Vancomycin-resistant enterococcal infections: epidemiology, clinical manifestations, and optimal management.
TL;DR: Combined therapies and newer agents hold promise for the future treatment of vancomycin-resistant Enterococcus infections, but further studies are needed to assess their possible clinical impact, especially in the treatment of serious infections.
Abstract: Since its discovery in England and France in 1986, vancomycin-resistant Enterococcus has increasingly become a major nosocomial pathogen worldwide. Enterococci are prolific colonizers, with tremendous genome plasticity and a propensity for persistence in hospital environments, allowing for increased transmission and the dissemination of resistance elements. Infections typically present in immunosuppressed patients who have received multiple courses of antibiotics in the past. Virulence is variable, and typical clinical manifestations include bacteremia, endocarditis, intra-abdominal and pelvic infections, urinary tract infections, skin and skin structure infections, and, rarely, central nervous system infections. As enterococci are common colonizers, careful consideration is needed before initiating targeted therapy, and source control is first priority. Current treatment options including linezolid, daptomycin, quinupristin/dalfopristin, and tigecycline have shown favorable activity against various vancomycin-resistant Enterococcus infections, but there is a lack of randomized controlled trials assessing their efficacy. Clearer distinctions in preferred therapies can be made based on adverse effects, drug interactions, and pharmacokinetic profiles. Although combination therapies and newer agents such as tedizolid, telavancin, dalbavancin, and oritavancin hold promise for the future treatment of vancomycin-resistant Enterococcus infections, further studies are needed to assess their possible clinical impact, especially in the treatment of serious infections.
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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
TL;DR: This guideline summarizes the current recommendations developed by the SIS task force on the treatment of patients who have IAI regarding risk assessment in individual patients; source control; the timing, selection, and duration of antimicrobial therapy; and suggested approaches to patients who fail initial therapy.
Abstract: Background: Previous evidence-based guidelines on the management of intra-abdominal infection (IAI) were published by the Surgical Infection Society (SIS) in 1992, 2002, and 2010. At the t...
351 citations
Cites background from "Vancomycin-resistant enterococcal i..."
...Consider use of linezolid or daptomycin for empiric therapy of patients known to be colonized with or at high risk for infection with VRE (Grade 2-...
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...Consider use of linezolid or daptomycin for empiric or pathogen-directed therapy of infections from vancomycin-resistant Enterococcus spp. (VRE) and as an alternative to vancomycin for infections from MRSA in adults and children (Grade 2-...
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...The risk of an infection from VRE is much higher in patients already colonized with VRE [93,96,102,103,106]....
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...Among the micro-organisms encountered in these patients are various multi–drug-resistant (MDR) gram-negative pathogens, such as Pseudomonas spp. and Acinetobacter spp., resistant grampositive cocci, including vancomycin-resistant Enterococcus spp. (VRE) and methicillin-resistant S. aureus (MRSA), and non-C. albicans spp. [15,32,33]....
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...B. Anti-enterococcal therapy Identify patients with HA-IAI who have post-operative infections, recent exposure to broad-spectrum antimicrobial therapy, signs of severe sepsis or septic shock, or known to be colonized with VRE as at risk for infection with Enterococcus spp. (Grade 2-...
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TL;DR: The spatiotemporal development of enterococcal biofilms and the factors that promote or inhibit biofilm formation are described and the environment, including the host and other co-colonizing microorganisms, affects biofilm development.
Abstract: Enterococci are ubiquitous members of the human gut microbiota and frequent causes of biofilm-associated opportunistic infections. Enterococci cause 25% of all catheter-associated urinary tract infections, are frequently isolated in wounds and are increasingly found in infective endocarditis, and all of these infections are associated with biofilms. Enterococcal biofilms are intrinsically tolerant to antimicrobials and thus are a serious impediment for treating infections. In this Review, we describe the spatiotemporal development of enterococcal biofilms and the factors that promote or inhibit biofilm formation. We discuss how the environment, including the host and other co-colonizing microorganisms, affects biofilm development. Finally, we provide an overview of current and future interventions to limit enterococcal biofilm-associated infections. Overall, enterococcal biofilms remain a pressing clinical problem, and there is an urgent need to better understand their development and persistence and to identify novel treatments.
213 citations
TL;DR: The factors that contribute to the rise of VRE as an important health care-associated pathogen, the utility of laboratory screening and various infection control strategies, and the available laboratory methods to identify VRE in clinical specimens are discussed.
Abstract: Infections attributable to vancomycin-resistant Enterococcus (VRE) strains have become increasingly prevalent over the past decade. Prompt identification of colonized patients combined with effective multifaceted infection control practices can reduce the transmission of VRE and aid in the prevention of hospital-acquired infections (HAIs). Increasingly, the clinical microbiology laboratory is being asked to support infection control efforts through the early identification of potential patient or environmental reservoirs. This review discusses the factors that contribute to the rise of VRE as an important health care-associated pathogen, the utility of laboratory screening and various infection control strategies, and the available laboratory methods to identify VRE in clinical specimens.
160 citations
TL;DR: The objective of this review is to outline the most frequent antibiotic-resistant bacteria and describe the advantageous and limitations of alternative methods that have been proposed to control them.
Abstract: Antibiotic resistance is one of the greatest challenges in the health system nowadays, representing a serious problem for public health. Initially, antibiotic-resistant strains were restricted to the hospital environment, but now they can be found everywhere. Globalization, excessive use of antibiotics in animal husbandry and aquaculture, use of multiple broad-spectrum agents, and lack of good antimicrobial stewardship can be listed as the factors most responsible for the spread of antibiotic resistance. The increase in the prevalence of antibiotic-resistant pathogens implies having fewer antimicrobial agents to treat infections. The estimate is that by 2050, there will be no effective antibiotic available, if no new drug is developed or discovered. This raises the need to search for alternative methods of controlling antibiotic-resistant pathogens. Considering this problem, the objective of this review is to outline the most frequent antibiotic-resistant bacteria and describe the advantageous and limitations of alternative methods that have been proposed to control them.
156 citations
Cites background from "Vancomycin-resistant enterococcal i..."
...Linezolid is the first-line drug for treatment of VRE infections, but the first reports of Linezolide-resistant VRE have appeared, reducing treatment options.(38) Some authors have also suggested daptomycin as an effective agent in the treatment of VRE infections....
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...A similar situation occurred in Europe, where the spread of hospital-related VRE occurred a decade later in the 2000.(38) VRE has been an emerging problem in some Brazilian hospitals since the 1990s....
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References
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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: The most common nosocomial pathogens may well survive or persist on surfaces for months and can thereby be a continuous source of transmission if no regular preventive surface disinfection is performed.
Abstract: Inanimate surfaces have often been described as the source for outbreaks of nosocomial infections. The aim of this review is to summarize data on the persistence of different nosocomial pathogens on inanimate surfaces. The literature was systematically reviewed in MedLine without language restrictions. In addition, cited articles in a report were assessed and standard textbooks on the topic were reviewed. All reports with experimental evidence on the duration of persistence of a nosocomial pathogen on any type of surface were included. Most gram-positive bacteria, such as Enterococcus spp. (including VRE), Staphylococcus aureus (including MRSA), or Streptococcus pyogenes, survive for months on dry surfaces. Many gram-negative species, such as Acinetobacter spp., Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa, Serratia marcescens, or Shigella spp., can also survive for months. A few others, such as Bordetella pertussis, Haemophilus influenzae, Proteus vulgaris, or Vibrio cholerae, however, persist only for days. Mycobacteria, including Mycobacterium tuberculosis, and spore-forming bacteria, including Clostridium difficile, can also survive for months on surfaces. Candida albicans as the most important nosocomial fungal pathogen can survive up to 4 months on surfaces. Persistence of other yeasts, such as Torulopsis glabrata, was described to be similar (5 months) or shorter (Candida parapsilosis, 14 days). Most viruses from the respiratory tract, such as corona, coxsackie, influenza, SARS or rhino virus, can persist on surfaces for a few days. Viruses from the gastrointestinal tract, such as astrovirus, HAV, polio- or rota virus, persist for approximately 2 months. Blood-borne viruses, such as HBV or HIV, can persist for more than one week. Herpes viruses, such as CMV or HSV type 1 and 2, have been shown to persist from only a few hours up to 7 days. The most common nosocomial pathogens may well survive or persist on surfaces for months and can thereby be a continuous source of transmission if no regular preventive surface disinfection is performed.
2,110 citations
"Vancomycin-resistant enterococcal i..." refers background in this paper
...VRE can persist for up to 60 minutes on hands and as long as 4 months on surfaces.(39,40) The common pathway for nosocomial VRE starts with acquisition via personto-person contact or exposure to contaminated objects....
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TL;DR: Enterococci are important human pathogens that are increasingly resistant to antimicrobial agents, including resistance to cephalosporins, clindamycin, tetracycline, and penicillinase-resistant penicillins such as oxacillin, among others.
Abstract: Enterococci are important human pathogens that are increasingly resistant to antimicrobial agents. These organisms were previously considered part of the genus Streptococcus but have recently been reclassified into their own genus, called Enterococcus. To date, 12 species pathogenic for humans have been described, including the most common human isolates, Enterococcus faecalis and E. faecium. Enterococci cause between 5 and 15% of cases of endocarditis, which is best treated by the combination of a cell wall-active agent (such as penicillin or vancomycin, neither of which alone is usually bactericidal) and an aminoglycoside to which the organism is not highly resistant; this characteristically results in a synergistic bactericidal effect. High-level resistance (MIC, greater than or equal to 2,000 micrograms/ml) to the aminoglycoside eliminates the expected bactericidal effect, and such resistance has now been described for all aminoglycosides. Enterococci can also cause urinary tract infections; intraabdominal, pelvic, and wound infections; superinfections (particularly in patients receiving expanded-spectrum cephalosporins); and bacteremias (often together with other organisms). They are now the third most common organism seen in nosocomial infections. For most of these infections, single-drug therapy, most often with penicillin, ampicillin, or vancomycin, is adequate. Enterococci have a large number of both inherent and acquired resistance traits, including resistance to cephalosporins, clindamycin, tetracycline, and penicillinase-resistant penicillins such as oxacillin, among others. The most recent resistance traits reported are penicillinase resistance (apparently acquired from staphylococci) and vancomycin resistance, both of which can be transferred to other enterococci. It appears likely that we will soon be faced with increasing numbers of enterococci for which there is no adequate therapy.
1,817 citations
"Vancomycin-resistant enterococcal i..." refers background in this paper
...In contrast, enterococci are able to cause monomicrobial peritonitis infections, most commonly in patients undergoing chronic peritoneal dialysis or suffering from liver cirrhosis, and treatment is considered more appropriate in these settings.(57)...
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...The common sources for seeding originate from the GI or GU tract.(57) Enterococcal endocarditis typically presents as a subacute course, with the most common clinical manifestations being the presence of a murmur, fever, weight loss, malaise, and generalized aches....
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TL;DR: The third iteration of the Infective Endocarditis "treatment" document developed by the American Heart Association under the auspices of the Committee on Rheumatic fever, endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease of the Young was presented in this article.
Abstract: Background—Despite advances in medical, surgical, and critical care interventions, infective endocarditis remains a disease that is associated with considerable morbidity and mortality. The continuing evolution of antimicrobial resistance among common pathogens that cause infective endocarditis creates additional therapeutic issues for physicians to manage in this potentially life-threatening illness. Methods and Results—This work represents the third iteration of an infective endocarditis “treatment” document developed by the American Heart Association under the auspices of the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease of the Young. It updates recommendations for diagnosis, treatment, and management of complications of infective endocarditis. A multidisciplinary committee of experts drafted this document to assist physicians in the evolving care of patients with infective endocarditis in the new millennium. This extensive document is accompanied by an executive summary that covers the key points of the diagnosis, antimicrobial therapy, and management of infective endocarditis. For the first time, an evidence-based scoring system that is used by the American College of Cardiology and the American Heart Association was applied to treatment recommendations. Tables also have been included that provide input on the use of echocardiography during diagnosis and treatment of infective endocarditis, evaluation and treatment of culture-negative endocarditis, and short-term and long-term management of patients during and after completion of antimicrobial treatment. To assist physicians who care for children, pediatric dosing was added to each treatment regimen. Conclusions—The recommendations outlined in this update should assist physicians in all aspects of patient care in the diagnosis, medical and surgical treatment, and follow-up of infective endocarditis, as well as management of associated complications. Clinical variability and complexity in infective endocarditis, however, dictate that these guidelines be used to support and not supplant physician-directed decisions in individual patient management. (Circulation. 2005; 111:e394-e433.)
1,568 citations
TL;DR: The authors live in an era when antibiotic resistance has spread at an alarming rate and dire predictions concerning the lack of effective antibacterial drugs occur with increasing frequency, so it is apposite to ask a few simple questions about these life-saving molecules.
Abstract: Antibiotics--compounds that are literally 'against life'--are typically antibacterial drugs, interfering with some structure or process that is essential to bacterial growth or survival without harm to the eukaryotic host harbouring the infecting bacteria. We live in an era when antibiotic resistance has spread at an alarming rate and when dire predictions concerning the lack of effective antibacterial drugs occur with increasing frequency. In this context it is apposite to ask a few simple questions about these life-saving molecules. What are antibiotics? Where do they come from? How do they work? Why do they stop being effective? How do we find new antibiotics? And can we slow down the development of antibiotic-resistant superbugs?
1,448 citations
"Vancomycin-resistant enterococcal i..." refers background in this paper
...Glycopeptide resistance arises when low-affinity pentapeptide precursors d-Ala-d-Lac or d-Ala-d-Ser are formed and high-affinity precursors d-Alad-Ala are eliminated.(26) Currently, eight phenotypic variants of acquired glycopeptide resistance in enterococci have been described (VanA, VanB, VanD, VanE, VanG, VanL, VanM, and VanN), with one type of intrinsic resistance (VanC) being unique to E....
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