The document discusses the global spread of the mcr-1 gene, which confers plasmid-mediated colistin resistance in Enterobacteriaceae. This poses a substantial public health risk as it limits treatment options for multidrug-resistant infections. Options for response include improved detection of mcr-1 via laboratory methods like PCR and whole genome sequencing, enhanced surveillance programs, infection control measures in healthcare settings, antimicrobial stewardship, and reducing colistin use in animals to prevent further spread. A One Health approach combining human and veterinary medicine is needed to monitor mcr-1 in food and the environment.
Multi-drug resistant tuberculosis (MDR-TB) arises from inadequate or incomplete treatment that allows bacteria to develop resistance to multiple drugs. MDR-TB bacteria resist key first-line drugs like isoniazid and rifampin and require lengthy treatment with second-line drugs. The development of drug resistance threatens global TB control and highlights the need for improved diagnostics, treatment monitoring, and antibiotic stewardship to limit resistance.
The document discusses rapid diagnosis of drug resistant tuberculosis. It provides an overview of conventional and newer diagnostic methods. Conventional methods like culture and drug susceptibility testing can take 8-12 weeks to identify resistance. Newer rapid phenotypic tests such as automated liquid cultures, thin layer agar cultures, TK medium and microscopic-observation drug susceptibility assay can reduce the time to 1-2 weeks but require specialized equipment. Molecular methods like real-time PCR and line probe assays that detect gene mutations associated with resistance have been commercialized and can provide results in 1-2 days, aiding early treatment decisions. Effective control of drug resistant tuberculosis will require scaling up rapid testing capacities and expanding use of novel molecular technologies.
This document discusses extensively drug resistant tuberculosis (XDR TB). It defines XDR TB as resistance to at least rifampin and isoniazid among first-line drugs, plus resistance to any fluoroquinolone and at least one second-line injectable drug. Globally, an estimated 9.7% of MDR TB cases have XDR TB. XDR TB has been reported in 105 countries as of 2014, with the highest rates in several Eastern European and Southern African countries. Treatment of XDR TB requires utilizing the few drugs the infection remains susceptible to in a lengthy 24-30 month regimen.
This document discusses multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). It defines MDR-TB as tuberculosis resistant to at least isoniazid and rifampicin, and defines XDR-TB as MDR-TB additionally resistant to fluoroquinolones and injectable second-line drugs. It also discusses mechanisms of drug resistance development, clinical factors promoting resistance, testing methods, categories of antituberculosis drugs, and public health responsibilities regarding treatment and prevention of drug-resistant tuberculosis.
This document discusses mechanisms of antibiotic resistance in bacteria. It begins by explaining that antibiotic resistance is a major public health threat and describing how bacteria can develop resistance through mutations or acquiring genetic material from other bacteria. The document then discusses the genetic basis of resistance and the major mechanisms bacteria use, including modifying antibiotics with enzymes, preventing antibiotics from reaching their targets, changing or bypassing antibiotic targets, and global adaptive processes. It provides detailed examples of specific resistance mechanisms like aminoglycoside modifying enzymes. In summary, the document provides an in-depth overview of the genetic basis and biochemical mechanisms that bacteria use to develop resistance to antibiotics.
1. Antimicrobial stewardship (AMS) programs are important for primary health care as most antibiotics are prescribed outside hospitals. AMS aims to optimize antibiotic treatment while minimizing antibiotic resistance.
2. ABS programs teach prescribing antibiotics only when truly needed, choosing narrow-spectrum antibiotics when possible to limit collateral damage, and reducing total antibiotic use by not treating viral infections.
3. Developing clear clinical treatment guidelines is important for AMS, but the challenge is implementing them in primary care settings and adapting them to local conditions and cultures.
This document discusses new insights into treatment strategies for critically ill patients, including optimal antibiotic dosing and the potential benefits of extended infusion of antibiotics. It also reviews evidence on the use of aerosolized colistin, inhalation antibiotics, statins, probiotics, and prophylactic antibiotics in preventing infections like ventilator-associated pneumonia in ICU patients. While some studies found decreased infection rates, ICU stay, or ventilation time with these approaches, larger trials are still needed to determine clear effects on mortality or define best practices. The document emphasizes individualizing care based on pharmacokinetic factors and calls for more research on optimization of antibiotic use in critical illness.
This document discusses drugs used to treat infections caused by Mycobacterium avium complex (MAC). MAC includes Mycobacterium avium and Mycobacterium intracellulare and can cause pulmonary disease and disseminated infection in immunocompromised patients like those with HIV/AIDS. Treatment of MAC pulmonary infection involves a triple drug regimen of a rifamycin, ethambutol, and a macrolide. Disseminated MAC disease is treated with clarithromycin and ethambutol. Drugs from several classes are used as prophylaxis or long-term suppression depending on a patient's CD4 count and symptoms.
Multi-drug resistant tuberculosis (MDR-TB) arises from inadequate or incomplete treatment that allows bacteria to develop resistance to multiple drugs. MDR-TB bacteria resist key first-line drugs like isoniazid and rifampin and require lengthy treatment with second-line drugs. The development of drug resistance threatens global TB control and highlights the need for improved diagnostics, treatment monitoring, and antibiotic stewardship to limit resistance.
The document discusses rapid diagnosis of drug resistant tuberculosis. It provides an overview of conventional and newer diagnostic methods. Conventional methods like culture and drug susceptibility testing can take 8-12 weeks to identify resistance. Newer rapid phenotypic tests such as automated liquid cultures, thin layer agar cultures, TK medium and microscopic-observation drug susceptibility assay can reduce the time to 1-2 weeks but require specialized equipment. Molecular methods like real-time PCR and line probe assays that detect gene mutations associated with resistance have been commercialized and can provide results in 1-2 days, aiding early treatment decisions. Effective control of drug resistant tuberculosis will require scaling up rapid testing capacities and expanding use of novel molecular technologies.
This document discusses extensively drug resistant tuberculosis (XDR TB). It defines XDR TB as resistance to at least rifampin and isoniazid among first-line drugs, plus resistance to any fluoroquinolone and at least one second-line injectable drug. Globally, an estimated 9.7% of MDR TB cases have XDR TB. XDR TB has been reported in 105 countries as of 2014, with the highest rates in several Eastern European and Southern African countries. Treatment of XDR TB requires utilizing the few drugs the infection remains susceptible to in a lengthy 24-30 month regimen.
This document discusses multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). It defines MDR-TB as tuberculosis resistant to at least isoniazid and rifampicin, and defines XDR-TB as MDR-TB additionally resistant to fluoroquinolones and injectable second-line drugs. It also discusses mechanisms of drug resistance development, clinical factors promoting resistance, testing methods, categories of antituberculosis drugs, and public health responsibilities regarding treatment and prevention of drug-resistant tuberculosis.
This document discusses mechanisms of antibiotic resistance in bacteria. It begins by explaining that antibiotic resistance is a major public health threat and describing how bacteria can develop resistance through mutations or acquiring genetic material from other bacteria. The document then discusses the genetic basis of resistance and the major mechanisms bacteria use, including modifying antibiotics with enzymes, preventing antibiotics from reaching their targets, changing or bypassing antibiotic targets, and global adaptive processes. It provides detailed examples of specific resistance mechanisms like aminoglycoside modifying enzymes. In summary, the document provides an in-depth overview of the genetic basis and biochemical mechanisms that bacteria use to develop resistance to antibiotics.
1. Antimicrobial stewardship (AMS) programs are important for primary health care as most antibiotics are prescribed outside hospitals. AMS aims to optimize antibiotic treatment while minimizing antibiotic resistance.
2. ABS programs teach prescribing antibiotics only when truly needed, choosing narrow-spectrum antibiotics when possible to limit collateral damage, and reducing total antibiotic use by not treating viral infections.
3. Developing clear clinical treatment guidelines is important for AMS, but the challenge is implementing them in primary care settings and adapting them to local conditions and cultures.
This document discusses new insights into treatment strategies for critically ill patients, including optimal antibiotic dosing and the potential benefits of extended infusion of antibiotics. It also reviews evidence on the use of aerosolized colistin, inhalation antibiotics, statins, probiotics, and prophylactic antibiotics in preventing infections like ventilator-associated pneumonia in ICU patients. While some studies found decreased infection rates, ICU stay, or ventilation time with these approaches, larger trials are still needed to determine clear effects on mortality or define best practices. The document emphasizes individualizing care based on pharmacokinetic factors and calls for more research on optimization of antibiotic use in critical illness.
This document discusses drugs used to treat infections caused by Mycobacterium avium complex (MAC). MAC includes Mycobacterium avium and Mycobacterium intracellulare and can cause pulmonary disease and disseminated infection in immunocompromised patients like those with HIV/AIDS. Treatment of MAC pulmonary infection involves a triple drug regimen of a rifamycin, ethambutol, and a macrolide. Disseminated MAC disease is treated with clarithromycin and ethambutol. Drugs from several classes are used as prophylaxis or long-term suppression depending on a patient's CD4 count and symptoms.
The document discusses strategies for selecting antibiotics based on patient factors and the causative organism. It provides examples of rational antibiotic selection for a pregnant woman with a UTI and a hospitalized man on warfarin taking antibiotics for a UTI. The document also discusses antibiotic policies, pre-treatment considerations like duration and route of administration, superinfections, and different types of hypersensitivity tests including skin prick, intradermal, and patch testing. It validates the use of cephalosporin skin testing to predict immediate hypersensitivity but notes negative tests do not rule out the possibility of hypersensitivity upon intravenous administration.
Drug resistance occurs through several mechanisms: mutation, selective pressure, and gene transfer allow microbes to develop resistance. Strategies to combat resistance include international collaboration on surveillance and incentives for new drugs, national treatment guidelines and education programs, and community efforts like rational antibiotic use and hygiene. Genetic changes allow microbes to develop resistance through various mechanisms like mutation, selective pressure, and horizontal gene transfer between microbes.
Recent advances in multi drug resistant tuberculosis &rntcpNursing Path
Tuberculosis persists as a global public health problem, with multi-drug resistant TB found in many countries including India. Studies have found MDR TB levels between 2-14% in some areas of India. The emergence of drug resistant TB can be prevented through adequate case finding, prompt diagnosis and effective treatment under DOTS programs. DOTS Plus programs were established to diagnose and treat MDR TB through quality assured drug susceptibility testing and the use of second line drugs administered properly under DOTS Plus guidelines. Contact management is also important to prevent the spread of MDR TB.
This document discusses antimicrobial resistance and provides definitions, history, and mechanisms. It defines antimicrobial resistance as the ability of microorganisms like bacteria, viruses, and parasites to stop antimicrobial drugs from working against them. The discovery of antimicrobials created new treatments but microbes developed resistance over time. Factors that contribute to resistance include overuse of antibiotics, lack of sanitation, and transmission of resistant genes between bacteria. Resistance occurs via natural and acquired mechanisms, the latter being a major clinical problem. Strategies to address resistance include prudent antibiotic use, developing new drugs, and alternative approaches like phage therapy.
This document discusses the rise of antibiotic resistance in bacteria and the threat of "superbugs". It outlines several bacteria that have developed resistance to multiple antibiotics, such as MRSA, ESBL-producing E. coli and Klebsiella, and NDM-1 producing bacteria resistant to nearly all antibiotics. The development of resistance occurs through spontaneous mutation, lateral gene transfer, and selection pressure from antibiotic overuse. Widespread antibiotic resistance poses serious risks to human health through difficult-to-treat infections and increased mortality. New approaches are urgently needed to address the growing superbug threat.
Antibiotic prescription and bacterial resistanceMamdouh Sabry
- Overuse of antibiotics, especially in patients with fever of unknown origin, can lead to increased bacterial resistance. When antibiotics are used prudently and appropriately, it can minimize excess use and enhance selecting the right antibiotic for the susceptible bacteria in a given patient.
- As antibiotic prescriptions rise, so does bacterial resistance. Bacteria can develop resistance through mutations, acquiring genetic material from other bacteria, or through selective pressure from antibiotic use that favors resistant strains.
- To combat rising resistance, guidelines should be followed for proper antibiotic indication, culture collection, infecting organism identification, appropriate antibiotic selection, dose, duration and modification after culture results. Prudent antibiotic use can help preserve the effectiveness of our existing antibiotics
This document provides an overview of general principles of antimicrobial therapy. It discusses key topics such as classes of antimicrobial agents based on their mechanism of action and targets, pharmacokinetic principles for dosing, types and goals of antimicrobial therapy including prophylaxis, empirical and definitive treatment. It also covers mechanisms of resistance, how resistance emerges evolutionarily, and principles of combination antimicrobial chemotherapy. The overall aim is to help readers understand fundamental concepts in antimicrobial drug selection, use and resistance.
This editorial discusses two notable articles published in the New England Journal of Medicine in February 2020 on treatments for HER2-positive metastatic breast cancer. The first article reports results from the HER2CLIMB trial showing that adding the oral HER2 inhibitor tucatinib to trastuzumab and capecitabine resulted in significantly longer progression-free and overall survival compared to placebo, including among patients with brain metastases. The second article reports results from a study showing activity of the antibody-drug conjugate trastuzumab deruxtecan in heavily pretreated patients. The editorial highlights these studies as major advances in HER2 blockade for metastatic breast cancer, particularly for later lines of therapy when options are limited.
MDR TB is tuberculosis caused by strains of Mycobacterium tuberculosis that are resistant to both isoniazid and rifampicin, the most potent anti-TB drugs. In India in 2012, MDR TB accounted for approximately 2.2% of new TB cases and 15% of retreatment cases. Diagnosis requires culture and drug susceptibility testing showing resistance to both isoniazid and rifampicin. Treatment follows WHO DOTS Plus guidelines and involves a regimen of several second-line drugs for 20 months or longer. Adherence to treatment is critical for successful treatment of MDR TB.
Staphylococcus Aureus in burn intensive care unitSantiagoZapata53
This is a presentation about an article (not mine) that develops an interesting topic for heatlh personal. Staphylococcus Aureus is the most common bacteria involved in post operative infections and one of the most important to consider when talking about nosocomial infections.
This document provides an overview of multidrug-resistant tuberculosis (MDR TB). It defines the different types of drug-resistant TB and discusses the epidemiology and mechanisms of drug resistance. It emphasizes the importance of proper diagnosis and treatment for managing drug-resistant TB. The key points are that improper or incomplete treatment can cause drug resistance to develop, MDR TB requires testing to identify resistance and an individualized treatment regimen using second-line drugs, and treatment must be closely monitored for at least 18-24 months.
Current scenario of antimicobial resistancevkatbcd
This document provides an overview of the current state of antimicrobial resistance (AMR) globally and in India. It discusses the history of antibiotic discovery and the consequent rise of resistance. Worldwide, antibiotic resistance poses a major burden according to analysts. In India, resistance levels to commonly used antibiotics like piperacillin-tazobactam are between 50-70% according to ICMR data from 2017. While some new drugs have been approved in recent years, resistance is emerging to these as well. Polymyxins and tigecycline remain treatments of last resort but have significant safety issues. Overall, the document concludes that a definite solution to the growing problem of AMR remains elusive.
This document summarizes new and emerging antibiotic treatments for multi-drug resistant bacteria, or "superbugs". It discusses several new classes of antibiotics targeting both Gram-positive and Gram-negative bacteria, including new cephalosporins, lipoglycopeptides, lipopeptides, streptogramins, carbapenems, and glycylcyclines. Concerns are raised about increasing antibiotic resistance and the lack of new antibiotic development, as well as the need to target emerging threats from multi-drug resistant Gram-negative bacteria.
This document summarizes treatment options for Methicillin-resistant Staphylococcus aureus (MRSA) infections. It discusses the evolution of antibiotic resistance in S. aureus and risk factors for MRSA infection. Current treatment options for MRSA skin, soft tissue, and bloodstream infections include vancomycin, linezolid, daptomycin, and newer agents like ceftaroline, dalbavancin, oritavancin, and delafloxacin. Guidelines from the Infectious Diseases Society of America are mentioned. Ongoing research is focused on developing new antibiotics that are more effective than vancomycin for treating MRSA.
Antimicrobial resistance for cliniciansSandro Zorzi
Slide from WHO CME ITALIAN COURSE
Antimicrobial resistance for clinicians
Core competencies for antimicrobial prescribing:
Understands the patient and the patient’s clinical needs
Understands treatment options and how they support the
patient’s clinical needs
Works in partnership with the patient and other healthcare
professionals to develop and implement a treatment plan
Communicates the treatment plan and its rationale clearly to
the patient and other health professionals
Monitors and reviews the patient’s response to treatment
This document discusses drug resistant tuberculosis (TB) and provides definitions, mechanisms, factors, diagnostic tests, treatment principles and regimens for multi-drug resistant TB (MDR-TB). It defines MDR-TB as resistance to at least isoniazid and rifampin and notes management requires specialized treatment units, reliable drug susceptibility testing, and directly observed long-term combination drug regimens using second-line drugs. Acceptable regimens are outlined based on patterns of resistance to first-line drugs.
Cefiderocol is a novel siderophore cephalosporin antibiotic being developed for the treatment of infections caused by carbapenem-resistant Gram-negative bacteria. A phase 2 clinical trial found intravenous cefiderocol to be non-inferior to imipenem-cilastatin for treating complicated urinary tract infections caused by multidrug-resistant Gram-negative pathogens. Cefiderocol utilizes bacterial iron transport systems to penetrate the outer membrane of Gram-negative bacteria and is highly stable against various carbapenemase enzymes. Its pharmacokinetics and safety profile support a dosage of 2g administered intravenously every 8 hours. These results provide a basis for submitting cefiderocol for FDA approval to treat serious Gram-negative
This study analyzed the antibiotic susceptibility patterns of gram-negative bacteria isolated from clinical samples at a large specialty hospital in India from 2014. It found that 81% of bacterial isolates were gram-negative bacilli, led by Enterobacteriaceae species, Acinetobacter spp., and Pseudomonas aeruginosa. Antibiotic resistance rates were high and increasing among these pathogens, particularly to beta-lactams, cephalosporins, fluoroquinolones, and carbapenems. The results demonstrate the growing threat of multidrug-resistant gram-negative infections and emphasize the need for prudent antibiotic use.
This document summarizes discussions from several sessions of a meeting on antimicrobial resistance and healthcare-associated infections. Key points include:
- Most countries submit antimicrobial consumption data close to the deadline, and there are specific rules for who can access and publish the data.
- It is important but challenging to compare hospital antimicrobial consumption data between countries due to differences in how data is collected. Both defined daily doses and packages are needed for comparison.
- A pilot hospital-based antimicrobial consumption survey was proposed to collect additional data starting in late 2015, but the protocol requires further review and clarification before implementation.
Presentation from the 3rd Joint Meeting of the Antimicrobial Resistance and Healthcare-Associated Infections (ARHAI) Networks, organised by the European Centre of Disease Prevention and Control - Stockholm, 11-13 February 2015
The document discusses strategies for selecting antibiotics based on patient factors and the causative organism. It provides examples of rational antibiotic selection for a pregnant woman with a UTI and a hospitalized man on warfarin taking antibiotics for a UTI. The document also discusses antibiotic policies, pre-treatment considerations like duration and route of administration, superinfections, and different types of hypersensitivity tests including skin prick, intradermal, and patch testing. It validates the use of cephalosporin skin testing to predict immediate hypersensitivity but notes negative tests do not rule out the possibility of hypersensitivity upon intravenous administration.
Drug resistance occurs through several mechanisms: mutation, selective pressure, and gene transfer allow microbes to develop resistance. Strategies to combat resistance include international collaboration on surveillance and incentives for new drugs, national treatment guidelines and education programs, and community efforts like rational antibiotic use and hygiene. Genetic changes allow microbes to develop resistance through various mechanisms like mutation, selective pressure, and horizontal gene transfer between microbes.
Recent advances in multi drug resistant tuberculosis &rntcpNursing Path
Tuberculosis persists as a global public health problem, with multi-drug resistant TB found in many countries including India. Studies have found MDR TB levels between 2-14% in some areas of India. The emergence of drug resistant TB can be prevented through adequate case finding, prompt diagnosis and effective treatment under DOTS programs. DOTS Plus programs were established to diagnose and treat MDR TB through quality assured drug susceptibility testing and the use of second line drugs administered properly under DOTS Plus guidelines. Contact management is also important to prevent the spread of MDR TB.
This document discusses antimicrobial resistance and provides definitions, history, and mechanisms. It defines antimicrobial resistance as the ability of microorganisms like bacteria, viruses, and parasites to stop antimicrobial drugs from working against them. The discovery of antimicrobials created new treatments but microbes developed resistance over time. Factors that contribute to resistance include overuse of antibiotics, lack of sanitation, and transmission of resistant genes between bacteria. Resistance occurs via natural and acquired mechanisms, the latter being a major clinical problem. Strategies to address resistance include prudent antibiotic use, developing new drugs, and alternative approaches like phage therapy.
This document discusses the rise of antibiotic resistance in bacteria and the threat of "superbugs". It outlines several bacteria that have developed resistance to multiple antibiotics, such as MRSA, ESBL-producing E. coli and Klebsiella, and NDM-1 producing bacteria resistant to nearly all antibiotics. The development of resistance occurs through spontaneous mutation, lateral gene transfer, and selection pressure from antibiotic overuse. Widespread antibiotic resistance poses serious risks to human health through difficult-to-treat infections and increased mortality. New approaches are urgently needed to address the growing superbug threat.
Antibiotic prescription and bacterial resistanceMamdouh Sabry
- Overuse of antibiotics, especially in patients with fever of unknown origin, can lead to increased bacterial resistance. When antibiotics are used prudently and appropriately, it can minimize excess use and enhance selecting the right antibiotic for the susceptible bacteria in a given patient.
- As antibiotic prescriptions rise, so does bacterial resistance. Bacteria can develop resistance through mutations, acquiring genetic material from other bacteria, or through selective pressure from antibiotic use that favors resistant strains.
- To combat rising resistance, guidelines should be followed for proper antibiotic indication, culture collection, infecting organism identification, appropriate antibiotic selection, dose, duration and modification after culture results. Prudent antibiotic use can help preserve the effectiveness of our existing antibiotics
This document provides an overview of general principles of antimicrobial therapy. It discusses key topics such as classes of antimicrobial agents based on their mechanism of action and targets, pharmacokinetic principles for dosing, types and goals of antimicrobial therapy including prophylaxis, empirical and definitive treatment. It also covers mechanisms of resistance, how resistance emerges evolutionarily, and principles of combination antimicrobial chemotherapy. The overall aim is to help readers understand fundamental concepts in antimicrobial drug selection, use and resistance.
This editorial discusses two notable articles published in the New England Journal of Medicine in February 2020 on treatments for HER2-positive metastatic breast cancer. The first article reports results from the HER2CLIMB trial showing that adding the oral HER2 inhibitor tucatinib to trastuzumab and capecitabine resulted in significantly longer progression-free and overall survival compared to placebo, including among patients with brain metastases. The second article reports results from a study showing activity of the antibody-drug conjugate trastuzumab deruxtecan in heavily pretreated patients. The editorial highlights these studies as major advances in HER2 blockade for metastatic breast cancer, particularly for later lines of therapy when options are limited.
MDR TB is tuberculosis caused by strains of Mycobacterium tuberculosis that are resistant to both isoniazid and rifampicin, the most potent anti-TB drugs. In India in 2012, MDR TB accounted for approximately 2.2% of new TB cases and 15% of retreatment cases. Diagnosis requires culture and drug susceptibility testing showing resistance to both isoniazid and rifampicin. Treatment follows WHO DOTS Plus guidelines and involves a regimen of several second-line drugs for 20 months or longer. Adherence to treatment is critical for successful treatment of MDR TB.
Staphylococcus Aureus in burn intensive care unitSantiagoZapata53
This is a presentation about an article (not mine) that develops an interesting topic for heatlh personal. Staphylococcus Aureus is the most common bacteria involved in post operative infections and one of the most important to consider when talking about nosocomial infections.
This document provides an overview of multidrug-resistant tuberculosis (MDR TB). It defines the different types of drug-resistant TB and discusses the epidemiology and mechanisms of drug resistance. It emphasizes the importance of proper diagnosis and treatment for managing drug-resistant TB. The key points are that improper or incomplete treatment can cause drug resistance to develop, MDR TB requires testing to identify resistance and an individualized treatment regimen using second-line drugs, and treatment must be closely monitored for at least 18-24 months.
Current scenario of antimicobial resistancevkatbcd
This document provides an overview of the current state of antimicrobial resistance (AMR) globally and in India. It discusses the history of antibiotic discovery and the consequent rise of resistance. Worldwide, antibiotic resistance poses a major burden according to analysts. In India, resistance levels to commonly used antibiotics like piperacillin-tazobactam are between 50-70% according to ICMR data from 2017. While some new drugs have been approved in recent years, resistance is emerging to these as well. Polymyxins and tigecycline remain treatments of last resort but have significant safety issues. Overall, the document concludes that a definite solution to the growing problem of AMR remains elusive.
This document summarizes new and emerging antibiotic treatments for multi-drug resistant bacteria, or "superbugs". It discusses several new classes of antibiotics targeting both Gram-positive and Gram-negative bacteria, including new cephalosporins, lipoglycopeptides, lipopeptides, streptogramins, carbapenems, and glycylcyclines. Concerns are raised about increasing antibiotic resistance and the lack of new antibiotic development, as well as the need to target emerging threats from multi-drug resistant Gram-negative bacteria.
This document summarizes treatment options for Methicillin-resistant Staphylococcus aureus (MRSA) infections. It discusses the evolution of antibiotic resistance in S. aureus and risk factors for MRSA infection. Current treatment options for MRSA skin, soft tissue, and bloodstream infections include vancomycin, linezolid, daptomycin, and newer agents like ceftaroline, dalbavancin, oritavancin, and delafloxacin. Guidelines from the Infectious Diseases Society of America are mentioned. Ongoing research is focused on developing new antibiotics that are more effective than vancomycin for treating MRSA.
Antimicrobial resistance for cliniciansSandro Zorzi
Slide from WHO CME ITALIAN COURSE
Antimicrobial resistance for clinicians
Core competencies for antimicrobial prescribing:
Understands the patient and the patient’s clinical needs
Understands treatment options and how they support the
patient’s clinical needs
Works in partnership with the patient and other healthcare
professionals to develop and implement a treatment plan
Communicates the treatment plan and its rationale clearly to
the patient and other health professionals
Monitors and reviews the patient’s response to treatment
This document discusses drug resistant tuberculosis (TB) and provides definitions, mechanisms, factors, diagnostic tests, treatment principles and regimens for multi-drug resistant TB (MDR-TB). It defines MDR-TB as resistance to at least isoniazid and rifampin and notes management requires specialized treatment units, reliable drug susceptibility testing, and directly observed long-term combination drug regimens using second-line drugs. Acceptable regimens are outlined based on patterns of resistance to first-line drugs.
Cefiderocol is a novel siderophore cephalosporin antibiotic being developed for the treatment of infections caused by carbapenem-resistant Gram-negative bacteria. A phase 2 clinical trial found intravenous cefiderocol to be non-inferior to imipenem-cilastatin for treating complicated urinary tract infections caused by multidrug-resistant Gram-negative pathogens. Cefiderocol utilizes bacterial iron transport systems to penetrate the outer membrane of Gram-negative bacteria and is highly stable against various carbapenemase enzymes. Its pharmacokinetics and safety profile support a dosage of 2g administered intravenously every 8 hours. These results provide a basis for submitting cefiderocol for FDA approval to treat serious Gram-negative
This study analyzed the antibiotic susceptibility patterns of gram-negative bacteria isolated from clinical samples at a large specialty hospital in India from 2014. It found that 81% of bacterial isolates were gram-negative bacilli, led by Enterobacteriaceae species, Acinetobacter spp., and Pseudomonas aeruginosa. Antibiotic resistance rates were high and increasing among these pathogens, particularly to beta-lactams, cephalosporins, fluoroquinolones, and carbapenems. The results demonstrate the growing threat of multidrug-resistant gram-negative infections and emphasize the need for prudent antibiotic use.
This document summarizes discussions from several sessions of a meeting on antimicrobial resistance and healthcare-associated infections. Key points include:
- Most countries submit antimicrobial consumption data close to the deadline, and there are specific rules for who can access and publish the data.
- It is important but challenging to compare hospital antimicrobial consumption data between countries due to differences in how data is collected. Both defined daily doses and packages are needed for comparison.
- A pilot hospital-based antimicrobial consumption survey was proposed to collect additional data starting in late 2015, but the protocol requires further review and clarification before implementation.
Presentation from the 3rd Joint Meeting of the Antimicrobial Resistance and Healthcare-Associated Infections (ARHAI) Networks, organised by the European Centre of Disease Prevention and Control - Stockholm, 11-13 February 2015
Patient Safety Collaboratives - Dr Chris Streather, Managing Director, South London AHSN
Presentation from the Patient Safety Collaborative launch event held in London on 14 October 2014
More information at http://www.nhsiq.nhs.uk/improvement-programmes/patient-safety/patient-safety-collaboratives.aspx
This document summarizes the current use of colistin in human and veterinary medicine in the European Union. It discusses the emergence of multidrug-resistant bacterial infections as a driver for increased colistin use in humans. While colistin has been used for decades in veterinary medicine, primarily orally in livestock, its importance for treating resistant infections in humans is growing. The document reviews colistin's toxicity issues, resistance mechanisms, and susceptibility testing challenges. It concludes that both human and veterinary antimicrobial use must be rationalized and colistin resistance monitored to understand potential impacts on animal and human health.
This study compared outcomes of patients with MDR/XDR Acinetobactor baumannii pneumonia treated with tigecycline or colistin. 70 patients received either tigecycline (n=30) or colistin (n=40). There were no significant differences in clinical outcomes between the two groups except nephrotoxicity, which only occurred in the colistin group. While the study indicates comparable efficacy, limitations include its small size, retrospective design, and exclusions. Further large randomized studies are still needed to properly evaluate tigecycline and optimal treatment combinations for MDR infections.
This document summarizes a research project developing new antibiotic peptides based on polymyxin. The research group has designed and synthesized over 90 analogs of polymyxin B peptides. Three lead analogs (103, 104, 105) show potent antibacterial activity against both gram-positive and gram-negative bacteria, including multi-drug resistant strains. Mechanism of action studies indicate these analogs act on bacterial membranes. Analog 103 was well-tolerated in mouse toxicity studies. The research group holds patents on the compounds and is seeking a partner for further development.
Carbapenem-resistant Acinetobacter baumannii poses a significant threat in healthcare settings across Europe. It can cause serious infections that are difficult to treat due to limited antibiotic options. The number of countries reporting spread and endemicity of carbapenem-resistant A. baumannii has increased in recent years. Increased detection and control efforts are needed to prevent it from becoming endemic in more European regions and healthcare facilities.
Colistin is a polymyxin antibiotic produced by Bacillus polymyxa that is effective against most gram-negative bacteria. It fell out of favor due to nephrotoxicity but remains a treatment of last resort for multidrug-resistant infections. There are two forms, colistin sulfate and colistimethate sodium, which are dosed differently and have different mechanisms of action, pharmacokinetics, and toxicity profiles. Resistance can develop with use but remains relatively rare currently.
This document provides classifications and details about various classes of antibacterial drugs. It summarizes protein synthesis inhibitors like aminoglycosides and oxazolidinones. It also summarizes cell envelope antibiotics that inhibit peptidoglycan synthesis and glycopeptides that inhibit cell wall formation. Finally, it summarizes beta-lactam antibiotics like penicillins and cephalosporins that inhibit cell wall cross-linking, and nucleic acid inhibitors like sulfonamides, quinolones, and rifampicin. Specific drugs are listed within each class along with basic indications, mechanisms of action, and pharmacokinetic properties.
This document discusses the antibiotic polymyxins, specifically colistin. It provides details on the chemical structure and formulations of colistin. It describes how colistin fell out of favor in the 1970s but is now being revived to treat infections caused by multidrug-resistant Gram-negative bacteria. The document discusses colistin's mechanism of action, spectrum of activity, dosing, toxicity, and resistance. It also summarizes studies showing colistin is effective against common multidrug-resistant pathogens and that combinations with other antibiotics can have synergistic effects.
Colistin is a polymyxin antibiotic produced by Bacillus polymyxa that is effective against most gram-negative bacteria. It fell out of favor due to nephrotoxicity but remains a treatment of last resort for multidrug-resistant infections. There are two forms, colistin sulfate and colistimethate sodium, which are not interchangeable. Dosing is complicated due to lack of standardization. Colistin works by disrupting bacterial membranes. While resistance is still rare, its increased use has led to some resistant strains emerging.
This document discusses mechanisms of multi-drug resistance in bacteria and cancer cells. It describes how organisms can develop resistance through mutation, gene transfer, decreased membrane permeability, and efflux pumps that remove drugs from cells. Specifically, it explains that bacteria resist antibiotics via enzymatic degradation, altered target sites, and increased efflux. Cancer cells similarly resist chemotherapy through efflux pumps like P-glycoprotein and MDR proteins that transport drugs out of cells. The key mechanisms of multi-drug resistance shared by bacteria and cancer are efflux pumps and enzymatic deactivation of drugs.
The document discusses urinary catheters and catheter-associated urinary tract infections (CAUTIs). It provides information on:
- The history and development of urinary catheters from the 1920s to present.
- Risk factors for bacteriuria associated with urinary catheters. Studies show rates of bacteriuria increase significantly within the first week of catheter placement.
- Core strategies and supplemental strategies recommended by healthcare organizations to prevent CAUTIs, such as only using catheters when necessary, maintaining a closed drainage system, and hand hygiene.
This document discusses the use of the old antibiotic colistin for treating infections caused by multidrug-resistant Gram-negative bacteria. It notes that colistin was largely replaced in the 1970s due to toxicity concerns but has been reintroduced for resistant infections. The document summarizes that the current dosing of colistin may be suboptimal, especially in critically ill patients; colistin is likely less nephrotoxic than originally thought; and colistin can be as effective as other antibiotics for treating ventilator-associated pneumonia.
The document discusses multi-drug resistant Gram-negative pathogens and current and emerging therapeutic approaches. It provides an overview of colistin, tigecycline, and fosfomycin - discussing their mechanisms of action, pharmacokinetics, clinical efficacy, and safety. Colistin is an old antibiotic that is seeing renewed use for resistant infections. Tigecycline is used off-label for extremely drug resistant infections but has limitations. Fosfomycin has broad-spectrum activity against resistant bacteria including ESBL producers.
Inappropriate Prescribing Of AntimicrobialsMmorshed217
This document discusses inappropriate combinations of antimicrobial agents. It begins by listing common resistant nosocomial pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa. It then examines different classes of antimicrobials and why certain combinations should be avoided. These include combining two beta-lactams which results in therapeutic duplication, or combining a beta-lactam with a carbapenem which can have an antagonistic effect. Other inappropriate combinations discussed are fluoroquinolones with macrolides due to additive QT prolongation effects, and dual anti-anaerobic coverage with metronidazole and clindamycin. The document provides alternatives and references several clinical trials.
The document discusses slow virus diseases and prion diseases. It describes how Björn Sigurðsson first introduced the slow virus concept and studied diseases like maedi, visna, and scrapie in sheep. These diseases have long incubation periods and involve the central nervous system. Prion diseases like Kuru, Creutzfeldt-Jakob disease, and mad cow disease are also described, noting they involve misfolded prion proteins and have characteristics like spongiform changes in the brain. Measles virus diseases like subacute sclerosing panencephalitis are also slow virus diseases that occur due to mutations in the measles virus.
Este documento presenta el caso clínico de un paciente hospitalizado por infección urinaria asociada a catéter vesical. El paciente empeoró y se aisló Klebsiella pneumoniae carbapenemasa productora (KPC) en hemocultivo. El documento discute opciones de tratamiento para infecciones por bacterias multirresistentes, incluyendo dosis y esquemas de colistimetato de sodio y otros antibióticos. También resume estudios sobre el impacto del uso de colistina inhalada como adyuvante del tratamiento con colistina intraven
Treatment of infections caused by MDR-Gramnegatives: Update (Literature review)PROANTIBIOTICOS
This document summarizes several studies related to the treatment of infections caused by multidrug-resistant Gram-negative bacteria. It reviews literature on carbapenemase-producing Enterobacteriaceae, combinations of "weird" antimicrobials for extremely drug-resistant Gram-negatives, and the optimization of antibiotic dosing. For carbapenemase-producing Enterobacteriaceae, combination therapy is generally recommended but outcomes are heterogeneous. Studies also investigated the efficacy of carbapenems depending on the carbapenemase genotype. The combination of colistin and glycopeptides showed potential benefit for some multidrug-resistant organisms. A randomized trial of colistin plus rifampin for XDR Acinetobacter did not find significant clinical benefit. Extended infusion
Management of antibiotic resistance uploadAnimesh Gupta
This document discusses antibiotic resistance and its management. It defines antibiotic resistance as when microorganisms become resistant to drugs that previously treated infections from them. It outlines various mechanisms of antibiotic resistance in microorganisms and lists priority resistant bacteria. It also discusses superbugs and different strategies to manage antibiotic resistance like prudent antibiotic use, infection control, developing new drugs, and reducing agricultural overuse of antibiotics.
The document discusses the emergence of antimicrobial resistance due to the introduction and use of antimicrobials in humans and animals. It states that while antimicrobial resistance genes have existed naturally for thousands of years, the widespread use of antimicrobials has applied strong selective pressure that has led to growing antimicrobial resistance among human and animal pathogens. It also describes some of the associations seen between antimicrobial use and the emergence of resistance in various settings and bacterial species.
This document discusses antimicrobial resistance (AMR) and strategies for combating it. It begins by defining AMR and explaining that microorganisms can develop resistance to multiple antimicrobial agents, becoming "superbugs." It then discusses the global toll of AMR, listing bacteria identified by the CDC as urgent, serious, or concerning threats. The document emphasizes the need for antimicrobial stewardship programs in healthcare facilities to optimize antibiotic use and reduce resistance. It outlines components of stewardship programs like developing treatment guidelines, monitoring antibiotic use and resistance trends, and improving prescribing and de-escalation of therapy. The goal of stewardship is to use the right drug, for the right person, for the right duration. The document stresses
This document presents the study protocol for a randomized clinical trial evaluating the efficacy and safety of adding metformin to standard antituberculosis treatment regimens. The trial aims to determine if metformin can help achieve sputum culture conversion faster when added to initial treatment for drug-sensitive pulmonary tuberculosis. Over 300 participants with newly diagnosed, smear-positive pulmonary TB will be randomized to receive either standard antituberculosis treatment or the same treatment plus metformin for the first two months. The primary outcome is time to sputum culture conversion, with secondary outcomes including time to detection of TB in culture, pharmacokinetic measures, safety, and immune responses. The results could provide evidence for a shorter, more effective TB treatment regimen.
This document outlines Patient Safety Goal 4 to tackle antimicrobial resistance as part of WHO's 3rd Global Patient Safety Challenge. It describes 3 indicators to monitor the incidence of MRSA, ESBL-Klebsiella Pneumoniae, and ESBL-E.coli infections. Data on newly identified multidrug resistant organism cases will be collected and the infection rates calculated monthly. Strategies like implementing antibiotic guidelines, stewardship programs, and national campaigns aim to optimize antibiotic use and contain the spread of antimicrobial resistance.
This study analyzed 200 pus samples to determine the incidence of methicillin-resistant Staphylococcus aureus (MRSA) and associated risk factors. 80 samples were found to contain S. aureus, of which 29 tested positive for the mecA gene, confirming MRSA. Testing methods like cefoxitin disk diffusion and oxacillin screen agar were compared to the PCR gold standard. The cefoxitin test showed 96.55% sensitivity and 96.22% specificity for detecting MRSA, outperforming oxacillin tests. Risk factors like hospital acquisition, diabetes, and sex were also analyzed. The study concludes that cefoxitin testing is an effective alternative to PCR for MRSA detection
This document discusses rational antibiotic use and resistance. It describes the mechanisms of different antibiotic classes and how bacteria develop resistance. Resistance occurs through genetic mutations or extrachromosomal elements like plasmids, which allow resistance genes to spread between bacteria. The document emphasizes using antibiotics appropriately based on diagnosis, obtaining cultures, and giving the minimum effective treatment to reduce resistance.
Best Practice for Colistin Susceptibility Testing: Methods and Evidence (Mini...Abdullatif Al-Rashed
Mini-Review presentation
Best Practice for Colistin Susceptibility Testing: Methods and Evidence
Clinical Microbiology Residency Program, King Fahd Hospital of the University
Al Khobar, Saudi Arabia
This document presents information on antimicrobial resistance (AMR). It defines AMR as microorganisms becoming resistant to antimicrobial drugs like antibiotics, antivirals, and antimalarials. The document discusses factors that contribute to AMR, including overuse of antibiotics. It describes mechanisms of resistance such as mutations, plasmids, and enzymes that inactivate drugs. It recommends strategies to control AMR like prudent antibiotic use, developing new drugs, and reducing unnecessary use in animals. The conclusion emphasizes that AMR is a global threat that requires strategies to prevent further resistance development.
Antimicrobial therapy of eukaryotic parasites pdf.pptxssuserdc3441
This document summarizes challenges related to developing drugs to treat eukaryotic microbial pathogens. It discusses how eukaryotic microbes are more similar to human hosts than prokaryotic pathogens, requiring drugs to target differences. It also notes that many eukaryotic pathogens have evolved immune evasion mechanisms, increasing the impact of persistent phenotypes. Additionally, clinical diagnosis and screening for drug resistance in eukaryotic pathogens can be more difficult than for bacteria. The document concludes by stating that developing effective vaccines for prevention of eukaryotic microbial infections has generally proven challenging.
GCMA-Tackling the menace of MDR gram negative pathogens with a novel BL-BLI-...Jigar Mehta
The patient presented with worsening respiratory status and fever. Klebsiella pneumoniae was isolated from BAL culture and rapid molecular testing detected OXA-48. OXA-48 is commonly reported in India and often co-produced with ESBLs. Given the detection of OXA-48 and the likelihood of ESBL co-production based on local epidemiology, ceftazidime-avibactam was initiated due to its activity against OXA-48 producers and many ESBLs.
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Mechanistic Studies and Modeling Reveal the Origin of Differential Inhibition...Ira Dicker
This study investigated why the second-generation HIV maturation inhibitor BMS-955176 has improved activity against polymorphic viruses compared to the first-generation inhibitor bevirimat. The researchers found that:
1) Bevirimat exhibited incomplete (less than 100%) inhibition of certain polymorphic viruses, even at high concentrations, allowing breakthrough of infectious virus.
2) Viruses with faster cleavage kinetics at the inhibitor's target site were less sensitive to bevirimat.
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This presentation discusses strategies to combat drug resistance in antibiotics and anticancer therapy. It covers antibiotic resistance, which can be intrinsic, acquired through mutation, or acquired via plasmids. Strategies to address antibiotic resistance include international collaboration, national policies and guidelines, and actions at the community and hospital levels. Mechanisms of resistance gene transfer between bacteria include conjugation, transduction, and transformation. For anticancer therapy, a key strategy is addressing multidrug resistance caused by ATP-binding cassette transporters that pump drugs out of cancer cells. Clinical trials aim to identify the transporters involved and use inhibitors to block drug efflux.
The document summarizes information about monoclonal antibodies (mAbs), including their definition as identical antibodies generated from a single B cell clone that target a single epitope. It describes the advantages of mAbs such as specificity and applications in treatment. The document outlines the preparation process for mAbs and different types including murine, chimeric, humanized, and fully human. It discusses uses of mAbs in diagnosis, therapy, and protein purification and some challenges and future prospects.
This document provides an introduction to principles of anti-microbial therapy. It discusses key topics including:
- Sir Alexander Fleming's discovery of penicillin in 1928.
- The definition of chemotherapy and agents used to treat infections and cancer.
- Factors considered in selecting appropriate anti-microbial agents, including the infecting organism, site of infection, and patient factors.
- Mechanisms of anti-microbial resistance that can develop, including genetic alterations in microbes and changes in target sites or drug accumulation.
- Complications of anti-microbial therapy like hypersensitivity, direct toxicity, and superinfections.
Similar to enterobacteriaceae-risk-assessment-diseases-caused-by-antimicrobial-resistant-microorganisms-europe-june-2016 (20)
Presentation from the ECDC expert consultation on Whole Genome Sequencing organised by the European Centre of Disease Prevention and Control - Stockholm, 19 November 2015
Presentation from the ECDC expert consultation on Whole Genome Sequencing organised by the European Centre of Disease Prevention and Control - Stockholm, 19 November 2015
Dag Harmsen presented on the evolvement and challenges of cgMLST for the harmonization of bacterial genome sequencing and analysis. Key points include:
- cgMLST (core genome multilocus sequence typing) involves identifying and comparing alleles across a fixed set of core genome genes and has been applied to outbreak investigation and global pathogen nomenclature.
- Tools for cgMLST analysis have been developed and improved to work on read, draft, and complete genome levels and allow scalable, additive analysis of single genes to whole genomes.
- Standardizing a hierarchical cgMLST-based approach and developing common nomenclature poses challenges but is important for microbial genotypic surveillance across laboratories and countries.
Presentation from the ECDC expert consultation on Whole Genome Sequencing organised by the European Centre of Disease Prevention and Control - Stockholm, 19 November 2015
Presentation from the ECDC expert consultation on Whole Genome Sequencing organised by the European Centre of Disease Prevention and Control - Stockholm, 19 November 2015
Presentation from the ECDC expert consultation on Whole Genome Sequencing organised by the European Centre of Disease Prevention and Control - Stockholm, 19 November 2015
Presentation from the 3rd Joint Meeting of the Antimicrobial Resistance and Healthcare-Associated Infections (ARHAI) Networks, organised by the European Centre of Disease Prevention and Control - Stockholm, 11-13 February 2015
Presentation from the 3rd Joint Meeting of the Antimicrobial Resistance and Healthcare-Associated Infections (ARHAI) Networks, organised by the European Centre of Disease Prevention and Control - Stockholm, 11-13 February 2015
Presentation from the 3rd Joint Meeting of the Antimicrobial Resistance and Healthcare-Associated Infections (ARHAI) Networks, organised by the European Centre of Disease Prevention and Control - Stockholm, 11-13 February 2015
Presentation from the 3rd Joint Meeting of the Antimicrobial Resistance and Healthcare-Associated Infections (ARHAI) Networks, organised by the European Centre of Disease Prevention and Control - Stockholm, 11-13 February 2015
Presentation from the 3rd Joint Meeting of the Antimicrobial Resistance and Healthcare-Associated Infections (ARHAI) Networks, organised by the European Centre of Disease Prevention and Control - Stockholm, 11-13 February 2015
Presentation from the 3rd Joint Meeting of the Antimicrobial Resistance and Healthcare-Associated Infections (ARHAI) Networks, organised by the European Centre of Disease Prevention and Control - Stockholm, 11-13 February 2015
Presentation from the 3rd Joint Meeting of the Antimicrobial Resistance and Healthcare-Associated Infections (ARHAI) Networks, organised by the European Centre of Disease Prevention and Control - Stockholm, 11-13 February 2015
Presentation from the 3rd Joint Meeting of the Antimicrobial Resistance and Healthcare-Associated Infections (ARHAI) Networks, organised by the European Centre of Disease Prevention and Control - Stockholm, 11-13 February 2015
Validation studies are essential to accurately assess the sensitivity, specificity, and predictive values of point prevalence surveys (PPS) of healthcare-associated infections (HAI). Previous validation studies of PPS have shown varied results, underscoring the need for formal evaluations. Without validation, true HAI prevalence is unknown and differences between locations cannot be properly investigated. International organizations can help support national validation efforts to improve HAI surveillance.
Presentation from the 3rd Joint Meeting of the Antimicrobial Resistance and Healthcare-Associated Infections (ARHAI) Networks, organised by the European Centre of Disease Prevention and Control - Stockholm, 11-13 February 2015
This document contains forms and instructions for conducting a point prevalence survey of healthcare-associated infections and antimicrobial use in European acute care hospitals. The forms collect data at the hospital, ward, patient, and national/regional level. Hospital data includes bed numbers, staffing levels, infection control activities and organizational culture. Ward data includes bed numbers, hand hygiene infrastructure. Patient data collects infection details, antimicrobial use, and patient characteristics for those with infections or receiving antibiotics. National data provides healthcare system context. The forms standardize data collection to allow prevalence comparisons across settings.
Presentation from the 3rd Joint Meeting of the Antimicrobial Resistance and Healthcare-Associated Infections (ARHAI) Networks, organised by the European Centre of Disease Prevention and Control - Stockholm, 11-13 February 2015
Presentation from the 3rd Joint Meeting of the Antimicrobial Resistance and Healthcare-Associated Infections (ARHAI) Networks, organised by the European Centre of Disease Prevention and Control - Stockholm, 11-13 February 2015
Presentation from the 3rd Joint Meeting of the Antimicrobial Resistance and Healthcare-Associated Infections (ARHAI) Networks, organised by the European Centre of Disease Prevention and Control - Stockholm, 11-13 February 2015
More from European Centre for Disease Prevention and Control (ECDC) (20)
2. RAPID RISK ASSESSMENT Plasmid-mediated colistin resistance in Enterobacteriaceae, 13 June 2016
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Improved surveillance
To gather more information on the extent of the spread and the prevalence of gram-negative bacteria carrying
the mcr-1 gene in the human and animal microbiomes, it is advisable to perform sentinel testing surveys of
food, animal, environmental and human isolates to determine the presence of the mcr-1 gene and characterise
the associated mobile genetic vectors. The compulsory monitoring of colistin resistance in zoonotic and
commensal bacteria isolated from food-producing animals and their meat is already in place in accordance with
EU legislation.
At the local level, healthcare facilities affected by sporadic cases or epidemic outbreaks of carbapenem-resistant
and other MDR Enterobacteriaceae should consider prospective, at least sentinel, colistin susceptibility testing
followed by PCR detection of the mcr-1 gene in colistin-resistant isolates to ascertain the introduction of the
mcr-1 gene into their facility and ensure its containment as part of their efforts to prevent and control MDR
bacteria. Testing of MDR Enterobacteriaceae isolates from patients with recent contact with healthcare facilities
in foreign countries for colistin susceptibility and for presence of the mcr-1 gene could also be considered, based
on available laboratory resources and following current national guidelines.
At the national level, there is a need for performing retrospective and prospective structured molecular testing
surveys of the prevalence of the mcr-1 gene in colistin-resistant isolates of carbapenem-resistant
Enterobacteriaceae (CRE) and other MDR Enterobacteriaceae. In the European Survey on Carbapenemase-
Producing Enterobacteriaceae (EuSCAPE) project, all EU/EEA Member States reported having a national
surveillance system for CRE in place supported by national reference identification of carbapenemase genes.
Performing additional phenotypic testing for co-resistance to colistin and molecular detection of the mcr-1 gene
on isolates collected within those sentinel, survey-based systems would be therefore valuable and feasible.
ECDC plans to initiate a new EU sentinel WGS-based surveillance module for CRE and extensively drug-resistant
Enterobacteriaceae (XDRE) infections, by means of periodically repeating structured, pan-EU surveys following
the sampling design of the EuSCAPE project. Analysis of WGS data from collected isolates will determine the
genetic complement and predict the phenotype by mobilome/resistome/virulome profiling and the identification
of genetic markers of high-risk clones and plasmids. This approach would enable identification of internationally
disseminated high-risk colistin-resistant CRE clones that carry the mcr-1 gene and monitor their geographical
distribution across EU/EEA countries.
Clinical management
Timely and reliable laboratory investigation of microbiological samples and timely reporting of the results is
essential to avoid a delay in the administration of appropriate antimicrobial treatment, which has been found to
be associated with increased morbidity and mortality. Colistin treatment should be accompanied by colistin
susceptibility testing. Patients with infections due to colistin-resistant bacteria are likely to benefit from
consultations with experts in infectious diseases or clinical microbiology, which ensures the best possible
therapeutic regimen considering the limited treatment options.
Actions to prevent transmission in healthcare settings
Infection control precautions
Adherence to standard infection control practices, including hand hygiene, environmental cleaning and adequate
reprocessing of medical devices, and adequate capacity of microbiological laboratories are the basis for
prevention of transmission of MDR bacteria.
Surveillance and detection of mcr-1 in healthcare facilities should be conducted as outlined above. Prompt
notification of patients who were identified as carriers or infected with colistin-resistant MDR gram-negative
bacteria to the clinical team and to the infection prevention and control/hospital hygiene team is essential.
The need for enhanced control measures such as contact isolation precautions, single-room isolation or
cohorting, and dedicated nursing for patients who tested positive, should be determined based on the antibiotic
resistance pattern of the detected mcr-1-carrying Enterobacteriaceae isolates. Such enhanced control measures
should be considered in particular for patients colonised or infected with isolates carrying both the mcr-1 gene
and carbapenemase genes. For patients colonised or infected with isolates carrying the mcr-1 gene in
combination with other resistance genes, individual decisions should be taken based on the resistance profile,
the likelihood of nosocomial transmission, and previous evidence of association with outbreaks. This decision
should take into account evidence on the spread of the strain and on control measures as soon as they become
available.
3. RAPID RISK ASSESSMENT Plasmid-mediated colistin resistance in Enterobacteriaceae, 13 June 2016
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Antimicrobial stewardship
Antimicrobial stewardship refers to coordinated programmes that implement interventions to ensure appropriate
antimicrobial prescribing with the aim to improve clinical efficacy of antimicrobial treatment and limit
antimicrobial resistance through reducing selective pressure. Although evidence for a specific beneficial effect of
antimicrobial stewardship on the emergence and spread of colistin resistance is currently lacking, reduction of
the use of broad-spectrum antimicrobials can reduce the emergence of carbapenem-resistant bacteria and
therefore obviate the need for colistin treatment. Implementation of comprehensive antimicrobial stewardship
programmes is therefore important. Caution should be exercised in using colistin-containing selective digestive
tract decontamination as it can promote selection and spread of colistin resistance, especially if plasmid-based.
Nevertheless, targeted and appropriate use of antimicrobial agents is not likely to fully reverse the current
resistance trends, and there is an urgent public health need to promote the development of new antibacterial
agents active against MDR gram-negative bacteria.
Actions to prevent spread of plasmid-based colistin
resistance in the community
One Health approach
It is important to carefully monitor the presence of mcr-1 and to try to avoid the potential transmission of mcr-1
via contaminated food. Close cooperation between veterinary medicine and human medicine, combined with
regular monitoring in domestically produced and imported foodstuffs, is needed to assess whether consumers
may be exposed to mcr-1-positive gram-negative bacteria via food.
Reduction of colistin use in animals
Prudent use of antimicrobials, and especially the reduction of colistin use in food-producing animals, would be
effective in minimising the further emergence and spread of MDR bacteria, including those carrying mcr-1, via
the food chain. Detailed guidance on the use of colistin in animals is available in a draft advice from the
European Medicines Agency (EMA) dated 26 May 2016. As indicated by EMA, emphasis should also be placed on
the improvement of the conditions of animal husbandry (e.g. biosecurity, hygienic conditions) and the
implementation of alternative measures that would reduce the need for antimicrobial agents and therefore also
reduce the development of antimicrobial-resistant bacteria in food-producing animals.
Source and date of request
ECDC internal decision, 30 May 2016.
Public health issue
The recent discovery of the mcr-1 gene, encoding the first transferable resistance mechanism to colistin, a last-
resort antimicrobial agent for infections by multidrug-resistant (MDR) gram-negative bacteria, raised widespread
concern that its dissemination within the human microbiome could lead to nosocomial outbreaks of virtually
untreatable infections. Follow-up reports have revealed worldwide spread of the mcr-1 gene by plasmid transfer to
diverse species and strains of Enterobacteriaceae, including MDR strains. In May 2016, the US CDC reported the
first human mcr-1 positive E. coli isolate detected in the United States.
This document assesses the risk for the patients and healthcare systems in the EU/EEA due to the global mcr-1
plasmid-mediated gene epidemic [44,45] and reviews the options for strengthening laboratory-based surveillance
and for mitigating further epidemic dissemination of mcr-1-positive MDR strains of Enterobacteriaceae in
healthcare facilities.
Consulted experts
In alphabetical order: Barbara Albiger, Dragoslav Domanovic, Anke Kohlenberg, Dominique Monnet, Diamantis
Plachouras, Marc Struelens
Consulted external experts: Jan Kluytmans (Amphia Hospital Breda), Gian Maria Rossolini (Florence Careggi
University Hospital, Florence), Christian Giske (Karolinska University Hospital, Stockholm) and colleagues from the
European Food Safety Authority (EFSA), the European Medicines Agency (EMA) and the European Commission –
Directorate-General for Health and Food Safety (SANTE).
4. RAPID RISK ASSESSMENT Plasmid-mediated colistin resistance in Enterobacteriaceae, 13 June 2016
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Health issue background information
The global rise of MDR gram-negative bacteria is alarming and represents an increasing threat to healthcare
delivery and patient safety in Europe and beyond. The past decades have seen a rapid increase of resistance to
penicillins, cephalosporins and carbapenems due to the global spread of extended-spectrum beta-lactamases
(ESBLs) and carbapenemases in gram-negative bacteria, first in Klebsiella pneumoniae and other Klebsiella species,
then in Escherichia coli [1,2]. Treatment alternatives for patients infected with MDR gram-negative bacteria
resistant to carbapenems and other key antimicrobial agents are often limited to combination therapy and to older
antimicrobial agents such as polymyxins, e.g. colistin.
Colistin (polymixin E) is a cationic, multicomponent lipopeptide antibacterial agent that is effective against most
gram-negative bacteria (including Acinetobacter, Pseudomonas, Escherichia and Klebsiella species) by disrupting
the bacterial cell membrane. Because of its nephrotoxicity, colistin was restricted to topical use and virtually
abandoned for systemic use when less toxic anti-gram-negative agents (e.g. beta-lactams, aminoglycosides)
became available. The increasing number of hospital outbreaks with carbapenem-resistant gram-negative bacteria
and the lack of new antimicrobial agents active against such MDR bacteria have compelled clinicians to reconsider
the value of colistin as a therapeutic option and reintroduce its systemic administration as a last resort treatment
for healthcare-associated infections due to carbapenem-resistant MDR gram-negative infections. For this reason, in
2012 WHO reclassified colistin as a critically important antibacterial agent for human medicine. The latest data
available from the European Surveillance of Antimicrobial Consumption Network (ESAC-Net) show that
consumption of colistin in human health in the EU/EEA almost doubled in Europe between 2010 and 2014 [3].
Colistin is used more frequently for treating infected patients in those EU/EEA countries that have the highest
prevalence of carbapenem-resistant Enterobacteriaceae (CRE). In some healthcare settings in these countries, as a
result of an increasing number of patients exposed to colistin and varying infection control practices, colistin
resistance has rapidly developed in carbapenem-resistant K. pneumoniae strains due to chromosomal mutations in
the genes involved in lipopolysaccharide biosynthesis.
In November 2015, the discovery of a transferable plasmid-mediated colistin resistance gene, mcr-1, in E. coli
challenged the concept that gram-negative bacteria only develop colistin resistance through chromosomal
mutations or adaptive mechanisms (e.g. changes of the bacterial cell outer membrane or presence of an efflux
pump). This new determinant of colistin resistance is transferable among bacterial strains and species by horizontal
transfer of mobile genetic elements [4]. In vitro self-transfer of the mcr-1 gene from conjugative plasmids has
been shown to occur at high frequency [4].
While the mcr-1 gene was first detected in Enterobacteriaceae in China, within the six months following its
discovery, plasmids carrying the mcr-1 gene were found in isolates from animals, food, the environment and
humans worldwide, including the EU (Figure 1).
5. RAPID RISK ASSESSMENT Plasmid-mediated colistin resistance in Enterobacteriaceae, 13 June 2016
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Figure 1. Geographic spread of the mcr-1 gene, updated from [6] as of 02 June 2016
Note: Maps are based on the latest peer-reviewed publications on the spread of the mcr-1 gene.
Reproduced under a Creative Commons Attribution (CC BY) licence.
6. RAPID RISK ASSESSMENT Plasmid-mediated colistin resistance in Enterobacteriaceae, 13 June 2016
6
Event background information
On 18 November 2015, Liu et al. reported the first description of plasmid-mediated colistin resistance (mcr-1 gene)
in food-producing animals, food and humans in China [4]. On 3 March 2016, a literature review published in
Eurosurveillance summarised the available information and knowledge on the extent of specimen/infection type,
the geographic and longitudinal spread of the mcr-1 gene, the variety of host species, the associated resistance
genes as well as the rate of transferability of the plasmid-mediated mcr-1 gene and showed that, within three
months of its discovery, the mcr-1 gene had been reported from most continents and found in bacteria from
various food animals, from the environment, from various types of meat and vegetables, and from infected
patients and asymptomatic human carriers including international travellers [6]. The first report on 26 May 2016 of
the mcr-1 gene in an E. coli isolate from a human specimen in the United States further extends the geographic
distribution of the gene, which has been reported to date in 27 countries (Figure 1).
A summary of the latest data on detection of the mcr-1 gene in animals, food and humans can be found in Table 9
of the updated European Medicine Agency (EMA) draft advice on the use of colistin products in animals within the
European Union, dated 26 May 2016 [5].
In the EU/EEA, the mcr-1 gene was identified in human samples starting from 2011 in Denmark, Germany, Italy,
the Netherlands, Spain, Sweden and the United Kingdom; in food-producing animals starting from 2005 in Belgium,
France, Germany, Italy, the Netherlands, Spain and the United Kingdom; from food starting from 2009 in Belgium,
Denmark, France, Portugal, the Netherlands and the United Kingdom [5,6] (Figure 1). Since the publication of the
updated EMA draft advice, there have been several additional reports of detection of the mcr-1 gene, including
reports of detection in isolates from human samples from Malaysia [7], South Africa [8], Egypt [9], the USA [10]
and China [11,12] and animal isolates from Brazil [13] and the UK [14].
Following the discovery of this new mechanism of resistance to colistin and given its biological potential for rapid
spread, the European Commission requested the Antimicrobial Advice ad hoc Expert Group (AMEG) of EMA to
update its 2013 advice on the Use of colistin products in animals within the European Union: development of
resistance and possible impact on human and animal health [15]. This update was endorsed by the Committee for
Medicinal Products for Veterinary Use (CVMP) and the Committee for Medicinal Products for Human Use (CHMP)
and launched on 26 May 2016 for a public consultation until 26 June 2016 [5]. The update recommends that the
sale of colistin for use in animals should be reduced and that its use in animals should be restricted to last-resort
treatment, The update also proposes appropriate risk management measures [5].
In line with the EMA update, this rapid risk assessment was initiated to update the information on the
dissemination and prevalence of mcr-1 mediated colistin resistance in humans in the EU/EEA and on new
developments in laboratory detection methods. In addition, it reviews the options for strengthening laboratory-
based surveillance systems for MDR, surveys the emerging antimicrobial resistant bacterial pathogens in human
health in the EU/EEA, and advises on mitigating the risk of further epidemic dissemination of mcr-1-positive, MDR
strains of Enterobacteriaceae in healthcare facilities.
Colistin resistance mechanisms
Some gram-negative bacteria (e.g. Morganella, Proteus, Providencia, Serratia and Burkholderia species) are
intrinsically resistant to colistin. Colistin resistance can be acquired in other, normally susceptible gram-negative
bacteria such as E. coli and K. pneumoniae by adaptive or mutational mechanisms that alter the bacterial outer
membrane, which is the site of action of colistin. Mutations in the genes (e.g. pmrHFIJFKLM operon, lpxACD,
pmrAB, phoQ and mgrB) involved in the synthesis of components of the bacterial outer membrane (i.e.
lipopolysaccharide [LPS] and its core component lipid A) or in its regulation can change the negative surface
charge of the outer membrane such that colistin is no longer able to bind and initiate membrane lysis [16,17]. The
recently discovered mcr-1 gene encodes for a phosphoethanolamine (PEt) transferase that adds PEt to lipid A,
which reduces the LPS anionic charge and, subsequently, its affinity to the cationic colistin. While the genes
involved in the synthesis of the bacterial outer membrane or in its regulation are usually located on the
chromosome, the mcr-1 gene is carried by mobile genetic elements such as plasmids [4]. Moreover, it was recently
found that the insertion of mobile genetic elements, such as insertion sequences (IS) or transposons carrying
ESBL/carbapenem-resistance genes into the regulatory gene mgrB, conferred not only resistance to extended-
spectrum cephalosporins/carbapenems but concomitantly colistin resistance [18,19]. These findings highlight the
critical role of mobile genetic elements carrying resistant genes in amplifying co-resistance and accelerating the
emergence of pandrug-resistant (PDR) bacteria.
7. RAPID RISK ASSESSMENT Plasmid-mediated colistin resistance in Enterobacteriaceae, 13 June 2016
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Laboratory detection of colistin resistance and genetic
identification of mcr-1
Colistin susceptibility testing is technically challenging due to several methodological issues. Polymyxins bind to a
range of plastics and glass, including the most common plastics (polystyrene and polypropylene) used in
microdilution trays used in laboratory susceptibility testing, raising reliability and reproducibility issues. These
issues were extensively investigated by the European Committee on Antimicrobial Susceptibility Testing (EUCAST)
and the Clinical Laboratories Standards Institute (CLSI). Both recommend microbroth dilution MIC determination as
the only reliable and reproducible colistin susceptibility test method under the condition that uncoated polystyrene
microtiter plates and cation-adjusted Mueller-Hinton culture broth are used without any other additives (i.e. in
particular polysorbate 80 and other surfactants). They currently do not recommend susceptibility testing by other
methods, including agar dilution, disk diffusion and gradient diffusion until historical data have been reviewed or
new study data have been generated. Work on validation of these methods is ongoing [20].
A rapid screening test for the detection of colistin resistance in Enterobacteriaceae in less than 2 hours has recently
been developed, based on the detection of glucose metabolisation associated with bacterial growth in a defined
concentration of colistin [21]. A new growth medium for screening polymyxin-resistant gram-negative isolates
(SyperPolyxin) has also been developed [22]. However, these tests have not yet been prospectively validated on a
large scale. They could be used in the near future as a first-step screening for colistin-resistant Enterobacteriaceae
before undertaking MIC determination and molecular investigations.
The direct detection of the mcr-1 gene can be achieved either by means of polymerase-chain reaction (PCR) assay
on genomic DNA or by whole-genome sequencing (WGS) and sequence homology search using dedicated
antimicrobial resistance gene identification applications such as ResFinder [23]. Protocols for PCR amplification and
sequencing have been developed for the detection, confirmation and molecular characterisation of the mcr-1
gene [4].
Prevalence of colistin resistance among human and animal
Enterobacteriaceae isolates in the EU
Surveillance of antimicrobial resistance among gram-negative bacilli causing human infection in the EU is based on
data on the bacterial resistance phenotypes among invasive clinical isolates for selected species, including E. coli
and K. pneumoniae, but does not monitor the frequency of molecular resistance mechanisms. The European
Antimicrobial Resistance Surveillance Network (EARS-Net) collects data based on routine clinical laboratory
antimicrobial susceptibility testing (AST) results. The availability of AST results for specific antimicrobial agents
depends on local testing protocols. These protocols are primarily designed to advise clinicians on patient therapy
and not for public health surveillance, i.e. many laboratories serving populations with low prevalence of colistin
resistance in clinical isolates do not routinely test isolates for colistin susceptibility. Although EARS-Net data on
colistin resistance are not complete, some countries, especially countries with an already high prevalence of
carbapenem resistance, report large numbers of colistin-resistant isolates [24]. Indeed, colistin resistance is
increasing in carbapenemase-producing Enterobacteriaceae (CPE) in Europe. In Italy, 43% of Klebsiella
pneumoniae carbapenemase (KPC)-producing K. pneumoniae isolates collected during a period of six months from
November 2013 to April 2014 [25] and 13% of carbapenem-resistant K. pneumoniae isolates from blood cultures
reported to EARS-Net in 2014 were also resistant to colistin [24]. In Romania and Greece, approximately 20% of
carbapenem-resistant K. pneumoniae isolates from blood cultures reported to EARS-Net in 2014 were resistant to
colistin [24]. This recent increase in colistin resistance follows the increasing trend in consumption of colistin in
human medicine, which has almost doubled between 2010 and 2014 in Europe [3] and is the highest in countries
with high prevalence rates of carbapenem and multidrug resistance in gram-negative bacilli. EARS-Net does not
collect molecular data on the presence of mcr-1 gene or other colistin resistance mechanism.
The latest available data on colistin resistance in Salmonella from humans, animals and food are provided in the
European Union summary report on antimicrobial resistance in zoonotic and indicator bacteria from 2014 [26].
Mandatory EU reporting for colistin resistance in Salmonella and indicator E. coli from animals and meat thereof
was launched in 2014 [27]. The overall percentage of colistin resistance in E. coli and Salmonella from poultry and
poultry meat is 2.6% and 8.5%, respectively [5].
Recent molecular studies of case reports and case series have determined the mechanisms of colistin resistance in
extensively drug-resistant (XDR) and PDR strains of Enterobacteriaceae. Investigation of a large collection of
colistin-resistant carbapenemase-producing K. pneumoniae isolates from Greece and Italy revealed that
inactivation of the chromosomal mgrB regulatory gene is a common mechanism of colistin resistance [28], and this
resistance mechanism was found to be prevalent also among colistin-resistant strains from other sources [29]. In
2015, the first complete genome sequence of a PDR strain of K. pneumoniae was described. This strain was
resistant to all commercially available antibiotics, and whole-genome analysis elucidated the insertion of a mobile
genetic element carrying the resistance to carbapenems into the chromosomal mgrB gene, making the bacterium
simultaneously resistant to carbapenem and colistin [18]. In 2016, a clinical isolate of ESBL-producing and colistin-
resistant K. pneumoniae was recovered from a patient treated with cefotaxime. The strain harboured an ESBL gene
8. RAPID RISK ASSESSMENT Plasmid-mediated colistin resistance in Enterobacteriaceae, 13 June 2016
8
associated with an IS element which transposed into the mgrB gene, again making it simultaneously resistant to
carbapenem and colistin [19]. These anecdotal findings suggest that, in addition to spread of mcr-1, acquisition of
other multidrug resistance determinants increases the likelihood of outbreaks of nosocomial infections by XDR or
PDR strains of Enterobacteriaceae, for which no effective treatment is available.
The prevalence of mcr-1 carrying isolates among colistin-resistant Enterobacteriaceae from humans and animals in
the EU is not known due to the lack of surveillance data at EU level. The rapid publication of cases of
retrospectively identified mcr-1 positive isolates from human, animals and environmental samples in several
EU/EEA countries is a testimony to the powerful information source provided by WGS analysis and public access to
sequence databases.
The available information so far suggests that the prevalence of transferable colistin resistance mediated by mcr-1
gene is still low among human isolates and among food-producing animal isolates of Enterobacteriaceae in Europe.
ECDC threat assessment for the EU
There are still major information gaps relating to the current prevalence of colistin resistance in human clinical
isolates in the EU/EEA, as the data on colistin resistance collected through EARS-Net are not complete and due to
inherent issues with methods for colistin susceptibility testing. In addition, there is also a general lack of
information on the historical and current prevalence of colistin resistance due to the mcr-1 gene and its evolution
in gram-negative bacteria that form part of animal, human and food microbiomes.
Clinical hazard of mcr-1: limited treatment options and
adverse prognosis
Despite its nephro- and neurotoxicity, colistin is increasingly used as one of the last available treatment options for
patients with severe infections caused by carbapenem-resistant Enterobacteriaceae and carbapenem-resistant
Acinetobacter baumannii and Pseudomonas aeruginosa. As parenteral colistin therapy is used mostly for infections
with carbapenem-resistant bacteria, it can function as a surrogate marker for carbapenem resistance for
surveillance purposes [30]. Whereas colistin resistance alone is not clinically relevant as long as other effective
antimicrobial agents such as cephalosporins, carbapenems or fluoroquinolones are active, it can shift an MDR strain
to an XDR or PDR phenotype when, as seen with several mcr-1-positive isolates, it is found in association with
multiple other resistance genes [5,6]. Enterobacteriaceae isolates that produce different carbapenemases such as
New Delhi Metallo-beta-lactamase (NDM)-5, NDM-9, Oxacillinase (OXA)-48, and Klebsiella pneumoniae
carbapenemase (KPC)-2 in association with colistin resistance mediated by mcr-1 [11,31-34] illustrate the diverse
combinations of resistance genes that can render these bacteria XDR.
Systemic infections with CRE are in general associated with fatality rates above 50% [35]. Colistin resistance
further limits the already scarce treatment options for patients with infections with CRE to the point where no
effective treatment is available and has been associated with an increased risk of fatal outcome [36].
Public health hazard: mcr-1 gene spread in the human
microbiome
Spread in healthcare settings
The mcr-1 gene has been detected in Enterobacteriaceae isolates from humans with severe infections [6].
Enterobacteriaceae such as E. coli and K. pneumoniae are frequent causes of healthcare-associated infections, and
the incidence of MDR E. coli and K. pneumoniae isolates is increasing steadily in the EU/EEA [24]. E. coli is
frequently exchanged between the environment, animals and humans and is part of the normal human intestinal
microbiome, but also a common cause of urinary tract infections as well as bloodstream infections [37]. Klebsiella
spp. and Enterobacter spp. are also associated with healthcare-associated infections and MDR outbreaks in acute
care settings. In the ECDC point prevalence survey of healthcare-associated infections and antimicrobial use in
acute care hospitals 2011–2012, Klebsiella spp. were isolated as the fifth most frequent organism in 8.7% of the
documented health-care associated infections, while Enterobacter spp. were isolated as the as the ninth most
frequent organism in 4.2% of the documented health-care associated infections [38].
The detection of mcr-1 in invasive Enterobacteriaceae isolates highlights the risk of increasing co-resistance in
pathogens that are already causing outbreaks of difficult-to-treat infections in hospitals. The mcr-1 gene has also
been detected in residents of long-term-care facilities [39]. The spread of mcr-1 might go unnoticed in healthcare
settings as colistin testing is not routinely performed in clinical laboratories, where testing is only carried out for
isolates already resistant to first-line antibiotics.
9. RAPID RISK ASSESSMENT Plasmid-mediated colistin resistance in Enterobacteriaceae, 13 June 2016
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Spread in the community
The use of colistin is much higher in animals than in humans. Estimates cite an average that is more than
600 times higher in food-producing animals than in humans (19 EU/EEA Member States included in the ECDC–
EFSA–EMA first joint report on the integrated analysis of the consumption of antimicrobial agents and occurrence
of antimicrobial resistance in bacteria from humans and food-producing animals) [40]. There is a larger number of
publications that have reported the detection of mcr-1 in isolates in animals than in humans. These findings might
be biased by the fact that there are more data available for animals and food.
The authors of the original publication had already hypothesised that mcr-1 first arose in animals and was
transmitted to humans [4]. There is additional evidence for the link between mcr-1 and animals such as the
association of mcr-1 with resistance genes widespread in animals and an IS originating from a common animal
pathogen [41]. Detection of the mcr-1 gene in farmers was shown to be associated with colistin use in Vietnamese
poultry farms. Farmers exposed to chickens – and especially mcr-1-positive chickens – had a higher risk of faecal
colonisation than individuals not exposed to poultry [42]. The multiple reports of mcr-1 from animal samples raise
the possibility that there is already a reservoir of mcr-1 in animals [5,6,41], indicating that measures directed only
at nosocomial transmission may not be sufficient.
The presence of mcr-1 in food-producing animals such as pigs, chickens and veal calves and various food products,
predominantly meat but also vegetables, has been described in several EU Member States including France,
Germany, the Netherlands, Belgium, Italy, Portugal and the UK [5,6]. The presence of the mcr-1 gene represents a
potential food hazard with possible subsequent incorporation into the human intestinal microbiome. However, the
extent of the risk cannot be quantified until further data are generated. Intestinal carriage of the mcr-1 gene could
be amplified in hospitalised patients by further genetic mobilisation and plasmid transfer to MDR strains under the
selective pressure of high antibiotic use in EU/EEA hospitals, e.g. carbapenems and colistin.
There are very limited data on the duration of human carriage of bacteria harbouring the mcr-1 gene, and further
studies investigating the longitudinal carriage are needed. In a study on acquisition of faecal colonisation of MDR
Enterobacteriaceae, the mcr-1 gene was detected in isolates from six Dutch travellers shortly after returning from
North Africa, Asia and South America. Subsequent samples from these travellers were negative after one month
[43]. However, the duration of carriage of mcr-1-positive bacteria might be different in immunocompromised
patients and patients exposed to antibiotics.
The mcr-1 gene was first detected in China in isolates from food-producing animals and several subsequent reports
document the detection of mcr-1 in Asia (Figure 1), although these data may be biased by the lack of testing in
other regions. In any event, it is likely that migration and travel can result in further spread of the mcr-1 gene
between regions and countries.
Conclusions and options for response
The recently recognised global distribution of a self-transferable plasmid-borne colistin resistance determinant
(mcr-1 gene) poses a substantial public health risk to the EU/EEA. This specific mode of molecular dissemination of
drug resistance is an example of a so-called plasmid-mediated gene epidemic [44,45].
This plasmid-mediated gene epidemic is of exceptional public health concern because it further limits treatment
options in patients with infections caused by multidrug-resistant (MDR) gram-negative bacteria and can spread
colistin resistance more easily between bacteria and humans than colistin resistance resulting from chromosomal
mutation. MDR gram-negative bacteria, including carbapenem-resistant Enterobacteriaceae strains that acquire the
mcr-1 gene, remain susceptible to only a few antimicrobial agents, which means that infections caused by these
strains are very difficult to treat and result in excess mortality. As the limited development of new antimicrobials is
unlikely to provide a solution anytime soon, it is crucial to take measures to control the spread of mcr-1 and thus
protect the activity of colistin.
Options for actions to reduce identified risks
Improved laboratory methods for colistin resistance and
mcr-1 detection
The European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the Clinical Laboratories Standards
Institute (CLSI) recommend MIC determination by microbroth dilution as the reference method for colistin
susceptibility testing. For the time being, these organisations do not recommend other methods (e.g. agar dilution,
disk diffusion or gradient diffusion) for colistin susceptibility testing until historical data have been reviewed or new
study data have been generated [20]. ECDC has added colistin to the priority panel of antimicrobial agents to test
for as part of the EU surveillance of antimicrobial-resistant Salmonella infections (revised EU surveillance protocol
10. RAPID RISK ASSESSMENT Plasmid-mediated colistin resistance in Enterobacteriaceae, 13 June 2016
10
to be published June 2016) and initiated a project with EUCAST to study the gradient strip MIC and disk diffusion
methods as an alternative.
PCR for mcr-1 detection could be conveniently combined with the detection of other resistance gene targets in
multiplex PCR-based assays used for the detection of multi-drug resistance determinants of epidemiological and
clinical importance in gram-negative bacilli, such as extended-spectrum beta-lactamases and carbapenemases.
Whole-genome sequencing (WGS) can be used for the detection or confirmation of the presence of the mcr-1 gene
and offers additional information about the associated plasmid vector, additional resistance genes, and strain type.
Improved surveillance
To gather more information on the extent of the spread and the prevalence of gram-negative bacteria carrying the
mcr-1 gene in the human and animal microbiomes, it is advisable to perform sentinel testing surveys of food,
animal, environmental and human isolates to determine the presence of the mcr-1 gene and characterise the
associated mobile genetic vectors. The compulsory monitoring of colistin resistance in zoonotic and commensal
bacteria isolated from food-producing animals and their meat is already in place in accordance with EU
legislation [27].
At the local level, healthcare facilities affected by sporadic cases or epidemic outbreaks of carbapenem-resistant
and other MDR Enterobacteriaceae should consider prospective, at least sentinel, colistin susceptibility testing
followed by PCR detection of the mcr-1 gene in colistin-resistant isolates to ascertain the introduction of the mcr-1
gene into their facility and ensure its containment as part of their efforts to prevent and control MDR bacteria.
Testing of MDR Enterobacteriaceae isolates from patients with recent contact with healthcare facilities in foreign
countries for colistin susceptibility and for presence of the mcr-1 gene could also be considered, based on available
laboratory resources and following current national guidelines.
At the national level, there is a need for performing retrospective and prospective structured molecular testing
surveys of the prevalence of the mcr-1 gene in colistin-resistant isolates of carbapenem-resistant
Enterobacteriaceae (CRE) and other MDR Enterobacteriaceae. In the European Survey on Carbapenemase-
Producing Enterobacteriaceae (EuSCAPE) project, all EU/EEA Member States reported having a national
surveillance system for CRE in place supported by national reference identification of carbapenemase genes.
Performing additional phenotypic testing for co-resistance to colistin and molecular detection of the mcr-1 gene on
isolates collected within those sentinel, survey-based systems would be therefore valuable and feasible.
ECDC plans to initiate a new EU sentinel WGS-based surveillance module for CRE and extensively drug-resistant
Enterobacteriaceae (XDRE) infections, by means of periodically repeating structured, pan-EU surveys following the
sampling design of the EuSCAPE project. Analysis of WGS data from collected isolates will determine the genetic
complement and predict the phenotype by mobilome/resistome/virulome profiling and the identification of genetic
markers of high-risk clones and plasmids. This approach would enable identification of internationally disseminated
high-risk colistin-resistant CRE clones that carry the mcr-1 gene and monitor their geographical distribution across
EU/EEA countries.
Clinical management
Timely and reliable laboratory investigation of microbiological samples and timely reporting of the results is
essential to avoid a delay in the administration of appropriate antimicrobial treatment, which has been found to be
associated with increased morbidity and mortality. Colistin treatment should be accompanied by colistin
susceptibility testing. Patients with infections due to colistin-resistant bacteria are likely to benefit from
consultations with experts in infectious diseases or clinical microbiology, which ensures the best possible
therapeutic regimen considering the limited treatment options.
Actions to prevent transmission in healthcare settings
Infection control precautions
Adherence to standard infection control practices, including hand hygiene, environmental cleaning and adequate
reprocessing of medical devices, and adequate capacity of microbiological laboratories are the basis for prevention
of transmission of MDR bacteria.
Surveillance and detection of mcr-1 in healthcare facilities should be conducted as outlined above. Prompt
notification of patients who were identified as carriers or infected with colistin-resistant MDR gram-negative
bacteria to the clinical team and to the infection prevention and control/hospital hygiene team is essential.
The need for enhanced control measures such as contact isolation precautions, single-room isolation or cohorting,
and dedicated nursing for patients who tested positive, should be determined based on the antibiotic resistance
pattern of the detected mcr-1-carrying Enterobacteriaceae isolates. Such enhanced control measures should be
considered in particular for patients colonised or infected with isolates carrying both the mcr-1 gene and
carbapenemase genes. For patients colonised or infected with isolates carrying the mcr-1 gene in combination with
11. RAPID RISK ASSESSMENT Plasmid-mediated colistin resistance in Enterobacteriaceae, 13 June 2016
11
other resistance genes, individual decisions should be taken based on the resistance profile, the likelihood of
nosocomial transmission, and previous evidence of association with outbreaks. This decision should take into
account evidence on the spread of the strain and on control measures as soon as they become available.
Antimicrobial stewardship
Antimicrobial stewardship refers to coordinated programmes that implement interventions to ensure appropriate
antimicrobial prescribing with the aim to improve clinical efficacy of antimicrobial treatment and limit antimicrobial
resistance through reducing selective pressure. Although evidence for a specific beneficial effect of antimicrobial
stewardship on the emergence and spread of colistin resistance is currently lacking, reduction of the use of broad-
spectrum antimicrobials can reduce the emergence of carbapenem-resistant bacteria and therefore obviate the
need for colistin treatment. Implementation of comprehensive antimicrobial stewardship programmes is therefore
important. Caution should be exercised in using colistin-containing selective digestive tract decontamination as it
can promote selection and spread of colistin resistance, especially if plasmid-based.
Nevertheless, targeted and appropriate use of antimicrobial agents is not likely to fully reverse the current
resistance trends, and there is an urgent public health need to promote the development of new antibacterial
agents active against MDR gram-negative bacteria.
Actions to prevent spread of plasmid-based colistin
resistance in the community
One Health approach
It is important to carefully monitor the presence of mcr-1 and to try to avoid the potential transmission of mcr-1
via contaminated food. Close cooperation between veterinary medicine and human medicine, combined with
regular monitoring in domestically produced and imported foodstuffs, is needed to assess whether consumers may
be exposed to mcr-1-positive gram-negative bacteria via food.
Reduction of colistin use in animals
Prudent use of antimicrobials, and especially the reduction of colistin use in food-producing animals, would be
effective in minimising the further emergence and spread of MDR bacteria, including those carrying mcr-1, via the
food chain. Detailed guidance on the use of colistin in animals is available in a draft advice from the European
Medicines Agency (EMA) dated 26 May 2016 [5]. As indicated by EMA, emphasis should also be placed on the
improvement of the conditions of animal husbandry (e.g. biosecurity, hygienic conditions) and the implementation
of alternative measures that would reduce the need for antimicrobial agents and therefore also reduce the rise in
antimicrobial-resistant bacteria in food-producing animals.
12. RAPID RISK ASSESSMENT Plasmid-mediated colistin resistance in Enterobacteriaceae, 13 June 2016
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