Ceftriaxone pharmacokinetics by a sensitive and simple LC-MS/MS method: Development and application.

Ceftriaxone is a third-generation cephalosporin, worldwide use as a first-line treatment for several infections, including life-threatening infections as meningitis or endocarditis. Nowadays, ceftriaxone use is changing, embracing high-dose schemes, new populations treated and requirement of dose individualization and optimization. These reasons warranted the development of new sensitive assays. This study aimed to develop and validate a fast and handy bioanalytical method for the quantification of ceftriaxone in human plasma covering a broad range of concentrations. The analysis was performed using high-performance liquid chromatography coupled to tandem mass spectrometry. Sample preparation was based on protein precipitation with acetonitrile followed by centrifugation. Chromatography separation was performed on Phenomenex Luna C18 column (5 µm, 150 × 2.0 mm) and a mobile phase consisting of 70 % of mobile phase A (10 mM of ammonium acetate and 1% formic acid in purified water) and 30 % mobile phase B (0.1 % formic acid in acetonitrile) at a flow rate of 500 µl/min on an isocratic program. Both the analyte and the internal standard were quantified using the positive electrospray ionization (ESI) mode within a single runtime of 5.00 min. The method was validated following the U.S. Food and Drug Administration guidelines over the concentration range of 3-1000 µg/mL. The within-run and between-run precision and accuracy were <15 %, and therefore met the standard regulatory acceptance criterion. In conclusion, a sensitive and robust LC-MS/MS method was developed for a fast quantitation of ceftriaxone concentrations in plasma samples with multiples applications in research and clinical therapeutic drug monitoring.

Ampicillin and Ceftriaxone Solution Stability at Different Temperatures in Outpatient Parenteral Antimicrobial Therapy.

The inclusion of ampicillin-containing regimens in outpatient parenteral antimicrobial therapy programs (OPAT) depends upon solution stability under conditions similar to those experienced in these programs. Lack of this information could hinder the inclusion in OPAT of patients suffering from Enterococcus faecalis infective endocarditis treated with ampicillin plus ceftriaxone. The purpose of this study is to determine the stability of ampicillin and ampicillin plus ceftriaxone solutions in a simulated outpatient setting conditions. Solutions of ampicillin 24 g/liter and ampicillin 24 g/liter combined with ceftriaxone 8 g/liter were stored at 25°C ± 2°C, 30°C ± 2°C and 37°C ± 2°C for 48 h. Chemical and physical stability were evaluated at 20, 24, 30, and 48 h after manufacturing. The solutions were considered stable if the percentage of intact drug was ≥90% and color and clearness remained unchanged. After 24 h of storage at a controlled temperature, ampicillin solution in 0.9% sodium chloride was found to be stable for 30 h at 25 and 30°C and for 24 h at 37°C. In the ampicillin plus ceftriaxone combined solution, both antibiotics were found to be stable after 30 h of storage at 25 and 30°C, but at 37°C, the stability criterion was not met at any time point. Our study offers solid evidence demonstrating that the concentrations of both drugs at two of the tested temperatures (25°C and 30°C) were stable for up to 30 h. Therefore, both ampicillin alone and ampicillin plus ceftriaxone solutions would be appropriate candidates for inclusion in OPAT programs.

Outpatient parenteral antimicrobial therapy in Enterococcus faecalis infective endocarditis.

WHAT IS KNOWN AND OBJECTIVE: Enterococcus faecalis is the third most common causal agent of infective endocarditis. Currently, the treatment recommended is a combination of ampicillin (2 g/4 h) plus ceftriaxone (2 g/12 h), so patients must remain hospitalized for almost 6 weeks to receive the treatment. They are not generally included in outpatient parenteral antimicrobial therapy programs because 2 different electronic pumps are required to administer these 2 antibiotics. To enable the treatment of patients with E. faecalis IE at home, we designed a continuation combination regimen of ceftriaxone 4 g once daily in a short infusion plus ampicillin 2 g/4 h using a programmable pump. METHODS: We analyzed a cohort of patients attended in an outpatient parenteral antimicrobial therapy program that has been working since 2012 in 2 tertiary hospitals. We selected patients attended in this program for E. faecalis IE treated with a continuation regimen of ampicillin 12 g daily (2 g/4 h) and ceftriaxone 4 g every 24 hours between July 2012 and March 2017. RESULTS AND DISCUSSION: Of the 720 patients included in the outpatient parenteral antimicrobial therapy program, 42 had infective endocarditis, and 4 (9.52%) were treated using the combination regimen described above. All patients were men, and all had left-sided native-valve infective endocarditis. All 4 patients received ampicillin 2 g every 4 hours and ceftriaxone 2 g every 12 hours in hospital, for a median duration of 25 days (IQR 15-32). Thereafter, in the program, they received the following regimen: a 30-minute infusion of ceftriaxone 4 g in 250 mL of saline solution, followed by ampicillin 12 g daily in 500 mL of saline solution delivered by a pump programmed to administer 2 g every 4 hours. Patients received this treatment at home for a median of 22.5 days (IQR 13-32). All patients achieved clinical and microbiological cure with no recurrences or complications after a lengthy follow-up period (median 365 days, IQR 221-406). No drug-related adverse events or problems with the pump system were reported. WHAT IS NEW AND CONCLUSIONS: Use of ceftriaxone 4 g in a single dose yields a mean plasma concentration of 30 µg/mL. Ceftriaxone also has a high plasma protein binding capability, and once this binding is saturated, there is no reason to administer higher doses. Therefore, it seems reasonable to use a dose of 4 g of ceftriaxone once daily to have a synergist effect with ampicillin within the vegetation, and enable the treatment of patients with E. faecalis infective endocarditis at home. In conclusion, the administration of ampicillin (2 g/4 h) plus ceftriaxone (4 g/24 h) as a continuation regimen in an outpatient parenteral antimicrobial therapy program may be as effective and safe as the usual lengthy in-hospital regimen (ampicillin 2 g/4 h and ceftriaxone 2 g/12 h) in patients with E. faecalis infective endocarditis.

Utilidad de la 18F-FDG PET/TC en un caso de sospecha de infección de injerto vascular / Usefulness of 18F-FDG PET/CT in a case of suspected vascular graft infection

La infección del injerto vascular protésico (VPGI) se asocia a una gran morbimortalidad. Es esencial un diagnóstico precoz y preciso para llevar a cabo el tratamiento más adecuado. Presentamos el caso de un varón de 74 años intervenido de by-pass aorto-bifemoral con sospecha clínica de infección de la prótesis vascular y pruebas complementarias no concluyentes, en el que se realiza un estudio PET/TC con 18F-FDG que muestra una captación patológica a nivel periprotésico sugestiva de infección, así como lesión incidental pulmonar sugestiva de neoplasia primaria. Una 18F-FDG PET/TC de control tras tratamiento antibiótico prolongado demostró una mejoría significativa en la captación en el injerto vascular. La 18F-FDG es un trazador prometedor para detectar VPGI, ya que los leucocitos activados tienen una gran demanda de la 18F-FDG y se acumulan en el lugar de la infección, y podría ayudar a definir la respuesta al tratamiento antibiótico (AU)

Vascular prosthetic graft infection (VPGI) is associated with high mortality and morbidity. An early and accurate diagnosis is essential in order to give the most appropriate treatment. The case is presented of a 74 year old male subjected to an aortobifemoral bypass graft, with clinical suspicion of VPGI with inconclusive tests. Later on an 18F-FDG PET/CT study showed a pathological uptake, suggestive of periprosthetic infection, as well as an incidental pulmonary lesion, suggestive of a primary neoplasm. A new 18F-FDG PET/CT showed a significant improvement in the uptake by the vascular graft after prolonged antibiotic treatment. 18F-FDG is a promising tracer for detecting VPGI as the accumulated activated white cells at the infection site have a high demand for 18F-FDG, and could help define the response to antibiotic treatment (AU)

Usefulness of 18F-FDG PET/CT in a case of suspected vascular graft infection. / Utilidad de la 18F-FDG PET/TC en un caso de sospecha de infección de injerto vascular.

Vascular prosthetic graft infection (VPGI) is associated with high mortality and morbidity. An early and accurate diagnosis is essential in order to give the most appropriate treatment. The case is presented of a 74 year old male subjected to an aortobifemoral bypass graft, with clinical suspicion of VPGI with inconclusive tests. Later on an 18F-FDG PET/CT study showed a pathological uptake, suggestive of periprosthetic infection, as well as an incidental pulmonary lesion, suggestive of a primary neoplasm. A new 18F-FDG PET/CT showed a significant improvement in the uptake by the vascular graft after prolonged antibiotic treatment. 18F-FDG is a promising tracer for detecting VPGI as the accumulated activated white cells at the infection site have a high demand for 18F-FDG, and could help define the response to antibiotic treatment.

Infiltrado pulmonar y fiebre tras la resolución de neumonía por Pneumocystis jirovecii en un paciente con infección por el VIH / Pulmonary infiltrates and fever in a HIV infected patient after pneumocystis jirovecii pneumonia

El diagnóstico de enfermedad por citomegalovirus (CMV) en el paciente con infección por VIH no resulta con frecuencia fácil y suele aparecer en el contexto de inmunosupresión severa por reactivación o reinfección del virus. Además, aunque tras la introducción de terapia antirretroviral de gran actividad (TARGA) la incidencia de enfermedad por CMV ha disminuido de forma drástica, es una entidad a tener en cuenta con considerable morbimortalidad. Presentamos el caso de un paciente con fiebre infiltrados pulmonares y dolor abdominal tras la resolución de una neumonía por P.jirovecii con aislamiento de CMV (shellvial positivo) en LBA y biopsia gástrica. Se plantea el posible diagnóstico de enfermedad digestiva y pulmonar por CMV iniciando tratamiento dirigido con respuesta clínica. En este paciente llama la atención la rápida progresión a SIDA desde el diagnóstico y resulta sugerente la hipótesis de que una confección simultánea de VIH y CMV fuese la responsable del rápido deterioro inmunológico (AU)

In HIV-infected patients, cytomegalovirus (CMV) disease diagnosis is usually difficult and disease results from reactivation of latent infection or reinfection in the context of severe immunosuppression. Although the introduction of highly active antiretroviral therapy (HAART) has resulted in an important decline of CMV disease, it has considerable morbidity and mortality rate. We present a case of a patient who presented fever, pulmonary infiltrates and abdominal pain after P.jirovecii pneumonia, with isolated of CMV (positive shell-vial) from LBA and gastric biopsy. We propose a possible diagnosis of digestive and pulmonary CMV disease and we initiated treatment for this with clinical response. It results surprising the rapid progression to SIDA of the patient and we can suggest that a co-infection HIV-CMV could be the cause for the rapid immunological damage (AU)

[Pulmonary infiltrates and fever in a HIV infected patient after Pneumocystis jirovecii pneumonia]. / Infiltrado pulmonar y fiebre tras la resolución de neumonía por Pneumocystis jirovecii en un paciente con infección por el VIH.

In HIV-infected patients, cytomegalovirus (CMV) disease diagnosis is usually difficult and disease results from reactivation of latent infection or reinfection in the context of severe immunosupression. Although the introduction of highly active antiretroviral therapy (HAART) has resulted in a important decline of CMV disease, it has considerable morbidity and mortality rate. We present a case of a patient who presented fever, pulmonary infiltrates and abdominal pain after P.jirovecii pneumonia, with isolated of CMV (positive shell-vial) from LBA and gastric biopsy. We propose a possible diagnosis of digestive and pulmonary CMV disease and we initiated treatment for this with clinical response. It results surprising the rapid progression to SIDA of the patient and we can suggest that a co-infection HIV-CMV could be the cause for the rapid immunological damage.

[Lung involvement in leptospirosis]. / Afectación pulmonar en la leptospirosis.

We reviewed a series of 5 cases of leptospirosis treated in our hospital between 1998 and 2004 and found that lung involvement was observed in 3 of the 5 cases. All patients met the criteria for the diagnosis of leptospirosis. Weil syndrome was diagnosed in 4 patients and anicteric leptospirosis in 1 patient. The 3 patients with lung sequelae were admitted into the intensive care unit because of severe respiratory failure. All patients responded to antibiotic treatment; 3 received doxycycline and 2 received doxycycline with penicillin G. Leptospirosis can lead to severe lung complications often requiring admission to the intensive care unit. The degree of severity is independent of the particular clinical syndrome (the anicteric form or Weil syndrome). Finally, despite the severity of the clinical picture, our patients responded to medical treatment and did not require invasive mechanical ventilation.

Afectación pulmonar en la leptospirosis / Lung involvement in leptospirosis

Hemos realizado una revisión retrospectiva de una serie de 5 casos de leptospirosis, en 3 de los cuales se detectó afectación pulmonar, ingresados entre 1998 y 2004 en nuestro hospital. Los 5 pacientes presentaron criterios confirmados de leptospirosis. Cuatro cumplían criterios de síndrome de Weil y el restante, de leptospirosis anictérica. Los 3 pacientes con secuelas pulmonares ingresaron en la unidad de cuidados intensivos por presentar insuficiencia respiratoria grave. Los 5 casos evolucionaron favorablemente con tratamiento antibiótico, 3 con doxiciclina y 2 con doxiciclina asociada a penicilina G. En conclusión, en la leptospirosis hay complicaciones pulmonares graves que requieren con frecuencia ingreso en la unidad de cuidados intensivos. El estado de gravedad es independiente del síndrome clínico: variante anictérica o síndrome de Weil. Por último, a pesar de la gravedad en su forma de presentación, en nuestra experiencia la evolución es favorable con tratamiento médico, sin necesidad de ventilación mecánica invasiva

We reviewed a series of 5 cases of leptospirosis treated in our hospital between 1998 and 2004 and found that lung involvement was observed in 3 of the 5 cases. All patients met the criteria for the diagnosis of leptospirosis. Weil syndrome was diagnosed in 4 patients and anicteric leptospirosis in 1 patient. The 3 patients with lung sequelae were admitted into the intensive care unit because of severe respiratory failure. All patients responded to antibiotic treatment; 3 received doxycycline and 2 received doxycycline with penicillin G. Leptospirosis can lead to severe lung complications often requiring admission to the intensive care unit. The degree of severity is independent of the particular clinical syndrome (the anicteric form or Weil syndrome). Finally, despite the severity of the clinical picture, our patients responded to medical treatment and did not require invasive mechanical ventilation

Sarcoidosis extrapulmonar como causa de fiebre de origen desconocido / Extrapulmonary sarcoidosis as the etiology in a patient with fever of unknown origin

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Empiema bacteriano espontáneo. Respuesta de los autores / Spontaneous bacterial empyema. Author's reply

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