Scientific Letter
Successful treatment of Panton–Valentine leukocidin-positive methicillin-resistant Staphylococcus aureus pneumonia with high doses of linezolid administered in continuous infusion
Tratamiento eficaz de una neumonia comunitaria producida por un Staphylococcus aureus resitente a meticilina leucocidina Panton-Valantin con altas dosis de linezolid en perfusión continua
F. Álvarez-Lermaa,
, R. Muñoz-Bermúdeza, M.A. Samper-Sáncheza, M.P. Gracia Arnillaa, S. Graub, S. Luqueb
Autor para correspondencia
a Service of Intensive Care Medicine, Hospital del Mar, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Universitat Autònoma de Barcelona, Barcelona, Spain
b Service of Hospital Pharmacy, Hospital del Mar, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Universitat Autònoma de Barcelona, Barcelona, Spain
Leído
8259
Vecesse ha leído el artículo
3025
Total PDF
5234
Total HTML
Compartir estadísticas
array:23 [ "pii" => "S0210569116300626" "issn" => "02105691" "doi" => "10.1016/j.medin.2016.04.006" "estado" => "S300" "fechaPublicacion" => "2017-01-01" "aid" => "926" "copyright" => "Elsevier España, S.L.U. y SEMICYUC" "copyrightAnyo" => "2016" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Med Intensiva. 2017;41:56-9" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 2736 "formatos" => array:3 [ "EPUB" => 176 "HTML" => 1668 "PDF" => 892 ] ] "itemSiguiente" => array:19 [ "pii" => "S0210569116300687" "issn" => "02105691" "doi" => "10.1016/j.medin.2016.05.001" "estado" => "S300" "fechaPublicacion" => "2017-01-01" "aid" => "932" "copyright" => "Elsevier España, S.L.U. y SEMICYUC" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "cor" "cita" => "Med Intensiva. 2017;41:60-1" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 3451 "formatos" => array:3 [ "EPUB" => 190 "HTML" => 2270 "PDF" => 991 ] ] "es" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Carta al Director</span>" "titulo" => "Conflictos de interés en la nueva definición de consenso para la sepsis y shock séptico (sepsis-3)" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "60" "paginaFinal" => "61" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Conflicts of interest in the new consensus based definition of sepsis and septic shock (sepsis-3)" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "J.A. Barea-Mendoza, I. Cortés-Puch, M. Chico-Fernández" "autores" => array:3 [ 0 => array:2 [ "nombre" => "J.A." "apellidos" => "Barea-Mendoza" ] 1 => array:2 [ "nombre" => "I." "apellidos" => "Cortés-Puch" ] 2 => array:2 [ "nombre" => "M." "apellidos" => "Chico-Fernández" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2173572717300012" "doi" => "10.1016/j.medine.2017.01.001" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173572717300012?idApp=WMIE" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210569116300687?idApp=WMIE" "url" => "/02105691/0000004100000001/v3_201702170036/S0210569116300687/v3_201702170036/es/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S0210569116301334" "issn" => "02105691" "doi" => "10.1016/j.medin.2016.06.005" "estado" => "S300" "fechaPublicacion" => "2017-01-01" "aid" => "949" "copyright" => "Elsevier España, S.L.U. y SEMICYUC" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Med Intensiva. 2017;41:55-6" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 2090 "formatos" => array:3 [ "EPUB" => 156 "HTML" => 1153 "PDF" => 781 ] ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Scientific Letter</span>" "titulo" => "Toward a personalized response approach in sepsis 4.0" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "55" "paginaFinal" => "56" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Hacia una estrategia de respuesta personalizada en sepsis 4.0" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 779 "Ancho" => 1622 "Tamanyo" => 45466 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Odds ratio for mortality in patients included in the study. <span class="elsevierStyleItalic">Abbreviation</span>: OR, odds ratio.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "C. de Haro, E. Torrents, R. Ferrer, A. Artigas, A. Rodriguez, I. Martin-Loeches" "autores" => array:6 [ 0 => array:2 [ "nombre" => "C." "apellidos" => "de Haro" ] 1 => array:2 [ "nombre" => "E." "apellidos" => "Torrents" ] 2 => array:2 [ "nombre" => "R." "apellidos" => "Ferrer" ] 3 => array:2 [ "nombre" => "A." "apellidos" => "Artigas" ] 4 => array:2 [ "nombre" => "A." "apellidos" => "Rodriguez" ] 5 => array:2 [ "nombre" => "I." "apellidos" => "Martin-Loeches" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210569116301334?idApp=WMIE" "url" => "/02105691/0000004100000001/v3_201702170036/S0210569116301334/v3_201702170036/en/main.assets" ] "en" => array:14 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Scientific Letter</span>" "titulo" => "Successful treatment of Panton–Valentine leukocidin-positive methicillin-resistant <span class="elsevierStyleItalic">Staphylococcus aureus</span> pneumonia with high doses of linezolid administered in continuous infusion" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "56" "paginaFinal" => "59" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "F. Álvarez-Lerma, R. Muñoz-Bermúdez, M.A. Samper-Sánchez, M.P. Gracia Arnilla, S. Grau, S. Luque" "autores" => array:6 [ 0 => array:4 [ "nombre" => "F." "apellidos" => "Álvarez-Lerma" "email" => array:1 [ 0 => "Falvarez@parcdesalutmar.cat" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "R." "apellidos" => "Muñoz-Bermúdez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "M.A." "apellidos" => "Samper-Sánchez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "M.P." "apellidos" => "Gracia Arnilla" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "S." "apellidos" => "Grau" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 5 => array:3 [ "nombre" => "S." "apellidos" => "Luque" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Service of Intensive Care Medicine, Hospital del Mar, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Universitat Autònoma de Barcelona, Barcelona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Service of Hospital Pharmacy, Hospital del Mar, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Universitat Autònoma de Barcelona, Barcelona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Tratamiento eficaz de una neumonia comunitaria producida por un <span class="elsevierStyleItalic">Staphylococcus aureus</span> resitente a meticilina leucocidina Panton-Valantin con altas dosis de linezolid en perfusión continua" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1093 "Ancho" => 1501 "Tamanyo" => 274767 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Thoracic CT scan at day 7 after hospital admission showing multiple cavities and important necrotic areas in the upper lobes compatible with pneumatoceles and bronchiectasis.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Pneumonia caused by methicillin-resistant <span class="elsevierStyleItalic">Staphylococcus aureus</span> (MRSA) strains producing a cytotoxin known as Panton–Valentin leukocidin (PVL) is a severe and difficult to treat disease.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–4</span></a> Linezolid has excellent epithelial lining fluid (ELF) penetration rates but drug concentrations in critically ill patients are highly variable.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5-8</span></a> We describe the clinical case of a patient with septic shock secondary to a community-acquired PVL-secreting MRSA pneumonia, in which linezolid plasma concentration within the therapeutic range were only reached with the use of higher than recommended doses (600<span class="elsevierStyleHsp" style=""></span>mg every 8<span class="elsevierStyleHsp" style=""></span>h) administered in continuous infusion.</p><p id="par0010" class="elsevierStylePara elsevierViewall">A 56-year-old Caucasian man was admitted on February 2, 2015 with a 4-day history of dyspnea, mucopurulent expectoration, and fever (>38<span class="elsevierStyleHsp" style=""></span>°C). His weight was 80<span class="elsevierStyleHsp" style=""></span>kg (body mass index [BMI] 27.7<span class="elsevierStyleHsp" style=""></span>kg/m<span class="elsevierStyleSup">2</span>), smoked 2–3 cigarettes a day, and consumed approximately 7 standard drinks daily. Physical examination revealed sinus tachycardia (160<span class="elsevierStyleHsp" style=""></span>beats/min), diaphoresis, hypertension (blood pressure [BP] 154/92<span class="elsevierStyleHsp" style=""></span>mmHg), and marked respiratory distress as well as bilateral crackles and disperse rhonchi up to the apex on lung auscultation. This caused a hypoxemic respiratory insufficiency with an initial PaO<span class="elsevierStyleInf">2</span> of 55<span class="elsevierStyleHsp" style=""></span>mmHg that did not improve despite an elevated inspired oxygen fraction (FiO<span class="elsevierStyleInf">2</span> 0.5) and noninvasive mechanical ventilation, for which he needed orotracheal intubation and ICU admission. Blood urea nitrogen was 32<span class="elsevierStyleHsp" style=""></span>mg/dL, serum creatinine 0.88<span class="elsevierStyleHsp" style=""></span>mg/dL, and glomerular filtration rate (Cockcroft–Gault equation) 106<span class="elsevierStyleHsp" style=""></span>mL/min, C-reactive protein 25.6<span class="elsevierStyleHsp" style=""></span>mg/L, procalcitonin 24.17<span class="elsevierStyleHsp" style=""></span>ng/mL, and lactic acid 5<span class="elsevierStyleHsp" style=""></span>mmol/L. Other laboratory data were unrevealing. Chest radiography revealed bilateral alveolar and interstitial infiltrates and alveolar condensation in the right upper lobe. The patient was tentatively diagnosed with CAP and was treated empirically with intravenous ceftriaxone (2<span class="elsevierStyleHsp" style=""></span>g every 24<span class="elsevierStyleHsp" style=""></span>h), intravenous levofloxacin (0.5<span class="elsevierStyleHsp" style=""></span>g every 12<span class="elsevierStyleHsp" style=""></span>h) (positive urinary detection of pneumococcal antigen), and oseltamivir (positive PCR assay detection of influenza A and B viruses in oropharyngeal swabs). During the first 24<span class="elsevierStyleHsp" style=""></span>h of ICU admission, the patient's condition deteriorated, with secondary septic shock and need of vasoactive drugs (norepinephrine 0.2 μg/kg/min). Microbiologically, a MRSA was isolated in cultures from bronchial aspirates and in four blood culture bottles (linezolid minimum inhibitory concentration [MIC]<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2<span class="elsevierStyleHsp" style=""></span>mg/L) on the day of admission. Each MRSA isolate carried the PVL genes. The MRSA strain was sent to the National Microbiology Center (Institute of Health Carlos III, Madrid). The initial empirical antibiotic treatment was discontinued and linezolid at a standard dose (600<span class="elsevierStyleHsp" style=""></span>mg every 12<span class="elsevierStyleHsp" style=""></span>h infused over 60<span class="elsevierStyleHsp" style=""></span>min) was administered.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Treatment with linezolid was maintained and the remaining antimicrobials were discontinued. Steady state plasma concentrations of linezolid were determined from the third day of treatment using a high-performance liquid chromatography technique, with a minimum plasma concentration state (<span class="elsevierStyleItalic">C</span><span class="elsevierStyleInf">min</span><span class="elsevierStyleSup">ss</span>) (or pre-dose) of 0.8<span class="elsevierStyleHsp" style=""></span>mg/L and maximum (<span class="elsevierStyleItalic">C</span><span class="elsevierStyleInf">max</span><span class="elsevierStyleSup">ss</span>) (at the end of infusion) of 4.8<span class="elsevierStyleHsp" style=""></span>mg/L, which were considered subtherapeutic (therapeutic range <span class="elsevierStyleItalic">C</span><span class="elsevierStyleInf">min</span><span class="elsevierStyleSup">ss</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>2<span class="elsevierStyleHsp" style=""></span>mg/L). Although blood cultures became negative on the fifth day of treatment, the patient showed a protracted respiratory clinical course with worsening of radiographic images, and according to drug susceptibility testing, antimicrobial coverage was expanded with intravenous clindamycin (600<span class="elsevierStyleHsp" style=""></span>mg every 8<span class="elsevierStyleHsp" style=""></span>h) and ciprofloxacin (400<span class="elsevierStyleHsp" style=""></span>mg every 8<span class="elsevierStyleHsp" style=""></span>h). In addition, the dosing interval of linezolid as well as the duration of the time of infusion were modified on several occasions based on results of plasma drug concentrations in order to achieve an optimal pharmacokinetic (PK) and pharmacodynamic (PD) ratio (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Seventeen days after starting treatment with linezolid, therapeutic levels were reached with a regimen of 600<span class="elsevierStyleHsp" style=""></span>mg every 8<span class="elsevierStyleHsp" style=""></span>h administered in continuous infusion, which coincided with eradication of PVL producing MRSA in pulmonary samples. Thoracic computed tomographic (CT) scans performed over the course of treatment revealing extensive involvement of the pulmonary parenchyma with multiple cavities and important necrotic areas in the upper lobes compatible with pneumatoceles and bronchiectasis (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The patient required mechanical ventilation during 73 days (with tracheostomy) with procedural sedation, analgesia, and prolonged muscle relaxation. After 5 weeks of treatment with linezolid, the patient was successfully weaned. Linezolid was administered for a total of 35 days, clindamycin for 29 days and ciprofloxacin for 19 days. He was discharged after a 3-month hospitalization. At the present time, his oxygen saturation on room air is >95%.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Mortality related to PVL-secreting MRSA pneumonia is around 70% despite the use of appropriate antimicrobials according to results of susceptibility testing.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> A combination of antimicrobials active against MRSA and with adequate penetration in the pulmonary parenchyma should be selected. Linezolid is a synthetic antibiotic belonging to the oxazolidinone family especially active against Gram-positive bacteria, including multiresistant pathogens, with 100% diffusion in the ELF.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Although in the technical specifications of linezolid, a standard dose of 600<span class="elsevierStyleHsp" style=""></span>mg every 12<span class="elsevierStyleHsp" style=""></span>h administered in 60-min intermittent infusion is recommended, recent pharmacokinetic studies have shown that the administration of this fixed dose in some population groups did not allow to reach an optimal predictive pharmacokinetic/pharmacodynamic (pk/pd) ratio of clinical efficacy of the drug (<span class="elsevierStyleItalic">C</span><span class="elsevierStyleInf">min</span><span class="elsevierStyleSup">ss</span><span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>2–4<span class="elsevierStyleHsp" style=""></span>mg/L), whereas it has also been related to overexposure (<span class="elsevierStyleItalic">C</span><span class="elsevierStyleInf">min</span><span class="elsevierStyleSup">ss</span><span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>mg/L) and higher risk of hematologic toxicity.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> These circumstances are frequent in ICU patients with severe sepsis or septic shock, in whom most factors associated with underexposure or overexposure to linezolid may be present.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9,10</span></a> Subtherapeutic linezolid concentrations have been related to glomerular filtration rates greater than 80<span class="elsevierStyleHsp" style=""></span>mL/min,<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> which is frequent in septic patients treated with vasoactive drugs as was in our patient.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Strategies for optimizing linezolid plasma levels include an increase in the total dose, by-reducing the dosing interval from 12<span class="elsevierStyleHsp" style=""></span>h to every 8 or 6<span class="elsevierStyleHsp" style=""></span>h, or extending the duration of infusion to 2–4<span class="elsevierStyleHsp" style=""></span>h (extended infusion) or using a continuous infusion.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9,10</span></a> Our patient in whom glomerular filtration rates >200<span class="elsevierStyleHsp" style=""></span>mL/min were recorded, a <span class="elsevierStyleItalic">C</span><span class="elsevierStyleInf">min</span><span class="elsevierStyleSup">ss</span><span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>4<span class="elsevierStyleHsp" style=""></span>mg/L were only obtained with the administration of a linezolid dose of 600<span class="elsevierStyleHsp" style=""></span>mg every 6–8<span class="elsevierStyleHsp" style=""></span>h in continuous infusion, which coincided with negativization of pulmonary exudate cultures. This high dose, between 1.5 and 2-fold higher than the standard recommended dose was well tolerated, without signs of toxicity, particularly without a decrease in platelet count or hemoglobin levels.</p><p id="par0035" class="elsevierStylePara elsevierViewall">In ICU patients with severe infections and increased renal clearance, linezolid should be administered at high doses and in continuous infusion with close monitorization of plasma drug levels.</p><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Source of funding</span><p id="par0055" class="elsevierStylePara elsevierViewall">None declared.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflicts of interest</span><p id="par0060" class="elsevierStylePara elsevierViewall">None declared.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Source of funding" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Conflicts of interest" ] 2 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1093 "Ancho" => 1501 "Tamanyo" => 274767 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Thoracic CT scan at day 7 after hospital admission showing multiple cavities and important necrotic areas in the upper lobes compatible with pneumatoceles and bronchiectasis.</p>" ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">GFR: glomerular filtration rate.</p>" "tablatextoimagen" => array:2 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Day of sampling \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Dose (mg) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Dosing interval doses \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Type and duration of infusion \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">GFR (mL/min) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">C</span><span class="elsevierStyleInf">min</span><span class="elsevierStyleSup">ss</span> (mg/L) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Platelet count (×10<span class="elsevierStyleSup">9</span>/L) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">February 13, 2015 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">600 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12<span class="elsevierStyleHsp" style=""></span>h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Intermittent (60<span class="elsevierStyleHsp" style=""></span>min) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">176 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">112 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">February 17, 2015 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">600 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12<span class="elsevierStyleHsp" style=""></span>h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Intermittent (60<span class="elsevierStyleHsp" style=""></span>min) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">239 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">85 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">February 23, 2015 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">600 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8<span class="elsevierStyleHsp" style=""></span>h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Extended (2<span class="elsevierStyleHsp" style=""></span>h) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">345 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">456 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">February 24, 2015 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">600 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6<span class="elsevierStyleHsp" style=""></span>h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Extended (2<span class="elsevierStyleHsp" style=""></span>h) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">267 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">531 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">February 26, 2015 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">600 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6<span class="elsevierStyleHsp" style=""></span>h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Extended (2<span class="elsevierStyleHsp" style=""></span>h) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">301 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">540 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1346722.png" ] ] 1 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Day of sampling \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Dose (mg) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Dosing interval doses \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Type and duration of infusion \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">GFR (mL/min) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">C</span><span class="elsevierStyleInf">min</span><span class="elsevierStyleSup">ss</span> (mg/L) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="char" valign="top" scope="col" style="border-bottom: 2px solid black">Platelet count (×10<span class="elsevierStyleSup">9</span>/L) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">March 2, 2015 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">600 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6<span class="elsevierStyleHsp" style=""></span>h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Continuous (6<span class="elsevierStyleHsp" style=""></span>h) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">301 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">544 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">March 6, 2015 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">600 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8<span class="elsevierStyleHsp" style=""></span>h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Continuous (8<span class="elsevierStyleHsp" style=""></span>h) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">275 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">527 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">March 9, 2015 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">600 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8<span class="elsevierStyleHsp" style=""></span>h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Continuous (8<span class="elsevierStyleHsp" style=""></span>h) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">333 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">467 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1346723.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Changes in doses, intervals between doses, forms of administration, and plasma concentrations of linezolid during the patient's stay in the ICU.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Emergence of community-acquired methicillin-resistant <span class="elsevierStyleItalic">Staphylococcus aureus</span> USA 300 clone as the predominant cause of skin and soft-tissue infections" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M.D. King" 1 => "B.J. Humphrey" 2 => "Y.F. Wang" 3 => "E.V. Kourbatova" 4 => "S.M. Ray" 5 => "H.M. Blumberg" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Ann. Intern. Med." "fecha" => "2006" "paginaInicial" => "309" "paginaFinal" => "317" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epidemiology and clinical presentation of Panton–Valentin leukocidin positive methicillin-resistant <span class="elsevierStyleItalic">Staphylococcus aureus</span>" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "N. Cobos-Triguero" 1 => "C. Pitart" 2 => "F. Marco" 3 => "J.A. Martínez" 4 => "M. Almela" 5 => "J. López" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Rev. Esp. Quimioter." "fecha" => "2010" "volumen" => "23" "paginaInicial" => "93" "paginaFinal" => "99" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20559608" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diagnosis and treatment of Panton–Valentine leukocidin (PVL)-associated staphylococcal pneumonia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "M.S. Morgan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ijantimicag.2007.04.019" "Revista" => array:6 [ "tituloSerie" => "Int. J. Antimicrob. Agents" "fecha" => "2007" "volumen" => "30" "paginaInicial" => "289" "paginaFinal" => "296" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17629464" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Appropriate antimicrobial therapy for community-acquired methicillin-resistant <span class="elsevierStyleItalic">Staphylococcus aureus</span> carrying the Panton–Valentine leukocidin genes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "K.A. Wargo" 1 => "E.H. Eiland" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1086/429509" "Revista" => array:6 [ "tituloSerie" => "Clin. Infect. Dis." "fecha" => "2005" "volumen" => "40" "paginaInicial" => "1376" "paginaFinal" => "1378" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15825047" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pharmacokinetics and intrapulmonary concentrations of linezolid administered to critically ill patients with ventilator-associated pneumonia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E. Boselli" 1 => "D. Breilh" 2 => "T. Rimmelé" 3 => "S. Djabarouti" 4 => "J. Toutain" 5 => "D. Chassard" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Crit. Care Med." "fecha" => "2005" "volumen" => "33" "paginaInicial" => "1529" "paginaFinal" => "1533" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16003058" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical pharmacokinetic/pharmacodynamic profile of linezolid in severely ill intensive care unit patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H. Dong" 1 => "X. Wang" 2 => "Y. Dong" 3 => "J. Lei" 4 => "H. Li" 5 => "H. You" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ijantimicag.2011.05.007" "Revista" => array:6 [ "tituloSerie" => "Int. J. Antimicrob. Agents" "fecha" => "2011" "volumen" => "38" "paginaInicial" => "296" "paginaFinal" => "300" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21741222" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Risk factors for a low linezolid trough plasma concentration in acute infections" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L. Morata" 1 => "M. Cuesta" 2 => "J.F. Rojas" 3 => "S. Rodriguez" 4 => "M. Brunet" 5 => "G. Casals" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1128/AAC.01694-12" "Revista" => array:6 [ "tituloSerie" => "Antimicrob. Agents Chemother." "fecha" => "2013" "volumen" => "57" "paginaInicial" => "1913" "paginaFinal" => "1917" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23403416" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Variability of linezolid concentrations after standard dosing in critically ill patients: a prospective observational study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Zoller" 1 => "B. Maier" 2 => "C. Hornuss" 3 => "C. Neugebauer" 4 => "G. Döbbeler" 5 => "D. Nagel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/cc13984" "Revista" => array:5 [ "tituloSerie" => "Crit. Care" "fecha" => "2014" "volumen" => "18" "paginaInicial" => "R148" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25011656" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Alveolar diffusion and pharmacokinetics of linezolid administered in continuous infusion to critically ill patients with ventilator-associated pneumonia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E. Boselli" 1 => "D. Breilh" 2 => "A. Caillault-Sergent" 3 => "S. Djabarouti" 4 => "C. Guillaume" 5 => "F. Xuereb" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/jac/dks022" "Revista" => array:6 [ "tituloSerie" => "J. Antimicrob. Chemother." "fecha" => "2012" "volumen" => "67" "paginaInicial" => "1207" "paginaFinal" => "1210" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22351682" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Linezolid pharmacokinetic/pharmacodynamic profile in critically ill septic patients: intermittent versus continuous infusion" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Adembri" 1 => "S. Fallani" 2 => "M.I. Cassetta" 3 => "S. Arrigucci" 4 => "A. Ottaviano" 5 => "P. Pecile" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ijantimicag.2007.09.009" "Revista" => array:6 [ "tituloSerie" => "Int. J. Antimicrob. Agents" "fecha" => "2008" "volumen" => "31" "paginaInicial" => "122" "paginaFinal" => "129" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18055183" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/02105691/0000004100000001/v3_201702170036/S0210569116300626/v3_201702170036/en/main.assets" "Apartado" => array:4 [ "identificador" => "19505" "tipo" => "SECCION" "es" => array:2 [ "titulo" => "Cartas Científicas" "idiomaDefecto" => true ] "idiomaDefecto" => "es" ] "PDF" => "https://static.elsevier.es/multimedia/02105691/0000004100000001/v3_201702170036/S0210569116300626/v3_201702170036/en/main.pdf?idApp=WMIE&text.app=https://medintensiva.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210569116300626?idApp=WMIE" ]
| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 9 | 11 | 20 |
| 2024 Octubre | 64 | 50 | 114 |
| 2024 Septiembre | 68 | 30 | 98 |
| 2024 Agosto | 82 | 43 | 125 |
| 2024 Julio | 38 | 29 | 67 |
| 2024 Junio | 76 | 59 | 135 |
| 2024 Mayo | 56 | 22 | 78 |
| 2024 Abril | 74 | 42 | 116 |
| 2024 Marzo | 88 | 28 | 116 |
| 2024 Febrero | 85 | 48 | 133 |
| 2024 Enero | 86 | 36 | 122 |
| 2023 Diciembre | 74 | 33 | 107 |
| 2023 Noviembre | 89 | 40 | 129 |
| 2023 Octubre | 70 | 38 | 108 |
| 2023 Septiembre | 51 | 41 | 92 |
| 2023 Agosto | 33 | 17 | 50 |
| 2023 Julio | 51 | 30 | 81 |
| 2023 Junio | 43 | 22 | 65 |
| 2023 Mayo | 64 | 30 | 94 |
| 2023 Abril | 41 | 25 | 66 |
| 2023 Marzo | 55 | 38 | 93 |
| 2023 Febrero | 73 | 35 | 108 |
| 2023 Enero | 85 | 21 | 106 |
| 2022 Diciembre | 72 | 39 | 111 |
| 2022 Noviembre | 57 | 53 | 110 |
| 2022 Octubre | 54 | 44 | 98 |
| 2022 Septiembre | 32 | 35 | 67 |
| 2022 Agosto | 52 | 48 | 100 |
| 2022 Julio | 39 | 44 | 83 |
| 2022 Junio | 41 | 24 | 65 |
| 2022 Mayo | 51 | 37 | 88 |
| 2022 Abril | 35 | 48 | 83 |
| 2022 Marzo | 58 | 43 | 101 |
| 2022 Febrero | 61 | 33 | 94 |
| 2022 Enero | 111 | 42 | 153 |
| 2021 Diciembre | 64 | 55 | 119 |
| 2021 Noviembre | 82 | 41 | 123 |
| 2021 Octubre | 107 | 103 | 210 |
| 2021 Septiembre | 56 | 37 | 93 |
| 2021 Agosto | 42 | 50 | 92 |
| 2021 Julio | 47 | 47 | 94 |
| 2021 Junio | 64 | 44 | 108 |
| 2021 Mayo | 61 | 62 | 123 |
| 2021 Abril | 135 | 100 | 235 |
| 2021 Marzo | 93 | 32 | 125 |
| 2021 Febrero | 75 | 33 | 108 |
| 2021 Enero | 74 | 37 | 111 |
| 2020 Diciembre | 73 | 36 | 109 |
| 2020 Noviembre | 41 | 24 | 65 |
| 2020 Octubre | 58 | 32 | 90 |
| 2020 Septiembre | 58 | 26 | 84 |
| 2020 Agosto | 39 | 21 | 60 |
| 2020 Julio | 44 | 22 | 66 |
| 2020 Junio | 42 | 18 | 60 |
| 2020 Mayo | 46 | 11 | 57 |
| 2020 Abril | 59 | 20 | 79 |
| 2020 Marzo | 30 | 15 | 45 |
| 2020 Febrero | 163 | 38 | 201 |
| 2020 Enero | 51 | 40 | 91 |
| 2019 Diciembre | 67 | 32 | 99 |
| 2019 Noviembre | 63 | 18 | 81 |
| 2019 Octubre | 92 | 27 | 119 |
| 2019 Septiembre | 63 | 21 | 84 |
| 2019 Agosto | 42 | 28 | 70 |
| 2019 Julio | 51 | 22 | 73 |
| 2019 Junio | 36 | 11 | 47 |
| 2019 Mayo | 54 | 33 | 87 |
| 2019 Abril | 50 | 21 | 71 |
| 2019 Marzo | 40 | 35 | 75 |
| 2019 Febrero | 56 | 48 | 104 |
| 2019 Enero | 49 | 36 | 85 |
| 2018 Diciembre | 88 | 30 | 118 |
| 2018 Noviembre | 54 | 89 | 143 |
| 2018 Octubre | 46 | 34 | 80 |
| 2018 Septiembre | 29 | 15 | 44 |
| 2018 Agosto | 23 | 13 | 36 |
| 2018 Julio | 23 | 19 | 42 |
| 2018 Junio | 37 | 22 | 59 |
| 2018 Mayo | 16 | 11 | 27 |
| 2018 Abril | 34 | 23 | 57 |
| 2018 Marzo | 20 | 9 | 29 |
| 2018 Febrero | 24 | 11 | 35 |
| 2018 Enero | 48 | 23 | 71 |
| 2017 Diciembre | 32 | 14 | 46 |
| 2017 Noviembre | 37 | 18 | 55 |
| 2017 Octubre | 29 | 11 | 40 |
| 2017 Septiembre | 24 | 16 | 40 |
| 2017 Agosto | 34 | 16 | 50 |
| 2017 Julio | 35 | 17 | 52 |
| 2017 Junio | 39 | 39 | 78 |
| 2017 Mayo | 110 | 38 | 148 |
| 2017 Abril | 49 | 8 | 57 |
| 2017 Marzo | 4 | 3 | 7 |
| 2017 Febrero | 14 | 7 | 21 |
| 2017 Enero | 0 | 3 | 3 |
| 2016 Diciembre | 0 | 2 | 2 |
Mostrar todo
