Perspectiva nacional y europea en el manejo de la infección por neumonías complicadas por SARM. Alex Soriano Hospital Clínic of Barcelona

Transcripción

1 Perspectiva nacional y europea en el manejo de la infección por neumonías complicadas por SARM Alex Soriano Hospital Clínic of Barcelona

2 Chastre J, et al. European perspective and update on the management of nosocomial pneumonia due to methicillinresistant Staphylococcus aureus after more than 10 years of experience with linezolid. Clin Microbiol Infect 2014; 20 (Supl 4): 1936

3 Freixas N, et al. Surveillance of methicillinresistant Staphylococcus aureus (MRSA) in acute care hospitals. Results of the VINCat Program ( ). Enferm Infecc Microbiol Clin 2012; 30 (Supl 3): 3942 % SARM (SAt/SARM) Nº camas > <

4 Evolución de la bacteriemia pors. aureus RM en el Hospital Clínic de Barcelona entre Urgencias IH Criterio: CSS Ingr. previo Consumo AB HD

5 Shorr AF et al. Validation of a Clinical Score for Assessing the Risk of Resistant Pathogens in Patients With Pneumonia Presenting to the Emergency Department. Clin Infect Dis 2012; 54: pacientes consecutivos que ingresaban por urgencias 1. Procedencia de un centro sociosanitario o residencia. 2. Hospitalización reciente >48h en los 3 meses previos. 3. Uso previo de antibióticos de amplio espectro durante el mes previo. 4. Inmunosupresión (SIDA, QT, corticoterapia). 5. Hemodiálisis o tratamiento domiciliario. 415 (42%)

6 Aliberti S, et al. Stratifying Risk Factors for MultidrugResistant Pathogens in Hospitalized Patients Coming From the Community With Pneumonia. Clin Infect Dis 2012; 54: 4708 %R % microorganismo S. pneumoniae S. aureus Enterobacterias P. aeruginosa L. pneumophila P. atípicos % %R colonización o infección previa

7 Bassetti M al. Risk factors and mortality of healthcareassociated and community acquired Staphylococcus aureus bacteraemia. Clin Microbiol Infect 2012; 18: 8629 %of patients receiving inappropriate empirical AB therpapy IEAT was independently associated with a higher mortality(or: 2.79) urgencias nosocomial

8 Etiología de la neumonía bacteriémica de acuerdo con el origen. Hospital Clínic de Barcelona (n=1364) Microorganismo EH (%) IH (%) RCS (%) S. aureus 56 (6.5) 46 (14) 16 (10) formas graves (shock) lesiones cavitadas jóvenes postgripal UDVP (EI) VM posttrauma ingreso prolongado (RM) residencia ingreso previo IRC, HD mort (%):

9 Guidelines for the Management of Adults with Hospitalacquired, Ventilatorassociated, and Healthcareassociated Pneumonia. ATS/IDSA. Am J Respir CritCare Med 2005; 171:

10 Evidencia publicada en forma de metaanálisis sobre la eficacia de linezolid vs glicopéptidos Autor/año Entidad/ Nº estudios CC EM Falagas 08 BeiBei 10 Thamlikitkul 12 Kalil 13 Jiang 13 Mao 13 Nemeth 14 Wang 14 G/12 G/9 N/6 N/9 N/12 G/9 G/7 N/ NA NA favorece a linezolid / favorece a vancomicina

11 Wunderick. et al. Analysis of 2 dobleblind studies of patients with MRSA nosocomial pneumonia. Chest 2003;124: LNZ VCN LNZ VCN CMI 2 mg/l (80%, 1 mg/l) Cmin: 510 mg/l

12 Young Ju Jung, et al. Effect of vancomycin plus rifampicin in the treatment of nosocomial methicillinresistant S. aureus pneumonia. CritCare Med 2010; 38: * * RifaR en 14 casos (34%)

13 Resultados según la dosis de vancomicina utilizada en pacientes con neumonía nosocomial por SARM referencia Dosis vanco Cmin diana (mg/l) Cmin* (mg/l) % vanco** % line** Wunderink 03 1 g/12h Kollef 04 1 g/12h Zephyr 15 mg/kg/12h > * niveles medios el tercer día ** % curación

14 Akinnusi ME, et al. Does linezolid modulate lung innate immunity in a murine model of methicillinresistants. aureus pneumonia? Crit Care Med 2011; 39: Laboratorio Log CFU/mL Modelo animal

15 Mitsutaka K, et al. Use of a Sensitive ChemiluminescenceBased Assay to Evaluate the Metabolic Suppression Activity of Linezolid on MRSA Showing Reduced Susceptibility to Vancomycin. J. Microbiol. Biotechnol. 2009; 19: Log UFC/mL Virulence capacity reduced Inhibition of toxin production More susceptible to PMN Decrease after 6h of exposition

16 Karau M, et al. Linezolid Is Superior to Vancomycin in Experimental Pneumonia Caused by SuperantigenProducing Staphylococcus aureus in HLA Class II Transgenic Mice. Antimicrobial Agents Chemother 2012; 56: horas de exposición VAN LNZ DR3: modelo transgénico (HLADR3). Cepa de SARM SEB+

17 MartínezOlondris P, et al. Efficacy of linezolid compared to vancomycin in an experimental model of pneumonia induced by MRSA in ventilated pigs. CritCare Med 2011; 40: 17

18 Nemeth J, et al. Bacteriostatic versus bactericidal antibiotics for patients with serious bacterial infections: systematic review and metaanalysis. J Antimicrob Chemother 2014 in press Modelo animal

19 Evidencia publicada en forma de metaanálisis sobre la eficacia de linezolid vs glicopéptidos Autor/año Entidad/ Nº estudios CC EM Mort Falagas 08 BeiBei 10 Thamlikitkul 12 Kalil 13 Jiang 13 Mao 13 Nemeth 14 Wang 14 G/12 G/9 N/6 N/9 N/12 G/9 G/7 N/ NA NA favorece a linezolid / favorece a vancomicina

20 Garin N, et al. βlactam Monotherapy vs βlactam Macrolide Combination Treatment in Moderately Severe CommunityAcquired Pneumonia (openrandomized). JAMA Intern Med 2014 (Oct) proportion of patients who did not reach clinical stability at day 7, defined as a HR< 100/min, SBP> 90 mmhg, tympanic We temperature were unable < 38ºC, to RR< demonstrate 24/min, and 0 2 noninferiority saturation >90% on ofroomair initial empirical (vital signswere measured at least twice a day). treatment with a βlactam agent alone in hospitalized patients with Time to clinical stability was defined as time moderately elapsed between severe the first communityacquired pneumonia antibiotic dose and the first time all 5 criteria were reached and maintained for a minimum of 24 hours

21 Evidencia publicada en forma de metaanálisis sobre la eficacia de linezolid vs glicopéptidos Autor/año Entidad/ Nº estudios CC EM Mort Plq IR Falagas 08 BeiBei 10 Thamlikitkul 12 Kalil 13 Jiang 13 Mao 13 Nemeth 14 Wang 14 G/12 G/9 N/6 N/9 N/12 G/9 G/7 N/ NA NA NA NA 0.50 favorece a linezolid / favorece a vancomicina

22 Bosso JA, et al. Relationship between Vancomycin Trough Concentrations and Nephrotoxicity: a Prospective Multicenter Trial. Antimicrob Agents Chemother 2011; 55: variable* OR for nephrotoxicity Trough >15 mg/l Duration Black race Heart failure Neoplasia with M Trough 15, 8.9% NPT Trough > 15, 29% NPT mean: 9 Median: 7.5 *prospective study including 288 patients that received vancomycin and levels were measured after 72h of therapy

23 Mensa J, et al. Guiá de tratamiento antimicrobiano de la infeccioń por Staphylococcus aureus. Rev Esp Quimiot2013; 26: 184 entidad SASM SARM