Pharmacokinetic/pharmacodynamic evaluation of amoxicillin, amoxicillin/clavulanate and ceftriaxone in the treatment of paediatric acute otitismedia in Spain

Introduction: Acute otitis media is the most common respiratory tract infection in infancy and early childhood that is managed with antimicrobial agents. Ninety-three per cent of the cases diagnosed in Spain are treated with antibiotics, and Streptococcus pneumoniae and untype able Haemophilus influenza are the most frequently isolated pathogens. The aim of this work was to evaluate the usefulness of amoxicillin, amoxicillin/clavulanate and ceftriaxone for the empirical treatment of acute otitis media, looking at the pharmacokinetic variability and the antimicrobial susceptibility of paediatric strains of the two main pathogens responsible for AOM in Spain, Streptococcus pneumoniae and Haemophilus influenzae. Methods: Free-drug plasma concentrations were simulated and the probability of target attainment a teach minimum inhibitory concentration and the cumulative fraction of response (CFR) were determined. Microbiological susceptibility information was extracted from SAUCE 3 surveillance. Results: CFR with amoxicillin varied from 83% to 96% against S. pneumoniae and from 78% to 86% agains tH. influenzae. CFR was always >85% with amoxicillin/clavulanate. With the 3-day ceftriaxone regimen, the probability of achieving free concentrations above MIC at 72 hours significantly increased compared to the single dose, with which CFR ranged from 70% to 84%. Conclusions: High-dose amoxicillin (at least 80 mg/kg/day) should be the first-line therapy in uncomplicated infections, whereas amoxicillin/clavulanate (40 mg/kg/day) should be the choice when additional coverage for H. influenzae is desired. Administration of 3 daily doses of ceftriaxone increases bacteriological eradication probability when compared with one-day regimen, although additional clinical evaluations are necessary to establish the best target attainment with ceftriaxone (AU)

Introducción: La otitis media aguda (OMA) es la infección del tracto respiratorio más común en la infanciaque es tratada con agentes antimicrobianos. El noventa y tres por ciento de los casos diagnosticados en España se tratan con antibióticos, siendo Streptococcus pneumoniae y Haemophilus influenzae no tipable los patógenos aislados más frecuentes. El objetivo de este trabajo ha sido evaluar la utilidad de amoxicilina,amoxicilina/clavulánico y ceftriaxona en el tratamiento empírico de OMA teniendo en cuenta la variabilidad farmacocinética y la sensibilidad antimicrobiana de las cepas pediátricas de los dos patógenos principales responsables de OMA en España, Streptococcus pneumoniae y Haemophilus influenzae. Métodos: Se simularon las concentraciones de fármaco libre para cada antibiótico y se calculó la probabilidad de alcanzar el objetivo terapéutico para cada valor de concentración mínima inhibitoria (CMI) y la fracción de respuesta acumulada (CFR).Resultados: La CFR de amoxicilina osció entre el 83% y el 96% frente a S. pneumoniae y entre el 78% y el86% para H. influenzae. En el caso de amoxicilina/clavulánico, la CFR fue siempre >85%. Con ceftriaxonadurante 3 días, la probabilidad de alcanzar concentraciones libres por encima de la CMI a las 72 horasfue significativamente superior a la probabilidad obtenida con una sola dosis, con valores de CFR que oscilaron entre el 70% y el 84%.Conclusiones: Amoxicilina a altas dosis debería ser la primera opción para el tratamiento de infecciones no complicadas, mientras que amoxicilina/clavulánico deberá utilizarse cuando se sospecha que H. influenzae puede ser responsable de la infección. La administración de ceftriaxona durante 3 días incrementa la probabilidad de erradicar la infección repecto a la administración de una única dosis, aunque son necesarios estudios clínicos para establecer el mejor objetivo terapéutico con ceftriaxona (AU)

Pharmacokinetic/pharmacodynamic evaluation of amoxicillin, amoxicillin/clavulanate and ceftriaxone in the treatment of paediatric acute otitis media in Spain.

INTRODUCTION: Acute otitis media is the most common respiratory tract infection in infancy and early childhood that is managed with antimicrobial agents. Ninety-three per cent of the cases diagnosed in Spain are treated with antibiotics, and Streptococcus pneumoniae and untypeable Haemophilus influenzae are the most frequently isolated pathogens. The aim of this work was to evaluate the usefulness of amoxicillin, amoxicillin/clavulanate and ceftriaxone for the empirical treatment of acute otitis media, looking at the pharmacokinetic variability and the antimicrobial susceptibility of paediatric strains of the two main pathogens responsible for AOM in Spain, Streptococcus pneumoniae and Haemophilus influenzae. METHODS: Free-drug plasma concentrations were simulated and the probability of target attainment at each minimum inhibitory concentration and the cumulative fraction of response (CFR) were determined. Microbiological susceptibility information was extracted from SAUCE 3 surveillance. RESULTS: CFR with amoxicillin varied from 83% to 96% against S. pneumoniae and from 78% to 86% against H. influenzae. CFR was always >85% with amoxicillin/clavulanate. With the 3-day ceftriaxone regimen, the probability of achieving free concentrations above MIC at 72 hours significantly increased compared to the single dose, with which CFR ranged from 70% to 84%. CONCLUSIONS: High-dose amoxicillin (at least 80 mg/kg/day) should be the first-line therapy in uncomplicated infections, whereas amoxicillin/clavulanate (40 mg/kg/day) should be the choice when additional coverage for H. influenzae is desired. Administration of 3 daily doses of ceftriaxone increases bacteriological eradication probability when compared with one-day regimen, although additional clinical evaluations are necessary to establish the best target attainment with ceftriaxone.

Descontaminación digestiva selectiva: repercusión en la carga de trabajo y el coste del laboratorio de microbiología y tendencias en la resistencia bacteriana / Selective decontamination of the digestive tract: Repercussions on microbiology laboratory workload and costs, and antibiotic resistance trends

Introducción Determinar la carga de trabajo y el coste para el laboratorio de microbiología así como el impacto en la flora microbiana y las tendencias de la resistencia bacteriana en el servicio de medicina intensiva (SMI) a partir de la introducción de la descontaminación digestiva selectiva. Métodos Se cuantificó la carga de trabajo y el coste total de microbiología así como la parte imputada al servicio peticionario en el año anterior y posterior a la introducción del procedimiento. Se valoró el cambio en la flora microbiana y se analizaron las tendencias de resistencia bacteriana durante 12 años en 21 combinaciones centinela antimicrobiano/microorganismo. Resultados La carga de trabajo imputada al SMI aumentó un 10% y el coste un 1,8% en el período posterior a la introducción del procedimiento (diferencias no significativas). El aumento de la carga de trabajo a costa de los cultivos de vigilancia epidemiológica se compensó con disminuciones significativas de broncoaspirados cuantitativos, hemocultivos, exudados, identificaciones y antibiogramas, y serología. El procedimiento se ha asociado a una disminución significativa de aislados de Acinetobacter y a un ascenso significativo de Enterococcus. Se han detectado 3 tendencias significativas de aumento de resistencia, las 3 en Pseudomonas aeruginosa (imipenem, tobramicina y ciprofloxacino).Conclusiones En este hospital, la implantación de este procedimiento no ha supuesto un aumento significativo de la carga de trabajo y el coste del laboratorio de microbiología, y se ha asociado a una marcada disminución de Acinetobacter y a un aumento de Enterococcus y de la resistencia a imipenem, tobramicina y ciprofloxacino en P. aeruginosa (AU)

Introduction This study determines the workload and cost of implementing selective digestive decontamination in the microbiology laboratory, and reports the impact on microbial flora and bacterial resistance trends in the intensive care unit (ICU).Methods The total microbiological workload and cost were quantified, as well as the part charged to the petitioning service, in the year before and the year after introducing the procedure. Changes in microbial flora were evaluated and bacterial resistance trends were analyzed over 12 years in 21 sentinel antimicrobial/microorganism combinations. Results The workload ascribed to the ICU increased by 10% and cost increased by 1.8% in the period after introduction of the procedure (non-significant differences). The increased workload resulting from epidemiological surveillance cultures was compensated by significant reductions in quantitative endotracheal aspirate cultures, blood cultures, exudate cultures, identification tests with antibiograms, and serologies. The procedure has been associated with a significant decrease in Acinetobacter isolates and a significant increase in Enterococcus. Three significant trends of increased resistance were detected, all of them in Pseudomonas aeruginosa (imipenem, tobramycin, and ciprofloxacin).Conclusions In our hospital, implementation of selective digestive decontamination did not cause a significant increase in the workload or costs in the microbiology laboratory. Selective digestive decontamination was associated with a significant decrease in Acinetobacter, an increase in Enterococcus, and higher resistance to imipenem, tobramycin and ciprofloxacin in P. aeruginosa(AU)

[Selective decontamination of the digestive tract: repercussions on microbiology laboratory workload and costs, and antibiotic resistance trends]. / Descontaminación digestiva selectiva: repercusión en la carga de trabajo y el coste del laboratorio de microbiología y tendencias en la resistencia bacteriana.

INTRODUCTION: This study determines the workload and cost of implementing selective digestive decontamination in the microbiology laboratory, and reports the impact on microbial flora and bacterial resistance trends in the intensive care unit (ICU). METHODS: The total microbiological workload and cost were quantified, as well as the part charged to the petitioning service, in the year before and the year after introducing the procedure. Changes in microbial flora were evaluated and bacterial resistance trends were analyzed over 12 years in 21 sentinel antimicrobial/microorganism combinations. RESULTS: The workload ascribed to the ICU increased by 10% and cost increased by 1.8% in the period after introduction of the procedure (non-significant differences). The increased workload resulting from epidemiological surveillance cultures was compensated by significant reductions in quantitative endotracheal aspirate cultures, blood cultures, exudate cultures, identification tests with antibiograms, and serologies. The procedure has been associated with a significant decrease in Acinetobacter isolates and a significant increase in Enterococcus. Three significant trends of increased resistance were detected, all of them in Pseudomonas aeruginosa (imipenem, tobramycin, and ciprofloxacin). CONCLUSIONS: In our hospital, implementation of selective digestive decontamination did not cause a significant increase in the workload or costs in the microbiology laboratory. Selective digestive decontamination was associated with a significant decrease in Acinetobacter, an increase in Enterococcus, and higher resistance to imipenem, tobramycin and ciprofloxacin in P. aeruginosa.

Relación entre la resistencia bacteriana intrahospitalaria y el consumo de antimicrobianos durante un período de 13 años / Relationship between in-hospital bacterial resistance and antimicrobial use over a 13-year period

Objetivo Analizar la relación entre el consumo de antimicrobianos y la sensibilidad en bacterias gramnegativas y grampositivas en un hospital general durante un período de 13 años. Métodos Se obtuvieron las series de consumo normalizadas de 58 antibióticos (dosis diarias definidas por 100 estancias por día) en el período de 1993 a 2005, así como también se obtuvieron las series de porcentajes de sensibilidad para todas las combinaciones posibles entre antibiótico y bacteria en este período. Se consideraron tanto las relaciones simples como las relaciones múltiples mediante la separación de las series del servicio de medicina intensiva de las del resto de los servicios medicoquirúrgicos. Se relacionaron las series consumo-sensibilidad mediante regresión lineal simple para los retardos 0, 1 y 2 años y se seleccionaron aquellas relaciones con coeficiente de determinación superior o igual a 0,5 y coeficiente de correlación de Pearson negativo. Estas relaciones se reanalizaron tanto mediante modelos de regresión autorregresivos para incluir la autocorrelación temporal de los residuales como mediante modelos de regresión con retardos de distribución polinómica que permitieron distribuir en el tiempo el efecto del consumo sobre la sensibilidad. Resultados El aumento de consumo de determinados antibióticos ha repercutido de forma negativa sobre la sensibilidad a otros antimicrobianos de manera inmediata (imipenem, cefalosporinas de tercera generación y piperacilina con tazobactam), mientras que otros antimicrobianos parecen tener una (..) (AU)

Objective To analyze the relationship between antimicrobial use and susceptibility in gram-negative and gram-positive bacteria in a general hospital during a 13-year period. Methods Normalized antimicrobial consumption (defined daily dose per 100 bed-days) was determined for 58 antibiotics for the period of 1993 to 2005, and susceptibility percentages were calculated for all possible antibiotic-microbial combinations for the same period. Both simple and multiple relationships were considered in 2 different settings: the intensive care unit and the remaining medical-surgical departments. Simple linear regression models for sensitivity-usage were employed, with delays of 0, 1, and 2 years; relationships with determination coefficients (r2) higher than 0.5 and negative correlation coefficients (r) were selected. These selected relationships were further analyzed using both autoregressive models to account for autocorrelation in the error term, and polynomial distributed lag regression models that allow distribution in time of the usage effect on sensitivity, considering all delays simultaneously. Results The increase in consumption of some antimicrobials has negatively influenced sensitivity to other antimicrobials, with an immediate influence in time for some of them (imipenem, 3rd generation cephalosporins, piperacillin-tazobactam), whereas for others a lag of 1 year (ciprofloxacin, amoxicillin-clavulanate, aminoglycosides) or even 2 years (consumption of macrolides-lincosamides on decreased susceptibility to cloxacillin in S. aureus) was observed. Conclusions The significant increment of antimicrobial use observed for many agents seems to produce a negative effect on the sensitivity to other antimicrobials, which is immediate in some relationships, but shows a time lag of 1 or 2 years in others (AU)

[Relationship between in-hospital bacterial resistance and antimicrobial use over a 13-year period]. / Relación entre la resistencia bacteriana intrahospitalaria y el consumo de antimicrobianos durante un período de 13 años.

OBJECTIVE: To analyze the relationship between antimicrobial use and susceptibility in gram-negative and gram-positive bacteria in a general hospital during a 13-year period. METHODS: Normalized antimicrobial consumption (defined daily dose per 100 bed-days) was determined for 58 antibiotics for the period of 1993 to 2005, and susceptibility percentages were calculated for all possible antibiotic-microbial combinations for the same period. Both simple and multiple relationships were considered in 2 different settings: the intensive care unit and the remaining medical-surgical departments. Simple linear regression models for sensitivity-usage were employed, with delays of 0, 1, and 2 years; relationships with determination coefficients (r2) higher than 0.5 and negative correlation coefficients (r) were selected. These selected relationships were further analyzed using both autoregressive models to account for autocorrelation in the error term, and polynomial distributed lag regression models that allow distribution in time of the usage effect on sensitivity, considering all delays simultaneously. RESULTS: The increase in consumption of some antimicrobials has negatively influenced sensitivity to other antimicrobials, with an immediate influence in time for some of them (imipenem, 3rd generation cephalosporins, piperacillin-tazobactam), whereas for others a lag of 1 year (ciprofloxacin, amoxicillin-clavulanate, aminoglycosides) or even 2 years (consumption of macrolides-lincosamides on decreased susceptibility to cloxacillin in S. aureus) was observed. CONCLUSIONS: The significant increment of antimicrobial use observed for many agents seems to produce a negative effect on the sensitivity to other antimicrobials, which is immediate in some relationships, but shows a time lag of 1 or 2 years in others.

[Antibiotic therapy in odontogenic infections in children and adolescents: pharmacokinetic/pharmacodynamic analysis]. / Utilización de antimicrobianos en las infecciones odontogénicas en niños y adolescentes: análisis farmacocinético/farmacodinámico (PK/PD).

INTRODUCTION: The objective of this study was to evaluate the efficacy of the most commonly used antimicrobial treatments in odontogenic infections in children and adolescents on the basis of pharmacokinetic/ pharmacodynamic (PK/PD) criteria. METHODS: Unbound drug plasma concentration-time curves were simulated with mean population pharmacokinetic parameters of amoxicillin, co-amoxiclav, cefuroxime axetil, spiramycin, clindamycin, azithromycin, and metronidazole. For drugs showing time-dependent antibacterial killing, the time above MIC90 of the pathogens studied was calculated (T>MIC). For drugs with concentration-dependent bactericidal activity, the area under the concentration-time curve (AUC)/MIC90 ratio was calculated. RESULTS: Adequate efficacy indexes (T>MIC>40%) against all the microorganisms examined with the exception of Veillonella spp. were obtained with co-amoxiclav (80 mg/kg/day). Clindamycin (40 mg/kg/day) obtained adequate PK/PD indexes except for Lactobacillus, Actinobacillus actinomycetemcomitans, penicillin-resistant Peptostreptococcus, and Eikenella corrodens. High-dose amoxicillin yielded unsatisfactory results against many bacterial species. Azithromycin and metronidazole showed inadequate efficacy indexes against the majority of pathogens studied (AUC/MIC90<25). CONCLUSION: When antibiotic therapy is needed for odontogenic infections in children and adolescents, the most active empirical therapeutic choice is co-amoxiclav with high doses of amoxicillin. Clindamycin can be used as an alternative option. These results should be confirmed in clinical trials, in which the PK/PD approach could be useful for the design and assessment of results.

Utilización de antimicrobianos en las infecciones odontogénicas en niños y adolescentes: análisis farmacocinético/farmacodinámico (PK/PD) / Antibiotic therapy in odontogenic infections in children and adolescents: pharmacokinetic/pharmacodynamic analysis

INTRODUCCIÓN. El objetivo de este estudio es evaluar la eficacia de los tratamientos más utilizados en infecciones odontogénicas en niños y adolescentes aplicando criterios farmacocinéticos/farmacodinámicos (PK/PD).MÉTODOS. Se han simulado las curvas de concentración plasmática libre-tiempo a partir de parámetros farmacocinéticos medios de amoxicilina, amoxicilina-ácido clavulánico, cefuroxima axetilo, espiramicina, clindamicina, azitromicina y metronidazol. Para los antibióticos con actividad dependiente del tiempo, se ha calculado el tiempo durante el cual las concentraciones permanecen por encima de la concentración inhibitoria mínima (CIM90)de los microorganismos (T > CIM). Para los antimicrobianos con actividad dependiente de la concentración, se ha calculado el cociente entre el área bajo la curva y la CIM90 (ABC/CIM90).RESULTADOS. Con amoxicilina-ácido clavulánico(80 mg/kg/día) se han obtenido índices de eficacia adecuados frente a los microorganismos estudiados(T > CIM > 40%), excepto para Veillonella spp. Clindamicina (40 mg/kg/día) también ha presentado índices PK/PD adecuados frente a la mayoría de los patógenos, excepto Lactobacillus, Actinobacillus actinomycetemcomitans, Peptostreptococcus resistente a penicilina y Eikenellacorrodens. Con dosis altas de amoxicilina los resultados nohan sido satisfactorios frente a varias especies bacterianas. Con azitromicina y metronidazol no se han alcanzado valores adecuados frente a la mayoría de patógenos (ABC/CIM90 < 25).CONCLUSIÓN. El tratamiento empírico más adecuado en infecciones odontogénicas en niños y adolescentes esamoxicilina-ácido clavulánico en altas dosis de amoxicilina, aunque se puede utilizar como alternativa clindamicina. Sería conveniente confirmar estos resultados mediante ensayos clínicos, para cuyo diseño y evaluación podría serde gran utilidad la aplicación de estudios PK/PD(AU)

INTRODUCTION. The objective of this study was to evaluate the efficacy of the most commonly used antimicrobial treatments in odontogenic infections in children and adolescents on the basis of pharmacokinetic/pharmacodynamic (PK/PD) criteria. METHODS. Unbound drug plasma concentration-time curves were simulated with mean population pharmacokinetic parameters of amoxicillin, co-amoxiclav, cefuroxime axetil, spiramycin, clindamycin, azithromycin, and metronidazole. For drugs showing time-dependent antibacterial killing, the time above MIC90 of the pathogens studied was calculated (T > MIC). For drugs with concentration dependent bactericidal activity, the area under the concentration-time curve (AUC)/MIC90 ratio was calculated. RESULTS. Adequate efficacy indexes (T > MIC > 40%) against all the microorganisms examined with the exception of Veillonella spp. were obtained with co-amoxiclav(80 mg/kg/day). Clindamycin (40 mg/kg/day) obtained ad equate PK/PD indexes except for Lactobacillus, Actinobacillus actinomy cetemcomitans, penicillin-resistant Peptostreptococcus, and Eikenella corrodens. High-dose amoxicillin yielded unsatisfactory results against many bacterial species. Azithromycin and metronidazole showed inadequate efficacy indexes against the majority of pathogens studied (AUC/MIC90 < 25).CONCLUSION. When antibiotic therapy is needed for odontogenic infections in children and adolescents, the most active empirical therapeutic choice is co-amoxiclav with high doses of amoxicillin. Clindamycin can be used as an alternative option. These results should be confirmed inclinical trials, in which the PK/PD approach could be useful for the design and assessment of results (AU)

What are the most appropriate antibiotics for the treatment of acute exacerbation of chronic obstructive pulmonary disease? A therapeutic outcomes model.

OBJECTIVES: To predict the clinical efficacy of several antimicrobials in the treatment of patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS: A probability model (therapeutic outcomes model) was used to predict the likelihood of clinical success with particular antimicrobial agents in the treatment of patients with AECOPD, both in those clinically diagnosed (total patients with an AECOPD diagnosis regardless of the cause) and in those with bacterial AECOPD. The model took into account the following variables: (i) the proportion of patients with a clinical diagnosis of AECOPD and non-bacterial disease; (ii) likelihood of spontaneous resolution of a non-bacterial infection; (iii) prevalence of subcauses (different bacterial species) in bacterial AECOPD; (iv) rates of spontaneous resolution of bacterial AECOPD; and (v) antimicrobial efficacy of each antibiotic against each bacterial species (susceptibility based on PK/PD breakpoints). RESULTS: Fluoroquinolones (levofloxacin, ciprofloxacin and moxifloxacin), a new third-generation oral cephalosporin (cefditoren) and high doses of amoxicillin/clavulanate were the antimicrobials with the highest predicted clinical efficacy both in mild-moderate AECOPD and in severe AECOPD (rates of 89.2% to 90.5% and 80.3% to 88.1%, respectively), whereas cefaclor, azithromycin, erythromycin and clarithromycin had the lowest predicted clinical efficacy (rates of 79.1% to 81.3% and 51.8% to 55.6% for mild-moderate and severe AECOPD, respectively), which was not much higher than that predicted for placebo (73.6% and 45.5%, respectively). CONCLUSIONS: According to our model, fluoroquinolones (levofloxacin, ciprofloxacin and moxifloxacin), cefditoren and amoxicillin/clavulanate are the most appropriate antibiotics for the treatment of patients with AECOPD in terms of predicted clinical efficacy, with wide differences with respect to other antibiotics commonly used in the treatment of these patients, such as clarithromycin and azithromycin.

[Pharmacokinetic/pharmacodynamic analysis of antibiotic therapy in dentistry and stomatology]. / Análisis farmacocinético/farmacodinámico (PK/PD) de la antibioterapia en odontoestomatología.

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.

Pharmacokinetic/pharmacodynamic evaluation of antimicrobial treatments of orofacial odontogenic infections.

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.

Análisis farmacocinético/farmacodinámico (PK/PD)de la antibioterapia en odontoestomatología / Pharmacokinetic/pharmacodynamic analysis of antibiotic therapy in dentistry and stomatology

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)