RESUMEN
OBJECTIVE: To evaluate the efficacy of antimicrobial therapy in oral odontogenic infections using estimated pharmacokinetic/pharmacodynamic parameters or efficacy indices, and to compare pharmacokinetic/pharmacodynamic breakpoints with National Committee for Clinical Laboratory Standards' (NCCLS) breakpoints. STUDY DESIGN: Retrospective literature search to obtain minimum inhibitory concentration (MIC) values, pharmacokinetic parameters of antimicrobials and NCCLS breakpoints. Pharmacokinetic simulations were carried out using WinNonlin software (Pharsight Corporation, Mountain View, CA, USA). METHODS: For antimicrobials with time-dependent activity, the time that the plasma drug concentration exceeds the MIC as the percentage of dose interval at steady state was calculated. For antimicrobials with concentration-dependent activity, the total area under the plasma concentration-time curve over 24 hours at steady state divided by the MIC was calculated. Pharmacokinetic/pharmacodynamic breakpoints were calculated according to these parameters. RESULTS: Only amoxicillin/clavulanic acid and clindamycin showed adequate efficacy indices against the most commonly isolated bacteria in odontogenic infections. Metronidazole reached good indices against anaerobes only. Pharmacokinetic/pharmacodynamic susceptibility breakpoints do not coincide exactly with NCCLS breakpoints. CONCLUSION: Owing to the scarcity of double-blind, clinical trials on the use of antimicrobials in endodontics, this study may be useful in determining the best antimicrobial treatment in these infections. However, as we have not used concentration data in infected tissue to determine pharmacokinetic/pharmacodynamic indices, it would be necessary to design clinical trials in order to confirm these results.
Asunto(s)
Antiinfecciosos/farmacocinética , Antiinfecciosos/uso terapéutico , Infecciones/tratamiento farmacológico , Enfermedades de la Boca/tratamiento farmacológico , Enfermedades Dentales/tratamiento farmacológico , Antiinfecciosos/farmacología , Área Bajo la Curva , Bacterias/efectos de los fármacos , Humanos , Infecciones/microbiología , Pruebas de Sensibilidad Microbiana , Boca/microbiología , Enfermedades de la Boca/microbiología , Enfermedades Dentales/microbiologíaRESUMEN
INTRODUCTION: This study evaluates the efficacy of various antimicrobial treatments for orofacial infections on the basis of pharmacokinetic/pharmacodynamic (PK/PD) criteria. METHODS: A complete a literature search was undertaken to establish the MIC90 values of the five microorganisms most frequently isolated in odontogenic infections and the pharmacokinetic parameters of 13 antibiotics used in these infections. Pharmacokinetic simulations were then carried out with mean population parameters and efficacy indexes were calculated for the 47 treatment regimens analyzed. For drugs showing time-dependent antibacterial killing, the time above MIC (t > MIC) was calculated. For drugs with concentration-dependent bactericidal activity, the AUC/MIC was calculated. RESULTS: Amoxicillin-clavulanic (500 mg/8 h or 1000 mg/12 h) and clindamycin (300 mg/6 h) in the time-dependent killing group and moxifloxacin (400 mg/24 h) in the concentration-dependent group showed adequate efficacy indexes against the five pathogens considered to be the most commonly implicated in odontogenic infections. The spiramycin plus metronidazole combination, present in the commercial formulation Rhodogyl, did not reach satisfactory PK/PD indexes. CONCLUSION: PK/PD indexes, which are useful predictors of the potential efficacy of antibacterial therapy, were used with ontogenic infections in the present study. The PK/PD simulations showed that amoxicillin-clavulanic, clindamycin and moxifloxacin were the most suitable antibiotics for this kind of infection. Clinical trials are required to confirm that this methodology is useful in these pathologic processes.
Asunto(s)
Antibacterianos/farmacología , Infecciones Bacterianas/tratamiento farmacológico , Enfermedades de la Boca/tratamiento farmacológico , Algoritmos , Combinación Amoxicilina-Clavulanato de Potasio/farmacocinética , Combinación Amoxicilina-Clavulanato de Potasio/farmacología , Combinación Amoxicilina-Clavulanato de Potasio/uso terapéutico , Antibacterianos/farmacocinética , Antibacterianos/uso terapéutico , Área Bajo la Curva , Compuestos Aza/farmacocinética , Compuestos Aza/farmacología , Compuestos Aza/uso terapéutico , Clindamicina/farmacocinética , Clindamicina/farmacología , Clindamicina/uso terapéutico , Ensayos Clínicos como Asunto/métodos , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada/farmacocinética , Quimioterapia Combinada/farmacología , Quimioterapia Combinada/uso terapéutico , Fluoroquinolonas , Fusobacterium nucleatum/efectos de los fármacos , Humanos , Pruebas de Sensibilidad Microbiana , Enfermedades de la Boca/microbiología , Moxifloxacino , Peptostreptococcus/efectos de los fármacos , Periodontitis/tratamiento farmacológico , Periodontitis/microbiología , Porphyromonas gingivalis/efectos de los fármacos , Prevotella intermedia/efectos de los fármacos , Quinolinas/farmacocinética , Quinolinas/farmacología , Quinolinas/uso terapéutico , Factores de Tiempo , Estreptococos Viridans/efectos de los fármacosRESUMEN
INTRODUCCIÓN. Evaluar la eficacia de diferentes tratamientos antimicrobianos en infecciones oro faciales utilizando criterios fármaco cinéticos/fármaco dinámicos (PK/PD).MÉTODOS. Tras llevar a cabo una revisión bibliográfica que permitió conocer los valores de concentración inhibitoria mínima (CIM90) de cinco de los microorganismos más frecuentemente aislados en infecciones odontógenas y los parámetros fármaco-cinéticos de 13 antibióticos utilizados en este tipo de infecciones, se realizaron simulaciones farmacocinéticas con parámetros poblacionales medios y se calcularon los índices de eficacia para las 47 pautas posológicas analizadas. Para los antibióticos dependientes de tiempo se calculó el tsupra CIM, mientras que para los dependientes de concentración se determinó el cociente ABC/CIM90.RESULTADOS. Amoxicilina-ácido clavulánico (500 mg/8 ho 1.000 mg/12 h) y clindamicina (300 mg/6 h), entre los antibióticos con actividad dependiente de tiempo, y moxifloxacino (400 mg/24 h) entre los dependientes de concentración mostraron índices de eficacia adecuados frente a los cinco microorganismos considerados como los más frecuentemente implicados en este tipo de infecciones. La combinación de espiramicina más metronidazol presente en la formulación comercial denominada Rhodogyl®, no alcanzó índices PK/PD satisfactorios. CONCLUSIÓN. Los índices PK/PD son herramientas útiles para predecir la eficacia potencial de la terapia antimicrobiana, y en este caso se han aplicado al tratamiento de infecciones odontógenas. Estas simulaciones PK/PD permiten concluir que amoxicilina-ácido clavulánico, clindamicina y moxifloxacino se presentan como los antibióticos más adecuados que se deben utilizar para el tratamiento de este tipo de infecciones. Sin embargo, sería importante contrastar los resultados obtenidos con un ensayo clínico para confirmar que esta metodología es útil en este tipo de procesos patológicos (AU)
INTRODUCTION. This study evaluates the efficacy of various antimicrobial treatments for oro facial infections on the basis of pharmacokinetic/pharmaco dynamic (PK/PD) criteria. METHODS. A complete a literature search was undertaken to establish the MIC90 values of the five microorganisms most frequently isolated in odontogenic infections and the pharmacokinetic parameters of 13 antibiotics used in these infections. Pharmacokinetic simulations were then carried out with mean population parameters and efficacy indexes were calculated for the 47 treatment regimens analyzed. For drugs showing time-dependent antibacterial killing, the time above MIC (t > MIC) was calculated. For drugs with concentration-dependent bactericidal activity, the AUC/MIC was calculated. RESULTS. Amoxicillin-clavulanic (500 mg/8 h or1000 mg/12 h) and clindamycin (300 mg/6 h) in the time-dependant killing group and moxifloxacin(400 mg/24 h) in the concentration-dependant group showed adequate efficacy indexes against the five pathogens considered to be the most commonly implicated in odontogenic infections. The spiramycin plus metronidazole combination, present in the commercial formulation Rhodogyl®, did not reach satisfactory PK/PD indexes. CONCLUSION. PK/PD indexes, which are useful predictors of the potential efficacy of antibacterial therapy, were used with ontogenic infections in the present study. The PK/PD simulations showed that amoxicillin-clavulanic, clindamycin and moxifloxacin were the most suitable antibiotics for this kind of infection. Clinical trials are required to confirm that this methodology is useful in these pathologic processes (AU)