31º CONFERENCIA MAGISTRAL MANUEL TAPIA (2017)
50 años de Infecciones Respiratorias: desde destruir bacteria hasta aprender a vivir con ella Doctor Antonio Anzueto. San Antonio, EEUU. SOCIEDAD ESPAÑOLA DE NEUMOLOGÍA Y CIRUGÍA TORÁCICA
Faculty Disclosures Personal financial interests in commercial entities that are relevant to my presentation: NONE Non-commercial, non-governmental interests relevant to my presentation : Member of the ATS/ERS Task force on COPD and COPD Exacerbations, Member of the ATS/IDSA CAP Guidelines committee GOLD Past Member of the Executive and current member Scientific Committee
Visualiza Puedes visualizar la 31ª Conferencia Manuel Tapia en el enlace https://www.youtube.com/watch?v=hnFKSd78ULk
1967
Fundación en Madrid, en 1967, de la Sociedad Española de Patología Respiratoria (SEPAR). Arch Bronconeumol 1971;8:11-8 - Vol. 8 Núm.1
1967
Agora - collection of sculptures by Polish artist Magdalena Abakanowicz. All 106 sculptures are 9 feet (2.7 m) tall and were made from a seamless piece of iron.
1987 – Prof. M. García Cosío (Montreal, Canadá) 1988 – Dr. F. Griffith Pearson (Toronto, Canadá) 1989 – Prof. Valentín Lourenço (Chicago, USA) 1990 – Prof. Peter Wagner (California, USA) 1991 – Dr. Jean François Dumon (Marsella, Francia) 1992 – Dr. Victorino Farga (París, Francia) 1993 – Prof. Manuel Paiva (Bruselas, Bélgica) 1994 – Prof. Richard Light (California, USA) 1995 - Dr. Alejandro E. Grassino (Montreal, Canadá) 1996 – Prof. J. Iasha Sznajder (Chicago, USA) 1997 – Dr. Roberto Rodríguez Roisin (Barcelona) 1998 – Dr. Dominique Robert (Lyon, Francia) 1999 – Dr. Josep Maria Antó Boqué (Barcelona) 2000 – Dr. Joaquín Sanchís Aldás (Barcelona) 2001 – Dr. Ferran Morell Brotad (Barcelona) 2002 – Dr. Bartolomé Celli (Boston, USA) 2003 Dr. Daniel Rodenstein (Bélgica)
2004 – Dr. Francisco Rodríguez Panadero (Sevilla) 2005 – Dr. César Picado Vallés (Barcelona) 2006 – Dr. José Antonio Caminero Luna (Las Palmas) 2007 – Dr. Federico Manresa Presas (Barcelona) 2008 – Dr. Moisés Selman (México) 2009 – Dr. Josep Maria Montserrat Canal (Barcelona) 2010 – Dr. Fernando Martínez (Tucson, Arizona. USA) 2011 – Dr. José Luis Álvarez-Sala Walther (Madrid) 2012 – Dr. Antoni Xaubet Mir (Barcelona) 2013 - Dr. Juan Ruiz Manzano (Barcelona) 2014 – Dr. Vicente Plaza Moral (Barcelona) 2015 - Dr. Lorenzo Fernández Fau (Madrid) 2016 – Dr. José Castillo Gómez (Sevilla)
Pulmonary/Critical Care Medicine: Areas of Interest • Critical Care Medicine – Acute Lung injury/ARDS – Mechanical Ventilation – Sepsis – Severe Pneumonia
• Pulmonary – COPD and COPD Exacerbations – Pneumonia – Neuromuscular Disease
Carrer Rationale
• Pharmacotherapy • Epidemiology
• ALI/ARDS • Mechanical Ventilation
Adult with Airway disease
• Exacerbations • CAP
What shape my life ?
my family
my patients
more patients
my teammates
My Long-Distance Friends Central America
UK
Colombia Venezuela
Italy Brazil Australia Peru
Chile
Argen&na
They give advice and lend a hand
D. Manuel Tapia MartĂnez Director del Hospital Nacional de Enfermedades Infecciosas
50 aĂąos de Infecciones Respiratorias: desde destruir bacteria hasta aprender a vivir con ella
St Augis)ne Plato Aristoteles Plo)nus Eistein Theory of thermodilu)on
Hauseer H The Phyloso. Review 1937; 46: 503
Past
Pasteur
Koch
Gram
“
Next to avoiding a fatal issue, our efforts must be directed to prevent the case going on to chronic bronchitis, especially in those who have had previous attacks R Douglas Powell, London 1878
�
“
….the most widespread and fatal of all acute diseases, pneumonia, is now Captain of the Men of Death.. Sir William Osler 4 th ed. The Principles and Practice of Medicine New York: D Appleton; 1901:108
”
Why were the lower airway believed to be sterile
Johanson et al NEJM 1969; 281:1136-1139
Colonization of the respiratory tract with Gram-negative bacilli among ICU patients
Johanson et al Annals of Internal Medicine 1972; 77:701-706.
Pathogenesis of Airway Infection Bacteria Airway cells
Cytokines, mediators
Gern JE, Busse WW. Clin Microbiol Rev. 1999;12:9–18.
How should we treat them?
Antibiotics
Domagk
.
Fleming
Present
“fall & rise� of bacteria in COPD Bacterial load (CFU/ml)
New strain / Individual factors / External modifying factors
Clinical threshold
Time (days) AE
AB
Cure
Time to relapse Modified from Miravitlles. Eur Respir J 2002: 20: 9s-19s
Bacterial load and airway inflammation
rho = 0.459 p = 0.02
Patel et al Thorax 2002
HCAP
?
CAP HAP
NHAP
Asp
n o i t ira
How should I treat a patient with Lung infections ? Is this treatment improving patient outcomes?
Introduction of new antibiotic classes
Pneumonia Mortality/ 100.000 patients
Gilbert K, Fine MJ; Sem Respir INF. 1994; 9:140-52
Pneumonia Guidelines 1943 1. A glass of water every hour. 2. Open air- on porch or with bedroom windows open. (If the patient is old and weak delete or modify this order. 3. To take a patient with active pneumonia to the x-ray room is not only a confession of complete incompetence, it may almost be said to be malpractice. 4. Apply flannel pneumonia jacket and chest compress if grateful to patient. 5. The bowels should be opened. 6. Alcoholics with pneumonia may become noisy and if they do, should be given alcoholic drinks. Clendening L and Hashinger EH. Methods of treatment. 8th ed. 1943. 564-569
Pneumonia Guidelines 1943
Pneumonia Guidelines 1943
Guidelines adherence is associated with improved outcome
Dambrava et al ERJ 2008; 32:892 Menendez et al ERJ 2007; 29:751
CAP - Kaplan-Meier plots cumulative 10-year survival Expected survival PSI < 90 Pneumococcal Pneumonia
PSI ≥ 90 to <120, PSI ≥ 120
Sandvall et al CID 2013;56:1145
Mortality of hospital admitted patients with invasive pneumococcal disease 1952-62
1966-95
1995-97
13% Mortality1 N = 1130
12% Mortality2 N = 4432
12% Mortality3 N = 5837
Although the management of critically ill patients has improved by far and there are no resistance problems with regard to S. pneumoniae, mortality of IPD remains tremendous. 1. 2. 3.
Austrian R, Gold J. Ann Intern Med 1964;60:759-76. Fine MJ, et al. JAMA 1996;275(2):134-41. Feikin DR, et al. Am J Public Health 2000;90(2):223-9.
Hospitalization for pneumonia was associated with increased short-term and long-term risk of CVD, suggesting that pneumonia may be a risk factor for CVD
Corrales-Medina VF, et al. JAMA 2015
Mouse
S. Pneumo cardiac micro-lesions and latter scaring
Brown et al AJRCCM 2015
Introduction of new antibiotic classes
Development of bacterial resistance
Carl Woese
Norman Pace
16S Ribosomal Subunit
Carl Woese Phylogenetic structure of the prokaryotic domain: the primary kingdoms Woese and Fox, 1977 PNAS 74(11) pp 5088-5090 Norman Pace Rapid determination of 16S ribosomal RNA sequences for phylogenetic analyses Lane et al, 1985 PNAS 82(20) pp 6955-6959
There are more bacteria out there than we first imagined.....
Zoetendal EG. et al. 2008. Gut. Nov;57(11):1605-15
Airway Phylogenetic Tree
Hilty M, et al. PLoS ONE 2010; 5: e8578.
Decline in microbiome diversity
Bacterial Communities in Healthy Subjects
Bassis et al; Mbio 2015 Mar 3,6(2) e00037
Does the indigenous bacterial microbiota is different in the lungs?
Erb-Downward et al. PLoS One. 2011;6(2):e16384.
Gut-Lung Axis of Immunoregulation Antigen
Antigen
Gut Immune System
Pulmonary Immune System
Microbiota
Immune Regulation Outcome of Pulmonary Challenge
Lung Microbiome Community Signatures in Chronic Lung Disease
Dickson et al., Annu Rev Physiol. 2016 78 481-504
Fecal Microbiota in critically ill patients
Lankema et al ICM 2016; 43:59
Species breakdown of all cultured isolates before and after treatment
Brill SE, et al. Thorax 2015
Characteristics of the microbiota in patients prior to and after azithromycin treatment
Slater et al Thorax 2014;69:673â&#x20AC;&#x201C;674
Antibiotics and Steroids have Differential Effects on the Microbiome in AECOP
Positive Changes in Relative Abundance (log2) indicate an increase in the latter time point compared. Huang et al., JCM J Clin Microbiol. 2014; 52(8):2813-23
Distribution of bacterial phyla at each time point after rhinovirus (RV) inoculation CONTROL
Molyneaux et a l AJRCCM 2013:188, 1224â&#x20AC;&#x201C;1231
COPD
ICS -Kapplan-Meier Estimate to first Pneumonia
SFP FP
Placebo
Crim et al ERJ 2009; 34:641
SAL
What happens to a drug after deposition in the lungs?
Ruge CA, et al. Lancet Respir Med 2013
Future
Diagnosis
Rapid Microbiological Diagnostic Platforms • LightCycler SeptiFast Test (Roche) • Matrix-assisted laser desorption-ionized time-offlight (MALDITOF) • Mass Spectrometry (MS, VITEK MS) • Polymerase Chain Reaction (PCR) • DNA-based microarray platforms (Mobidiag) • Verigene gram-positive blood culture assay (Nanosphere)
SYMP-ARI Study
CONTROL
Brendish et al Lancet Respiratory 2017 on line May 2016
COPD
MinION (Oxford Nanopore Technologies, Oxford UK) palmsized DNA sequencer
Pendleton et al AJRCCM 2017 on line May 2017
Lateral Thinking
HOST!
theGRID by Charis Tsevis
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Options
Targets of antimicrobials in the bacteria replisome
van Eijk et al Ant Micro and Chem Therapy 217;72:1275
7 January 2016 â&#x20AC;˘ 5:44pm SCIENCE
First new antibiotic in 30 years discovered in major breakthrough Teixobactin has been found to treat many common bacterial infections such as tuberculosis, septicaemia and C. diff, and could be available within five years. Northeastern University in Boston, Massachusetts, have discovered a way of using an electronic chip to grow the microbes in the soil and then isolate their antibiotic chemical compounds.
Lacto-bacillus supplement: time to microbiologically confirmed VAP Lacto-‐bacillus
No-‐ Lacto-‐bacillus
Morrow et al AJRCCM 2010;182:1058–1064
Fecal Microbiota Transplantation
Bafeta et al Ann Inter Med 2017; on line May 30 2017
Epithelium immune response
Evans et al BJP 2011; 163: 195
Infection
Restitutio ad integrum
Muller-Redetzky et al Eur Respir Rev 2015; 24:516
Mortality: G-CSF in Pneumonia
What is a Stem Cell?
Mesenchymal Stem Cells
Whatâ&#x20AC;&#x2122;s next ?
Human Microbial Metagenomics: Understanding Our Microbial Selves
â&#x20AC;&#x153; ..Is the journey and not the arrival that matters..
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HOST!
Muchas Gracias!!!
HOST!
Microbiota: Mycobiota
HOST!
tym Â
The National Institutes of Health Human Microbiome Project
Naturally Ocurring Exacerbations: Changes in the Microbiome
tym Â
Huang et al, JCM, J Clin Microbiol. 2014; 52(8): 2813-23
Bacterial Families Hang out Together
tym Â
Huang et al, JCM, J Clin Microbiol. 2014; 52(8): 2813-23
Variation Across Age
tym Â
Yatsunenko et al, Nature, 2012
What is a Stem Cell?
tym Â
tym Â
Bacterial Communities in Health Subjects
Bassis et al; Mbio 2015 Mar 3,6(2) e00037
The gut microbiota can also be altered by antibiotics, medications and diet
Dietary Phenols
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Antibiotics
Microbiota
Probiotics
Fiber, sugar, starch
GI Mucosal Cells
Medications
31ยบ CONFERENCIA MAGISTRAL MANUEL TAPIA (2017)