Author
Maria Virginia Villegas
Bio: Maria Virginia Villegas is an academic researcher from El Bosque University. The author has contributed to research in topics: Klebsiella pneumoniae & Medicine. The author has an hindex of 34, co-authored 80 publications receiving 7068 citations.
Papers published on a yearly basis
Papers
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University of Tübingen1, World Health Organization2, University of Cape Town3, European Centre for Disease Prevention and Control4, Utrecht University5, Tel Aviv University6, Laval University7, Boston University8, Centers for Disease Control and Prevention9, European Medicines Agency10, Food and Drug Administration11, Biomedical Advanced Research and Development Authority12, University of Melbourne13, University of Otago14, George Washington University15
TL;DR: Future development strategies should focus on antibiotics that are active against multidrug-resistant tuberculosis and Gram-negative bacteria, and include antibiotic-resistant bacteria responsible for community-acquired infections.
Abstract: Summary Background The spread of antibiotic-resistant bacteria poses a substantial threat to morbidity and mortality worldwide. Due to its large public health and societal implications, multidrug-resistant tuberculosis has been long regarded by WHO as a global priority for investment in new drugs. In 2016, WHO was requested by member states to create a priority list of other antibiotic-resistant bacteria to support research and development of effective drugs. Methods We used a multicriteria decision analysis method to prioritise antibiotic-resistant bacteria; this method involved the identification of relevant criteria to assess priority against which each antibiotic-resistant bacterium was rated. The final priority ranking of the antibiotic-resistant bacteria was established after a preference-based survey was used to obtain expert weighting of criteria. Findings We selected 20 bacterial species with 25 patterns of acquired resistance and ten criteria to assess priority: mortality, health-care burden, community burden, prevalence of resistance, 10-year trend of resistance, transmissibility, preventability in the community setting, preventability in the health-care setting, treatability, and pipeline. We stratified the priority list into three tiers (critical, high, and medium priority), using the 33rd percentile of the bacterium's total scores as the cutoff. Critical-priority bacteria included carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa , and carbapenem-resistant and third-generation cephalosporin-resistant Enterobacteriaceae. The highest ranked Gram-positive bacteria (high priority) were vancomycin-resistant Enterococcus faecium and meticillin-resistant Staphylococcus aureus . Of the bacteria typically responsible for community-acquired infections, clarithromycin-resistant Helicobacter pylori , and fluoroquinolone-resistant Campylobacter spp, Neisseria gonorrhoeae , and Salmonella typhi were included in the high-priority tier. Interpretation Future development strategies should focus on antibiotics that are active against multidrug-resistant tuberculosis and Gram-negative bacteria. The global strategy should include antibiotic-resistant bacteria responsible for community-acquired infections such as Salmonella spp, Campylobacter spp, N gonorrhoeae , and H pylori . Funding World Health Organization.
3,184 citations
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University of Miami1, Jackson Memorial Hospital2, University of Paris-Sud3, Case Western Reserve University4, United States Department of Veterans Affairs5, Israel Ministry of Health6, National and Kapodistrian University of Athens7, National University of Ireland, Galway8, University of Verona9, University of Barcelona10, Rush University Medical Center11, University of Madras12, University of East Anglia13, Public Health England14, Centers for Disease Control and Prevention15, Royal Brisbane and Women's Hospital16, University of Calgary17, Peking University18, AstraZeneca19
TL;DR: The epidemiology of Klebsiella pneumoniae carbapenemases across continents is summarized, issues around detection, present antibiotic options and those in development, treatment outcome and mortality, and infection control are discussed.
Abstract: Klebsiella pneumoniae carbapenemases (KPCs) were originally identified in the USA in 1996. Since then, these versatile β-lactamases have spread internationally among Gram-negative bacteria, especially K pneumoniae, although their precise epidemiology is diverse across countries and regions. The mortality described among patients infected with organisms positive for KPC is high, perhaps as a result of the limited antibiotic options remaining (often colistin, tigecycline, or aminoglycosides). Triple drug combinations using colistin, tigecycline, and imipenem have recently been associated with improved survival among patients with bacteraemia. In this Review, we summarise the epidemiology of KPCs across continents, and discuss issues around detection, present antibiotic options and those in development, treatment outcome and mortality, and infection control. In view of the limitations of present treatments and the paucity of new drugs in the pipeline, infection control must be our primary defence for now.
1,314 citations
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TL;DR: Genetic structures surrounding the carbapenem-hydrolyzing Ambler class A blaKPC gene were characterized in several KPC-positive Klebsiella pneumoniae and Pseudomonas aeruginosa strains isolated from the United States, Colombia, and Greece.
Abstract: Genetic structures surrounding the carbapenem-hydrolyzing Ambler class A bla KPC gene were characterized in several KPC-positive Klebsiella pneumoniae and Pseudomonas aeruginosa strains isolated from the United States, Colombia, and Greece. The bla KPC genes were associated in all cases with transposon-related structures. In the K. pneumoniae YC isolate from the United States, the β-lactamase bla KPC-2 gene was located on a novel Tn 3 -based transposon, Tn 4401 . Tn 4401 was 10 kb in size, was delimited by two 39-bp imperfect inverted repeat sequences, and harbored, in addition to the β-lactamase bla KPC-2 gene, a transposase gene, a resolvase gene, and two novel insertion sequences, IS Kpn6 and IS Kpn7 . Tn 4401 has been identified in all isolates. However, two isoforms of this transposon were found: Tn 4401 a was found in K. pneumoniae YC and K. pneumoniae GR from the United States and Greece, respectively, and differed by a 100-bp deletion, located just upstream of the bla KPC-2 gene, compared to the sequence of Tn 4401 b, which was found in the Colombian isolates. In all isolates tested, Tn 4401 was flanked by a 5-bp target site duplication, the signature of a recent transposition event, and was inserted in different open reading frames located on plasmids that varied in size and nature. Tn 4401 is likely at the origin of carbapenem-hydrolyzing β-lactamase KPC mobilization to plasmids and its further insertion into various-sized plasmids identified in nonclonally related K. pneumoniae and P. aeruginosa isolates.
468 citations
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TL;DR: A review of Acinetobacter outbreaks summarizes factors related to the presence and recognition of organism transmission and describes the implementation of control and prevention measures directed at limiting spread of infection as mentioned in this paper.
Abstract: This review of Acinetobacter outbreaks summarizes factors related to the presence and recognition of organism transmission and describes the implementation of control and prevention measures directed at limiting spread. Exogenous transmission of Acinetobacter should be considered when infections are endemic and when case rates increase. Increasing or new antimicrobial resistances in a collection of isolates also suggest transmission, and transmission can be definitively confirmed when isolates are found to be indistinguishable from or related to one another by a discriminatory genotyping test. An investigation for a common source should be conducted. When a common source cannot be found and eliminated, or once an endemically transmitted organism is established, containment or prevention efforts may require aggressive interventions, complex interventions, or both. Colonization at multiple sites, the relative ease of induction of antibiotic resistance in the organism following patient exposure to multiple drugs, and long-term environmental survival provide enhanced opportunities for the transmission of Acinetobacter between and among patients. New approaches and interventional trials are needed to define effective measures for the prevention and control of Acinobacter infections.
395 citations
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TL;DR: TOC summary: Clones harboring different plasmids with identical genetic structure could be the origin of worldwide spread.
Abstract: Klebsiella pneumoniaeisolates that produce carbapenemases (KPCs) are rapidly disseminating worldwide. To determine their genetic background, we investigated 16 blaKPC-2-harboring K. pneumoniae isolates from 5 countries. The isolates were multidrug resistant, possessed the blaKPC-2 gene, and differed by additional Beta-lactamase content. They harbored a naturally chromosome-encoded bla gene (blaSHV-1 [12.5%], blaSHV-11 [68.7%], or blaOKP-AVB [18.8%]) and several acquired and plasmid-encoded genes (blaTEM-1 [81.3%], blaCTX-M-2 [31.3%], blaCTX-M-12 [12.5%], blaCTX-M-15 [18.7%], and blaOXA-9 [37.5%]). The blaKPC-2 gene was always associated with 1 of the Tn4401 isoforms (a, b, or c). Tn4401 was inserted on different-sized plasmids that belonged to different incompatibility groups. Several blaKPC-containing K. pneumoniae clones were found: 9 different pulsotypes with 1 major (sequence type 258) and 7 minor distinct allelic profiles. Different clones harboring different plasmids but having identical genetic structure, Tn4401, could be at the origin of the worldwide spread of this emerging resistance gene.
304 citations
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Gregory A. Roth1, Gregory A. Roth2, Degu Abate3, Kalkidan Hassen Abate4 +1025 more•Institutions (333)
TL;DR: Non-communicable diseases comprised the greatest fraction of deaths, contributing to 73·4% (95% uncertainty interval [UI] 72·5–74·1) of total deaths in 2017, while communicable, maternal, neonatal, and nutritional causes accounted for 18·6% (17·9–19·6), and injuries 8·0% (7·7–8·2).
5,211 citations
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TL;DR: The emergence of MCR-1 heralds the breach of the last group of antibiotics, polymyxins, by plasmid-mediated resistance, in Enterobacteriaceae and emphasise the urgent need for coordinated global action in the fight against pan-drug-resistant Gram-negative bacteria.
Abstract: Summary Background Until now, polymyxin resistance has involved chromosomal mutations but has never been reported via horizontal gene transfer. During a routine surveillance project on antimicrobial resistance in commensal Escherichia coli from food animals in China, a major increase of colistin resistance was observed. When an E coli strain, SHP45, possessing colistin resistance that could be transferred to another strain, was isolated from a pig, we conducted further analysis of possible plasmid-mediated polymyxin resistance. Herein, we report the emergence of the first plasmid-mediated polymyxin resistance mechanism, MCR-1, in Enterobacteriaceae. Methods The mcr-1 gene in E coli strain SHP45 was identified by whole plasmid sequencing and subcloning. MCR-1 mechanistic studies were done with sequence comparisons, homology modelling, and electrospray ionisation mass spectrometry. The prevalence of mcr-1 was investigated in E coli and Klebsiella pneumoniae strains collected from five provinces between April, 2011, and November, 2014. The ability of MCR-1 to confer polymyxin resistance in vivo was examined in a murine thigh model. Findings Polymyxin resistance was shown to be singularly due to the plasmid-mediated mcr-1 gene. The plasmid carrying mcr-1 was mobilised to an E coli recipient at a frequency of 10 −1 to 10 −3 cells per recipient cell by conjugation, and maintained in K pneumoniae and Pseudomonas aeruginosa . In an in-vivo model, production of MCR-1 negated the efficacy of colistin. MCR-1 is a member of the phosphoethanolamine transferase enzyme family, with expression in E coli resulting in the addition of phosphoethanolamine to lipid A. We observed mcr-1 carriage in E coli isolates collected from 78 (15%) of 523 samples of raw meat and 166 (21%) of 804 animals during 2011–14, and 16 (1%) of 1322 samples from inpatients with infection. Interpretation The emergence of MCR-1 heralds the breach of the last group of antibiotics, polymyxins, by plasmid-mediated resistance. Although currently confined to China, MCR-1 is likely to emulate other global resistance mechanisms such as NDM-1. Our findings emphasise the urgent need for coordinated global action in the fight against pan-drug-resistant Gram-negative bacteria. Funding Ministry of Science and Technology of China, National Natural Science Foundation of China.
3,647 citations
01 Sep 2008
TL;DR: The Methodology used to Prepare the Guideline Epidemiology Incidence Etiology and Recommendations for Assessing Response to Therapy Suggested Performance Indicators is summarized.
Abstract: Executive Summary Introduction Methodology Used to Prepare the Guideline Epidemiology Incidence Etiology Major Epidemiologic Points Pathogenesis Major Points for Pathogenesis Modifiable Risk Factors Intubation and Mechanical Ventilation Aspiration, Body Position, and Enteral Feeding Modulation of Colonization: Oral Antiseptics and Antibiotics Stress Bleeding Prophylaxis, Transfusion, and Glucose Control Major Points and Recommendations for Modifiable Risk Factors Diagnostic Testing Major Points and Recommendations for Diagnosis Diagnostic Strategies and Approaches Clinical Strategy Bacteriologic Strategy Recommended Diagnostic Strategy Major Points and Recommendations for Comparing Diagnostic Strategies Antibiotic Treatment of Hospital-acquired Pneumonia General Approach Initial Empiric Antibiotic Therapy Appropriate Antibiotic Selection and Adequate Dosing Local Instillation and Aerosolized Antibiotics Combination versus Monotherapy Duration of Therapy Major Points and Recommendations for Optimal Antibiotic Therapy Specific Antibiotic Regimens Antibiotic Heterogeneity and Antibiotic Cycling Response to Therapy Modification of Empiric Antibiotic Regimens Defining the Normal Pattern of Resolution Reasons for Deterioration or Nonresolution Evaluation of the Nonresponding Patient Major Points and Recommendations for Assessing Response to Therapy Suggested Performance Indicators
2,961 citations
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TL;DR: This review details the significant advances that have been made in understanding of this remarkable organism over the last 10 years, including current taxonomy and species identification, issues with susceptibility testing, mechanisms of antibiotic resistance, global epidemiology, clinical impact of infection, host-pathogen interactions, and infection control and therapeutic considerations.
Abstract: Acinetobacter baumannii has emerged as a highly troublesome pathogen for many institutions globally. As a consequence of its immense ability to acquire or upregulate antibiotic drug resistance determinants, it has justifiably been propelled to the forefront of scientific attention. Apart from its predilection for the seriously ill within intensive care units, A. baumannii has more recently caused a range of infectious syndromes in military personnel injured in the Iraq and Afghanistan conflicts. This review details the significant advances that have been made in our understanding of this remarkable organism over the last 10 years, including current taxonomy and species identification, issues with susceptibility testing, mechanisms of antibiotic resistance, global epidemiology, clinical impact of infection, host-pathogen interactions, and infection control and therapeutic considerations.
2,915 citations
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TL;DR: In this paper , the authors presented the most comprehensive estimates of AMR burden to date, which can be divided into five broad components: number of deaths where infection played a role, proportion of infectious deaths attributable to a given infectious syndrome, proportionof infectious syndrome deaths attributed to a particular pathogen, the percentage of a given pathogen resistant to an antibiotic of interest, and the excess risk of death or duration of an infection associated with this resistance.
2,710 citations