Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017

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.

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Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: A microbiological and molecular biological study

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

Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia the official statement of the American Thoracic Society and the Infectious Disease Society of America (特集 救急診療ガイドライン) -- (海外のガイドライン)

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.

Acinetobacter baumannii: Emergence of a Successful Pathogen

http://www.thelancet.com/article/S0140673621027240/pdf

Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis

Carbapenemases are a growing concern worldwide since they threaten the efficacy of carbapenems, the most potent β-lactam antibiotics. Nonmetallocarbapenemase class A (NMC-A) was identified in 1990 from a clinical isolate of Enterobacter cloacae, and since its first report in France ([1][1]), this

First report of a nonmetallocarbapenemase class A carbapenemase in an Enterobacter cloacae isolate from Colombia.

Abstract The term difficult-to-treat resistance has been recently coined to identify Gram-negative bacteria exhibiting resistance to all fluoroquinolones and all β-lactam categories, including carbapenems. Such bacteria are posing serious challenges to clinicians trying to identify the best therapeutic option for any given patient. Delayed appropriate therapy has been associated with worse outcomes including increase in length of stay, increase in total in-hospital costs and ∼20% increase in the risk of in-hospital mortality. In addition, time to appropriate antibiotic therapy has been shown to be an independent predictor of 30 day mortality in patients with resistant organisms. Improving and anticipating aetiological diagnosis through optimizing not only the identification of phenotypic resistance to antibiotic classes/agents, but also the identification of specific resistance mechanisms, would have a major impact on reducing the frequency and duration of inappropriate early antibiotic therapy. In light of these considerations, the present paper reviews the increasing need for rapid diagnosis of bacterial infections and efficient laboratory workflows to confirm diagnoses and facilitate prompt de-escalation to targeted therapy, in line with antimicrobial stewardship principles. Rapid diagnostic tests currently available and future perspectives for their use are discussed. Early appropriate diagnostics and treatment of MDR Gram-negative infections require a multidisciplinary approach that includes multiple different diagnostic methods and further consensus of algorithms, protocols and guidelines to select the optimal antibiotic therapy.

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Early appropriate diagnostics and treatment of MDR Gram-negative infections

La resistencia a los antimicrobianos (RAM) es una amenaza para la salud publica mundial. Los programas de optimizacion del uso de antimicrobianos (PROAs) son programas que promueven su adecuado uso, mejoran los resultados clinicos, economicos y contribuyen a contener la RAM.  Objetivos: evaluar las fases de diagnostico e implementacion temprana de los PROAs en tres hospitales de alta complejidad pertenecientes al Sistema de Seguridad Social del Peru. Metodos: Estudio multicentrico cuasi experimental. La estructuracion de los programas, las lineas de base microbiologicas, el consumo de antimicrobianos y los consensos fueron evaluadas durante los periodos de diagnostico inicial y durante la implementacion temprana de los PROAs. Resultados: Posterior a la implementacion, los hospitales duplicaron la puntuacion de recursos disponibles para los programas (6.75 vs 13.75). La prevalencia de enterobacterias portadoras de betalactamasas de espectro extendido era del 50-60% mientras que la resistencia a carbapenemicos en Pseudomonas aeruginosa promedio el 69%. La dosis diaria definida de ceftriaxona fue de 13.63, 7.35 para vancomicina y 6.73 para meropenem en promedio. Los hospitales A y C disminuyeron el uso de antimicrobianos en un 30-50%.  A traves de estrategias disenadas por equipos multidisciplinarios para implementar los PROAs, se logro disminuir tempranamente el consumo de antimicrobianos de amplio espectro.

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Programas de optimización del uso de antimicrobianos en Perú: Un acuerdo sobre lo fundamental

2. Fridkin S et al. Vital signs: improving antibiotic use among hospitalized patients. MMWR Morb Mortal Wkly Rep 2014;63:194-200. 3. CDC. Core Elements of Hospital Antibiotic Stewardship Programs. Atlanta, GA: US Department of Health and Human Services, CDC; 2014. Available at http://www.cdc.gov/getsmart/healthcare/ implementation/core-elements.html. Current Antimicrobial Stewardship Practices in Latin America: where are we? Juan S. Muñoz1, Gabriel Motoa1, Kevin Escandón-Vargas1, Luis Bavestrello2 , Rodolfo E. Quirós3, Cristhian Hernández-Gómez1, Christian Pallares1, María V. Villegas1

Current Antimicrobial Stewardship Practices in Latin America: Where Are we?

Multidrug-resistant nonfermenters are a worldwide threat. Pseudomonas aeruginosa and Acinetobacter baumannii have been associated with high mortality and treatment failures. In addition, therapeutic options are increasingly narrowed, mainly due to widespread resistance in these pathogens and a shortage of new antimicrobial compounds. Hence, old, potent but toxic antibiotics such as the polymyxins are re-emerging as therapeutic options. Maximizing pharmacokinetics/pharmacodynamics with existing agents is also a worthwhile approach to explore. This problem exemplifies the critical need for new drug development for multidrug-resistant Gram-negative microorganisms.

Maria Virginia Villegas

Papers

First report of a nonmetallocarbapenemase class A carbapenemase in an Enterobacter cloacae isolate from Colombia.

Early appropriate diagnostics and treatment of MDR Gram-negative infections

Programas de optimización del uso de antimicrobianos en Perú: Un acuerdo sobre lo fundamental

Current Antimicrobial Stewardship Practices in Latin America: Where Are we?

Treatment options for multidrug-resistant nonfermenters.