scholarly journals Plasmid Dynamics in KPC-Positive Klebsiella pneumoniae during Long-Term Patient Colonization

mBio ◽  
2016 ◽  
Vol 7 (3) ◽  
Author(s):  
Sean Conlan ◽  
Morgan Park ◽  
Clayton Deming ◽  
Pamela J. Thomas ◽  
Alice C. Young ◽  
...  
Keyword(s):  
Health Care ◽  
Antibiotic Resistance ◽  
Klebsiella Pneumoniae ◽  
Health Care Facilities ◽  
Resistant Bacteria ◽  
Whole Genome ◽  
Antibiotic Resistant ◽  
Carbapenem Resistant ◽  
Clinical Center

ABSTRACT Carbapenem-resistant Klebsiella pneumoniae strains are formidable hospital pathogens that pose a serious threat to patients around the globe due to a rising incidence in health care facilities, high mortality rates associated with infection, and potential to spread antibiotic resistance to other bacterial species, such as Escherichia coli . Over 6 months in 2011, 17 patients at the National Institutes of Health (NIH) Clinical Center became colonized with a highly virulent, transmissible carbapenem-resistant strain of K. pneumoniae . Our real-time genomic sequencing tracked patient-to-patient routes of transmission and informed epidemiologists’ actions to monitor and control this outbreak. Two of these patients remained colonized with carbapenemase-producing organisms for at least 2 to 4 years, providing the opportunity to undertake a focused genomic study of long-term colonization with antibiotic-resistant bacteria. Whole-genome sequencing studies shed light on the underlying complex microbial colonization, including mixed or evolving bacterial populations and gain or loss of plasmids. Isolates from NIH patient 15 showed complex plasmid rearrangements, leaving the chromosome and the bla KPC -carrying plasmid intact but rearranging the two other plasmids of this outbreak strain. NIH patient 16 has shown continuous colonization with bla KPC -positive organisms across multiple time points spanning 2011 to 2015. Genomic studies defined a complex pattern of succession and plasmid transmission across two different K. pneumoniae sequence types and an E. coli isolate. These findings demonstrate the utility of genomic methods for understanding strain succession, genome plasticity, and long-term carriage of antibiotic-resistant organisms. IMPORTANCE In 2011, the NIH Clinical Center had a nosocomial outbreak involving 19 patients who became colonized or infected with bla KPC -positive Klebsiella pneumoniae . Patients who have intestinal colonization with bla KPC -positive K. pneumoniae are at risk for developing infections that are difficult or nearly impossible to treat with existing antibiotic options. Two of those patients remained colonized with bla KPC -positive Klebsiella pneumoniae for over a year, leading to the initiation of a detailed genomic analysis exploring mixed colonization, plasmid recombination, and plasmid diversification. Whole-genome sequence analysis identified a variety of changes, both subtle and large, in the bla KPC -positive organisms. Long-term colonization of patients with bla KPC -positive Klebsiella pneumoniae creates new opportunities for horizontal gene transfer of plasmids encoding antibiotic resistance genes and poses complications for the delivery of health care.

scholarly journals Prevalence of Antibiotic-Resistant Bacteria ESKAPE among Healthy People Estimated by Monitoring of Municipal Wastewater

Antibiotics ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 495
Author(s):  
Masateru Nishiyama ◽  
Susan Praise ◽  
Keiichi Tsurumaki ◽  
Hiroaki Baba ◽  
Hajime Kanamori ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
General Population ◽  
Municipal Wastewater ◽  
Treatment Plant ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Municipal Wastewater Treatment ◽  
Antibiotic Resistant ◽  
Carbapenem Resistant ◽  
Wastewater Samples

There is increasing attention toward factors that potentially contribute to antibiotic resistance (AR), as well as an interest in exploring the emergence and occurrence of antibiotic resistance bacteria (ARB). We monitored six ARBs that cause hospital outbreaks in wastewater influent to highlight the presence of these ARBs in the general population. We analyzed wastewater samples from a municipal wastewater treatment plant (MWWTP) and hospital wastewater (HW) for six species of ARB: Carbapenem-resistant Enterobacteria (CARBA), extended-spectrum β-lactamase producing Enterobacteria (ESBL), multidrug-resistant Acinetobacter (MDRA), multidrug-resistant Pseudomonas aeruginosa (MDRP), methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococci (VRE). We registered a high percentage of ARBs in MWWTP samples (>66%) for all ARBs except for MDRP, indicating a high prevalence in the population. Percentages in HW samples were low (<78%), and no VRE was detected throughout the study. CARBA and ESBL were detected in all wastewater samples, whereas MDRA and MRSA had a high abundance. This result demonstrated the functionality of using raw wastewater at MWWTP to monitor the presence and extent of ARB in healthy populations. This kind of surveillance will contribute to strengthening the efforts toward reducing ARBs through the detection of ARBs to which the general population is exposed.

scholarly journals Fighting Antibiotic-Resistant Klebsiella pneumoniae with “Sweet” Immune Targets

mBio ◽  
2018 ◽  
Vol 9 (3) ◽  
Author(s):  
Roberto Adamo ◽  
Immaculada Margarit
Keyword(s):  
Klebsiella Pneumoniae ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Therapeutic Approaches ◽  
Antibiotic Resistant ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Surface Polysaccharides ◽  
Resistant Strains ◽  
Murine Monoclonal Antibodies

ABSTRACT Antibiotics and vaccines have greatly impacted human health in the last century by dramatically reducing the morbidity and mortality associated with infectious diseases. The recent challenge posed by the emergence of multidrug-resistant bacteria could possibly be addressed by novel immune prophylactic and therapeutic approaches. Among the newly threatening pathogens, Klebsiella pneumoniae is particularly worrisome in the nosocomial setting, and its surface polysaccharides are regarded as promising antigen candidates. The majority of Klebsiella carbapenem-resistant strains belong to the sequence type 158 (ST258) lineage, with two main clades expressing capsular polysaccharides CPS1 and CPS2. In a recent article, S. D. Kobayashi and colleagues (mBio 9:e00297-18, 2018, https://doi.org/10.1128/mBio.00297-18) show that CPS2-specific IgGs render ST258 clade 2 bacteria more sensitive to human serum and phagocytic killing. E. Diago-Navarro et al. (mBio 9:e00091-18, 2018, https://doi.org/10.1128/mBio.00091-18) generated two murine monoclonal antibodies recognizing distinct glycotopes of CPS2 that presented functional activity against multiple ST258 strains. These complementary studies represent a step toward the control of this dangerous pathogen.

scholarly journals Colonization with selected antibiotic resistant bacteria among a cohort of Sri Lankan university students

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Thilini Munasinghe ◽  
Gihani Vidanapathirana ◽  
Shahlina Kuthubdeen ◽  
Asela Ekanayake ◽  
Sacheera Angulmaduwa ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
University Students ◽  
Nasal Swab ◽  
Rectal Swab ◽  
High Rate ◽  
Resistant Bacteria ◽  
Sensitivity Testing ◽  
Antibiotic Resistant ◽  
Carbapenem Resistant ◽  
Microbiological Methods

Abstract Background Antibiotic Resistance is an imminent global public health threat. Antibiotic resistance emerged in healthcare settings and has now moved on to the community settings. This study was conducted to identify the rates of asymptomatic colonization with selected antibiotic resistant organisms, (Methicillin Resistant Staphylococcus aureus (MRSA), Extended Spectrum Beta Lactamase (ESBL) producing Escherichia coli and Klebsiella spp and carbapenem resistant E.coli and Klebsiella spp) - among a group of university students in Sri Lanka. Identification of genetic determinants of MRSA and ESBL was an additional objective of the study. Methods A self - collected nasal swab and a peri-rectal swab collected after passing stools were obtained. Routine microbiological methods were used for the isolation S.aureus from the nasal swab and E.coli and Klebsiella species from the peri-rectal swab. Antibiotic sensitivity testing was performed as recommended by clinical and laboratory standard institute (CLSI). Three (3) genes that are responsible for ESBL production; blaCTX-M, blaSHV, and blaTEM were tested using previously described primers and PCR procedures. Identification of MecA and PVL genes attributed to MRSA was also done with PCR. Results A total of 322 participants between 21 and 28 years were recruited representing 5 different faculties of study. Seventy one (22.0%) were colonized with S.aureus and 14 among them with MRSA, making the MRSA colonization rate of 4.3%. Forty five (15%) of the participants were colonized with an ESBL producing E.coli or Klebsiella spp. No one was colonized with carbapenem resistant E.coli or Klebsiella species. Of the 45 ESBL producers the commonest genetic determinant identified was blaCTX-M (n = 36), while 16 isolates had blaTEM and 7 had blaSHV. Similarly, of the 14 isolates identified as MRSA, 3 (21.4%) were found to be PVL positive while 11 (78.6%) were MecA positive. Conclusions A high rate of colonization with ESBL producing E.coli and Klebsiella species was noted in our study group.

scholarly journals A trimethoprim derivative impedes antibiotic resistance evolution

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Madhu Sudan Manna ◽  
Yusuf Talha Tamer ◽  
Ilona Gaszek ◽  
Nicole Poulides ◽  
Ayesha Ahmed ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Resistant Bacteria ◽  
Gene Encoding ◽  
Antibiotic Resistant ◽  
E Coli ◽  
Resistance Evolution ◽  
Evolutionary Trajectories ◽  
Evolution Of Resistance

AbstractThe antibiotic trimethoprim (TMP) is used to treat a variety of Escherichia coli infections, but its efficacy is limited by the rapid emergence of TMP-resistant bacteria. Previous laboratory evolution experiments have identified resistance-conferring mutations in the gene encoding the TMP target, bacterial dihydrofolate reductase (DHFR), in particular mutation L28R. Here, we show that 4’-desmethyltrimethoprim (4’-DTMP) inhibits both DHFR and its L28R variant, and selects against the emergence of TMP-resistant bacteria that carry the L28R mutation in laboratory experiments. Furthermore, antibiotic-sensitive E. coli populations acquire antibiotic resistance at a substantially slower rate when grown in the presence of 4’-DTMP than in the presence of TMP. We find that 4’-DTMP impedes evolution of resistance by selecting against resistant genotypes with the L28R mutation and diverting genetic trajectories to other resistance-conferring DHFR mutations with catalytic deficiencies. Our results demonstrate how a detailed characterization of resistance-conferring mutations in a target enzyme can help identify potential drugs against antibiotic-resistant bacteria, which may ultimately increase long-term efficacy of antimicrobial therapies by modulating evolutionary trajectories that lead to resistance.

scholarly journals Whole-Genome Sequencing To Identify Drivers of Carbapenem-Resistant Klebsiella pneumoniae Transmission within and between Regional Long-Term Acute-Care Hospitals

2019 ◽  
Vol 63 (11) ◽  
Author(s):  
Jennifer H. Han ◽  
Zena Lapp ◽  
Frederic Bushman ◽  
Ebbing Lautenbach ◽  
Ellie J. C. Goldstein ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Treatment Options ◽  
Health Care Facilities ◽  
Resistant Organism ◽  
Whole Genome ◽  
Content Type ◽  
Transmission Rates ◽  
Carbapenem Resistant

ABSTRACT Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an antibiotic resistance threat of the highest priority. Given the limited treatment options for this multidrug-resistant organism (MDRO), there is an urgent need for targeted strategies to prevent transmission. Here, we applied whole-genome sequencing to a comprehensive collection of clinical isolates to reconstruct regional transmission pathways and analyzed this transmission network in the context of statewide patient transfer data and patient-level clinical data to identify drivers of regional transmission. We found that high regional CRKP burdens were due to a small number of regional introductions, with subsequent regional proliferation occurring via patient transfers among health care facilities. While CRKP was predicted to have been imported into each facility multiple times, there was substantial variation in the ratio of intrafacility transmission events per importation, indicating that amplification occurs unevenly across regional facilities. While myriad factors likely influence intrafacility transmission rates, an understudied one is the potential for clinical characteristics of colonized and infected patients to influence their propensity for transmission. Supporting the contribution of high-risk patients to elevated transmission rates, we observed that patients colonized and infected with CRKP in high-transmission facilities had higher rates of carbapenem use, malnutrition, and dialysis and were older. This report highlights the potential for regional infection prevention efforts that are grounded in genomic epidemiology to identify the patients and facilities that make the greatest contribution to regional MDRO prevalence, thereby facilitating the design of precision interventions of maximal impact.

scholarly journals Occurrence of Antibiotic-Resistant Bacteria in Therapy Pools and Surrounding Surfaces

2018 ◽  
Vol 15 (12) ◽  
pp. 2666
Author(s):  
Daniela Koeck ◽  
Stefanie Huber ◽  
Nadera Hanifi ◽  
Manfred Köster ◽  
Martina Schierling ◽  
...  
Keyword(s):  
Health Care ◽  
Water Treatment ◽  
Water Samples ◽  
Health Care Facilities ◽  
Resistant Bacteria ◽  
Antibiotic Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Pool Water ◽  
Number Of Patients ◽  
Care Facilities

The number of patients colonized with antibiotic-resistant bacteria is increasing in health care facilities. Because transmission of antibiotic-resistant bacteria is feared, there exist reports that the affected patients are frequently excluded from hydrotherapy, which is a non-invasive and beneficial treatment used for patients with different diseases. Data from the literature suggest that deficient water disinfection measures exist, which are not always sufficient to kill all released bacteria. If the pool water is not disinfected properly, it may also infect the bathers. Immunocompromised patients are particularly susceptible to be infected with (antibiotic-resistant) bacteria. In order to determine the distribution of antibiotic-resistant bacteria in the pool water treatment system and the pool environment and to estimate the associated transmission risk we analyzed samples from eleven health care facilities. Antibiotic-resistant bacteria were found in the water and surface samples collected. One hundred and two antibiotic-resistant isolates from water samples and 307 isolates from surrounding surfaces were obtained, respectively. The majority of the isolates belonged to non-fermenting Gram-negative rods, like Pseudomonas spp. Some isolates were resistant to a wide range of the tested antibiotics. The results indicate a relation between the number of isolates in water samples and the number of patients using the pools in combination with deficiencies in water treatment. In the pool environment the highest number of isolates was obtained from barefoot areas and floor cleaning equipment.

Advances in Data-Driven Responses to Preventing Spread of Antibiotic Resistance Across Health-Care Settings

2019 ◽  
Vol 41 (1) ◽  
pp. 6-12 ◽  
Author(s):  
Scott K Fridkin
Keyword(s):  
Public Health ◽  
Health Care ◽  
Antibiotic Resistance ◽  
Big Data ◽  
Bacterial Infections ◽  
Care Delivery ◽  
Data Driven ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Health Care Settings

Abstract Among the most urgent and serious threats to public health are 7 antibiotic-resistant bacterial infections predominately acquired during health-care delivery. There is an emerging field of health-care epidemiology that is focused on preventing health care–associated infections with antibiotic-resistant bacteria and incorporates data from patient transfers or patient movements within and between facilities. This analytic field is being used to help public health professionals identify best opportunities for prevention. Different analytic approaches that draw on uses of big data are being explored to help target the use of limited public health resources, leverage expertise, and enact effective policy to maximize an impact on population-level health. Here, the following recent advances in data-driven responses to preventing spread of antibiotic resistance across health-care settings are summarized: leveraging big data for machine learning, integration or advances in tracking patient movement, and highlighting the value of coordinating response across institutions within a region.

scholarly journals Network Integrative Genomic and Transcriptomic Analysis of Carbapenem-ResistantKlebsiella pneumoniaeStrains Identifies Genes for Antibiotic Resistance and Virulence

mSystems ◽  
2019 ◽  
Vol 4 (4) ◽  
Author(s):  
Muyoung Lee ◽  
Naina Adren Pinto ◽  
Chan Yeong Kim ◽  
Sunmo Yang ◽  
Roshan D’Souza ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Klebsiella Pneumoniae ◽  
Carbapenem Resistance ◽  
Clinical Isolates ◽  
Functional Modules ◽  
Antibiotic Resistant ◽  
Content Type ◽  
Functional Association ◽  
Carbapenem Resistant ◽  
Tract Infections

ABSTRACTGlobal increases in the use of carbapenems have resulted in several strains of Gram-negative bacteria acquiring carbapenem resistance, thereby limiting treatment options.Klebsiella pneumoniaeis a common carbapenem-resistant pathogenic bacterium that is widely studied to identify novel antibiotic resistance mechanisms and drug targets. Antibiotic-resistant clinical isolates generally harbor many genetic alterations, and the identification of responsible mutations would provide insights into the molecular mechanisms of antibiotic resistance. We propose a method to prioritize mutated genes responsible for antibiotic resistance on the basis of expression changes in their local subnetworks, hypothesizing that mutated genes that show significant expression changes among the corresponding functionally associated genes are more likely to be involved in the carbapenem resistance. For network-based gene prioritization, we developed KlebNet (www.inetbio.org/klebnet), a genome-scale cofunctional network ofK. pneumoniaegenes. Using KlebNet, we reconstructed the functional modules for carbapenem resistance and virulence and identified the functional association between antibiotic resistance and virulence. Using complementation assays with the top candidate genes, we were able to validate a novel gene that negatively regulated carbapenem resistance and four novel genes that positively regulated virulence inGalleria mellonellalarvae. Therefore, our study demonstrated the feasibility of network-based identification of genes required for antibiotic resistance and virulence of human-pathogenic bacteria.IMPORTANCEKlebsiella pneumoniaeis a major bacterial pathogen that causes pneumonia and urinary tract infections in human.K. pneumoniaeinfections are treated with carbapenem, but carbapenem-resistantK. pneumoniaehas been spreading worldwide. We are able to identify antimicrobial-resistant genes among mutated genes of the antibiotic-resistant clinical isolates. However, they usually harbor many mutated genes, including those that cause weak or neutral functional effects. Therefore, we need to prioritize the mutated genes to identify the more likely candidates for the follow-up functional analysis. For this study, we present a functional network ofK. pneumoniaegenes and propose a network-based method of prioritizing the mutated genes of the resistant clinical isolates. We also reconstructed the network-based functional modules for carbapenem resistance and virulence and retrieved the functional association between antibiotic resistance and virulence. This study demonstrated the feasibility of network-based analysis of clinical genomics data for the study ofK. pneumoniaeinfection.

scholarly journals Whole Genome Sequencing of Klebsiella pneumoniae Strain Unravels a New Model for the Development of Extensive Drug Resistance in Enterobacteriaceae

2018 ◽  
Vol 12 (1) ◽  
pp. 195-199 ◽  
Author(s):  
Mubarak Alfaresi
Keyword(s):  
Klebsiella Pneumoniae ◽  
Single Molecule ◽  
Resistant Bacteria ◽  
Whole Genome ◽  
Carbapenem Resistant ◽  
Extensive Drug Resistance ◽  
Location Map ◽  
Imminent Risk ◽  
Carbapenem Resistant Enterobacteriaceae ◽  
Complete Account

Introduction: Increased incidence of carbapenem-resistant Enterobacteriaceae (CRE) has been reported worldwide. The WHO warns about the imminent risk to global health if the spread of resistant bacteria is not contained. Materials and Methods: Here, single molecule real time sequencing was used to analyse the whole genome and resistome of SKGH01, a strain of Klebsiella pneumoniae. Results and Discussions: The data showed that SKGH01 was resistant to all commercially available antibiotics. A complete account of extensively drug-resistant (XDR) CRE at a genomic level and the entire location map of all antibiotic resistance components are here presented. Additionally, this work proposes a model of XDR acquisition in Enterobacteriaceae.

Issues in the Management of Resistant Bacteria in Long-Term–Care Facilities

1999 ◽  
Vol 20 (05) ◽  
pp. 362-366 ◽  
Author(s):  
Suzanne F. Bradley
Keyword(s):  
Antibiotic Resistance ◽  
Nursing Homes ◽  
Long Term Care ◽  
Nursing Home Residents ◽  
Resistant Bacteria ◽  
Term Care ◽  
Antibiotic Resistant ◽  
Care Facilities ◽  
Scant Attention

AbstractThe prevalence of antibiotic-resistant bacteria in the long-term–care setting and the risk to nursing home residents is still unknown. Few studies have been done in community-based nursing homes, and most have focused on colonization rather than infection rates. Concerns about methicillin-resistantStaphylococcus aureusand vancomycin-resistant enterococci have been expressed most often, while relatively scant attention has been paid to the problem of antibiotic resistance in gram-negative bacilli. Antibiotic resistance precautions need to be developed for nursing homes that are simple, effective, inexpensive, and recognize the unique rehabilitative and long-term custodial missions of chronic-care facilities.

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