Optimization of antimicrobial treatment in sepsis

Sepsis represents a serious risk to the life of any patient, which is why it is crucial to start an effective treatment in all its extremes as soon as possible, that is, the chosen antibiotics must have activity against the pathogen that produces the condition and, in addition, they must be dosed considering the patient’s situation in all its extremes. It should be considered that it will be necessary to adjust the dose when there is edema (drugs with reduced volume of distribution), hypoproteinemia (drugs bound to proteins in a high proportion), obesity, and also when they require the use of external techniques such as ECMO or any of the different types of hemodialysis and hemofiltration. (AU)

Pharmacokinetics/Pharmacodynamics and tolerability of cefiderocol in the clinical setting

Cefiderocol is a new cephalosporin with a catechol in its chemical structure faciliting its access to the interior of bacteria through iron channels. In addition, it is broadly stable to beta-lactamases. The pharmacokinetic profile is a beta-lactam one: no oral absorption, and with a wide distribution within the vascular space and the interstitial fluid of well vascularized tissues, reaching therapeutic concentrations in the alveolar lavage fluid and within the macrophage. The binding of cefiderocol to human plasma proteins, primarily albumin, is moderate (range 40-60%). The terminal elimination half-life in healthy adult subjects was 2 to 3 hours. Cefiderocol is mainly renally eliminated, so dose adjustments are recommended in subjects with moderate / severe renal impairment, in case of dialysis, and probably in patients with external clearance. Like other beta-lactams, the PK / PD parameter that has been shown to best correlate with efficacy is the efficacy time of unbound plasma concentrations (%fT>MIC), which must be close to 100% to achieve a bactericidal effect. This is possible with 2 g in a 3-hour infusion every 8 hours. In controlled trials appears to be well tolerated, similar to comparators: meropenem or imipenem-cilastatin. Cefiderocol has no apparent clinically significant effect on ECG parameters nor on plasma iron values. (AU)

[Liposomal amphotericin B: Clinical pharmacology, pharmacokinetics and pharmacodynamics]. / Anfotericina B liposomal: farmacología clínica, farmacocinética y farmacodinamia.

Liposomal amphotericin B is a lipid formulation of the antifungal drug amphotericin B with some distinguishing characteristics in its pharmacological behavior that entail some clinical differences of great interest. The significant improvement in the systemic and renal tolerability is one of them. This fact is related to the great stability of the liposome, promoted by its negative charge, the presence of cholesterol and the remarkable thermo-stability of the remaining lipids that compose it. In this situation, amphotericin B seems to be released from the liposome not spontaneously but when the liposome binds to the ergosterol in the fungal cell membrane. For this reason, there is almost no free amphotericin B in plasma or tissues, although it seems that its availability is greater when there is fungal infection. As a consequence, when the pharmacokinetic behavior is studied, the concentration and availability of liposomal amphotericin B are very high, and its volume of distribution is reduced in comparison with the other formulations.

The pharmacodynamic bases of the prescription of antimicrobials

In the past, the dose of an antibiotic was chosen, always from among those that were well tolerated, by considering those with the ability to exceed the MIC of bacteria in plasma. This approach, which has still not widely changed, is contrasted with the pharmacokinetic and pharmacodynamic (PK/PD) relationships, which indicate that the efficacy of antibiotics is directly related to parameters that relate the sequence of concentrations over time with a parameter of the MIC effect in vitro. Until now, three types of PK/PD relationships have been established for antibiotics: the inhibitory coefficient (Cmax/MIC), the efficacy time (T>CMI) and the relationship between the exposure of the drug and the MIC (AUC/MIC)

No disponible

Ceftobiprole: pharmacokinetics and PK/PD profile

Ceftobiprole shows many similar pharmacokinetic properties to other cephalosporins, except for not being orally bioactive, and that it is administered by IV infusion as the prodrug ceftobiprole medocaril, which is subsequently hydrolyzed in the blood into the active molecule. Distribution focus in extracellular fluid and active antibiotic concentration has been proven in different corporal tissues using dosing regimen of 500 mg intravenous infusion over 2 h every 8 h. Ceftobiprole is eliminated exclusively into the urine, thus the reason why dose adjustment is required for patients with moderate or severe renal impairment, or increased creatinine clearance. However, there is no need for dose adjustments related with other comorbidities and patients' conditions such as age, body weight. Although considering distribution features, molecular weight and dose fraction, increase dosing regimen might be necessary in patients using renal replacement therapy. The half-life of ceftobiprole is more than 3 h, allowing to easily reach optimal PK/PD parameters with the infusion time of 2 h, using the usual dosing regimen

No disponible

Perfil farmacológico del isavuconazol / Pharmacological profile of isavuconazole

El isavuconazol es un nuevo azol, emparentado estructuralmente con el fluconazol y el voriconazol, que presenta una absorción por vía oral muy elevada, sin efecto de primer paso, y que no es interferida por la presencia de alimentos, modificaciones del pH gástrico, ni por la mucositis. Su distribución es muy elevada, probablemente también a líquido cefalorraquídeo, a pesar de que circula en plasma unido a proteínas en un porcentaje importante. Se elimina en su totalidad por el metabolismo mediante la isoenzima CYP3A4, de ahí que se recomiende evitar el uso conjunto de inductores potentes de esta isoenzima. Además, presenta capacidad de inhibir de forma moderada la CYP3A4 y de inducir de forma débil la CYP2B6 y la glucoproteína P. En cualquier caso, esta actividad inhibitoria parece inferior a la que presentan otros azoles, lo que deriva en un uso más sencillo en el manejo de las interacciones con otros fármacos, que es probablemente la ventaja más importante de este antifúngico

Isavuconazole is a new azole, structurally related to fluconazole and voriconazole, that presents a very high oral absorption with no first-pass effect which is not interfered by the presence of food, gastric pH modifications, or mucositis. Its distribution volume is very high, probably also to cerebrospinal fluid, in spite of the fact that it circulates highly bound to plasma proteins. It is extensively metabolized through the CYP3A4 isoenzyme. Due to this reason, it is recommended to avoid co-administration with strong CYP3A4 inducers. In addition, isavuconazole may inhibit CYP3A4. Moreover, it may induce CYP2B6 and P-glycoprotein. Interestingly, this inhibitory activity seems to be lower compared to other azoles. Therefore, the management of any interaction with other medicines is easier, which is probably the most important advantage of this antifungal

[Pharmacological profile of isavuconazole]. / Perfil farmacológico del isavuconazol.

Isavuconazole is a new azole, structurally related to fluconazole and voriconazole, that presents a very high oral absorption with no first-pass effect which is not interfered by the presence of food, gastric pH modifications, or mucositis. Its distribution volume is very high, probably also to cerebrospinal fluid, in spite of the fact that it circulates highly bound to plasma proteins. It is extensively metabolized through the CYP3A4 isoenzyme. Due to this reason, it is recommended to avoid co-administration with strong CYP3A4 inducers. In addition, isavuconazole may inhibit CYP3A4. Moreover, it may induce CYP2B6 and P-glycoprotein. Interestingly, this inhibitory activity seems to be lower compared to other azoles. Therefore, the management of any interaction with other medicines is easier, which is probably the most important advantage of this antifungal.

Equinocandinas: aspectos aplicados de la farmacología / Echinocandins: applied pharmacology

Las equinocandinas comparten las propiedades farmacodinámicas pero presentan algunas diferencias en su comportamiento farmacocinético, cuestión de interés en la práctica asistencial. No se absorben por vía oral. Su distribución en el organismo es un tanto especial ya que alcanzan concentraciones intracelulares elevadas, aunque en alguno de los fármacos puede ser reducida. Se fijan en elevada proporción a proteínas plasmáticas, por lo que al menos en el caso de la anidulafungina y la caspofungina se recomienda la administración de una dosis de carga; es discutible que no se realice con la micafungina. Se eliminan a través del metabolismo no microsómico, por lo que la concentración urinaria es muy reducida. En el proceso de eliminación biliar participan algunas proteínas transportadoras que probablemente son el origen de las interacciones descritas con la caspofungina y la micafungina. Estos dos fármacos han de ser utilizados con precaución en pacientes con alteración grave de la función hepática, pero todos ellos pueden utilizarse sin precauciones especiales cuando existe insuficiencia renal o el paciente precisa la utilización de técnicas de depuración externa (AU)

The echinocandins share pharmacodynamic properties, although there are some interesting differences in their pharmacokinetic behaviour in the clinical practice. They are not absorbed by the oral route. They have a somewhat special distribution in the organism, as some of them can reach high intracellular concentrations while, with some others, the concentration is reduced. They are highly bound to plasma proteins, thus it is recommended to administer a loading dose for anidulafungin and caspofungin, although this procedure is not yet clear with micafungin. Echinocandins are excreted via a non-microsomal metabolism, so the urinary concentration is very low. Some carrier proteins that take part in the biliary clearance process are probably involved in the interactions described with caspofungin and micafungin. These two drugs must be used with caution in patients with severely impaired hepatic function, while all of them can be used without special precautions when there is renal impairment or the patient requires renal replacement therapy (AU)

[Echinocandins: Applied pharmacology]. / Equinocandinas: aspectos aplicados de la farmacología.

The echinocandins share pharmacodynamic properties, although there are some interesting differences in their pharmacokinetic behaviour in the clinical practice. They are not absorbed by the oral route. They have a somewhat special distribution in the organism, as some of them can reach high intracellular concentrations while, with some others, the concentration is reduced. They are highly bound to plasma proteins, thus it is recommended to administer a loading dose for anidulafungin and caspofungin, although this procedure is not yet clear with micafungin. Echinocandins are excreted via a non-microsomal metabolism, so the urinary concentration is very low. Some carrier proteins that take part in the biliary clearance process are probably involved in the interactions described with caspofungin and micafungin. These two drugs must be used with caution in patients with severely impaired hepatic function, while all of them can be used without special precautions when there is renal impairment or the patient requires renal replacement therapy.

[Bacteraemia and infection of the vascular catheter in the haematology patient: positioning and management based on the Delphi method]. / Bacteriemia e infección del catéter vascular en el ámbito hematológico: posicionamiento y actitudes de manejo basados en el método Delphi.

OBJECTIVE: Infectious complications are an important cause of morbidity and mortality in haematological patients with febrile neutropenia. The aim of this study was to develop a consensus document of recommendations to optimize the management of febrile neutropenic patients with haematological or vascular catheter infections in areas where there is no solid scientific evidence. METHODS: After reviewing the scientific evidence, a scientific committee composed of experts in haematology and infectious diseases developed a survey with 55 statements. A two- round modified Delphi method was used to achieve consensus. RESULTS: The online survey was answered by 52 experts in the field of haematology and infectious diseases. After two rounds of evaluation, a consensus was possible in 43 of the 55 statements (78.2%): 40 in agreement and 3 in disagreement. Recommendations are given related to empirical antibiotic treatment of patients with febrile neutropenia, mechanisms of action, toxicity and synergism of antibiotics in this context, modifications of antibiotic treatment in the course of febrile neutropenia, and the management of central vascular catheter infections in the haematological setting. CONCLUSIONS: There is a high degree of agreement among experts on some controversial issues concerning the management of febrile neutropenia and catheter infection in hematologic patients. This agreement has resulted in recommendations that may be useful in clinical practice.

Bacteriemia e infección del catéter vascular en el ámbito hematológico: posicionamiento y actitudes de manejo basados en el método Delphi / Bacteraemia and infection of the vascular catheter in the haematology patient: positioning and management based on the Delphi method

Introducción. Las complicaciones infecciosas son una causa importante de morbi-mortalidad en los pacientes hematológicos con neutropenia febril. El objetivo del presente trabajo fue desarrollar un documento de recomendaciones consensuado para optimizar el manejo del paciente hematológico con neutropenia febril o infecciones por catéteres vasculares en áreas en las que no se dispone de una sólida evidencia científica. Material y métodos. Tras la revisión de las evidencias científico-médicas, un comité científico formado por especialistas expertos en hematología y enfermedades infecciosas elaboró una encuesta con 55 aseveraciones. Para el consenso se utilizó un método Delphi modificado con dos rondas de evaluación. Resultados. La encuesta fue respondida online por 52 especialistas en hematología y en enfermedades infecciosas. Tras las dos rondas de evaluación fue posible el consenso en 43 de los 55 ítems planteados (un 78,2%): 40 en el acuerdo y 3 en el desacuerdo. Con ello, se proporcionan una serie de recomendaciones relativas al tratamiento antibiótico empírico del paciente con neutropenia febril, a cuestiones relacionadas con mecanismos de acción, toxicidad y sinergia de los antibióticos en este contexto, a las modificaciones del tratamiento antibiótico en el curso de la neutropenia febril y al manejo de las infecciones de catéter vascular central en el ámbito hematológico. Conclusiones. Existe un alto grado de acuerdo entre los expertos consultados sobre algunos aspectos controvertidos relativos al manejo de la neutropenia febril y la infección por catéter en pacientes hematológicos. Este acuerdo se ha traducido en unas recomendaciones que pueden ser de utilidad en la práctica clínica (AU)

Introduction. Infectious complications are an important cause of morbidity and mortality in haematological patients with febrile neutropenia. The aim of this study was to develop a consensus document of recommendations to optimize the management of febrile neutropenic patients with haematological or vascular catheter infections in areas where there is no solid scientific evidence. Materials and Methods. After reviewing the scientific evidence, a scientific committee composed of experts in haematology and infectious diseases developed a survey with 55 statements. A two- round modified Delphi method was used to achieve consensus. Results. The online survey was answered by 52 experts in the field of haematology and infectious diseases. After two rounds of evaluation, a consensus was possible in 43 of the 55 statements (78.2%): 40 in agreement and 3 in disagreement. Recommendations are given related to empirical antibiotic treatment of patients with febrile neutropenia, mechanisms of action, toxicity and synergism of antibiotics in this context, modifications of antibiotic treatment in the course of febrile neutropenia, and the management of central vascular catheter infections in the haematological setting. Conclusions. There is a high degree of agreement among experts on some controversial issues concerning the management of febrile neutropenia and catheter infection in hematologic patients. This agreement has resulted in recommendations that may be useful in clinical practice (AU)

[Liposomal amphotericin B: a unique pharmacokinetic profile. An unfinished story]. / Anfotericina B forma liposómica: un perfil farmacocinético exclusivo. Una historia inacabada.

Amphotericin B in its lipid formulation continues to be the reference drug in the treatment of systemic fungal infections despite the time elapse since the development of this compound. The absence of fungal resistance, pharmacokinetics, and the better tolerability profile as compared with the remaining formulations of amphotericin B are sufficient reasons to justify its prominent therapeutic role. The liposome containing liposomal amphotericin B is very stable in relation to the presence of cholesterol and phospholipids are not thermolabile, so that free amphotericin B is almost inexistent (<1%), which explains the reduced incidence of effects related to the drug administration, and a reduction in the incidence of nephrotoxicity (half than that with amphotericin B lipid complex) and that even in some studies at doses of 1 mg/kg has been shown to be negligible. This profile explains the very high plasma drug concentrations and the reduced distribution volume and clearance, with a very prolonged elimination half-life. There are evidences showing that the liposome through amphotericin B is capable of binding to ergosterol present in the fungal membrane and only at this moment would be the antifungal released to exert its pharmacological effects.

Anfotericina B forma liposómica: un perfil farmacocinético exclusivo. Una historia inacabada / Liposomal amphotericin B: a unique pharmacokinetic profile. An unfinished story

La anfotericina B en su formulación liposómica continúa siendo un fármaco de referencia en el tratamiento de las infecciones fúngicas sistémicas a pesar del tiempo transcurrido desde que se desarrolló. La ausencia de resistencias de los hongos, la farmacocinética, y el mejor perfil de tolerabilidad en relación con el resto formulaciones de anfotericina B, son motivos suficientes para justificar su protagonismo, El liposoma que contiene la anfotericina B liposómica es muy estable en relación con la presencia de colesterol y los fosfolípidos no presentan termolabilidad, por ello la anfotericina B apenas está presente en forma libre (<1%) lo que explica la baja incidencia de efectos relacionados con la administración y la reducción de la incidencia de nefrotoxicidad (mitad que con la anfotericina B complejo lipidico) y que incluso en algún estudio a dosis de 1 mg/kg se ha mostrado inexistente. Este perfil justifica concentraciones plasmáticas muy elevadas y un volumen de distribución y aclaramiento reducidos, con una semivida de eliminación muy prolongada. Existen evidencias que señalan que el liposoma a través de la anfotericina B es capaz de fijarse al ergosterol presente en membrana de hongo y sólo en ese momento se produciría la liberación del antifúngico que ejercería su efecto farmacológico(AU)

Amphotericin B in its lipid formulation continues to be the reference drug in the treatment of systemic fungal infections despite the time elapse since the development of this compound. The absence of fungal resistance, pharmacokinetics, and the better tolerability profile as compared with the remaining formulations of amphotericin B are sufficient reasons to justify its prominent therapeutic role. The liposome containing liposomal amphotericin B is very stable in relation to the presence of cholesterol and phospholipids are not thermolabile, so that free amphotericin B is almost inexistent (< 1%), which explains the reduced incidence of effects related to the drug administration, and a reduction in the incidence of nephrotoxicity (half than that with amphotericin B lipid complex) and that even in some studies at doses of 1 mg/kg has been shown to be negligible. This profile explains the very high plasma drug concentrations and the reduced distribution volume and clearance, with a very prolonged elimination half-life. There are evidences showing that the liposome through amphotericin B is capable of binding to ergosterol present in the fungal membrane and only at this moment would be the antifungal released to exert its pharmacological effects(AU)

Recommendations for the treatment of invasive fungal infection caused by filamentous fungi in the hematological patient

El tratamiento antifúngico del paciente hematológico ha alcanzado una gran complejidad con la llegada de nuevos antifúngicos y pruebas diagnósticas que han dado lugar a diferentes estrategias terapéuticas. La utilización del tratamiento más adecuado en cada caso es fundamental en infecciones con tanta mortalidad. La disponibilidad de recomendaciones como éstas, realizadas con la mejor evidencia por un amplio panel de 48 expertos, en las que se intenta responder a cuándo está indicado tratar y con qué hacerlo considerando diferentes aspectos del paciente (riesgo de infección fúngica, manifestaciones clínicas, galactomanano, TC de tórax y profilaxis realizada), puede ayudar a los clínicos a mejorar los resultados(AU)

Antifungal treatment in the hematological patient has reached a high complexity with the advent of new antifungals and diagnostic tests, which have resulted in different therapeutic strategies. The use of the most appropriate treatment in each case is essential in infections with such a high mortality. The availability of recommendations as those here reported based on the best evidence and developed by a large panel of 48 specialists aimed to answer when is indicated to treat and which agents should be used, considering different aspects of the patient (risk of fungal infection, clinical manifestations, galactomanann test, chest CT scan and previous prophylaxis) may help clinicians to improve the results(AU)

[New therapeutic strategies for multiple myeloma. Efficacy and cost-effectiveness analyses]. / Nuevas estrategias terapéuticas en el tratamiento del mieloma múltiple. Análisis de su eficacia y coste-efectividad.

The objective of the present article is the review of the most important therapeutic innovations in the treatment of multiple myeloma in terms of efficacy and cost-effectiveness. Besides autologous transplant with peripheral-blood stem-cell, thalidomide establishes as one of the most powerful therapeutic tools in induction and maintenance treatment and together with lenalidomide and bortezomib as therapy for relapsing/refractory multiple myeloma. Considering, the last named situation thalidomide can be an adequate therapeutical option in combination with dexamethasone. Under a strictly pharmacoeconomic point of view, lenalidomide and bortezomib seem to be additional alternatives in patients previously treated with thalidomide.

Nuevas estrategias terapéuticas en el tratamiento del mieloma múltiple. Análisis de su eficacia y coste-efectividad / New therapeutic strategies for multiple myeloma. Efficacy and cost-effectiveness analyses

El objetivo del presente artículo es revisar las principales innovaciones terapéuticas en el tratamiento del mieloma múltiple, desde el punto de vista de su eficacia y coste-efectividad. Aparte del autotrasplante de progenitores hematopoyéticos, la talidomida se establece como uno de los principales recursos terapéuticos en el tratamiento de inducción y de extensión de la respuesta, conjuntamente con la lenalidomida y el bortezomib en el tratamiento de rescate en el mieloma múltiple refractario/recidivante. Con respecto al tratamiento de este último, la talidomida puede ser una opción adecuada en combinación con la dexametasona. Desde un punto de vista estrictamente farmacoeconómico, la lenalidomida y el bortezomib constituyen alternativas especialmente válidas en pacientes tratados previamente con talidomida

The objective of the present article is the review of the most important therapeutic innovations in the treatment of multiple myeloma in terms of efficacy and cost-efectiveness. Besides autologous transplant with peripheral-blood stem-cell, thalidomide establishes as one of the most powerful therapeutic tools in induction and maintenance treatment and together with lenalidomide and bortezomib as therapy for relapsing/refractory multiple myeloma. Considering, the last named situation thalidomide can be an adequate therapeutical option in combination with dexamethasone. Under a strictly pharmacoeconomic point of view, lenalidomide and bortezomib seem to be additional alternatives in patients previously treated with thalidomide (AU)

[Fosfomycin trometamol: multiple-dose regimen for the treatment of lower urinary tract infections]. / Fosfomicina trometamol. Dosis múltiples como pauta larga en el tratamiento de las infecciones urinarias bajas.

INTRODUCTION: A short antibiotic regimen is recommended for the treatment of uncomplicated lower urinary tract infection. Nevertheless, the treatment to follow in other situations is not so clearly defined. When the person affected by lower urinary tract infection is not a young woman, it is recommended to treat at least 7 days, and quinolones or cotrimoxazole are the antibiotics most often used. However, because of the frequency of drug resistance in this type if infection, it is advisable to apply antibiotics with lower rates of resistance, such as fosfomycin trometamol, for longer treatment periods than the often-used single dose. METHODS: Using the data on urinary elimination of fosfomycin after a single dose obtained in a prior study in healthy volunteers, we simulated the urinary concentrations of this antibiotic following administration of two doses. In addition, we calculated the interval of administration required to achieve urinary concentrations greater than 16 mg/L, the critical concentration of sensitivity for Escherichia coli, one of the most commonly implicated microorganisms in these infections. RESULTS: Fosfomycin concentrations in urine persisted above the defined cut-off for 161 hours after administration of two 3-g doses of fosfomycin trometamol, 72 hours apart. This implied an efficacy time of 66% in a period of 7 days. CONCLUSION: From the pharmacokinetic viewpoint, the optimum dosage of fosfomycin trometamol to achieve appropriate urinary concentrations along 7 days is administration of two 3-g doses, 72 hours apart.

Fosfomicina trometamol. Dosis múltiples como pauta larga en el tratamiento de las infecciones urinarias bajas / Fosfomycin trometamol: Multiple-dose regimen for the treatment of lower urinary tract infections

Introducción. El tratamiento de las infecciones urinarias del tracto inferior no complicadas se realiza con pautas de tratamiento cortas. En otras circunstancias no está tan clara la pauta que hay que seguir. Cuando la infección urinaria del tracto inferior no se produce en una mujer joven, la recomendación terapéutica es la utilización de antibióticos durante al menos 7 días, y son las quinolonas y el cotrimoxazol los antibióticos utilizados con mayor frecuencia. Pero debido al porcentaje de resistencias de los microorganismos implicados en este tipo de infecciones, es aconsejable evaluar otras pautas de tratamiento, de forma que habría que evaluar, entre otros, el uso de antibióticos con un menor índice de resistencias como fosfomicina trometamol, en períodos de tratamiento más largos que el uso tan extendido en dosis única. Métodos. Desde los datos de eliminación urinaria de fosfomicina obtenidos en voluntarios sanos en un estudio previo, se han simulado las concentraciones de este antibiótico en orina tras la administración de 2 dosis. Se ha calculado el intervalo más idóneo para mantener concentraciones urinarias por encima del punto de corte de Escherichia coli para fosfomicina (16 mg/l), uno de los microorganismos implicados con mayor frecuencia en este tipo de infecciones. Resultados. Las concentraciones de fosfomicina en orina se mantienen por encima del punto de corte durante 161 h cuando se administran 2 dosis de 3 g de fosfomicina trometamol separadas 72 h. Éste supone un tiempo de eficacia del 96% en un período total de 7 días. Conclusión. La pauta teórica, desde el punto de vista farmacocinético, para conseguir concentraciones de fosfomicina en orina por encima del punto de corte de E. coli es la administración de 2 dosis de 3 g de fosfomicina trometamol separadas 72 h (AU)

Introduction. A short antibiotic regimen is recommended for the treatment of uncomplicated lower urinary tract infection. Nevertheless, the treatment to follow in other situations is not so clearly defined. When the person affected by lower urinary tract infection is not a young woman, it is recommended to treat at least 7 days, and quinolones or cotrimoxazole are the antibiotics most often used. However, because of the frequency of drug resistance in this type if infection, it is advisable to apply antibiotics with lower rates of resistance, such as fosfomycin trometamol, for longer treatment periods than the often-used single dose. Methods. Using the data on urinary elimination of fosfomycin after a single dose obtained in a prior study in healthy volunteers, we simulated the urinary concentrations of this antibiotic following administration of two doses. In addition, we calculated the interval of administration required to achieve urinary concentrations greater than 16 mg/L, the critical concentration of sensitivity for Escherichia coli, one of the most commonly implicated microorganisms in these infections. Results. Fosfomycin concentrations in urine persisted above the defined cut-off for 161 hours after administration of two 3-g doses of fosfomycin trometamol, 72 hours apart. This implied an efficacy time of 66% in a period of 7 days. Conclusion. From the pharmacokinetic viewpoint, the optimum dosage of fosfomycin trometamol to achieve appropriate urinary concentrations along 7 days is administration of two 3-g doses, 72 hours apart (AU)