Posts filed under ‘Resistencia bacteriana’
Journal of Antimicrobial Chemotherapy August 2016 V.71 N.8 P.2066-2070
Stefan Schwarz and Alan P. Johnson
1Institute of Farm Animal Genetics, Friedrich-Loeffler-Institut (FLI), Neustadt-Mariensee, Germany
2Department of Healthcare-Associated Infection and Antimicrobial Resistance, National Infection Service, Public Health England, London NW9 5EQ, UK
In this Leading article, we summarize current knowledge of the occurrence of the first and so far only transferable colistin resistance gene, mcr-1. Its location on a conjugative plasmid is likely to have driven its spread into a range of enteric bacteria in humans and animals. Screening studies have identified mcr-1 in five of the seven continents and retrospective studies in China have identified this gene in Escherichia coli originally isolated in the 1980s, while the first European isolate dates back to 2005. Based on the widespread use of colistin in pigs and poultry in several countries and the higher number of mcr-1-carrying isolates of animal origin than of human origin, it is tempting to assume that this resistance may have emerged in the animal sector. Whatever its origin, interventions to reduce its further spread will require an integrated global one-health approach, comprising robust antibiotic stewardship to reduce unnecessary colistin use, improved infection prevention, and control and surveillance of colistin usage and resistance in both veterinary and human medicine.
The mcr-1 gene encoding colistin resistance in Escherichia coli has been around since the 1980s, appears to be ubiquitous and may have emerged in the animal sector, but interventions to reduce its further spread will require an integrated global one-health approach.
Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society
Clin Infect Diseases July 14, 2016
Andre C. Kalil1,a, Mark L. Metersky2,a, Michael Klompas3,4, John Muscedere5, Daniel A. Sweeney6, Lucy B. Palmer7, Lena M. Napolitano8, Naomi P. O’Grady9, John G. Bartlett10, Jordi Carratalà11, Ali A. El Solh12, Santiago Ewig13, Paul D. Fey14, Thomas M. File Jr15, Marcos I. Restrepo16, Jason A. Roberts17,18, Grant W. Waterer19, Peggy Cruse20, Shandra L. Knight20, and Jan L. Brozek21
1Department of Internal Medicine, Division of Infectious Diseases, University of Nebraska Medical Center, Omaha
2Division of Pulmonary and Critical Care Medicine, University of Connecticut School of Medicine, Farmington
3Brigham and Women’s Hospital and Harvard Medical School
4Harvard Pilgrim Health Care Institute, Boston, Massachusetts
5Department of Medicine, Critical Care Program, Queens University, Kingston, Ontario, Canada
6Division of Pulmonary, Critical Care and Sleep Medicine, University of California, San Diego
7Department of Medicine, Division of Pulmonary Critical Care and Sleep Medicine, State University of New York at Stony Brook
8Department of Surgery, Division of Trauma, Critical Care and Emergency Surgery, University of Michigan, Ann Arbor
9Department of Critical Care Medicine, National Institutes of Health, Bethesda
10Johns Hopkins University School of Medicine, Baltimore, Maryland
11Department of Infectious Diseases, Hospital Universitari de Bellvitge, Bellvitge Biomedical Research Institute, Spanish Network for Research in Infectious Diseases, University of Barcelona, Spain
12Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, University at Buffalo, Veterans Affairs Western New York Healthcare System, New York
13Thoraxzentrum Ruhrgebiet, Department of Respiratory and Infectious Diseases, EVK Herne and Augusta-Kranken-Anstalt Bochum, Germany
14Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha
15Summa Health System, Akron, Ohio
16Department of Medicine, Division of Pulmonary and Critical Care Medicine, South Texas Veterans Health Care System and University of Texas Health Science Center at San Antonio
17Burns, Trauma and Critical Care Research Centre, The University of Queensland
18Royal Brisbane and Women’s Hospital, Queensland
19School of Medicine and Pharmacology, University of Western Australia, Perth, Australia
20Library and Knowledge Services, National Jewish Health, Denver, Colorado
21Department of Clinical Epidemiology and Biostatistics and Department of Medicine, McMaster University, Hamilton, Ontario, Canada
It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient’s individual circumstances.
These guidelines are intended for use by healthcare professionals who care for patients at risk for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), including specialists in infectious diseases, pulmonary diseases, critical care, and surgeons, anesthesiologists, hospitalists, and any clinicians and healthcare providers caring for hospitalized patients with nosocomial pneumonia. The panel’s recommendations for the diagnosis and treatment of HAP and VAP are based upon evidence derived from topic-specific systematic literature reviews.
J Am Heart Assoc. 2016 Apr 18;5(4).
Park LP, Chu VH, Peterson G, Skoutelis A, Lejko-Zupa T, Bouza E, Tattevin P, Habib G, Tan R, Gonzalez J, Altclas J, Edathodu J, Fortes CQ, Siciliano RF, Pachirat O, Kanj S, Wang A; International Collaboration on Endocarditis (ICE) Investigators.
Clara L, Sanchez M, Casabé J, Cortes C, Nacinovich F, Fernandez Oses P, Ronderos R, Sucari A, Thierer J, Kogan S, Spelman D, Athan E, Harris O, Kennedy K, Gordon D, Papanicolas L, Korman T, Kotsanas D, Dever R, Jones P, Konecny P, Lawrence R, Rees D, Ryan S, Feneley MP, Harkness J, Jones P, Ryan S, Jones P, Ryan S, Jones P, Post J, Reinbott P, Ryan S, Gattringer R, Wiesbauer F, Andrade AR, de Brito AC, Guimarães AC, Grinberg M, Mansur AJ, Strabelli TM, Vieira ML, de Medeiros Tranchesi RA, Paiva MG, de Oliveira Ramos A, Weksler C, Ferraiuoli G, Golebiovski W, Lamas C, Karlowsky JA, Keynan Y, Morris AM, Rubinstein E, Jones SB, Garcia P, Fica A, Mella RM, Fernandez R, Franco L, Jaramillo AN, Barsic B, Bukovski S, Krajinovic V, Pangercic A, Rudez I, Vincelj J, Freiberger T, Pol J, Zaloudikova B, Ashour Z, El Kholy A, Mishaal M, Osama D, Rizk H, Aissa N, Alauzet C, Alla F, Campagnac C, Doco-Lecompte T, Selton-Suty C, Casalta JP, Fournier PE, Raoult D, Thuny F, Delahaye F, Delahaye A, Vandenesch F, Donal E, Donnio PY, Flecher E, Michelet C, Revest M, Chevalier F, Jeu A, Rémadi JP, Rusinaru D, Tribouilloy C, Bernard Y, Chirouze C, Hoen B, Leroy J, Plesiat P, Naber C, Neuerburg C, Mazaheri B, Naber C, Neuerburg C, Athanasia S, Deliolanis I, Giamarellou H, Thomas T, Giannitsioti E, Mylona E, Paniara O, Papanicolaou K, Pyros J, Mylona E, Paniara O, Papanikolaou K, Pyros J, Sharma G, Francis J, Nair L, Thomas V, Venugopal K, Hannan MM, Hurley JP, Cahan A, Gilon D, Israel S, Korem M, Strahilevitz J, Rubinstein E, Strahilevitz J, Durante-Mangoni E, Mattucci I, Pinto D, Agrusta F, Senese A, Ragone E, Utili R, Cecchi E, De Rosa F, Forno D, Imazio M, Trinchero R, Grossi P, Lattanzio M, Toniolo A, Goglio A, Raglio A, Ravasio V, Rizzi M, Suter F, Carosi G, Magri S, Signorini L, Kanafani Z, Kanj SS, Sharif-Yakan A, Abidin I, Tamin SS, Martínez ER, Soto Nieto GI, van der Meer JT, Chambers S, Holland D, Morris A, Raymond N, Read K, Murdoch DR, Dragulescu S, Ionac A, Mornos C, Butkevich OM, Chipigina N, Kirill O, Vadim K, Vinogradova T, Halim M, Liew YY, Tan RS, Logar M, Mueller-Premru M, Commerford P, Commerford A, Deetlefs E, Hansa C, Ntsekhe M, Almela M, Armero Y, Azqueta M, Castañeda X, Cervera C, Falces C, Garcia-de-la-Maria C, Fita G, Gatell JM, Heras M, Llopis J, Marco F, Mestres CA, Miró JM, Moreno A, Ninot S, Paré C, Pericas JM, Ramirez J, Rovira I, Sitges M, Anguera I, Font B, Guma JR, Bermejo J, Garcia Fernández MA, Gonzalez-Ramallo V, Marín M, Muñoz P, Pedromingo M, Roda J, Rodríguez-Créixems M, Solis J, Almirante B, Fernandez-Hidalgo N, Tornos P, de Alarcón A, Parra R, Alestig E, Johansson M, Olaison L, Snygg-Martin U, Pachirat P, Pussadhamma B, Senthong V, Casey A, Elliott T, Lambert P, Watkin R, Eyton C, Klein JL, Bradley S, Kauffman C, Bedimo R, Corey GR, Crowley AL, Douglas P, Drew L, Fowler VG, Holland T, Lalani T, Mudrick D, Samad Z, Sexton D, Stryjewski M, Woods CW, Lerakis S, Cantey R, Steed L, Wray D, Dickerman SA, Bonilla H, DiPersio J, Salstrom SJ, Baddley J, Patel M, Stancoven A, Levine D, Riddle J, Rybak M, Cabell CH, Baloch K, Corey GR, Dixon CC, Fowler VG Jr, Harding T, Jones-Richmond M, Sanderford B, Sanderford B, Stafford J, Stafford J, Anstrom K, Athan E, Bayer AS, Cabell CH, Corey GR, Fowler VG Jr, Hoen B, Karchmer AW, Miró JM, Murdoch DR, Sexton DJ, Bayer AS, Cabell CH, Chu V, Corey GR, Durack DT, Eykyn S, Fowler VG Jr, Hoen B, Miró JM, Moreillon P, Olaison L, Raoult D, Rubinstein E, Sexton DJ.
Host factors and complications have been associated with higher mortality in infective endocarditis (IE). We sought to develop and validate a model of clinical characteristics to predict 6-month mortality in IE.
METHODS AND RESULTS:
Using a large multinational prospective registry of definite IE (International Collaboration on Endocarditis [ICE]-Prospective Cohort Study [PCS], 2000-2006, n=4049), a model to predict 6-month survival was developed by Cox proportional hazards modeling with inverse probability weighting for surgery treatment and was internally validated by the bootstrapping method. This model was externally validated in an independent prospective registry (ICE-PLUS, 2008-2012, n=1197). The 6-month mortality was 971 of 4049 (24.0%) in the ICE-PCS cohort and 342 of 1197 (28.6%) in the ICE-PLUS cohort. Surgery during the index hospitalization was performed in 48.1% and 54.0% of the cohorts, respectively. In the derivation model, variables related to host factors (age, dialysis), IE characteristics (prosthetic or nosocomial IE, causative organism, left-sided valve vegetation), and IE complications (severe heart failure, stroke, paravalvular complication, and persistent bacteremia) were independently associated with 6-month mortality, and surgery was associated with a lower risk of mortality (Harrell’s C statistic 0.715). In the validation model, these variables had similar hazard ratios (Harrell’s C statistic 0.682), with a similar, independent benefit of surgery (hazard ratio 0.74, 95% CI 0.62-0.89). A simplified risk model was developed by weight adjustment of these variables.
Six-month mortality after IE is ≈25% and is predicted by host factors, IE characteristics, and IE complications. Surgery during the index hospitalization is associated with lower mortality but is performed less frequently in the highest risk patients. A simplified risk model may be used to identify specific risk subgroups in IE.
Telavancin hospital-acquired pneumonia trials: impact of Gram-negative infections and inadequate Gram-negative coverage on clinical efficacy and all-cause mortality.
Clin Infect Dis. 2015 Sep 15;61 Suppl 2:S87-93.
Lacy MK1, Stryjewski ME2, Wang W1, Hardin TC1, Nogid B1, Luke DR1, Shorr AF3, Corey GR4, Barriere SL1.
1Theravance Biopharma US, South San Francisco, California.
2Department of Medicine, Section of Infectious Diseases, Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno” (CEMIC), Ciudad Autónoma de Buenos Aires, Argentina.
3Pulmonary and Critical Care Medicine, Washington Hospital Center, Washington D.C.
4Department of Medicine, Duke Clinical Research Institute, Durham, North Carolina.
When hospital-acquired or ventilator-associated bacterial pneumonia (HABP/VABP) is caused by gram-positive and gram-negative pathogens or both (mixed infections), the adequacy of gram-negative coverage (GNC) can confound the assessment of a gram-positive agent under study. This analysis examines the influence of gram-negative infections and the adequacy of GNC on clinical efficacy and all-cause mortality in the telavancin HABP/VABP phase 3 ATTAIN trials (Assessment of Telavancin for Treatment of Hospital-Acquired Pneumonia).
This post hoc analysis evaluated 3 patient groups from ATTAIN: (1) gram-positive-only infections, (2) gram-positive-only and mixed infections-adequate GNC, and (3) gram-negative-only infections and mixed infections with inadequate GNC. For each, clinical efficacy at test of cure and all-cause mortality at day 28 were compared for telavancin and vancomycin.
In the ATTAIN safety population there were 16 more deaths in the telavancin arms than in the vancomycin arms. Of these, 13 were in patients with gram-negative-only infections (n = 9) or with mixed infections and inadequate GNC (n = 4) and all had estimated baseline creatinine clearances of <30ml/min. Based on this analysis, clinical response and all-cause mortality could be confounded because there were more patients with gram-negative pathogens at baseline and more patients received inadequate treatment of these gram-negative infections in the telavancin groups.
Telavancin for Acute Bacterial Skin and Skin Structure Infections, a Post Hoc Analysis of the Phase 3 ATLAS Trials in Light of the 2013 FDA Guidance.
Antimicrob Agents Chemother. 2015 Oct;59(10):6170-4.
Pushkin R1, Barriere SL1, Wang W2, Corey GR3, Stryjewski ME4.
1Theravance Biopharma US, Inc., South San Francisco, California, USA.
2Theravance Biopharma US, Inc., South San Francisco, California, USA WWang@theravance.com.
3Duke Clinical Research Institute and Division of Infectious Diseases, Duke University Medical Center, Durham, North Carolina, USA.
4Department of Medicine, Section of Infectious Diseases, Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno (CEMIC), Buenos Aires, Argentina.
Two phase 3 ATLAS trials demonstrated noninferiority of telavancin compared with vancomycin for complicated skin and skin structure infections. Data from these trials were retrospectively evaluated according to 2013 U.S. Food and Drug Administration (FDA) guidance on acute bacterial skin and skin structure infections. This post hoc analysis included patients with lesion sizes of ≥75 cm(2) and excluded patients with ulcers or burns (updated all-treated population; n = 1,127). Updated day 3 (early) clinical response was defined as a ≥20% reduction in lesion size from baseline and no rescue antibiotic. Updated test-of-cure (TOC) clinical response was defined as a ≥90% reduction in lesion size, no increase in lesion size since day 3, and no requirement for additional antibiotics or significant surgical procedures. Day 3 (early) clinical responses were achieved in 62.6% and 61.0% of patients receiving telavancin and vancomycin, respectively (difference, 1.7%, with a 95% confidence interval [CI] of -4.0% to 7.4%). Updated TOC visit cure rates were similar for telavancin (68.0%) and vancomycin (63.3%), with a difference of 4.8% (95% CI, -0.7% to 10.3%). Adopting current FDA guidance, this analysis corroborates previous noninferiority findings of the ATLAS trials of telavancin compared with vancomycin.
Potential role for telavancin in bacteremic infections due to gram-positive pathogens: focus on Staphylococcus aureus.
Clin Infect Dis. 2015 Mar 1;60(5):787-96.
Corey GR1, Rubinstein E2, Stryjewski ME3, Bassetti M4, Barriere SL5.
1Department of Medicine, Duke Clinical Research Institute, Durham, North Carolina.
2Section of Infectious Diseases, Department of Internal Medicine and Medical Microbiology, University of Manitoba, Winnipeg, Canada.
3Department of Medicine, Section of Infectious Diseases, Centro de Educación Médica e Investigaciones Clínicas ‘Norberto Quirno’ (CEMIC), Ciudad Autónoma de Buenos Aires, Argentina.
4Infectious Diseases Division, Santa Maria Misericordia University Hospital, Piazzale Santa Maria della Misericordia, Udine, Italy.
5Theravance Biopharma US, Inc., South San Francisco, California.
Staphylococcus aureus bacteremia (SAB) is one of the most common serious bacterial infections and the most frequent invasive infection due to methicillin-resistant S. aureus (MRSA). Treatment is challenging, particularly for MRSA, because of limited treatment options. Telavancin is a bactericidal lipoglycopeptide antibiotic that is active against a range of clinically relevant gram-positive pathogens including MRSA. In experimental animal models of sepsis telavancin was shown to be more effective than vancomycin. In clinically evaluable patients enrolled in a pilot study of uncomplicated SAB, cure rates were 88% for telavancin and 89% for standard therapy. Among patients with infection due to only gram-positive pathogens enrolled in the 2 phase 3 studies of telavancin for treatment of hospital-acquired pneumonia, cure rates for those with bacteremic S. aureus pneumonia were 41% (9/22, telavancin) and 40% (10/25, vancomycin) with identical mortality rates. These data support further evaluation of telavancin in larger, prospective studies of SAB
Clin Infect Dis. 2014 Jan;58 Suppl 1:S10-9.
Stryjewski ME1, Corey GR.
1Department of Medicine and Division of Infectious Diseases, Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno” (CEMIC), Buenos Aires, Argentina.
The horizontal transmission of methicillin resistance to Staphylococcus aureus (MRSA) in hospital and community settings, and growing prevalence of these strains, presents a significant clinical challenge to the management of serious infections worldwide. While infection control initiatives have stemmed the rising prevalence, MRSA remains a significant pathogen. More recently, evidence that MRSA is becoming resistant to glycopeptides and newer therapies raises concern about the use of these therapies in clinical practice. Vancomycin resistance has become evident in select clinical settings through rising MICs, growing awareness of heteroresistance, and emergence of intermediate-resistant and fully resistant strains. While resistance to linezolid and daptomycin remains low overall, point mutations leading to resistance have been described for linezolid, and horizontal transmission of cfr-mediated resistance to linezolid has been reported in clinical isolates. These resistance trends for newer therapies highlight the ongoing need for new and more potent antimicrobial therapies.