA-48). Multivariable logistic regression models, stratified by facility type, were used to determine independent risk factors. Of 5,357 patients, half (55%) were from the ACH. CPE prevalence was 1.3% in the ACH and 0.7% in ILTCFs (P = 0.029). After adjusting for sociodemographics, screening year, and facility type, the odds of CPE colonization increased significantly with a hospital stay of ≥3 weeks (adjusted odds ratio [aOR], 2.67; 95% confidence interval [CI], 1.17 to 6.05), penicillin use (aOR, 3.00; 95% CI, 1.05 to 8.56), proton pump inhibitor use (aOR, 3.20; 95% CI, 1.05 to 9.80), dementia (aOR, 3.42; 95% CI, 1.38 to 8.49), connective tissue disease (aOR, 5.10; 95% CI, 1.19 to 21.81), and prior carbapenem-resistant Enterobacteriaceae (CRE) carriage (aOR, 109.02; 95% CI, 28.47 to 417.44) in the ACH. For ILTCFs, presence of wounds (aOR, 5.30; 95% CI, 1.01 to 27.72), respiratory procedures (aOR, 4.97; 95% CI, 1.09 to 22.71), vancomycin-resistant enterococcus carriage (aOR, 16.42; 95% CI, 1.52 to 177.48), and CRE carriage (aOR, 758.30; 95% CI, 33.86 to 16,982.52) showed significant association. Genomic analysis revealed only possible intra-ACH transmission and no evidence for ACH-to-ILTCF transmission. Although CPE colonization was predominantly in the ACH, risk factors varied between facilities. Targeted screening and precautionary measures are warranted.
Subject(s)
Carbapenem-Resistant Enterobacteriaceae , Enterobacteriaceae Infections , Anti-Bacterial Agents/therapeutic use , Bacterial Proteins/genetics , Carbapenem-Resistant Enterobacteriaceae/genetics , Cross-Sectional Studies , Delivery of Health Care , Enterobacteriaceae Infections/drug therapy , Enterobacteriaceae Infections/epidemiology , Hospitals , Humans , Singapore , beta-Lactamases/geneticsABSTRACT
OBJECTIVES: To estimate the transmission rate of carbapenemase-producing Enterobacteriaceae (CPE) in households with recently hospitalized CPE carriers. METHODS: We conducted a prospective case-ascertained cohort study. We identified the presence of CPE in stool samples from index subjects, household contacts and companion animals and environmental samples at regular intervals. Linked transmissions were identified by WGS. A Markov model was constructed to estimate the household transmission potential of CPE. RESULTS: Ten recently hospitalized index patients and 14 household contacts were included. There were seven households with one contact, two households with two contacts, and one household with three contacts. Index patients were colonized with blaOXA-48-like (nâ=â4), blaKPC-2 (nâ=â3), blaIMP (nâ=â2), and blaNDM-1 (nâ=â1), distributed among divergent species of Enterobacteriaceae. After a cumulative follow-up time of 9.0 years, three family members (21.4%, 3/14) acquired four different types of CPE in the community (hazard rate of 0.22/year). The probability of CPE transmission from an index patient to a household contact was 10% (95% CI 4%-26%). CONCLUSIONS: We observed limited transmission of CPE from an index patient to household contacts. Larger studies are needed to understand the factors associated with household transmission of CPE and identify preventive strategies.