1 Nuevas Moléculas ¿Existen? ¿Serán eficaces?
2 Adrián Camacho-Ortiz Coordinador de Epidemiología Hospitalaria,Profesor del Servicio de Infectología Hospital Universitario “Dr. José Eleuterio González”
3 Conflictos de interés Speaker Merk Sharp Dome Stendhal Pfizer BayerAztra Zeneca
4 75% C difficile NAP1 (like)A grandes rasgos … 30-40% BLEE 75% C difficile NAP1 (like) ~50% P aeruginosa MDR 10% VRE 50-60% MRSA 90% A baumannii MDR Impresión personal
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6 “One of the biggest issues is money “
7 Activity spectrum/resistant pathogens targeted Phase and indication1 Late-stage pipeline: systemic antibiotics recently approved, in registration or in phase III of clinical development Drug (brand name) - Company Antibiotic class Activity spectrum/resistant pathogens targeted Phase and indication1 Regulatory status US European Union Ceftazidime+ avibactam Cephalosporin + new BLI Gram‒, including MDR P. aeruginosa, ESBL KPC Approved February 2015 for cIAI in combination with metronidazole, and for cUTI in patients who have limited or no alternative treatment options, in phase III for HAP/VAP and cIAI Approved Feb 2015 Not submitted yet Ceftolozane+ tazobactam Cephalosporn + BLI Gram‒, including carbapenem, piperacillin+tazobactam and ceftazidime-resistant Pseudomonas aeruginosa, ESBL Approved for cUTI and cIAI, in phase III for VAP and phase I for paediatric use Approved December 2014 Under review since August 2014 Swiss Med Wkly. 2015;145:w14167
8 Activity spectrum/resistant pathogens targetedLate-stage pipeline: systemic antibiotics recently approved, in registration or in phase III of clinical development Drug (brand name) - Company Antibiotic class Activity spectrum/resistant pathogens targeted Phase and indication1 Regulatory status US European Union Ceftobiprole Cephalosporin Gram+ and ‒, MRSA, VRSA, penicillin- and ceftriaxone-resistant Streptococcus pneumoniae, Enterobacteriaceae, P. aeruginosa Approved for CABP and HAP, excluding VAP Not submitted (additional phase III data required Approved October 2013 Oritavancin Glycopeptide Gram+, including MRSA Approved for ABSSSI, in phase I for paediatric use Approved August 2014 Approved May 2015 Dalbavancin Approved for ABSSSI, in phase III for CABP and phase I and III for paediatric use Approved May 2014 Approved March 2015 Swiss Med Wkly. 2015;145:w14167
9 Activity spectrum/resistant pathogens targetedLate-stage pipeline: systemic antibiotics recently approved, in registration or in phase III of clinical development. Drug (brand name) - Company Antibiotic class Activity spectrum/resistant pathogens targeted Phase and indication1 Regulatory status US European Union Eravacycline Tetracycline Gram+ and ‒, including CRE, ESBL-producing strains, MDR Acinetobacter baumanii, VRE, MRSA Phase III for cUTI and cIAI4 NA Plazomicin Aminogylcoside Gram‒, including CRE Phase III for bloodstream infection and nosocomial pneumonia caused by CRE5 Delafloxacin Fluoroquinolone Gram+ and ‒, including MRSA Phase III for ABSSSI Solithromycin Macrolide Gram+, including macrolide-resistant strains Phase III for CABP and uncomplicated gonorrhoea, in phase I for paediatric use Swiss Med Wkly. 2015;145:w14167
10 Confidence intervals for the difference in clinical cure rates at test-of-cure, individual and integrated community-acquired pneumonia studies (clinically evaluable [CE] and modified intent-to-treat efficacy [MITTE] populations) Ceftaroline Confidence intervals for the difference in clinical cure rates at test-of-cure, individual and integrated community-acquired pneumonia studies (clinically evaluable [CE] and modified intent-to-treat efficacy [MITTE] populations). FOCUS, Ceftaroline Community Acquired Pneumonia Trial versus Ceftriaxone in Hospitalized Patients. Thomas M. File, Jr et al. Clin Infect Dis. 2010;51:
11 Confidence intervals for the difference in clinical cure rates at test-of-cure, individual and integrated community-acquired pneumonia studies (microbiologically evaluable [ME] and microbiological modified intent-to-treat efficacy [mMITTE] populations) Ceftaroline Confidence intervals for the difference in clinical cure rates at test-of-cure, individual and integrated community-acquired pneumonia studies (microbiologically evaluable [ME] and microbiological modified intent-to-treat efficacy [mMITTE] populations). FOCUS, Ceftaroline Community Acquired Pneumonia Trial versus Ceftriaxone in Hospitalized Patients. Thomas M. File, Jr et al. Clin Infect Dis. 2010;51:
12 Differences in early clinical response between Tedizolid and linezolid according to clinically relevant host and disease factors (A) and baseline severity measures (B) in the ITT population Differences in early clinical response between tedizolid and linezolid according to clinically relevant host and disease factors (A) and baseline severity measures (B) in the ITT population. The results are the weighted (by study) difference and adjusted confidence interval. [n/n], number of subjects in the subgroup in the tedizolid arm/number of subjects in the subgroup in the linezolid arm. BMI, body mass index; ITT, intent-to-treat; IV, intravenous; LZD, linezolid; SIRS, systemic inflammatory response syndrome; TZD, tedizolid; WBC, white blood cell. Andrew F. Shorr et al. Antimicrob. Agents Chemother. 2015;59:
13 Patients with platelet counts below the lower limit of normal (LLN) (<150,000 cells/mm3) over time. *, P < 0.05 Patients with platelet counts below the lower limit of normal (LLN) (<150,000 cells/mm3) over time. *, P < EOT, end-of-therapy. Andrew F. Shorr et al. Antimicrob. Agents Chemother. 2015;59:
14 Characteristics of the Patients in the Intention-to-Treat PopulationTable 1 Characteristics of the Patients in the Intention-to-Treat Population. Boucher HW et al. N Engl J Med 2014;370: Once-Weekly Dalbavancin versus Daily Conventional Therapy for Skin Infection N Engl J Med 2014;370(23):
15 Primary and Secondary Efficacy End PointsTable 2 Primary and Secondary Efficacy End Points. Boucher HW et al. N Engl J Med 2014;370: Once-Weekly Dalbavancin versus Daily Conventional Therapy for Skin Infection N Engl J Med 2014;370(23):
16 Safety, Tolerability, and Pharmacokinetic Properties of Intravenous Delafloxacin After Single and Multiple Doses in Healthy Volunteers Hoover R. et al Clin Ther 2016 Jan 1;38(1):53-65.
17 A randomized, double-blind, Phase 2 study to evaluate subjective and objective outcomes in patients with acute bacterial skin and skin structure infections treated with Delafloxacin, linezolid or vancomycin Kingsley J. J Antimicrob Chemother Mar;71(3):821-9.
18 Ceftazidime-avibactam activity against multidrug-resistant Pseudomonas aeruginosa isolated in U.S. medical centers in 2012 and 2013 Antimicrob Agents Chemother. 2015;59(6):3656-9
19 ¿Que es nuevo?
20 Bubba: “como te decía…el camarón es la fruta del mar” Puedes… barbecue it boil it, broil it bake it, saute it shrimp-kabobs shrimp creole shrimp gumbo Pan fried deep fried stir-fried pineapple shrimp lemon shrimp coconut shrimp pepper shrimp shrimp soup shrimp stew shrimp salad shrimp and potatoes shrimp burger shrimp sandwich “y creo que eso es todo” Oxazolidinonas Tedizolid Cadazolid Beta lactámicos Ceftarolina Ceftobiprole Ceftazidima AVB Imipenem/relebactam Meropenem/RPX7009 Aminoglucósidos Plazomicina Fluoroquinolonas Tetraciclinas Delafloxacino Omadaciclina Eravaciclina
21 Uso clínico ÷ resistencia
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24 Waskman screening Platform
25 iChip 10,000 extractos vs S aureus Eleftheria terrae Teixobactin(aquabacteriace) 16S DNA Teixobactin
26 IChip
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28 Teixobactina vs VancomicinaNature Jan 22;517(7535):455-9
29 ¿En qué etapa funciona? Eleftheria terrae S. aureusIncorporación de 3H-thimidina (DNA), 3H- uridina (RNA), 3H-leucina (protein), and 3H- glucosamina (peptidoglucano) S. aureus Nature Jan 22;517(7535):455-9
30 Cocos, bacilos y Micobacterias….pero no BGNNature Jan 22;517(7535):455-9
31 ¿Antirretrovirales para tratamiento antibacteriano?Paso 1 LukED + Linf-TCD4 CCR5 Paso 2 Antagonistas de CCR5 (Maraviroc) Impide lisis de CCR5(+) Paso 3 LukED purificado aplicado a ratones Ccr5 –/– Ccr5 +/+ Alonzo, F. et al. CCR5 is a receptor for Staphylococcus aureus leukotoxin ED. Nature 493, 51–55 (2013)
32 Lisozimas: Actividad vs N-acetilmuramolhidrolases que hidrolisan la fracción de unión β (1,4) glucosidica entre el acíso N-acetil- muramico y N-acetilglucosamina G - Listeria PlyP35 P. aeruginosa KZ144 Bacillus amyloliquefaciens Lys1521 G + Endolisinas Permeabilizador de ME Artilisinas Future Microbiol. (2015) 10(3), 377–390
33 Antibodies to watch in 2015.MAbs. 2015;7(1):1-8
34 No hay blancos diferentesNuevas Moléculas ¿Existen? ¿Serán eficaces? Pocas No hay blancos diferentes Duraran poco
35 Lo que si sé es que necesitamos buscar nuevos blancos de acciónNuevas Moléculas ¿Existen? ¿Serán eficaces? No lo sé Lo que si sé es que necesitamos buscar nuevos blancos de acción el panorama es sombrío si no cuidamos lo que tenemos
36 Gracias