Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance
European Centre for Disease Prevention and Control1, Centers for Disease Control and Prevention2, Tel Aviv Sourasky Medical Center3, Tufts University4, ALFA5, Karolinska University Hospital6, University of Geneva7, University of California, Los Angeles8, Royal Brisbane and Women's Hospital9, Brown University10, Brigham and Women's Hospital11
TL;DR: A group of international experts came together through a joint initiative by the European Centre for Disease Prevention and Control and the Centers for Disease Control and Prevention, to create a standardized international terminology with which to describe acquired resistance profiles in Staphylococcus aureus, Enterococcus spp.
About: This article is published in Clinical Microbiology and Infection.The article was published on 2012-03-01 and is currently open access. It has received 8695 citations till now. The article focuses on the topics: Extensively drug resistant bacteria & Multiple drug resistance.
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TL;DR: The panel of experts, having emphasised the importance of initiating aetiologic treatment for any degree of hepatic disease at the earliest possible stage, extended its work to all the complications of cirrhosis which had not been covered by the European Association for the Study of the Liver guidelines.
1,534 citations
Cites background from "Multidrug-resistant, extensively dr..."
...However, the spread of resistant bacteria in the healthcare environment during the last two decades has led to an alarming increase in the number of infections caused by multi-drug resistant organisms (MDROs)(264) that are defined by an acquired non-susceptibility to at least one agent in three or more antimicrobial categories.(265) Patients with advanced cirrhosis are highly susceptible to the development of infections caused by MDROs, because they require repeated hospitalisa-...
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...or to pandrug resistance (PDR) bacteria defined by a non-susceptibility to all agents in all antimicrobial categories.(265) The shift requires an active surveillance in patients at risk, in order to identify patients who are colonised or infected by these...
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TL;DR: Genotypic and phenotypic methods that provide relevant information for diagnostic laboratories are presented and recent works in relation to recently identified mechanisms of polymyxin resistance, including chromosomally encoded resistance traits as well as the recently identified plasmid-encoded polymyXin resistance determinant MCR-1 are presented.
Abstract: Polymyxins are well-established antibiotics that have recently regained significant interest as a consequence of the increasing incidence of infections due to multidrug-resistant Gram-negative bacteria. Colistin and polymyxin B are being seriously reconsidered as last-resort antibiotics in many areas where multidrug resistance is observed in clinical medicine. In parallel, the heavy use of polymyxins in veterinary medicine is currently being reconsidered due to increased reports of polymyxin-resistant bacteria. Susceptibility testing is challenging with polymyxins, and currently available techniques are presented here. Genotypic and phenotypic methods that provide relevant information for diagnostic laboratories are presented. This review also presents recent works in relation to recently identified mechanisms of polymyxin resistance, including chromosomally encoded resistance traits as well as the recently identified plasmid-encoded polymyxin resistance determinant MCR-1. Epidemiological features summarizing the current knowledge in that field are presented.
922 citations
Cites background from "Multidrug-resistant, extensively dr..."
...However, the increasing prevalence of multidrug-resistant (MDR) Gram-negative bacteria (31), particularly K....
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TL;DR: The panel selected seven PICO (population–intervention–comparison–outcome) questions that generated a series of recommendations for HAP/VAP diagnosis, treatment and prevention that were adopted by the ERS/ESICM/ESCMID/ALAT panel.
Abstract: The most recent European guidelines and task force reports on hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) were published almost 10 years ago. Since then, further randomised clinical trials of HAP and VAP have been conducted and new information has become available. Studies of epidemiology, diagnosis, empiric treatment, response to treatment, new antibiotics or new forms of antibiotic administration and disease prevention have changed old paradigms. In addition, important differences between approaches in Europe and the USA have become apparent. The European Respiratory Society launched a project to develop new international guidelines for HAP and VAP. Other European societies, including the European Society of Intensive Care Medicine and the European Society of Clinical Microbiology and Infectious Diseases, were invited to participate and appointed their representatives. The Latin American Thoracic Association was also invited. A total of 15 experts and two methodologists made up the panel. Three experts from the USA were also invited (Michael S. Niederman, Marin Kollef and Richard Wunderink). Applying the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) methodology, the panel selected seven PICO (population–intervention–comparison–outcome) questions that generated a series of recommendations for HAP/VAP diagnosis, treatment and prevention.
710 citations
TL;DR: The acquisition of antimicrobial resistance genes by ESKAPE pathogens has reduced the treatment options for serious infections, increased the burden of disease, and increased death rates due to treatment failure and requires a coordinated global response for antim antibiotic resistance surveillance.
Abstract: Antimicrobial-resistant ESKAPE ( Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens represent a global threat to human health. The acquisition of antimicrobial resistance genes by ESKAPE pathogens has reduced the treatment options for serious infections, increased the burden of disease, and increased death rates due to treatment failure and requires a coordinated global response for antimicrobial resistance surveillance. This looming health threat has restimulated interest in the development of new antimicrobial therapies, has demanded the need for better patient care, and has facilitated heightened governance over stewardship practices.
674 citations
Cites background from "Multidrug-resistant, extensively dr..."
...More recently, a variant enzyme termed AAC(6=)-Ib-cr, which confers low-level plasmid-mediated aminoglycoside and ciprofloxacin resistance, has been described in K. pneumoniae, Enterobacter spp., A. baumannii, and P. aeruginosa (172–175)....
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...Of the four AAC subclasses, the AAC(1) and AAC(3) enzymes target amino group positions 1 and 3 of the central 2-deoxystreptamine ring, respectively, whereas the AAC(2=) and AAC(6=) subclasses modify the respective 2= and 6= amino group positions of the 2,6-dideoxy-2,6-diamino-glucose ring (166)....
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...Based on their biochemical activity, there are three classes of AMEs (i.e., aminoglycoside acetyltransferases [AACs], aminoglycoside phosphotransferases [APHs], and aminoglycoside nucleotidyltransferases [ANTs])....
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...Of the four AAC subclasses, the AAC(1) and AAC(3) enzymes target amino group positions 1 and 3 of the central 2-deoxystreptamine ring, respectively, whereas the AAC(2...
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...Likewise, expression of the bifunctional AAC(6=)-APH(2 ) enzyme, which resides on the common Tn4001 transposon, accounts for high-level gentamicin resistance in both S. aureus and Enterococcus spp. (including MRSA and VRE strains) worldwide (152)....
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Royal Free Hospital1, Carlos III Health Institute2, University of California, San Diego3, Paris Diderot University4, University of Padua5, University of Graz6, Université libre de Bruxelles7, University of Bologna8, Saarland University9, Katholieke Universiteit Leuven10, University of Barcelona11, King's College London12, Virginia Commonwealth University13, Yale University14, University College London15
TL;DR: An in-depth review and a position statement on bacterial infections in cirrhosis are reported, which suggest that research on biomarkers of early infection may be useful in early diagnosis and treatment of infections.
664 citations
Cites background from "Multidrug-resistant, extensively dr..."
...MR bacteria are pathogens resistant to 3 or more of the main antibiotic families, including b-lactams [7]....
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References
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Tufts Medical Center1, University of California, San Diego2, Boston Children's Hospital3, University of California, Los Angeles4, Los Angeles Biomedical Research Institute5, Providence Portland Medical Center6, United States Department of Veterans Affairs7, Case Western Reserve University8, University of Virginia9, Johns Hopkins University School of Medicine10
TL;DR: An update on potentially effective antibacterial drugs in the late-stage development pipeline is provided, in the hope of encouraging collaboration between industry, academia, the National Institutes of Health, the Food and Drug Administration, and the Centers for Disease Control and Prevention work productively together.
Abstract: The Infectious Diseases Society of America (IDSA) continues to view with concern the lean pipeline for novel therapeutics to treat drug-resistant infections, especially those caused by gram-negative pathogens. Infections now occur that are resistant to all current antibacterial options. Although the IDSA is encouraged by the prospect of success for some agents currently in preclinical development, there is an urgent, immediate need for new agents with activity against these panresistant organisms. There is no evidence that this need will be met in the foreseeable future. Furthermore, we remain concerned that the infrastructure for discovering and developing new antibacterials continues to stagnate, thereby risking the future pipeline of antibacterial drugs. The IDSA proposed solutions in its 2004 policy report, “Bad Bugs, No Drugs: As Antibiotic R&D Stagnates, a Public Health Crisis Brews,” and recently issued a “Call to Action” to provide an update on the scope of the problem and the proposed solutions. A primary objective of these periodic reports is to encourage a community and legislative response to establish greater financial parity between the antimicrobial development and the development of other drugs. Although recent actions of the Food and Drug Administration and the 110th US Congress present a glimmer of hope, significant uncertainly remains. Now, more than ever, it is essential to create a robust and sustainable antibacterial research and development infrastructure—one that can respond to current antibacterial resistance now and anticipate evolving resistance. This challenge requires that industry, academia, the National Institutes of Health, the Food and Drug Administration, the Centers for Disease Control and Prevention, the US Department of Defense, and the new Biomedical Advanced Research and Development Authority at the Department of Health and Human Services work productively together. This report provides an update on potentially effective antibacterial drugs in the late-stage development pipeline, in the hope of encouraging such collaborative action.
4,256 citations
"Multidrug-resistant, extensively dr..." refers background in this paper
...The problem of increasing antimicrobial resistance is even more threatening when considering the very limited number of new antimicrobial agents that are in development [8,9]....
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TL;DR: The frequency of selected antimicrobial resistance patterns among pathogens causing device-associated and procedure-associated healthcare-associated infections reported by hospitals in the National Healthcare Safety Network (NHSN) is described.
Abstract: Objective. To describe antimicrobial resistance patterns for healthcare-associated infections (HAIs) reported to the National Healthcare Safety Network (NHSN) during 2009-2010. Methods. Central line-associated bloodstream infections, catheter-associated urinary tract infections, ventilator-associated pneumonia, and surgical site infections were included. Pooled mean proportions of isolates interpreted as resistant (or, in some cases, nonsusceptible) to selected antimicrobial agents were calculated by type of HAI and compared to historical data. Results. Overall, 2,039 hospitals reported 1 or more HAIs; 1,749 (86%) were general acute care hospitals, and 1,143 (56%) had fewer than 200 beds. There were 69,475 HAIs and 81,139 pathogens reported. Eight pathogen groups accounted for about 80% of reported pathogens: Staphylococcus aureus (16%), Enterococcus spp. (14%), Escherichia coli (12%), coagulase-negative staphylococci (11%), Candida spp. (9%), Klebsiella pneumoniae (and Klebsiella oxytoca; 8%), Pseudomonas aeruginosa (8%), and Enterobacter spp. (5%). The percentage of resistance was similar to that reported in the previous 2-year period, with a slight decrease in the percentage of S. aureus resistant to oxacillins (MRSA). Nearly 20% of pathogens reported from all HAIs were the following multidrug-resistant phenotypes: MRSA (8.5%); vancomycin-resistant Enterococcus (3%); extended-spectrum cephalosporin-resistant K. pneumoniae and K. oxytoca (2%), E. coli (2%), and Enterobacter spp. (2%); and carbapenem-resistant P. aeruginosa (2%), K. pneumoniae/oxytoca (<1%), E, coli (<1%), and Enterobacter spp. (<1%). Among facilities reporting HAIs with 1 of the above gram-negative bacteria, 20%-40% reported at least 1 with the resistant phenotype. Conclusion. While the proportion of resistant isolates did not substantially change from that in the previous 2 years, multidrug-resistant gram-negative phenotypes were reported from a moderate proportion of facilities.
3,470 citations
TL;DR: A meta-analysis was performed to summarize the impact of methicillin-resistance on mortality in Staphylococcus aureus bacteremia and explored the reasons for heterogeneity by means of subgroup analyses.
Abstract: A meta-analysis was performed to summarize the impact of methicillin-resistance on mortality in Staphylococcus aureus bacteremia. A search of the MEDLINE database for studies published during the period of 1 January 1980 through 31 December 2000 and a bibliographic review identified English-language studies of S. aureus bacteremia. Studies were included if they contained the numbers of and mortality rates for patients with methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) bacteremia. Data were extracted on demographic characteristics of the patients, adjustment for severity and comorbid illness, source of bacteremia, and crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for in-hospital mortality. When the results were pooled with a random-effects model, a significant increase in mortality associated with MRSA bacteremia was evident (OR, 1.93; 95% CI, 1.54-2.42; P<.001); significant heterogeneity was present. We explored the reasons for heterogeneity by means of subgroup analyses. MRSA bacteremia is associated with significantly higher mortality rate than is MSSA bacteremia.
2,008 citations
TL;DR: More rapid diagnostic testing of ESBL-producing bacteria and the possible modification of guidelines for community-onset bacteraemia associated with UTIs are required.
Abstract: The medical community relies on clinical expertise and published guidelines to assist physicians with choices in empirical therapy for system-based infectious syndromes, such as community-acquired pneumonia and urinary-tract infections (UTIs). From the late 1990s, multidrug-resistant Enterobacteriaceae (mostly Escherichia coli) that produce extended-spectrum beta lactamases (ESBLs), such as the CTX-M enzymes, have emerged within the community setting as an important cause of UTIs. Recent reports have also described ESBL-producing E coli as a cause of bloodstream infections associated with these community-onset UTIs. The carbapenems are widely regarded as the drugs of choice for the treatment of severe infections caused by ESBL-producing Enterobacteriaceae, although comparative clinical trials are scarce. Thus, more rapid diagnostic testing of ESBL-producing bacteria and the possible modification of guidelines for community-onset bacteraemia associated with UTIs are required.
1,811 citations
"Multidrug-resistant, extensively dr..." refers background in this paper
...) require special mention; these organisms can be resistant to all currently available antimicrobial agents or remain susceptible only to older, potentially more toxic agents such as the polymyxins, leaving limited and suboptimal options for treatment [5–7]....
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TL;DR: The data suggest that clinical efforts should be aimed at reducing the administration of inadequate antimicrobial treatment to hospitalized patients with bloodstream infections, especially individuals infected with antibiotic-resistant bacteria and Candida species.
1,757 citations
"Multidrug-resistant, extensively dr..." refers background in this paper
...Infections with MDROs can lead to inadequate or delayed antimicrobial therapy, and are associated with poorer patient outcomes [1–4]....
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