Letter to the Editor
Cystic Fibrosis and Piperacillin/Tazobactam: Adverse Reactions
Fibrosis quística y piperacilina tazobactam: reacciones adversas
Layla Diab Cáceres
, María Celeste Marcos, Rosa María Girón Moreno
Corresponding author
Servicio de Neumología, Hospital Universitario de La Princesa, Madrid, Spain
Read
8069
Timeswas read the article
2133
Total PDF
5936
Total HTML
Share statistics
array:23 [ "pii" => "S157921291500316X" "issn" => "15792129" "doi" => "10.1016/j.arbr.2015.10.003" "estado" => "S300" "fechaPublicacion" => "2015-12-01" "aid" => "1154" "copyright" => "SEPAR" "copyrightAnyo" => "2015" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "cor" "cita" => "Arch Bronconeumol. 2015;51:664-5" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 3344 "formatos" => array:3 [ "EPUB" => 123 "HTML" => 2528 "PDF" => 693 ] ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0300289615001039" "issn" => "03002896" "doi" => "10.1016/j.arbres.2015.02.014" "estado" => "S300" "fechaPublicacion" => "2015-12-01" "aid" => "1154" "copyright" => "SEPAR" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "cor" "cita" => "Arch Bronconeumol. 2015;51:664-5" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 3385 "formatos" => array:3 [ "EPUB" => 108 "HTML" => 2494 "PDF" => 783 ] ] "es" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Carta al Director</span>" "titulo" => "Fibrosis quística y piperacilina tazobactam: reacciones adversas" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "664" "paginaFinal" => "665" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Cystic Fibrosis and Piperacillin-tazobactam: Adverse Reactions" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Layla Diab Cáceres, María Celeste Marcos, Rosa María Girón Moreno" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Layla" "apellidos" => "Diab Cáceres" ] 1 => array:2 [ "nombre" => "María Celeste" "apellidos" => "Marcos" ] 2 => array:2 [ "nombre" => "Rosa María" "apellidos" => "Girón Moreno" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S157921291500316X" "doi" => "10.1016/j.arbr.2015.10.003" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S157921291500316X?idApp=UINPBA00003Z" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289615001039?idApp=UINPBA00003Z" "url" => "/03002896/0000005100000012/v2_201511280826/S0300289615001039/v2_201511280826/es/main.assets" ] ] "itemAnterior" => array:19 [ "pii" => "S1579212915003171" "issn" => "15792129" "doi" => "10.1016/j.arbr.2015.10.004" "estado" => "S300" "fechaPublicacion" => "2015-12-01" "aid" => "1155" "copyright" => "SEPAR" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "cor" "cita" => "Arch Bronconeumol. 2015;51:663-4" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 2325 "formatos" => array:3 [ "EPUB" => 133 "HTML" => 1697 "PDF" => 495 ] ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Immune-mediated Leukopenia due to <span class="elsevierStyleItalic">Chlamydophila pneumoniae</span> Pneumonia" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "663" "paginaFinal" => "664" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Leucopenia inmunomediada secundaria a neumonía por <span class="elsevierStyleItalic">Chlamydophila pneumoniae</span>" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 550 "Ancho" => 995 "Tamanyo" => 87530 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Chest computed tomography showing right lower lobe consolidation.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Cristina Rosario Martín, Blanca Navarro Cubells, Francisco Carrión Valero" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Cristina" "apellidos" => "Rosario Martín" ] 1 => array:2 [ "nombre" => "Blanca" "apellidos" => "Navarro Cubells" ] 2 => array:2 [ "nombre" => "Francisco" "apellidos" => "Carrión Valero" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0300289615001040" "doi" => "10.1016/j.arbres.2015.03.004" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289615001040?idApp=UINPBA00003Z" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1579212915003171?idApp=UINPBA00003Z" "url" => "/15792129/0000005100000012/v1_201512080104/S1579212915003171/v1_201512080104/en/main.assets" ] "en" => array:15 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Cystic Fibrosis and Piperacillin/Tazobactam: Adverse Reactions" "tieneTextoCompleto" => true "saludo" => "To the Editor," "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "664" "paginaFinal" => "665" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Layla Diab Cáceres, María Celeste Marcos, Rosa María Girón Moreno" "autores" => array:3 [ 0 => array:4 [ "nombre" => "Layla" "apellidos" => "Diab Cáceres" "email" => array:1 [ 0 => "layladch@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "María Celeste" "apellidos" => "Marcos" ] 2 => array:2 [ "nombre" => "Rosa María" "apellidos" => "Girón Moreno" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Neumología, Hospital Universitario de La Princesa, Madrid, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Fibrosis quística y piperacilina tazobactam: reacciones adversas" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Cystic fibrosis (CF) patients commonly have chronic lung infections and frequent exacerbations caused by a range of bacteria, including <span class="elsevierStyleItalic">Pseudomonas aeruginosa (P. aeruginosa)</span> and <span class="elsevierStyleItalic">Achromobacter xylosoxidan</span>, requiring multiple cycles of antibiotics such as piperacillin/tazobactam. This combination has been associated in the literature with increased bone marrow toxicity, and it should be used with caution.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We report 2 cases of CF patients, presenting with fever and myelotoxicity caused by piperacillin/tazobactam administered for <span class="elsevierStyleItalic">P. aeruginosa</span> infection, who required a switch to another antibiotic.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The first patient was a 20-year-old man with CF genotype F508del/F508, colonized with methicillin-resistant <span class="elsevierStyleItalic">Staphylococcus aureus</span> and <span class="elsevierStyleItalic">P. aeruginosa</span>. He was admitted for a respiratory exacerbation, with increased cough, greenish expectoration, weight loss, and worsening lung function, manifesting as forced vital capacity (FVC) 2950<span class="elsevierStyleHsp" style=""></span>ml (53%), forced expiratory volume in 1<span class="elsevierStyleHsp" style=""></span>second (FEV<span class="elsevierStyleInf">1</span>) 1885<span class="elsevierStyleHsp" style=""></span>ml (42%), and FEV<span class="elsevierStyleInf">1</span>/FVC 63.90. Treatment was started with intravenous piperacillin/tazobactam 4/0.5<span class="elsevierStyleHsp" style=""></span>g every 8<span class="elsevierStyleHsp" style=""></span>hours, and tobramycin 400<span class="elsevierStyleHsp" style=""></span>mg/24<span class="elsevierStyleHsp" style=""></span>h. The patient was discharged after 10 days to complete treatment at home. He was readmitted 7 days later with fever, myalgia, and epigastralgia. Clinical laboratory tests showed anemia (hemoglobin 11.3<span class="elsevierStyleHsp" style=""></span>g/dl) and leukopenia (2940/mm<span class="elsevierStyleSup">3</span>), with a normal blood smear. Piperacillin/tazobactam was switched to ceftazidime, while the aminoglycoside was maintained, leading to an improvement in laboratory parameters.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Our second case was a 23-year-old man with CF genotype F508del/unknown mutation with the following lung function status: FVC 2950<span class="elsevierStyleHsp" style=""></span>ml (60%); FEV<span class="elsevierStyleInf">1</span>: 1670<span class="elsevierStyleHsp" style=""></span>ml (42%); and FEV<span class="elsevierStyleInf">1</span>/FVC (56.56%); along with chronic <span class="elsevierStyleItalic">P. aeruginosa</span> bronchial infection. In view of symptoms of respiratory infection and functional decline, treatment was started with piperacillin/tazobactam 4/0.5<span class="elsevierStyleHsp" style=""></span>g/8<span class="elsevierStyleHsp" style=""></span>h and tobramycin 400<span class="elsevierStyleHsp" style=""></span>mg/24<span class="elsevierStyleHsp" style=""></span>h. On day 17 of treatment, he developed fever (39.5<span class="elsevierStyleHsp" style=""></span>°C) with no other accompanying signs. Clinical laboratory tests revealed anemia (hemoglobin 12.5<span class="elsevierStyleHsp" style=""></span>g/dl), thrombocytopenia (96,000/mm<span class="elsevierStyleSup">3</span>) (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>), coagulation changes (prothrombin activity 56% and cephalin time 41.6 s), and hepatic involvement (GOT 170<span class="elsevierStyleHsp" style=""></span>U/l, GPT 51<span class="elsevierStyleHsp" style=""></span>U/l, GGT 24<span class="elsevierStyleHsp" style=""></span>U/l, and LDH 1462<span class="elsevierStyleHsp" style=""></span>U/l). Piperacillin/tazobactam was switched to levofloxacin. On day 4 after admission, the patient's platelet count (165,000/mm<span class="elsevierStyleSup">3</span>), coagulation parameters (prothrombin activity 102% y and cephalin time 29.6<span class="elsevierStyleHsp" style=""></span>s), and liver function (GOT 18<span class="elsevierStyleHsp" style=""></span>U/l, GPT 27<span class="elsevierStyleHsp" style=""></span>U/l, GGT 19<span class="elsevierStyleHsp" style=""></span>U/l, LDH 285<span class="elsevierStyleHsp" style=""></span>U/l) improved.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Several papers have been published on the adverse effects of piperacillin/tazobactam in CF patients. For reasons that are still unclear, these events seem to be more common in CF than in the general population.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">3</span></a> Risk factors include a high accumulative dose of antibiotics in a short period of time and prolonged treatments (>10 days).<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">1–3</span></a> Haptene-induced hemolytic anemia<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">4</span></a> has been reported to respond well to intravenous immunoglobulin.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">2</span></a> Leukopenia, thrombocytopenia, fever, and hypersensitivity reactions that range from pruritis and skin rash to anaphylactic shock<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">5</span></a> have also been reported, but no cases of coagulation changes or liver toxicity have been published.</p><p id="par0030" class="elsevierStylePara elsevierViewall">In our experience, CF patients show increased adverse effects to piperacillin/tazobactam, so they should be used with caution in this population. One of our patients, who was a frequent exacerbator (requiring ≥2 intravenous antibiotics/year),<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">6</span></a> received piperacillin/tazobactam in an attempt to improve results obtained with previous antibiotic combinations. We conclude that this drug may be considered for use in second-line treatment, but it is inadvisable to use it for periods longer than 14 days. High doses should also be avoided, even for short periods of time.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflict of Interests</span><p id="par0035" class="elsevierStylePara elsevierViewall">The authors state that they have no conflict of interests.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflict of Interests" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Diab Cáceres L, Marcos MC, Girón Moreno RM. Fibrosis quística y piperacilina tazobactam: reacciones adversas. Arch Bronconeumol. 2015;51:664–665.</p>" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">F: female; iv: intravenous; M: male; NR: not reported; PTZ: piperacillin/tazobactam.</p>" "tablatextoimagen" => array:1 [ 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">Reference \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">Year \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">Number of Patients \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">Age/Sex \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 \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">Onset of Symptoms (day) \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">Adverse Effects (%) \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">Treatment \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Reichardt P.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1996–1998 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Accumulated dose over 14 days 4.9<span class="elsevierStyleHsp" style=""></span>g/kg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Fever, general malaise, and headacheLeukopenia and thrombocytopenia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PTZ discontinuation \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Bandara M.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">3</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2010 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">39/F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.5<span class="elsevierStyleHsp" style=""></span>g iv every 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">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hemolytic anemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Transfusion, steroids, iv immunoglobulin, PTZ discontinuation \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Zanetti R.C.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">2</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2013 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">19/F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hemolytic anemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Transfusion, inmunoglobulina iv, PTZ discontinuation \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Marik P.E.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">4</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2013 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">24/M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hemolytic anemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Transfusion, steroids, inmunoglobulina iv, PTZ discontinuation \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab958659.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Adverse Reactions Associated With Piperacillin/Tazobactam in Cystic Fibrosis.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:6 [ 0 => array:3 [ "identificador" => "bib0035" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Leukocytopenia, thrombocytopenia and fever related to piperacillin/tazobactam treatment. A retrospective analysis in 38 children with cystic fibrosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "P. Reichardt" 1 => "W. Handrick" 2 => "A. Linke" 3 => "R. Schille" 4 => "W. Kiess" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Infection" "fecha" => "1999" "volumen" => "27" "paginaInicial" => "355" "paginaFinal" => "356" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10624596" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0040" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hemolytic anemia as a result of piperacillin/tazobactam administration: a case report and discussion of pathophysiology" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "R.C. Zanetti" 1 => "A.K. Biswas" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Mil Med" "fecha" => "2013" "volumen" => "178" "paginaInicial" => "e 1045" "paginaFinal" => "e 1047" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0045" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Piperacillin-induced immune hemolytic anemia in an adult with cystic fibrosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M. Bandara" 1 => "D.B. Seder" 2 => "G. Garratty" 3 => "R.M. Leger" 4 => "J.B. Zuckerman" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1155/2010/161454" "Revista" => array:5 [ "tituloSerie" => "Case Rep Med" "fecha" => "2010" "volumen" => "2010" "paginaInicial" => "161454" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20589083" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0050" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Life-threatening piperacilin-induced inmune haemolysis in a patient with cystic fibrosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "P.E. Marik" 1 => "P. Parekh" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:2 [ "tituloSerie" => "BMJ Case Rep" "fecha" => "2013" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0055" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hypersensitivity to antibiotics in patients with cystic fibrosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "J.F. Roehmel" 1 => "C. Schwarz" 2 => "A. Mehl" 3 => "P. Stock" 4 => "D. Staab" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jcf.2013.10.002" "Revista" => array:6 [ "tituloSerie" => "J Cyst Fibros" "fecha" => "2014" "volumen" => "13" "paginaInicial" => "205" "paginaFinal" => "211" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24169544" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0060" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Predictors of pulmonary exacerbations in patients with cystic fibrosis infected with multi-resistant bacteria" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.K. Block" 1 => "K.L. Vandemheen" 2 => "E. Tullis" 3 => "D. Fergusson" 4 => "S. Doucette" 5 => "D. Haase" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/thx.2006.061366" "Revista" => array:6 [ "tituloSerie" => "Thorax" "fecha" => "2006" "volumen" => "61" "paginaInicial" => "969" "paginaFinal" => "974" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16844728" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/15792129/0000005100000012/v1_201512080104/S157921291500316X/v1_201512080104/en/main.assets" "Apartado" => array:4 [ "identificador" => "45358" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/15792129/0000005100000012/v1_201512080104/S157921291500316X/v1_201512080104/en/main.pdf?idApp=UINPBA00003Z&text.app=https://archbronconeumol.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S157921291500316X?idApp=UINPBA00003Z" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 4 | 1 | 5 |
| 2024 October | 101 | 13 | 114 |
| 2024 September | 107 | 22 | 129 |
| 2024 August | 100 | 34 | 134 |
| 2024 July | 74 | 20 | 94 |
| 2024 June | 90 | 44 | 134 |
| 2024 May | 88 | 37 | 125 |
| 2024 April | 50 | 33 | 83 |
| 2024 March | 61 | 13 | 74 |
| 2024 February | 34 | 25 | 59 |
| 2023 March | 9 | 6 | 15 |
| 2023 February | 72 | 30 | 102 |
| 2023 January | 68 | 28 | 96 |
| 2022 December | 80 | 29 | 109 |
| 2022 November | 94 | 28 | 122 |
| 2022 October | 77 | 57 | 134 |
| 2022 September | 75 | 24 | 99 |
| 2022 August | 68 | 33 | 101 |
| 2022 July | 42 | 37 | 79 |
| 2022 June | 51 | 33 | 84 |
| 2022 May | 50 | 33 | 83 |
| 2022 April | 57 | 29 | 86 |
| 2022 March | 76 | 47 | 123 |
| 2022 February | 67 | 35 | 102 |
| 2022 January | 66 | 38 | 104 |
| 2021 December | 57 | 42 | 99 |
| 2021 November | 70 | 43 | 113 |
| 2021 October | 60 | 36 | 96 |
| 2021 September | 64 | 52 | 116 |
| 2021 August | 78 | 32 | 110 |
| 2021 July | 36 | 29 | 65 |
| 2021 June | 80 | 46 | 126 |
| 2021 May | 84 | 31 | 115 |
| 2021 April | 239 | 92 | 331 |
| 2021 March | 130 | 45 | 175 |
| 2021 February | 84 | 31 | 115 |
| 2021 January | 75 | 16 | 91 |
| 2020 December | 72 | 18 | 90 |
| 2020 November | 83 | 17 | 100 |
| 2020 October | 73 | 20 | 93 |
| 2020 September | 55 | 23 | 78 |
| 2020 August | 58 | 17 | 75 |
| 2020 July | 58 | 22 | 80 |
| 2020 June | 47 | 13 | 60 |
| 2020 May | 62 | 26 | 88 |
| 2020 April | 91 | 29 | 120 |
| 2020 March | 76 | 18 | 94 |
| 2020 February | 51 | 26 | 77 |
| 2020 January | 64 | 24 | 88 |
| 2019 December | 50 | 13 | 63 |
| 2019 November | 45 | 29 | 74 |
| 2019 October | 50 | 16 | 66 |
| 2019 September | 62 | 22 | 84 |
| 2019 August | 51 | 17 | 68 |
| 2019 July | 50 | 30 | 80 |
| 2019 June | 89 | 22 | 111 |
| 2019 May | 48 | 16 | 64 |
| 2019 April | 68 | 47 | 115 |
| 2019 March | 70 | 32 | 102 |
| 2019 February | 69 | 19 | 88 |
| 2019 January | 52 | 23 | 75 |
| 2018 December | 72 | 24 | 96 |
| 2018 November | 78 | 21 | 99 |
| 2018 October | 116 | 19 | 135 |
| 2018 September | 77 | 5 | 82 |
| 2018 May | 28 | 0 | 28 |
| 2018 April | 64 | 7 | 71 |
| 2018 March | 74 | 6 | 80 |
| 2018 February | 41 | 6 | 47 |
| 2018 January | 61 | 7 | 68 |
| 2017 December | 46 | 6 | 52 |
| 2017 November | 60 | 5 | 65 |
| 2017 October | 66 | 4 | 70 |
| 2017 September | 54 | 9 | 63 |
| 2017 August | 57 | 9 | 66 |
| 2017 July | 50 | 11 | 61 |
| 2017 June | 69 | 19 | 88 |
| 2017 May | 66 | 5 | 71 |
| 2017 April | 77 | 4 | 81 |
| 2017 March | 44 | 6 | 50 |
| 2017 February | 82 | 7 | 89 |
| 2017 January | 40 | 6 | 46 |
| 2016 December | 48 | 16 | 64 |
| 2016 November | 74 | 34 | 108 |
| 2016 October | 71 | 61 | 132 |
| 2016 September | 81 | 36 | 117 |
| 2016 August | 74 | 19 | 93 |
| 2016 July | 54 | 18 | 72 |
Show all
