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1.
PLoS One ; 19(5): e0302929, 2024.
Article in English | MEDLINE | ID: mdl-38713699

ABSTRACT

BACKGROUND: Recognised as essential for high-quality dementia service, person-centred care aims to understand and respect the unique needs of each individual. Self-experience practices may offer caregivers an opportunity to acquire knowledge, empathy, and skills related to person-centred care, especially through recreating experiences similar to dementia. Given the need to enhance the understanding of self-experience practices in dementia care, a more comprehensive investigation of these training interventions for (future) caregivers is needed. METHODS: We conducted a scoping review to map the evidence on the use of self-experience practices in dementia training. We systematically searched Cochrane Library, MEDLINE via PubMed, CINAHL, and Web of Science. We also searched for grey literature, as well as registry entries, and conducted backward citation tracking of included reviews. We analysed data on intervention characteristics, factors influencing the implementation, and learning outcomes based on Kirkpatrick's model. RESULTS: We included 44 reports across 30 intervention programmes. The majority of reports (91%) were published from 2016 onwards, with 32% originating from the USA and 25% from the UK. We identified passive, interactive, immersive, and multicomponent self-experience interventions in dementia education and training. Learning outcomes based on Kirkpatrick's model were fairly distributed across all identified modalities. Both consumers and providers emphasised aspects related to the development and implementation of practices, particularly organisational-related considerations such as temporal and spatial planning of trainings. CONCLUSIONS: Our review highlights diverse interventions incorporating self-experience practices, with an increasing role for technological tools. While self-experience interventions engage participants, the impact on individuals with dementia and organisational levels remain largely unreported. Our overview, informed by current literature, underscores unique considerations and challenges associated with dementia-related self-experience practices. Implementing and evaluating complex training interventions using self-experience practices should consider ethical aspects. TRIAL REGISTRATION: Registry: Registered within the Open Science Framework (available at https://osf.io/fycxa/).


Subject(s)
Caregivers , Dementia , Humans , Dementia/therapy , Caregivers/psychology , Patient-Centered Care
3.
Sensors (Basel) ; 21(23)2021 Nov 30.
Article in English | MEDLINE | ID: mdl-34883995

ABSTRACT

The global population is aging in an unprecedented manner and the challenges for improving the lives of older adults are currently both a strong priority in the political and healthcare arena. In this sense, preventive measures and telemedicine have the potential to play an important role in improving the number of healthy years older adults may experience and virtual coaching is a promising research area to support this process. This paper presents COLAEVA, an interactive web application for older adult population clustering and evolution analysis. Its objective is to support caregivers in the design, validation and refinement of coaching plans adapted to specific population groups. COLAEVA enables coaching caregivers to interactively group similar older adults based on preliminary assessment data, using AI features, and to evaluate the influence of coaching plans once the final assessment is carried out for a baseline comparison. To evaluate COLAEVA, a usability test was carried out with 9 test participants obtaining an average SUS score of 71.1. Moreover, COLAEVA is available online to use and explore.


Subject(s)
Mentoring , Telemedicine , Aged , Data Mining , Humans , Internet , Population Groups
4.
Article in English | MEDLINE | ID: mdl-34206808

ABSTRACT

Preventive care and telemedicine are expected to play an important role in reducing the impact of an increasingly aging global population while increasing the number of healthy years. Virtual coaching is a promising research area to support this process. This paper presents a user-centered virtual coach for older adults at home to promote active and healthy aging and independent living. It supports behavior change processes for improving on cognitive, physical, social interaction and nutrition areas using specific, measurable, achievable, relevant, and time-limited (SMART) goal plans, following the I-Change behavioral change model. Older adults select and personalize which goal plans to join from a catalog designed by domain experts. Intervention delivery adapts to user preferences and minimizes intrusiveness in the user's daily living using a combination of a deterministic algorithm and incremental machine learning model. The home becomes an augmented reality environment, using a combination of projectors, cameras, microphones and support sensors, where common objects are used for projection and sensed. Older adults interact with this virtual coach in their home in a natural way using speech and body gestures on projected user interfaces with common objects at home. This paper presents the concept from the older adult and the caregiver perspectives. Then, it focuses on the older adult view, describing the tools and processes available to foster a positive behavior change process, including a discussion about the limitations of the current implementation.


Subject(s)
Healthy Aging , Mentoring , Telemedicine , Goals , Motivation
5.
mSphere ; 6(4): e0039321, 2021 08 25.
Article in English | MEDLINE | ID: mdl-34259555

ABSTRACT

Antimicrobial susceptibility in Pseudomonas aeruginosa is dependent on a complex combination of host and pathogen-specific factors. Through the profiling of 971 clinical P. aeruginosa isolates from 590 patients and collection of paired patient metadata, we show that antimicrobial resistance is associated with not only patient-centric factors (e.g., cystic fibrosis and antipseudomonal prescription history) but also microbe-specific phenotypes (e.g., mucoid colony morphology). Additionally, isolates from different sources (e.g., respiratory tract, urinary tract) displayed rates of antimicrobial resistance that were correlated with source-specific antimicrobial prescription strategies. Furthermore, isolates from the same patient often displayed a high degree of heterogeneity, highlighting a key challenge facing personalized treatment of infectious diseases. Our findings support novel relationships between isolate and patient-level data sets, providing a potential guide for future antimicrobial treatment strategies. IMPORTANCE P. aeruginosa is a leading cause of nosocomial infection and infection in patients with cystic fibrosis. While P. aeruginosa infection and treatment can be complicated by a variety of antimicrobial resistance and virulence mechanisms, pathogen virulence is rarely recorded in a clinical setting. In this study, we discovered novel relationships between antimicrobial resistance, virulence-linked morphologies, and isolate source in a large and variable collection of clinical P. aeruginosa isolates. Our work motivates the clinical surveillance of virulence-linked P. aeruginosa morphologies as well as the tracking of source-specific antimicrobial prescription and resistance patterns.


Subject(s)
Anti-Bacterial Agents/pharmacology , Drug Resistance, Multiple, Bacterial , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/physiology , Adolescent , Adult , Aged , Child , Child, Preschool , Cross Infection , Female , Humans , Infant , Male , Microbial Sensitivity Tests , Middle Aged , Phenotype , Pseudomonas Infections/microbiology , Pseudomonas aeruginosa/genetics , Pseudomonas aeruginosa/isolation & purification , Virulence Factors , Young Adult
6.
Water Res ; 176: 115707, 2020 Jun 01.
Article in English | MEDLINE | ID: mdl-32224328

ABSTRACT

Antimicrobial resistance has been recognized as a threat to human health. The role of hospital sinks acting as a reservoir for some of the most concerning antibiotic resistant organisms, carbapenemase producing Enterobacterales (CPE) is evident but not well understood. Strategies to prevent establishment, interventions to eliminate these reservoirs and factors which drive persistence of CPE are not well established. We use a uniquely designed sink lab to transplant CPE colonized hospital sink plumbing with an aim to understand CPE dynamics in a controlled setting, notably exploiting both molecular and culture techniques. After ex situ installation the CPE population in the sink plumbing drop from previously detectable to undetectable levels. The addition of nutrients is followed by a quick rebound in CPE detection in the sinks after as many as 37 days. We did not however detect a significant shift in microbial community structure or the overall resistance gene carriage in longitudinal samples from a subset of these transplanted sinks using whole shotgun metagenomic sequencing. Comparing nutrient types in a benchtop culture study model, protein rich nutrients appear to be the most supportive for CPE growth and biofilm formation ability. The role of nutrients exposure is determining factor for maintaining a high bioburden of CPE in the sink drains and P-traps. Therefore, limiting nutrient disposal into sinks has reasonable potential with regard to decreasing the CPE wastewater burden, especially in hospitals seeking to control an environmental reservoir.


Subject(s)
Klebsiella pneumoniae , beta-Lactamases , Bacterial Proteins , Humans , Nutrients
7.
Article in English | MEDLINE | ID: mdl-31345843

ABSTRACT

The recent development of new antimicrobials active against carbapenemase-producing Enterobacteriales (CPE) has brought new hope for the treatment of infections due to these organisms. However, the evolving epidemiology of bacteria with carbapenemases may complicate management, as providers are faced with treating patients colonized by bacteria producing multiple carbapenemases. Here, we present the clinical course and treatment of Raoultella planticola bacteremia in a cirrhotic patient known to be colonized with both blaKPC- and blaOXA-48-carrying organisms.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacteremia/drug therapy , Bacteremia/microbiology , Enterobacteriaceae Infections/drug therapy , Enterobacteriaceae Infections/microbiology , Enterobacteriaceae/genetics , Adult , Bacterial Proteins/genetics , Enterobacteriaceae/isolation & purification , Enterobacteriaceae/pathogenicity , Escherichia coli/isolation & purification , Fibrosis/complications , Humans , Klebsiella oxytoca/genetics , Klebsiella oxytoca/pathogenicity , Male , beta-Lactamases/genetics
8.
J Clin Microbiol ; 57(10)2019 10.
Article in English | MEDLINE | ID: mdl-31340992

ABSTRACT

With multidrug-resistant (MDR) Enterobacterales on the rise, a nontoxic antimicrobial agent with a unique mechanism of action such as fosfomycin seems attractive. However, establishing accurate fosfomycin susceptibility testing for non-Escherichia coli isolates in a clinical microbiology laboratory remains problematic. We evaluated fosfomycin susceptibility by multiple methods with 96 KPC-producing clinical isolates of multiple strains and species collected at a single center between 2008 and 2016. In addition, we assessed the presence of fosfomycin resistance genes from whole-genome sequencing (WGS) data using NCBI's AMRFinder and custom HMM search. Susceptibility testing was performed using a glucose-6-phosphate-supplemented fosfomycin Etest and Kirby-Bauer disk diffusion (DD) assays, and the results were compared to those obtained by agar dilution. Clinical Laboratory and Standards Institute (CLSI) breakpoints for E. coli were applied for interpretation. Overall, 63% (60/96) of isolates were susceptible by Etest, 70% (67/96) by DD, and 88% (84/96) by agar dilution. fosA was detected in 80% (70/88) of previously sequenced isolates, with species-specific associations and alleles, and fosA-positive isolates were associated with higher MIC distributions. Disk potentiation testing was performed using sodium phosphonoformate to inhibit fosA and showed significant increases in the zone diameter of DD testing for isolates that were fosA positive compared to those that were fosA negative. The addition of sodium phosphonoformate (PPF) corrected 10/14 (71%) major errors in categorical agreement with agar dilution. Our results indicate that fosA influences the inaccuracy of susceptibility testing by methods readily available in a clinical laboratory compared to agar dilution. Further research is needed to determine the impact of fosA on clinical outcomes.


Subject(s)
Anti-Bacterial Agents/pharmacology , Bacterial Proteins/genetics , Drug Resistance, Bacterial , Fosfomycin/pharmacology , Klebsiella Infections/microbiology , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/genetics , beta-Lactamases/genetics , Bacterial Proteins/biosynthesis , Genome, Bacterial , Humans , Klebsiella pneumoniae/isolation & purification , Microbial Sensitivity Tests , Whole Genome Sequencing , beta-Lactamases/biosynthesis
9.
Clin Infect Dis ; 67(2): 171-178, 2018 07 02.
Article in English | MEDLINE | ID: mdl-29409044

ABSTRACT

Background: The increasing prevalence of nosocomial carbapenemase-producing Enterobacteriaceae is a concern. However, the role of the environment in multispecies outbreaks remains poorly understood. There is increasing recognition that hospital wastewater plumbing may play a role. Methods: Covers were installed on all hoppers (a "toilet-like" waste disposal system) in adult intensive care units (ICUs) of a university hospital; additionally in the surgical ICU, sink trap heating and vibration devices were also installed. Patient acquisitions of Klebsiella pneumoniae carbapenemase-producing organisms (KPCOs) for patients who were admitted to an intervention unit were compared for 18-month preintervention and intervention periods. Results: Sixty hopper covers and 23 sink trap devices were installed. Fifty-six new multispecies KPCO acquisitions occurred preintervention compared to 30 during the intervention. Decreases for all KPCO acquisitions (odds ratio [OR], 0.51; 95% confidence interval [CI], 0.31-0.81; P = .003) and KPCO-positive clinical cultures (OR, 0.29; 95% CI, 0.17-0.48; P < .001) per admission in patients exposed to an intervention unit were observed. The incidence rate ratio was 0.51-fold (95% CI, 0.43-0.61) lower for all KPCO acquisitions during the intervention. The effect of the sink trap devices alone could not be determined, although the proportion of sink drain cultures positive for KPCO decreased (12/15 [80%] sites sampled preintervention vs 40/840 [5%] sampled during the intervention; P = .001). Conclusions: An intervention targeting wastewater plumbing fixtures, by installation of hopper covers, demonstrated a decrease in patient KPCO acquisitions. Considering wastewater reservoirs in nosocomial transmission of multispecies carbapenemase-producing Enterobacteriaceae may be critical.


Subject(s)
Infection Control/methods , Intensive Care Units , Klebsiella Infections/prevention & control , Klebsiella pneumoniae/isolation & purification , Wastewater/microbiology , Bacterial Proteins/metabolism , Bathroom Equipment/microbiology , Carbapenem-Resistant Enterobacteriaceae/isolation & purification , Carrier State/microbiology , Cross Infection , Disease Outbreaks/prevention & control , Hospitals, University , Humans , Infection Control/instrumentation , Klebsiella pneumoniae/enzymology , Prospective Studies , Sanitary Engineering/methods , beta-Lactamases/metabolism
10.
J Med Syst ; 41(10): 158, 2017 Sep 02.
Article in English | MEDLINE | ID: mdl-28866846

ABSTRACT

Australia's investment in the national MyHealthRecord has not been successfully communicated to the myriad of stakeholder groups, resulting in negative perceptions about the system and serious consequences for the uptake of the MyHealthRecord. Local stakeholder attitudes and perceptions will be crucial in setting the scene for success or failure with MyHealthRecord. A survey was undertaken to identify primary healthcare provider perceptions of the MyHealthRecord system, and capture the perceived enablers and barriers for use of the MyHealthRecord system. Almost all (89%) of the twenty-seven (27) respondents had previously heard of the MyHealthRecord system prior to completing the survey. Enablers included a decrease in duplication of effort and an increase in continuity of care. However, concerns about the perceived impact on healthcare provider time, privacy, access controls, and the need for full participation will need to be managed if MyHealthRecord is to be successfully implemented. The MyHealthRecord system will only be perceived as trustworthy when there is full participation by healthcare organisations, providers, and consumers. If Australian consumers become participants in an opt-out approach, it will be a catalyst for participation by healthcare organisations and providers. Incentives to encourage MyHealthRecord participation need to be extended to all healthcare providers as healthcare provider attitudes are influential with consumers. Therefore MyHealthRecord training and education needs to be targeted towards healthcare providers. Research into the attitudes of the local healthcare provider cohort is valuable in creating a change management strategy for maximising local success.


Subject(s)
Primary Health Care , Attitude of Health Personnel , Australia , Health Personnel , Health Records, Personal , Perception
11.
Article in English | MEDLINE | ID: mdl-28373185

ABSTRACT

The Klebsiella pneumoniae carbapenemase gene (blaKPC) is typically located within mobile transposon Tn4401 Enhanced KPC expression has been associated with deletions in the putative promoter region upstream of blaKPC Illumina sequences from blaKPC-positive clinical isolates from a single institution were mapped to a Tn4401b reference sequence, which carries no deletions. The novel isoform Tn4401h (188-bp deletion [between istB and blaKPC]) was present in 14% (39/281) of clinical isolates. MICs showed that Escherichia coli strains containing plasmids with Tn4401a and Tn4401h were more resistant to meropenem (≥16 and ≥16, respectively), ertapenem (≥8 and 4, respectively), and cefepime (≥64 and 4, respectively) than E. coli strains with Tn4401b (0.5, ≤0.5, and ≤1, respectively). Quantitative real-time PCR (qRT-PCR) demonstrated that Tn4401a had a 16-fold increase and Tn4401h a 4-fold increase in blaKPC mRNA levels compared to the reference Tn4401b. A lacZ reporter plasmid was used to test the activity of the promoter regions from the different variants, and the results showed that the Tn4401a and Tn4401h promoter sequences generated higher ß-galactosidase activity than the corresponding Tn4401b sequence. Further dissection of the promoter region demonstrated that putative promoter P1 was not functional. The activity of the isolated P2 promoter was greatly enhanced by inclusion of the P1-P2 intervening sequence. These studies indicated that gene expression could be an important consideration in understanding resistance phenotypes predicted by genetic signatures in the context of sequencing-based rapid diagnostics.


Subject(s)
Anti-Bacterial Agents/pharmacology , Bacterial Proteins/genetics , Carbapenems/pharmacology , DNA Transposable Elements/genetics , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/genetics , beta-Lactamases/genetics , Bacterial Proteins/biosynthesis , Cefepime , Cephalosporins/pharmacology , Ertapenem , Escherichia coli/drug effects , Escherichia coli/genetics , Humans , Klebsiella Infections/microbiology , Klebsiella pneumoniae/isolation & purification , Meropenem , Microbial Sensitivity Tests , Promoter Regions, Genetic/genetics , Sequence Deletion/genetics , Thienamycins/pharmacology , beta-Galactosidase/genetics , beta-Galactosidase/metabolism , beta-Lactamases/biosynthesis , beta-Lactams/pharmacology
12.
Article in English | MEDLINE | ID: mdl-28031204

ABSTRACT

Carbapenemase genes in Enterobacteriaceae are mostly described as being plasmid associated. However, the genetic context of carbapenemase genes is not always confirmed in epidemiological surveys, and the frequency of their chromosomal integration therefore is unknown. A previously sequenced collection of blaKPC-positive Enterobacteriaceae from a single U.S. institution (2007 to 2012; n = 281 isolates from 182 patients) was analyzed to identify chromosomal insertions of Tn4401, the transposon most frequently harboring blaKPC Using a combination of short- and long-read sequencing, we confirmed five independent chromosomal integration events from 6/182 (3%) patients, corresponding to 15/281 (5%) isolates. Three patients had isolates identified by perirectal screening, and three had infections which were all successfully treated. When a single copy of blaKPC was in the chromosome, one or both of the phenotypic carbapenemase tests were negative. All chromosomally integrated blaKPC genes were from Klebsiella spp., predominantly K. pneumoniae clonal group 258 (CG258), even though these represented only a small proportion of the isolates. Integration occurred via IS15-ΔI-mediated transposition of a larger, composite region encompassing Tn4401 at one locus of chromosomal integration, seen in the same strain (K. pneumoniae ST340) in two patients. In summary, we identified five independent chromosomal integrations of blaKPC in a large outbreak, demonstrating that this is not a rare event. blaKPC was more frequently integrated into the chromosome of epidemic CG258 K. pneumoniae lineages (ST11, ST258, and ST340) and was more difficult to detect by routine phenotypic methods in this context. The presence of chromosomally integrated blaKPC within successful, globally disseminated K. pneumoniae strains therefore is likely underestimated.


Subject(s)
Chromosomes, Bacterial/chemistry , DNA, Bacterial/genetics , Gene Expression Regulation, Bacterial , Klebsiella pneumoniae/genetics , Mutagenesis, Insertional , beta-Lactamases/genetics , Chromosome Mapping , Chromosomes, Bacterial/metabolism , Clone Cells , DNA Transposable Elements , DNA, Bacterial/metabolism , Humans , Isoenzymes/genetics , Isoenzymes/metabolism , Klebsiella Infections/epidemiology , Klebsiella Infections/microbiology , Klebsiella pneumoniae/enzymology , Mutation Rate , Sequence Analysis, DNA , Virginia/epidemiology , beta-Lactamases/metabolism
13.
Infect Control Hosp Epidemiol ; 35(4): 350-5, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24602938

ABSTRACT

OBJECTIVE: To compare direct laboratory costs of different methods for perirectal screening for carbapenemase-producing Enterobacteriaceae (CPE) colonization. DESIGN: Cost-benefit analysis. SETTING: A university hospital and affiliated long-term acute care hospital (LTACH). PARTICIPANTS: Inpatients from the hospital or LTACH. METHODS: Perirectal samples were collected from inpatients at risk for exposure to CPE. In 2009, we compared the accuracy of the Centers for Disease Control and Prevention (CDC)-recommended CPE screening method with similar methods incorporating a chromogenic agar (CA). We then performed a cost projection analysis using 2012 screening results for the CA method, the CDC method, and a molecular assay with wholesale pricing based on the 2009 analysis. Comparisons of turnaround and personnel time were also performed. RESULTS: A total of 185 (2.7%) of 6,860 samples were confirmed as CPE positive during 2012. We previously found that the CDC protocol had a lower sensitivity than the CA method and predicted that the CDC protocol would have missed 92 of the CPE-positive screening results, whereas the modified protocol using CA would have missed 26, assuming similar prevalence and performance. Turnaround time was 3 days using the CDC and CA-modified protocols compared with 1 day for molecular testing. The estimated annual total program cost and total technologist's hours would be the following: CA-modified protocol, $37,441 and 376 hours; CDC protocol, $22,818 and 482 hours; and molecular testing, $224,596 and 343 hours. CONCLUSIONS: The CDC screening protocol appeared to be the least expensive perirectal screening method. However, expense must be weighed against a lower sensitivity and extra labor needed for additional work-up of non-CPE isolates. The molecular test has the shortest turnaround time but the greatest expense.


Subject(s)
Bacterial Proteins/biosynthesis , Clinical Laboratory Techniques/economics , Klebsiella pneumoniae/isolation & purification , beta-Lactamases/biosynthesis , Bacterial Proteins/isolation & purification , Clinical Laboratory Techniques/methods , Cost-Benefit Analysis , Hospitals, University , Humans , Klebsiella pneumoniae/enzymology , Sensitivity and Specificity , Virginia , beta-Lactamases/isolation & purification
14.
J Clin Microbiol ; 51(4): 1291-3, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23390272

ABSTRACT

The currently recommended phenotypic test for the detection of carbapenemase-producing members of the family Enterobacteriaceae is the modified Hodge test (MHT). However, the MHT lacks specificity. Here we demonstrate an alternative phenotypic test, the indirect carbapenemase test, for the detection of blaKPC-producing isolates that has specificity superior to that of the MHT for non-Klebsiella Enterobacteriaceae.


Subject(s)
Anti-Bacterial Agents/pharmacology , Bacterial Proteins/analysis , Bacteriological Techniques/methods , Enterobacteriaceae/drug effects , Enterobacteriaceae/enzymology , beta-Lactamases/analysis , beta-Lactams/pharmacology , Humans , Prospective Studies , Sensitivity and Specificity
15.
J Clin Microbiol ; 51(2): 680-3, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23175248

ABSTRACT

OXA-48 has emerged as a major carbapenemase associated with the Enterobacteriaceae in Europe, North Africa, and Asia. We report the first two clinical cases of OXA-48-type carbapenemase-producing Enterobacteriaceae in the United States from patients recently hospitalized in Saudi Arabia and India. Each is more carbapenem resistant than nearly all previously reported OXA-48-type-producing Enterobacteriaceae.


Subject(s)
Klebsiella Infections/microbiology , Klebsiella pneumoniae/classification , Klebsiella pneumoniae/drug effects , beta-Lactam Resistance , beta-Lactamases/biosynthesis , Anti-Bacterial Agents/pharmacology , Female , Humans , Klebsiella Infections/diagnosis , Klebsiella pneumoniae/genetics , Microbial Sensitivity Tests , Middle Aged , Multilocus Sequence Typing , United States , beta-Lactam Resistance/genetics , beta-Lactamases/genetics
16.
mBio ; 2(6): e00204-11, 2011.
Article in English | MEDLINE | ID: mdl-22045989

ABSTRACT

Carbapenem-resistant Enterobacteriaceae (CRE) have emerged as major causes of health care-associated infections worldwide. This diverse collection of organisms with various resistance mechanisms is associated with increased lengths of hospitalization, costs of care, morbidity, and mortality. The global spread of CRE has largely been attributed to dissemination of a dominant strain of Klebsiella pneumoniae producing a serine ß-lactamase, termed K. pneumoniae carbapenemase (KPC). Here we report an outbreak of KPC-producing CRE infections in which the degree of horizontal transmission between strains and species of a promiscuous plasmid is unprecedented. Sixteen isolates, comprising 11 unique strains, 6 species, and 4 genera of bacteria, were obtained from 14 patients over the first 8 months of the outbreak. Of the 11 unique strains, 9 harbored the same highly promiscuous plasmid carrying the KPC gene bla(KPC). The remaining strains harbored distinct bla(KPC) plasmids, one of which was carried in a strain of Klebsiella oxytoca coisolated from the index patient and the other generated from transposition of the bla(KPC) element Tn4401. All isolates could be genetically traced to the index patient. Molecular epidemiological investigation of the outbreak was aided by the adaptation of nested arbitrary PCR (ARB-PCR) for rapid plasmid identification. This detailed molecular genetic analysis, combined with traditional epidemiological investigation, provides insights into the highly fluid dynamics of drug resistance transmission during the outbreak. IMPORTANCE The ease of horizontal transmission of carbapenemase resistance plasmids across strains, species, and genera of bacteria observed in this study has several important public health and epidemiological implications. First, it has the potential to promote dissemination of carbapenem resistance to new populations of Enterobacteriaceae, including organisms of low virulence, leading to the establishment of reservoirs of carbapenem resistance genes in patients and/or the environment and of high virulence, raising the specter of untreatable community-associated infections. Second, recognition of plasmid-mediated outbreaks, such as those described here, is problematic because analysis of resistance plasmids from clinical isolates is laborious and technically challenging. Adaptation of nested arbitrary PCR (ARB-PCR) to investigate the plasmid outbreak facilitated our investigation, and the method may be broadly applicable to other outbreaks due to other conserved mobile genetic elements. Whether infection control measures that focus on preventing transmission of drug-resistant clones are effective in controlling dissemination of these elements is unknown.


Subject(s)
Bacterial Proteins/genetics , Carbapenems/pharmacology , Drug Resistance, Bacterial , Enterobacteriaceae Infections/microbiology , Enterobacteriaceae/genetics , Klebsiella pneumoniae/enzymology , Plasmids/genetics , beta-Lactamases/genetics , Adult , Aged , Aged, 80 and over , Bacterial Proteins/metabolism , DNA Transposable Elements , Disease Outbreaks , Enterobacteriaceae/classification , Enterobacteriaceae/drug effects , Enterobacteriaceae/enzymology , Enterobacteriaceae Infections/epidemiology , Female , Gene Transfer, Horizontal , Humans , Klebsiella pneumoniae/genetics , Male , Middle Aged , Phylogeny , Plasmids/metabolism , Young Adult , beta-Lactamases/metabolism
17.
J Pediatr Surg ; 45(1): 84-7; discussion 87-8, 2010 Jan.
Article in English | MEDLINE | ID: mdl-20105585

ABSTRACT

PURPOSE: Intestinal failure (IF)-associated liver disease (IFALD) complicates the treatment of children with IF receiving parenteral nutrition (PN). We hypothesized that prevention or resolution of IFALD was possible in most children and that this would result in improved outcomes. METHODS: We reviewed prospectively gathered data on all children referred to the intestinal rehabilitation and transplantation center at our institution. Total bilirubin level (TB) was used as the marker for IFALD. Patients were grouped based on TB at referral and at subsequent inpatient stays and outpatient visits. Standard treatment consisted of cycling of PN, limiting lipid infusion, enteral stimulation, use of ursodeoxycholic acid, and surgical intervention when necessary. Outcomes such as mortality, dependence on PN, and need for transplantation were assessed. Statistical analyses were performed using Fisher's exact, Mann-Whitney U, and Wilcoxon signed rank tests. RESULTS: Ninety-three patients with intestinal failure and on PN were treated at our center from 2003 to 2009. Median age at referral was 5 months (0.5-264 months). Prematurity was a complicating factor in 63 patients and necrotizing enterocolitis was the most common diagnosis. Eighty-two children had short bowel syndrome, whereas the remaining 11 had extensive motility disorders. 97% of children required significant alteration of their PN administration. At referral, 76 of 93 children had TB 2.0 mg/dL or higher, and 17 had TB below 2.0 mg/dL. TB normalized in 57 of 76 children with elevated TB at referral, and TB remained elevated in 19. Normalization of TB was associated with a mortality of 5.2%, and transplantation was needed in 5.2%. Conversely, when TB remained elevated, mortality was 58% (P = .0002 vs TB normalized), and transplantation occurred in 58% owing to failure of surgical and medical rehabilitation. CONCLUSIONS: Most children referred for treatment of IF have IFALD. A dedicated IF rehabilitation program can reverse IFALD in many children, and this is associated with improved outcome.


Subject(s)
Bilirubin/blood , Biomarkers/blood , Enteral Nutrition/methods , Intestinal Diseases/therapy , Liver Diseases/therapy , Parenteral Nutrition/adverse effects , Child , Child, Preschool , Cholestasis, Intrahepatic/etiology , Cholestasis, Intrahepatic/mortality , Cholestasis, Intrahepatic/therapy , Enterocolitis, Necrotizing/complications , Enterocolitis, Necrotizing/mortality , Enterocolitis, Necrotizing/therapy , Fat Emulsions, Intravenous/therapeutic use , Gastrointestinal Motility , Humans , Infant , Infant, Newborn , Infant, Premature/blood , Intestinal Diseases/mortality , Intestinal Diseases/surgery , Intestinal Obstruction/mortality , Intestinal Obstruction/surgery , Intestinal Obstruction/therapy , Intestine, Small/transplantation , Intestines/transplantation , Liver Diseases/etiology , Liver Diseases/mortality , Liver Diseases/surgery , Organ Transplantation , Parenteral Nutrition/mortality , Patient Care Team , Postoperative Complications/mortality , Referral and Consultation , Rehabilitation Centers , Short Bowel Syndrome/mortality , Short Bowel Syndrome/surgery , Short Bowel Syndrome/therapy , Treatment Outcome , Ursodeoxycholic Acid
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