Dalbavancin as sequential therapy in infective endocarditis: Real-life experience in elder and comorbid patients.

OBJECTIVES: This study aimed to evaluate the effectiveness of dalbavancin as sequential therapy in patients with infective endocarditis (IE) due to gram positive bacteria (GPB) in a real-life heterogenous cohort with comorbid patients. METHODS: A single center retrospective cohort study including all patients with definite IE treated with dalbavancin between January 2017 and February 2022 was developed. A 6-month follow-up was performed. The main outcomes were clinical cure rate, clinical and microbiological relapse, 6-month mortality, and adverse effects (AEs) rate. RESULTS: The study included 61 IE episodes. The median age was 78.5 years (interquartile range [IQR] 63.2-85.2), 78.7% were male, with a median Charlson comorbidity index of 7 (IQR 4-9) points. Overall, 49.2% suffered native valve IE. The most common microorganism was Staphylococcus aureus (26.3%) followed by Enterococcus faecalis (21.3%). The median duration of initial antimicrobial therapy and dalbavancin therapy were 27 (IQR 20-34) and 14 days (IQR 14-28) respectively. The total reduction of hospitalization was 1090 days. The most frequent dosage was 1500mg of dalbavancin every 14 days (96.7%). An AE was detected in 8.2% of patients, only one (1.6%) was attributed to dalbavancin (infusion reaction). Clinical cure was achieved in 86.9% of patients. One patient (1.6%) with Enterococcus faecalis IE suffered relapse. The 6-month mortality was 11.5%, with only one IE-related death (1.6%). CONCLUSION: This study shows a high efficacy of dalbavancin in a heterogeneous real-world cohort of IE patients, with an excellent safety profile. Dalbavancin allowed a substantial reduction of in-hospital length of stay.

Dalbavancin as consolidation antibiotic treatment in infective endocarditis, cardiac implantable electronic devices infection and bacteremia: Clinical experience of 7 years.

INTRODUCTION: Dalbavancin (DBV), a novel lipoglycopeptide with activity against Gram-positive bacterial infections, is approved for the treatment of acute bacterial skin and skin structure infections (ABSSSIs). It has linear dose-related pharmacokinetics allowing a prolonged interval between doses. It would be a good option for the treatment of patients with Gram-positive cardiovascular infections. METHODS: Retrospective analysis of patients with cardiovascular infection (infective endocarditis, bacteremia, implantable electronic device infection) treated with DBV at Hospital Clínico San Carlos (Madrid) for 7 years (2016-2022). Patients were divided in two study groups: 1) Infective endocarditis (IE), 2) Bacteremia. Epidemiological, clinical, microbiological and therapeutic data were analyzed. RESULTS: A total of 25 patients were treated with DBV for cardiovascular infection. IE was the most common indication (68%), followed by bacteremia (32%) with male predominance in both groups (64% vs 62%) and median age of 67,7 and 57,5 years, respectively. 100% of blood cultures were positive to Gram-positive microorganisms (Staphylococcus spp., Streptococcus spp. or Enterococcus spp.) in both study groups. Previously to DBV, all patients received other antibiotic therapy, both in the group of IE (median: 80 days) as in bacteremia (14,8 days). The main reason for the administration of DBV was to continue intravenous antimicrobial therapy outside the hospital in both the EI group (n = 15) and the bacteremia group (n = 8). DBV was used as consolidation therapy in a once- or twice-weekly regimen. Microbiological and clinical successes were reached in 84% of cases (n = 21), 76,4% in IE group and 100% in bacteremia group. No patient documented adverse effects during long-term dalbavancin treatment. CONCLUSION: DBV is an effective and safety treatment as consolidation antibiotic therapy in IE and bacteremia produced by Gram-positive microorganisms.

Addressing catheter lock therapy: Does heparin reduce the bioactivity of dalbavancin when together in solution during freezing?

INTRODUCTION: The possible use of dalbavancin as a catheter lock solution was previously demonstrated by our study group. However, it was needed to assess whether heparin could affect dalbavancin bioactivity during freezing storage. METHODS: We tested the bioactivity of a dalbavancin+heparin (DH) vs. dalbavancin (D) against Staphylococcal biofilms comparing DH median value of cfu counts and metabolic activity with that obtained for D before and during storage under freezing up to 6 months. RESULTS: Despite there was a slight decrease in the median percentage reduction of metabolic activity at month 3 in Staphylococcus epidermidis between DH and D (97.6 vs. 100, p=0.037), considering the clinical criteria, no significant reduction in any of the variables tested was observed at the end of the experiment between D and DH solutions. CONCLUSION: The addition of heparin to a dalbavancin lock solution did not affect its bioactivity against staphylococcal biofilms irrespective of its preservation time under freezing.

In vitro activity of ceftobiprole and dalbavancin against a collection of coagulase-negative staphylococci isolates from clinical samples with reduced susceptibility to daptomycin and/or resistant to linezolid or glycopeptides / Evaluación de la actividad in vitro de ceftobiprol y dalbavancina frente a estafilococos coagulasa negativos con sensibilidad disminuida a daptomicina y/o resistentes a linezolid o glucopéptidos aislados de muestras clínicas

Introduction:The aim was to investigate the in vitro activity of ceftobiprole and dalbavancin against a collection of coagulase-negative staphylococci (CoNS) isolates with reduced susceptibility to daptomycin or resistant to linezolid and/or glycopeptides. Methods: A total of 228 CoNS were tested using the Vitek-2 AST-626 cards (bioMérieux) and MIC of daptomycin, linezolid, vancomycin and teicoplanin were confirmed by Etest Strips (bioMérieux). Susceptibility testing for ceftobiprole and dalbavancin were performed by CLSI broth microdilution methodology. Results were interpreted according to 2021 EUCAST clinical breakpoints. Results: Ceftobiprole and dalbavancin were active against 96.0% and 93.0% of CoNS, respectively, MIC90 were 2 and 0.125mg/L. MICs of ceptobiprole were higher against S. hominis and S. haemolyticus (MIC90 4mg/L). Dalbavancin exhibited higher MICs against S. haemolyticus and CoNS with reduced susceptibility to daptomycin and resistant to teicoplanin. Conclusion: Ceftobiprole and dalbavancin demonstrated a high in vitro activity against our collection of CoNS isolates.(AU)

Introducción: El objetivo fue evaluar la actividad in vitro de dalbavancina y ceftobiprol frente a estafilococos coagulasa negativos (ECN) con sensibilidad disminuida a daptomicina y/o resistentes a linezolid o glucopéptidos. Métodos: Se testó la sensibilidad de 228 ECN con tarjetas VITEK®2 AST-626 (bioMérieux) y las CMI de daptomicina, linezolid, vancomicina y teicoplanina fueron confirmadas con tiras Etest® (bioMérieux). El ensayo de sensibilidad frente a ceftobiprol y dalbavancina se realizó mediante microdilución en caldo (metodología CLSI). Los resultados se interpretaron siguiendo los puntos de corte de EUCAST 2021. Resultados: Ceftobiprol y dalbavancina fueron activos en el 96,0 y 93% de ECN, las CMI90 fueron 2 y 0,125mg/L, respectivamente. Las CMI de ceftobiprol fueron superiores en Staphylococcus hominis y Staphylococcus haemolyticus (CMI90 4mg/L). Dalbavancina exhibió mayores CMI en S. haemolyticus y en ECN con sensibilidad disminuida a daptomicina o resistentes a teicoplanina. Conclusión: Ceftobiprol y dalbavancina han demostrado una potente actividad in vitro frente a esta colección de ECN.(AU)

Efectividad y eficiencia de la dalbavancina en condiciones reales de uso / Effectiveness and efficiency of dalbavancin in real clinical practice use

Objetivos: El tratamiento de las infecciones por Gram positivos supone un reto asistencial, en un contexto en el que están aumentando las resistencias antibióticas. La dalbavancina, gracias a su alta vida media y alta actividad frente a Gram positivos, puede ser una buena opción terapéutica. Nuestros objetivos son conocer los usos, efectividad y eficiencia de la dalbavancina en pacientes del Hospital General Universitario de Valencia. Métodos: Se realiza un estudio descriptivo retrospectivo y un análisis de costes de los pacientes tratados con dalbavancina en el Hospital General Universitario de Valencia. Resultados: 15 pacientes (con 17 episodios de infección) fueron incluidos, con un Charlson medio de 3,7. Se trataron 4 infecciones de piel y partes blandas, 6 infecciones osteoarticulares y 7 infecciones intravasculares, aislándose en el 70,6% de los casos un Gram positivo. La tasa de curación fue del 59%, sin efectos adversos por la dalbavancina ni exitus en relación con la infección. Se evitaron 239 días de hospitalización, lo cual supone un ahorro de 6.556,02 € por paciente. Conclusiones: Series clínicas como la actual permiten analizar el papel de la dalbavancina en la práctica médica habitual y demuestran su importante función en el ahorro de recursos económicos. (AU)

Objectives: The treatment of Gram-positive infections it’s a medical challenge, in a context in which antibiotic resistances are increasing. Dalbavancin, due to its long half-life and high activity against Gram-positive bacteria, could be a good therapeutic option. Our objectives are to know the uses, effectiveness and efficiency of dalbavancin in patients of the General University Hospital of Valencia. Methods: A retrospective descriptive study and a cost analysis of patients treated with dalbavancin are carried out at the General University Hospital of Valencia. Results: 15 patients (with 17 episodes of infection) were included, with a mean Charlson index of 3.7. Were treated 4 skin and soft tissue infections, 6 osteoarticular infections and 7 intravascular infections. A Gram-positive bacteria was isolated in 70.6% of the patients. The cure rate was 59%, with no adverse effects due to dalbavancin or death in relation to infection. 239 days of hospitalization were saved with outpatient treatment, which means a saving of € 6,556.02 per patient. Conclusions: Clinical series like ours allow us to analyse the role of dalbavancin in routine medical practice and demonstrate its important function in saving economic resources. (AU)

In vitro activity of ceftobiprole and dalbavancin against a collection of coagulase-negative staphylococci isolates from clinical samples with reduced susceptibility to daptomycin and/or resistant to linezolid or glycopeptides.

INTRODUCTION: The aim was to investigate the in vitro activity of ceftobiprole and dalbavancin against a collection of coagulase-negative staphylococci (CoNS) isolates with reduced susceptibility to daptomycin or resistant to linezolid and/or glycopeptides. METHODS: A total of 228 CoNS were tested using the Vitek-2 AST-626 cards (bioMérieux) and MIC of daptomycin, linezolid, vancomycin and teicoplanin were confirmed by Etest Strips (bioMérieux). Susceptibility testing for ceftobiprole and dalbavancin were performed by CLSI broth microdilution methodology. Results were interpreted according to 2021 EUCAST clinical breakpoints. RESULTS: Ceftobiprole and dalbavancin were active against 96.0% and 93.0% of CoNS, respectively, MIC90 were 2 and 0.125mg/L. MICs of ceptobiprole were higher against S. hominis and S. haemolyticus (MIC90 4mg/L). Dalbavancin exhibited higher MICs against S. haemolyticus and CoNS with reduced susceptibility to daptomycin and resistant to teicoplanin. CONCLUSION: Ceftobiprole and dalbavancin demonstrated a high in vitro activity against our collection of CoNS isolates.

Utilización de antibióticos restringidos en la práctica clínica: ceftolozano/tazobactam, ceftazidima/avibactam, ceftarolina y dalbavancina / Use of restricted antibiotics in clinical practice: ceftolozane/tazobactam, ceftazidime/avibactam, ceftaroline and dalbavancin

Objetivo: Evaluar la utilización en la práctica clínica de cuatro antibióticos de amplio espectro o innovadores: ceftolozano/tazobactam, ceftazidima/avibactam, ceftarolina y dalbavancina. Métodos: Estudio retrospectivo en que se han recogido datos de los pacientes que han recibido dichos antibióticos entre julio de 2018 y junio de 2019 en un hospital terciario. Se recogen las condiciones de uso y los resultados en efectividad a los 30 días para dalbavancina, y para el resto de antimicrobianos a los 3-5 días del inicio, a los 14 y a los 30 días para determinar mortalidad. Resultados: Se recogieron datos de 51 pacientes, con una mediana de edad de 63 años. La infección más comúnmente tratada fue neumonía (41,2%). Tres pacientes (5,9%) recibieron la terapia en estudio como primera línea y 43 (84,3%) recibieron antibióticos concomitantes. En el 66,7% de las infecciones se había aislado previamente un microorganismo sensible. En el 19,6% de los casos el cultivo fue negativo. En el grupo dalbavancina, el 75% de los pacientes se curaron a los 30 días. En el resto de antimicrobianos, el tratamiento resultó efectivo a los 3-5 días en el 65,1%. El 51,2% se curaron a los 14 días y un 30,2% fallecieron a los 30 días. Conclusiones: Los resultados de efectividad resultan comparables a estudios publicados con diseños similares. Se detecta la importancia de fomentar un uso adecuado de los antibióticos, como tratamientos dirigidos o empíricos en casos de riesgo de resistencias, priorizando su desescalada. Es esencial la implantación de equipos multidisciplinares PROA. (AU)

Objective: To evaluate the use in clinical practice of four recently marketed antibiotics: ceftolozane/tazobactam, ceftazidime/avibactam, ceftaroline, and dalbavancin. Methods: Retrospective study in which data have been collected from patients who have received these antibiotics between July 2018 and June 2019, in a third-level hospital. The conditions of use and the results in clinical efficacy measured in three periods have been studied: 3-5 days after the start of treatment, 14 days and 30 days to determine mortality. Results: Data were collected from a total of 51 patients, with a median age of 63 years. The most commonly treated infection was pneumonia (41.2%). Three patients (5.9%) received study therapy as the first line of treatment and 43 (84.3%) received concomitant antibiotics. In 66.7% of the infections, a sensitive microorganism to the antibiotic under study had been previously isolated. In 19.6% of the cases, the culture was negative. In the dalbavancin group, 75% of the pacients cured at day 30. In the other groups, the treatment was effective at 3-5 days in 65.1% of the cases. 51.2% experienced clinical cure at 14 days and 30.2% died at 30 days. Conclusions: The effectiveness results are comparable to published studies with similar designs. The importance of promoting an adequate use of antibiotics is detected, as directed or empirical treatments in cases of risk of resistance, prioritizing their de-escalation. The implementation of multidisciplinary PROA teams is essential. (AU)

Experiencia con el uso de dalbavancina en la infección profunda de pie diabético / Experience in the use of dalbavancin in diabetic foot infection

Objetivo: Describir la experiencia clínica con dalbavancina en el tratamiento de la infección de pie diabético en una unidad multidisciplinar de un hospital de segundo nivel. Métodos: Estudio descriptivo retrospectivo de pacientes con infección de pie diabético tratados con dalbavancina en la Unidad de Pie Diabético del Hospital Universitario Fundación Alcorcón de septiembre de 2016 a diciembre de 2019. Se recogieron parámetros demográficos y comorbilidades, características de la infección y del tratamiento con dalbavancina. Se estimó la tasa de curación a los 90 días tras finalizar el tratamiento. Resultados: Un total de 23 pacientes con infección de pie diabético (osteomielitis) fueron tratados con dalbavancina; 19 eran hombres con una edad media de 65 años. Los microorganismos más frecuentemente aislados fueron Staphylococcus aureus (11) y Corynebacterium striatum (7). En 22 casos se usó dalbavancina como terapia de segunda elección, en 11 debido a toxicidad de otros antibióticos. La mediana de duración del tratamiento fue de 5 (4-7) semanas; la dosis más frecuente de dalbavancina (8 pacientes) fue de 1.000mg seguido de 500mg semanales durante 5 semanas. Tres pacientes presentaron efectos secundarios leves (náuseas y molestias gastrointestinales). A los 90 días de finalizar el tratamiento, el 87% (20) de los pacientes se curaron (IC95%: 65,2-94,52%). Conclusión: Los pacientes con osteomielitis por microorganismos grampositivos que recibieron como parte del tratamiento multidisciplinar antibioterapia con dalbavancina tuvieron una elevada tasa de curación, con una adecuada tolerancia y escasos efectos secundarios. Dalbavancina ofrece una alternativa segura en el tratamiento de la infección profunda de pie diabético.(AU)

Objective: To describe the clinical experience with dalbavancin in the treatment of diabetic foot infection in a multidisciplinary unit of a second level hospital. Methods: A retrospective, descriptive study was made with all patients with diabetic foot infection treated with dalbavancin in the Diabetic Foot Unit of Hospital Universitario Fundación Alcorcón, covering the period from September 2016 to December 2019. Demographic parameters and comorbidities, characteristics of the infection and treatment with dalbavancin were recorded. The cure rate was estimated at 90 days after finishing the treatment. Results: A total of 23 patients with diabetic foot infection (osteomyelitis) started treatment with dalbavancin, 19 were men and the mean age was 65 years. The microorganisms most frequently isolated for the indication of treatment with dalbavancin were Staphylococcus aureus (11) and Corynebacterium striatum (7). Dalbavancin was used as a second choice therapy in 22 cases, in 11 due to toxicity from other antibiotics. The median duration of treatment was 5 (4-7) weeks; the most frequent dose of dalbavancin (8 patients) was 1000mg followed by 500mg weekly for 5 weeks. 3 patients presented mild side effects (nausea and gastrointestinal discomfort). At 90 days after completion of dalbavancin therapy, 87% (20) of the patients were cured (95% CI: 65.2%-94.52%). Conclusion: Patients with osteomyelitis due to gram-positive microorganisms who received as part of the multidisciplinary antibiotic treatment with dalbavancin, had a high rate of cure with adequate tolerance and few side effects. Dalbavancin offers a safe alternative in treating deep diabetic foot infection.(AU)

Experience in the use of dalbavancin in diabetic foot infection.

OBJECTIVE: To describe the clinical experience with dalbavancin in the treatment of diabetic foot infection in a multidisciplinary unit of a second level hospital. METHODS: A retrospective, descriptive study was made with all patients with diabetic foot infection treated with dalbavancin in the Diabetic Foot Unit of Hospital Universitario Fundación Alcorcón, covering the period from September 2016 to December 2019. Demographic parameters and comorbidities, characteristics of the infection and treatment with dalbavancin were recorded. The cure rate is estimated at 90 days after finishing the treatment. RESULTS: A total of 23 patients with diabetic foot infection (osteomyelitis) started treatment with dalbavancin, 19 were men and the mean age was 65 years. The microorganisms most frequently isolated for the indication of treatment with dalbavancin were Staphylococcus aureus (11) and Corynebacterium striatum (7). Dalbavancin was used as a second choice therapy in 22 cases, in 11 due to toxicity from other antibiotics. The median duration of treatment was 5 (4-7) weeks; the most frequent dose of dalbavancin (8 patients) was 1000 mg followed by 500 mg weekly for 5 weeks. 3 patients presented mild side effects (nausea and gastrointestinal discomfort). At 90 days after completion of dalbavancin therapy, 87% (20) of the patients were cured (95% CI: 65.2%-94.52%). CONCLUSION: Patients with osteomyelitis due to gram-positive microorganisms who received as part of the multidisciplinary antibiotic treatment with dalbavancin, had a high rate of cure with adequate tolerance and few side effects. Dalbavancin offers a safe alternative in treating deep diabetic foot infection.

Experience in the use of dalbavancin in diabetic foot infection. / Experiencia con el uso de dalbavancina en la infección profunda de pie diabético.

OBJECTIVE: To describe the clinical experience with dalbavancin in the treatment of diabetic foot infection in a multidisciplinary unit of a second level hospital. METHODS: A retrospective, descriptive study was made with all patients with diabetic foot infection treated with dalbavancin in the Diabetic Foot Unit of Hospital Universitario Fundación Alcorcón, covering the period from September 2016 to December 2019. Demographic parameters and comorbidities, characteristics of the infection and treatment with dalbavancin were recorded. The cure rate was estimated at 90 days after finishing the treatment. RESULTS: A total of 23 patients with diabetic foot infection (osteomyelitis) started treatment with dalbavancin, 19 were men and the mean age was 65 years. The microorganisms most frequently isolated for the indication of treatment with dalbavancin were Staphylococcus aureus (11) and Corynebacterium striatum (7). Dalbavancin was used as a second choice therapy in 22 cases, in 11 due to toxicity from other antibiotics. The median duration of treatment was 5 (4-7) weeks; the most frequent dose of dalbavancin (8 patients) was 1000mg followed by 500mg weekly for 5 weeks. 3 patients presented mild side effects (nausea and gastrointestinal discomfort). At 90 days after completion of dalbavancin therapy, 87% (20) of the patients were cured (95% CI: 65.2%-94.52%). CONCLUSION: Patients with osteomyelitis due to gram-positive microorganisms who received as part of the multidisciplinary antibiotic treatment with dalbavancin, had a high rate of cure with adequate tolerance and few side effects. Dalbavancin offers a safe alternative in treating deep diabetic foot infection.

Dalbavancina como tratamiento prolongado de rescate en infección protésica articular / Dalbavancin as prolonged-salvage treatment in prosthetic joint infection

Dalbavancina es un agente antibacteriano perteneciente al grupo de los lipoglicopéptidos semisintéticos de larga vida media, con gran actividad sobre microorganismos grampositivos y con un perfil de efectos adversos aceptable. Hasta la fecha, ha sido autorizada para el tratamiento de infecciones de piel y tejidos blandos en adultos, sin indicación en infecciones de hueso y articulaciones.La mayoría de los casos de infección protésica articular descritos en la literatura con dalbavancina en tratamiento prolongado, han sido durante un periodo no superior a 4 semanas.Se describen una serie de casos de infección osteoarticular de material protésico tratados de forma prolongada y como rescate con dalbavancina. (AU)

Dalbavancin is an antibacterial agent that belongs to the group of semi-synthetic lipoglicopeptides of long half-life, with great activity in gram-positive microorganisms and with an acceptable adverse effects profile. To date, it has been authorized for the treatment of skin and soft tissue infections in adults, with no indication of bone and joint infections.Most cases of joint prosthetic infection described in the literature with dalbavancin in prolonged treatment have been for a period not exceeding 4 weeks.A series of cases of prosthetic joint infection treated for a long time and as salvage with dalbavancin are described. (AU)

Septic arthritis in a native knee due to Corynebacterium striatum. / Artritis séptica de rodilla nativa por Corynebacterium striatum.

We describe a case of septic arthritis in a native knee due to Corynebacterium striatum, gram-positive bacilli that are usually commensal organisms of skin and mucosal membranes, but are seldom implicated in native septic arthritis. An 84-year-old man with Corynebacterium striatum septic arthritis of his native left knee and no response to conventional antibiotic therapy. Thus, the patient was allowed to take dalbavancin for compassionate use, with an excellent clinical outcome. This case emphasizes de role of Corynebacterium striatum in native joint infections and highlights the importance of early detection and appropriate treatment in improving the clinical outcome.

[Dalbavancin breakpoints and recommendations for in vitro study of its activity]. / Puntos de corte de dalbavancina y recomendaciones para el estudio de su actividad in vitro.

Dalbavancin is a semisynthetic lipoglycopeptide approved for the treatment of acute skin and soft tissue infections due to Gram-positive microorganisms susceptible to this antimicrobial agent. The FDA (Food and Drug Administration) and the EUCAST (European Committee on Antimicrobial Susceptibility Testing) have established clinical breakpoints to interpret the results of the antibiogram (expressed as MIC [minimum inhibitory concentration]) with approved doses (1g intravenously [IV] followed by 0.5g IV at day 8 or 1.5g IV in a single dose). The EUCAST has also determined PK/PD (pharmacokinetic/pharmacodynamic) breakpoints -susceptible, ≤ 0.25mg/L; resistant, > 0.25mg/L-, established recommendations for in vitro susceptibility testing (addition of polysorbate-80 to the growth media) and subrogate values based on the vancomycin-susceptible category to interpret dalbavancin susceptibility in the absence of in vitro study of this antimicrobial.

[Update on antibiotic resistance in Gram-positive bacteria]. / Actualización en la resistencia antibiótica en Gram positivos.

Antimicrobial resistance among Gram-positive bacteria, especially in Staphylococcus aureus, Enterococcus faecium, Enterococcus faecalis, and Streptococcus pneumoniae, is a serious threat to public health. These microorganisms have multiple resistance mechanisms to agents currently used in clinical practice. Many of these resistance mechanisms are common to all 4 of these bacterial species, but other mechanisms seem to be more specific. The prevalence and dissemination of these mechanisms varies considerably, depending on the microorganism. This review discusses the resistance mechanisms to the most clinically relevant antibiotics, with particular emphasis on the new mechanisms described for widely used antibiotics and for newer agents such as lipopeptides, lipoglycopeptides, glycylcyclines and oxazolidinones.

[Analysis of dalbavancin in animal models]. / Análisis de dalbavancina en modelos experimentales.

Multiresistant Gram-positive infections continue to pose a major clinical challenge and the development of new antibiotics is always desirable. Dalbavancin is a lipoglycopeptide with a prolonged half-life that allows long dosing intervals. In experimental models, its activity has been evaluated in distinct models and microorganisms, which limits the conclusions that can be drawn; however, the largest number of studies have been conducted in Staphylococcus aureus infection. Overall, dalbavancin has shown concentration-dependent efficacy and the parameters best explaining its activity are maximal pharmacodynamic concentration/minimal inhibitory concentration and the area under the curve/minimal inhibitory concentration. In these experimental models, dalbavancin has shown good distribution, a prolonged half-life in all animal species and efficacy that is mostly similar to that of previous glycopeptides but with lower doses and with longer dosing intervals. Of note, the efficacy of dalbavancin is not altered by methicillin resistance or the glycopeptide sensitivity of S. aureus. In the case of difficult-to-treat staphylococcal infections (eg, endocarditis, foreign body infections), an adequate dosing interval and high dosage seem to play an important role in the efficacy of the drug. All in all, experimental models can still provide greater knowledge of this new antibiotic to guide clinical research and determine its role in the treatment of distinct infections produced by Gram-positive microorganisms.

[Dalbavancin: pharmacokinetic and pharmacodynamic parameters]. / Dalbavancina: parámetros farmacocinéticos y farmacodinámicos.

Dalbavancin is a new lipoglycopeptide antibiotic whose structure influences its pharmacokinetic profile. It is not absorbed after oral administration and is therefore administered intravenously. It is distributed through intracellular fluid, reaching adequate concentrations in the skin, bone, blister fluid and synovial fluid. Plasma protein binding is very high. Concentrations in brain tissue and cerebrospinal fluid (CSF) are inadequate. Excretion is through non-microsomal metabolism with inactive metabolites and through the kidneys by glomerular filtration. Dalbavancin is eliminated slowly, as shown by its clearance value and its terminal elimination half-life, which exceeds 300 hours. This means that adequate concentrations of the drug remain in plasma and tissues for a prolonged period and explains the dosing regimen: a first dose of 1g followed 7 days later by a 500mg dose. The pharmacokinetics are linear and show little intra- and interindividual variability. There are no pharmacokinetic interactions. Dose adjustment is not required for patients with mild or moderate renal insufficiency (creatinine clearance ≥ 30 to 79ml/min). Dosage adjustment is not required in patients regularly receiving elective haemodialysis (3 times/week) and the drug can be administered without consideration of haemodialysis times. In patients with chronic renal insufficiency, whose creatinine clearance is < 30ml/min and who are not regularly receiving elective haemodialysis, the recommended dose should be reduced to 750mg per week, followed 1 week later by 375mg. Dosage adjustment does not seem necessary in patients with liver failure or in older patients. There is no information on the most appropriate dosage in children. The pharmacokinetic/pharmacodynamics parameter that best describes the effectiveness of dalbavancin is the ratio between the area under the curve and the minimum inhibitory concentration.

[Evaluation of clinical evidence for dalbavancin]. / Evaluación de la evidencia clínica con dalbavancina.

Gram-positive infections are currently a therapeutic challenge because of the emergence of strains resistant to first-line antibiotics. Consequently, in the last few years, new antibiotics have been developed with activity against multiresistant Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and strains with intermediate sensitivity to vancomycin. Among the new antibiotics approved for the treatment of these microorganisms, dalbavancin is a semisynthetic lipoglycopeptide derived from teicoplanin, but has a superior efficacy profile to the latter. Studies published to date have confirmed the efficacy, safety and tolerability of dalbavancin in the treatment of skin and soft tissue infections caused by Gram-positive microorganisms sensitive to this drug and position it as a therapeutic option in Gram-positive catheter-related sepsis. Dalbavancin has an excellent safety profile and pharmacokinetics that allow its intravenous administration in a single weekly dose, making it a therapeutic option for outpatient use. Dalbavancin could also be an attractive alternative for patients requiring prolonged antibiotic therapy, with the aim of avoiding the need for a permanent intravenous line and its associated risks, such as infection and/or septic thrombophlebitis.

[Potential indications of dalbavancin in clinical practice]. / Potenciales indicaciones de dalbavancina en la práctica clínica.

Dalbavancin is a semisynthetic lipoglycopeptide with two properties that distinguish it from other members of the antibiotic family from which it is derived: a greater intrinsic activity and a very prolonged mean half-life that allows weekly or twice-weekly dosing with a single 1000mg or 1500mg dose, respectively. Because of this half-life, dalbavancin is a unique antibiotic. This drug allows the design of new treatment strategies that facilitate early hospital discharge without the need for vascular access and with guaranteed treatment adherence. Dalbavancin could be used to resolve some of the problems that commonly occur in the management of infections in daily clinical practice, particularly in consolidation therapy in acute processes, infections requiring prolonged treatment and in the prophylaxis of some recurrent processes caused by Gram-positive cocci.

[Antimicrobial spectrum of dalbavancin. Mechanism of action and in vitro activity against Gram-positive microorganisms]. / Espectro antimicrobiano de dalbavancina. Mecanismo de acción y actividad in vitro frente a microorganismos Gram positivos.

Because of the increase in bacterial resistance, there is a need for new antimicrobial agents. Dalbavancin is a semisynthetic glycopeptide that inhibits the late stages of bacterial cell wall synthesis in the same way as vancomycin, but in addition, its lipophilic side chain anchors dalbavancin to the cellular membrane and allows enhanced activity compared with that of vancomycin. Dalbavancin possesses a broad spectrum of in vitro activity against Gram-positive aerobic and anaerobic microorganisms, being 4-8 times more potent than vancomycin. The spectrum of dalbavancin includes staphylococci, enterococci, streptococci, and anaerobic Gram-positive cocci and bacilli. It is active against different species of multiresistant microorganisms, including methicillin-resistant Staphylococcus aureus and penicillin-resistant viridans streptococci and Streptococcus pneumoniae. Although it shows in vitro activity against Enterococcus spp., it is inactive against isolates expressing the VanA phenotype of vancomycin resistance. It also shows slow bactericidal activity against S. aureus, coagulase-negative staphylococci, and Streptococcus pyogenes. In general, the MIC90 (minimum inhibitory concentration 90%) against the majority of the microorganisms is 0.06mg/L and, more than 98% of the isolates that have been tested are inhibited at concentrations of ≤ 0.12mg/L. Dalbavancin is an interesting addition to the therapeutic armamentarium for the treatment of infections caused by Gram-positive microorganisms, including multidrug-resistant isolates.