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Programas de optimización de uso de antimicrobianos
Clinical Infectious Diseases. 2007 ; 44:159–77
Enf Infecc Microbiol Clin. 2012; 30; 22.e1–22.e23
Programas de optimización de uso de antimicrobianos
Objetivos generales de los PROA
▪ Mejorar los resultados clínicos del tratamiento de las infecciones
▪ Mejorar la calidad de la prescripción de los antimicrobianos
▪ Disminuir los efectos adversos relacionados con el empleo de los
antimicrobianos
- reducir las resistencias
- reducir la incidencia de diarrea asociada a Clostridium difficile
▪ Mejorar el coste-efectividad de los tratamientos antimicrobianos
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Dellit et al. Clin Infect Dis. 2007;44:159–77
Rodriguez-Baño et al. Enferm Infecc Microbiol Clin.
2012;30:22.e1–22.e23
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•
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eSpecífico
Medible
reAlizable
Relevante
preciso en el Tiempo
Antimicrobial resistance
▪ Increasing prevalence of multi-drug resistance isolates
Klebsiella pneumoniae
(% of invasive isolates with combined resistance to
fluoroquinolones, 3rd-gen. cephalosporins
and aminoglycosides)
Pseudomonas aeruginosa
(% of invasive isolates with resistance to ≥3
antibiotic groups among piperacillintazobactam, ceftazidime, fluoroquinolones,
aminoglycosides and carbapenems)
ECDC. Antimicrobial resistance surveillance in Europe 2015. Annual Report of the European Antimicrobial Resistance Surveillance Network (EARS-Net). 2017
Resistencia a los antimicrobianos
Líneas Estratégicas
Programas de
resistencia
“cero”
Proyectos de
investigación en
resistencias
Programas
IRAS y
PROA
Formación propia
y de otros
profesionales
Diagnóstico
microbiológico
rápido
Interés del “clínico” por el resultado microbiológico
Actuación del laboratorio de microbiología
interés
toma de
muestra
1. Evolución clínica adecuada, …
2. Evolución clínica inadecuada, cambio
de actitud clínica y terapéutica, …
3. Necesidad de resultados (datos):
protocolos, publicaciones, informes,…
2
3
1
24 h 48 h 72 h
3-5 días
tiempo
?
Edwards et al. Arch Intern Med 1973; 132:678-82; Spencely et al. J Infect 1979; 1:23-26
Cunney et al. Int J Antimicrob Chemother 2000; 14:13-9; R. Cantón (experiencia personal)
Sepsis
▪ Sepsis: life-threatening organ dysfunction caused by a dysregulated
host response to infection
- bacteraemia is identified in only about 30% of patients with sepsis,
depending on previous antibiotic treatment
- early clinical sings of sepsis (fever, tachycardia and leucocytosis)
are non-specific and overlap with sings of systemic inflammatory
response syndrome (SIRS) of non-infectious origin
- other sings (arterial hypotension, thrombocytopenia or increased
lactate concentrations) suggests progression to organ dysfunction
▪ Delay in diagnosis … delay adequate treatment, prolongs
length of stay and increases mortality
Martin et al. NEJM 2003; 348:1546-54; Angus & Van der Poll NEJM 2013;369:840-51
Wacker et al. Lancet Infect Dis 2013; 13:426-35; Singer et al. JAMA 2016;315:801-10
Need for an early diagnosis and
microbiological results
early recognition is particularly important because prompt
management of septic patients may improve outcomes
Sepsis
▪ Prompt and specific treatment in patients with severe sepsis
and septic shock improves outcome
Survival rates when
using initial therapy:
- appropriate:
52.0%
- inappropriate: 10.3%
Kumar et al. Chest 2009; 136:1237-48
Biomarkers
Microbiological studies
Blood
cultures
Crit Care Med
2014;41:580-637
▪ The increase in survival is associated with the number of
interventions, including microbiological studies (blood cultures)
and modification of antimicrobial treatment
▪ Reduction of length of stay (LOS) in survivors in whom
microbiological studies were performed
- from 41.0±26.3 to 36.2±34.8 days (p=0.043)
▪ Reduction of mortality:
- from 57.3% to 37.5% (p=.001)
Clinical microbiology lab: rapid diagnosis
▪ Decrease time of laboratory processes
- optimization and improvement of processes to
decrease time of reporting
- pre-analytic and post-analytic processes
- reporting system (electronic systems)
- automation
▪ Rapid diagnosis
- implementation of rapid laboratory techniques
-molecular techniques, mass spectrometry, ...
- implementation of point-of-care techniques
Bacteraemia diagnosis: blood cultures
▪ Blood sampling
▪ Inoculation of bottles
▪ Introduction of bottles in automatic systems
▪ Growth alert: Gram stain
▪ Preliminary information (phone alert)
▪ Preliminary identification / antibiogram
▪ Definitive identification / antibiogram
▪ Definitive report
0
+1 +2-5 +3-6 +4-7
time (days)
Bacteraemia diagnosis: blood cultures
▪ Blood sampling
▪ Inoculation of bottles
▪ Introduction of bottles in automatic systems
▪ Growth alert: Gram stain
▪ Preliminary information (phone alert)
▪ Preliminary identification / antibiogram
▪ Definitive identification / antibiogram
▪ Definitive report
0
+1 +2-5 +3-6 +4-7
time (days)
Bacteraemia diagnosis: blood cultures
▪ Blood sampling
▪ Inoculation of bottles
▪ Introduction of bottles in automatic systems
▪ Growth alert: Gram stain
▪ Preliminary information (phone alert)
▪ Preliminary identification / antibiogram
▪ Definitive identification / antibiogram
▪ Definitive report
0
+1 +2-5 +3-6 +4-7
time (days)
Bacteraemia diagnosis: blood cultures
Actions to improve the diagnosis of bateraemia
Theoretical reduction
▪ Detection of organisms in patient’s blood
no. of days
- Endotoxin detection (LPS)
- Fluorogenic probe hybridization (FISH)
- Detection of bacterial DNA (16s DNA rRNA)
2-3
2-3
2-3
▪ Detection of organisms in positive bottles
- Fluorogenic probe hybridization (FISH)
- Direct MIC panel inoculation with positive bottles
- Detection of bacterial DNA (16s DNA rRNA)
- MALDI TOF in positive bottles: identification and/
or detection of resistant mechanism
1-2
1-2
1-2
1-2
Bacteraemia diagnosis
Advantages and shortcomings of novel molecular methods in the
diagnosis of bacteremia
Advantages of novel methods
Shortcomings/challenges of novel met
Faster than conventional BCs
Critical hours (1-2 h) after diagnosis of sepsis are still lost
May yield better sensitivity than BCs Pathogen panels may not include all potential organisms
Decreased detection of blood
culture contaminants (?)
Phenotypic susceptibility result not available
Better detection in antimicrobialpretreated patients
Detects DNAemia, not bacteremia. May detect dead
organisms (finding does not necessitate living bacteria)
May detect specific resistance
profiles (e.g., mecA gene)
Discordant results in studies with conventional BCs,
Lack of ideal reference method makes difficult to evaluate
the real clinical impact
Extensive clinical evaluation still needed
BC: blood culture
Huttunen et al. Int J Infect Dis 2013; 17e934-8
Bacteraemia diagnosis: microarrays
Direct detection of microorganisms in blood
Tissari et al. Accurate and rapid
identificaton of bacterial species
from positive blood cultures
with a DNA-based microarray
platform: an observational
study. Lancet 2010; 375:224-30
http://www.mobidiag.com/
Bacteraemia diagnosis: blood cultures
Actions to improve the diagnosis of bacteraemia
▪ Detection of organisms in patient’s blood
Theoretical reduction
no. of days
- Endotoxin detection (LPS)
- Fluorogenic probe hybridization (FISH)
- Detection of bacterial DNA (16s DNA rRNA)
2-3
2-3
2-3
▪ Detection of organisms in positive bottles
- Fluorogenic probe hybridization (FISH)
- Direct MIC panel inoculation with positive bottles
- Detection of bacterial DNA (16s DNA rRNA)
- MALDI TOF in positive bottles: identification and/
or detection of resistant mechanism
1-2
1-2
1-2
1-2
Advances in Clinical Microbiology: Mass spectrometry
▪ 1975 Mass spectrometry: application to bacterial identification
Anhalt JP. Identification of bacteria ussing mass spectrometry.
Anal Chem 1975; 47:219-25
▪ 2009
Application of mass spectrometry (MALDI TOF) to routine
identification in clinical microbiology laboratories
Bacteraemia diagnosis: MALDI TOF
What is the added value for the patient?
MALDI-TOF MS: clinical impact
2012; 7:e32589
- 153 episodes of bacteremia:
- 89 during the intervention period
- 64 during the control period
- 28.8 h reduction of the time necessary to identify the organisms
- Increase of 11.3% (p<0.01) of patients with an adequate
antimicrobial treatment (75.3% vs. 64.0%)
MALDI-TOF MS: clinical impact
MALDI-TOF MS: clinical impact
Clinical/treatment outcomes
Kaplan-Meier survival analysis
Also save costs!
Huang et al. Clin Infect Dis 2013; 57:1237-45
MALDI-TOF MS: economical impact
Pérez KK, et al Arch Pathol Lab Med. 2013;137:1247–54
MALDI-TOF MS: clinical and economical impact
-19.547 $
Less opportunity to be
infected and/or
colonized with
multi-drug resistant
organisms
Pérez KK, et al Arch Pathol Lab Med. 2013;137:1247–54
Bacteraemia diagnosis: blood cultures
▪ Blood sampling
▪ Inoculation of bottles
▪ Introduction of bottles in automatic systems
▪ Growth alert: Gram stain
▪ Preliminary information (phone alert)
▪ Preliminary identification / antibiogram
▪ Definitive identification / antibiogram
▪ Definitive report
0
+1 +2-5 +3-6 +4-7
time (days)
▪ Direct MIC panel inoculation with positive bottles and with result
of Gram stain
▪ Correct identification : 90% Gram-(–), 33% Gram-(+)
▪ Reduction in reporting time: 24 hours
Direct inoculation
of antibiograms
J Microbiol Methods. 2014; 98:50-8
▪ Diferencia de crecimiento de
SARM y SASM con y sin cefoxitina
▪ Resultados en 6-horas
Estudio rápido de sensibilidad a los antimicrobianos
Bacteraemia diagnosis: blood cultures
▪ Blood sampling
▪ Inoculation of bottles
▪ Introduction of bottles in automatic systems
▪ Growth alert: Gram stain
▪ Preliminary information (phone alert)
▪ Preliminary identification / antibiogram
▪ Definitive identification / antibiogram
▪ Definitive report
0
+1 +2-5 +3-6 +4-7
time (days)
¿Diagnóstico rápido en el paciente con sepsis?
¿Reducción del tiempo en
la obtención de resultados
en el laboratorio?
¿Reducción del tiempo en
el manejo clínico del
paciente?
Mejoría de los indicadores
del laboratorio
Mejor uso de
antimicrobianos
Mejoría clínica
Reducción de mortalidad
Reducción de costos
Reducción del tiempo de
respuesta