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 qu&#237;stica y piperacilina tazobactam&#58; 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&#58; Adverse Reactions"
          ]
        ]
        "contieneTextoCompleto" => array:1 [
          "es" => true
        ]
        "contienePdf" => array:1 [
          "es" => true
        ]
        "autores" => array:1 [
          0 => array:2 [
            "autoresLista" => "Layla Diab C&#225;ceres, Mar&#237;a Celeste Marcos, Rosa Mar&#237;a Gir&#243;n Moreno"
            "autores" => array:3 [
              0 => array:2 [
                "nombre" => "Layla"
                "apellidos" => "Diab C&#225;ceres"
              ]
              1 => array:2 [
                "nombre" => "Mar&#237;a Celeste"
                "apellidos" => "Marcos"
              ]
              2 => array:2 [
                "nombre" => "Rosa Mar&#237;a"
                "apellidos" => "Gir&#243;n 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 neumon&#237;a 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&#46; 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&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Cristina Rosario Mart&#237;n, Blanca Navarro Cubells, Francisco Carri&#243;n Valero"
          "autores" => array:3 [
            0 => array:2 [
              "nombre" => "Cristina"
              "apellidos" => "Rosario Mart&#237;n"
            ]
            1 => array:2 [
              "nombre" => "Blanca"
              "apellidos" => "Navarro Cubells"
            ]
            2 => array:2 [
              "nombre" => "Francisco"
              "apellidos" => "Carri&#243;n 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&#47;Tazobactam&#58; Adverse Reactions"
    "tieneTextoCompleto" => true
    "saludo" => "To the Editor&#44;"
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "664"
        "paginaFinal" => "665"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "Layla Diab C&#225;ceres, Mar&#237;a Celeste Marcos, Rosa Mar&#237;a Gir&#243;n Moreno"
        "autores" => array:3 [
          0 => array:4 [
            "nombre" => "Layla"
            "apellidos" => "Diab C&#225;ceres"
            "email" => array:1 [
              0 => "layladch&#64;gmail&#46;com"
            ]
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
          1 => array:2 [
            "nombre" => "Mar&#237;a Celeste"
            "apellidos" => "Marcos"
          ]
          2 => array:2 [
            "nombre" => "Rosa Mar&#237;a"
            "apellidos" => "Gir&#243;n Moreno"
          ]
        ]
        "afiliaciones" => array:1 [
          0 => array:2 [
            "entidad" => "Servicio de Neumolog&#237;a&#44; Hospital Universitario de La Princesa&#44; Madrid&#44; Spain"
            "identificador" => "aff0005"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "Fibrosis qu&#237;stica y piperacilina tazobactam&#58; reacciones adversas"
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Cystic fibrosis &#40;CF&#41; patients commonly have chronic lung infections and frequent exacerbations caused by a range of bacteria&#44; including <span class="elsevierStyleItalic">Pseudomonas aeruginosa &#40;P&#46; aeruginosa&#41;</span> and <span class="elsevierStyleItalic">Achromobacter xylosoxidan</span>&#44; requiring multiple cycles of antibiotics such as piperacillin&#47;tazobactam&#46; This combination has been associated in the literature with increased bone marrow toxicity&#44; and it should be used with caution&#46;<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&#44; presenting with fever and myelotoxicity caused by piperacillin&#47;tazobactam administered for <span class="elsevierStyleItalic">P&#46; aeruginosa</span> infection&#44; who required a switch to another antibiotic&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The first patient was a 20-year-old man with CF genotype F508del&#47;F508&#44; colonized with methicillin-resistant <span class="elsevierStyleItalic">Staphylococcus aureus</span> and <span class="elsevierStyleItalic">P&#46; aeruginosa</span>&#46; He was admitted for a respiratory exacerbation&#44; with increased cough&#44; greenish expectoration&#44; weight loss&#44; and worsening lung function&#44; manifesting as forced vital capacity &#40;FVC&#41; 2950<span class="elsevierStyleHsp" style=""></span>ml &#40;53&#37;&#41;&#44; forced expiratory volume in 1<span class="elsevierStyleHsp" style=""></span>second &#40;FEV<span class="elsevierStyleInf">1</span>&#41; 1885<span class="elsevierStyleHsp" style=""></span>ml &#40;42&#37;&#41;&#44; and FEV<span class="elsevierStyleInf">1</span>&#47;FVC 63&#46;90&#46; Treatment was started with intravenous piperacillin&#47;tazobactam 4&#47;0&#46;5<span class="elsevierStyleHsp" style=""></span>g every 8<span class="elsevierStyleHsp" style=""></span>hours&#44; and tobramycin 400<span class="elsevierStyleHsp" style=""></span>mg&#47;24<span class="elsevierStyleHsp" style=""></span>h&#46; The patient was discharged after 10 days to complete treatment at home&#46; He was readmitted 7 days later with fever&#44; myalgia&#44; and epigastralgia&#46; Clinical laboratory tests showed anemia &#40;hemoglobin 11&#46;3<span class="elsevierStyleHsp" style=""></span>g&#47;dl&#41; and leukopenia &#40;2940&#47;mm<span class="elsevierStyleSup">3</span>&#41;&#44; with a normal blood smear&#46; Piperacillin&#47;tazobactam was switched to ceftazidime&#44; while the aminoglycoside was maintained&#44; leading to an improvement in laboratory parameters&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Our second case was a 23-year-old man with CF genotype F508del&#47;unknown mutation with the following lung function status&#58; FVC 2950<span class="elsevierStyleHsp" style=""></span>ml &#40;60&#37;&#41;&#59; FEV<span class="elsevierStyleInf">1</span>&#58; 1670<span class="elsevierStyleHsp" style=""></span>ml &#40;42&#37;&#41;&#59; and FEV<span class="elsevierStyleInf">1</span>&#47;FVC &#40;56&#46;56&#37;&#41;&#59; along with chronic <span class="elsevierStyleItalic">P&#46; aeruginosa</span> bronchial infection&#46; In view of symptoms of respiratory infection and functional decline&#44; treatment was started with piperacillin&#47;tazobactam 4&#47;0&#46;5<span class="elsevierStyleHsp" style=""></span>g&#47;8<span class="elsevierStyleHsp" style=""></span>h and tobramycin 400<span class="elsevierStyleHsp" style=""></span>mg&#47;24<span class="elsevierStyleHsp" style=""></span>h&#46; On day 17 of treatment&#44; he developed fever &#40;39&#46;5<span class="elsevierStyleHsp" style=""></span>&#176;C&#41; with no other accompanying signs&#46; Clinical laboratory tests revealed anemia &#40;hemoglobin 12&#46;5<span class="elsevierStyleHsp" style=""></span>g&#47;dl&#41;&#44; thrombocytopenia &#40;96&#44;000&#47;mm<span class="elsevierStyleSup">3</span>&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#44; coagulation changes &#40;prothrombin activity 56&#37; and cephalin time 41&#46;6 s&#41;&#44; and hepatic involvement &#40;GOT 170<span class="elsevierStyleHsp" style=""></span>U&#47;l&#44; GPT 51<span class="elsevierStyleHsp" style=""></span>U&#47;l&#44; GGT 24<span class="elsevierStyleHsp" style=""></span>U&#47;l&#44; and LDH 1462<span class="elsevierStyleHsp" style=""></span>U&#47;l&#41;&#46; Piperacillin&#47;tazobactam was switched to levofloxacin&#46; On day 4 after admission&#44; the patient&#39;s platelet count &#40;165&#44;000&#47;mm<span class="elsevierStyleSup">3</span>&#41;&#44; coagulation parameters &#40;prothrombin activity 102&#37; y and cephalin time 29&#46;6<span class="elsevierStyleHsp" style=""></span>s&#41;&#44; and liver function &#40;GOT 18<span class="elsevierStyleHsp" style=""></span>U&#47;l&#44; GPT 27<span class="elsevierStyleHsp" style=""></span>U&#47;l&#44; GGT 19<span class="elsevierStyleHsp" style=""></span>U&#47;l&#44; LDH 285<span class="elsevierStyleHsp" style=""></span>U&#47;l&#41; improved&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Several papers have been published on the adverse effects of piperacillin&#47;tazobactam in CF patients&#46; For reasons that are still unclear&#44; these events seem to be more common in CF than in the general population&#46;<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 &#40;&#62;10 days&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">1&#8211;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&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">2</span></a> Leukopenia&#44; thrombocytopenia&#44; fever&#44; 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&#44; but no cases of coagulation changes or liver toxicity have been published&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">In our experience&#44; CF patients show increased adverse effects to piperacillin&#47;tazobactam&#44; so they should be used with caution in this population&#46; One of our patients&#44; who was a frequent exacerbator &#40;requiring &#8805;2 intravenous antibiotics&#47;year&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">6</span></a> received piperacillin&#47;tazobactam in an attempt to improve results obtained with previous antibiotic combinations&#46; We conclude that this drug may be considered for use in second-line treatment&#44; but it is inadvisable to use it for periods longer than 14 days&#46; High doses should also be avoided&#44; even for short periods of time&#46;</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&#46;</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" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Diab C&#225;ceres L&#44; Marcos MC&#44; Gir&#243;n Moreno RM&#46; Fibrosis qu&#237;stica y piperacilina tazobactam&#58; reacciones adversas&#46; Arch Bronconeumol&#46; 2015&#59;51&#58;664&#8211;665&#46;</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&#58; female&#59; iv&#58; intravenous&#59; M&#58; male&#59; NR&#58; not reported&#59; PTZ&#58; piperacillin&#47;tazobactam&#46;</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&nbsp;\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&nbsp;\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&nbsp;\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&#47;Sex&nbsp;\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&nbsp;\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 &#40;day&#41;&nbsp;\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 &#40;&#37;&#41;&nbsp;\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&nbsp;\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&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1996&#8211;1998&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NR&nbsp;\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&#46;9<span class="elsevierStyleHsp" style=""></span>g&#47;kg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Fever&#44; general malaise&#44; and headacheLeukopenia and thrombocytopenia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">PTZ discontinuation&nbsp;\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&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">3</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2010&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">39&#47;F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#46;5<span class="elsevierStyleHsp" style=""></span>g iv every 6<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hemolytic anemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Transfusion&#44; steroids&#44; iv immunoglobulin&#44; PTZ discontinuation&nbsp;\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&#46;C&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">2</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">19&#47;F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hemolytic anemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Transfusion&#44; inmunoglobulina iv&#44; PTZ discontinuation&nbsp;\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&#46;E&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">4</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">24&#47;M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hemolytic anemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Transfusion&#44; steroids&#44; inmunoglobulina iv&#44; PTZ discontinuation&nbsp;\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&#47;Tazobactam in Cystic Fibrosis&#46;</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&#44; thrombocytopenia and fever related to piperacillin&#47;tazobactam treatment&#46; A retrospective analysis in 38 children with cystic fibrosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "P&#46; Reichardt"
                            1 => "W&#46; Handrick"
                            2 => "A&#46; Linke"
                            3 => "R&#46; Schille"
                            4 => "W&#46; 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&#47;tazobactam administration&#58; a case report and discussion of pathophysiology"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "R&#46;C&#46; Zanetti"
                            1 => "A&#46;K&#46; 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&#46; Bandara"
                            1 => "D&#46;B&#46; Seder"
                            2 => "G&#46; Garratty"
                            3 => "R&#46;M&#46; Leger"
                            4 => "J&#46;B&#46; 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&#46;E&#46; Marik"
                            1 => "P&#46; 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&#46;F&#46; Roehmel"
                            1 => "C&#46; Schwarz"
                            2 => "A&#46; Mehl"
                            3 => "P&#46; Stock"
                            4 => "D&#46; 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&#46;K&#46; Block"
                            1 => "K&#46;L&#46; Vandemheen"
                            2 => "E&#46; Tullis"
                            3 => "D&#46; Fergusson"
                            4 => "S&#46; Doucette"
                            5 => "D&#46; 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"
]
Share
Journal Information
Vol. 51. Issue 12.
Pages 664-665 (December 2015)
Vol. 51. Issue 12.
Pages 664-665 (December 2015)
Letter to the Editor
Full text access
Cystic Fibrosis and Piperacillin/Tazobactam: Adverse Reactions
Fibrosis quística y piperacilina tazobactam: reacciones adversas
Visits
8069
Layla Diab Cáceres
Corresponding author
layladch@gmail.com

Corresponding author.
, María Celeste Marcos, Rosa María Girón Moreno
Servicio de Neumología, Hospital Universitario de La Princesa, Madrid, Spain
This item has received
Article information
Full Text
Bibliography
Download PDF
Statistics
Tables (1)
Table 1. Adverse Reactions Associated With Piperacillin/Tazobactam in Cystic Fibrosis.
Full Text
To the Editor,

Cystic fibrosis (CF) patients commonly have chronic lung infections and frequent exacerbations caused by a range of bacteria, including Pseudomonas aeruginosa (P. aeruginosa) and Achromobacter xylosoxidan, 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.1

We report 2 cases of CF patients, presenting with fever and myelotoxicity caused by piperacillin/tazobactam administered for P. aeruginosa infection, who required a switch to another antibiotic.

The first patient was a 20-year-old man with CF genotype F508del/F508, colonized with methicillin-resistant Staphylococcus aureus and P. aeruginosa. He was admitted for a respiratory exacerbation, with increased cough, greenish expectoration, weight loss, and worsening lung function, manifesting as forced vital capacity (FVC) 2950ml (53%), forced expiratory volume in 1second (FEV1) 1885ml (42%), and FEV1/FVC 63.90. Treatment was started with intravenous piperacillin/tazobactam 4/0.5g every 8hours, and tobramycin 400mg/24h. 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 11.3g/dl) and leukopenia (2940/mm3), with a normal blood smear. Piperacillin/tazobactam was switched to ceftazidime, while the aminoglycoside was maintained, leading to an improvement in laboratory parameters.

Our second case was a 23-year-old man with CF genotype F508del/unknown mutation with the following lung function status: FVC 2950ml (60%); FEV1: 1670ml (42%); and FEV1/FVC (56.56%); along with chronic P. aeruginosa bronchial infection. In view of symptoms of respiratory infection and functional decline, treatment was started with piperacillin/tazobactam 4/0.5g/8h and tobramycin 400mg/24h. On day 17 of treatment, he developed fever (39.5°C) with no other accompanying signs. Clinical laboratory tests revealed anemia (hemoglobin 12.5g/dl), thrombocytopenia (96,000/mm3) (Table 1), coagulation changes (prothrombin activity 56% and cephalin time 41.6 s), and hepatic involvement (GOT 170U/l, GPT 51U/l, GGT 24U/l, and LDH 1462U/l). Piperacillin/tazobactam was switched to levofloxacin. On day 4 after admission, the patient's platelet count (165,000/mm3), coagulation parameters (prothrombin activity 102% y and cephalin time 29.6s), and liver function (GOT 18U/l, GPT 27U/l, GGT 19U/l, LDH 285U/l) improved.

Table 1.

Adverse Reactions Associated With Piperacillin/Tazobactam in Cystic Fibrosis.

Reference  Year  Number of Patients  Age/Sex  Dose  Onset of Symptoms (day)  Adverse Effects (%)  Treatment 
Reichardt P.1  1996–1998  32  NR  Accumulated dose over 14 days 4.9g/kg  11  Fever, general malaise, and headacheLeukopenia and thrombocytopenia  PTZ discontinuation 
Bandara M.3  2010  39/F  4.5g iv every 6Hemolytic anemia  Transfusion, steroids, iv immunoglobulin, PTZ discontinuation 
Zanetti R.C.2  2013  19/F  NR  13  Hemolytic anemia  Transfusion, inmunoglobulina iv, PTZ discontinuation 
Marik P.E.4  2013  24/M  NR  15  Hemolytic anemia  Transfusion, steroids, inmunoglobulina iv, PTZ discontinuation 

F: female; iv: intravenous; M: male; NR: not reported; PTZ: piperacillin/tazobactam.

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.3 Risk factors include a high accumulative dose of antibiotics in a short period of time and prolonged treatments (>10 days).1–3 Haptene-induced hemolytic anemia4 has been reported to respond well to intravenous immunoglobulin.2 Leukopenia, thrombocytopenia, fever, and hypersensitivity reactions that range from pruritis and skin rash to anaphylactic shock5 have also been reported, but no cases of coagulation changes or liver toxicity have been published.

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),6 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.

Conflict of Interests

The authors state that they have no conflict of interests.

References
[1]
P. Reichardt, W. Handrick, A. Linke, R. Schille, W. Kiess.
Leukocytopenia, thrombocytopenia and fever related to piperacillin/tazobactam treatment. A retrospective analysis in 38 children with cystic fibrosis.
Infection, 27 (1999), pp. 355-356
[2]
R.C. Zanetti, A.K. Biswas.
Hemolytic anemia as a result of piperacillin/tazobactam administration: a case report and discussion of pathophysiology.
Mil Med, 178 (2013), pp. e 1045-e 1047
[3]
M. Bandara, D.B. Seder, G. Garratty, R.M. Leger, J.B. Zuckerman.
Piperacillin-induced immune hemolytic anemia in an adult with cystic fibrosis.
Case Rep Med, 2010 (2010), pp. 161454
[4]
P.E. Marik, P. Parekh.
Life-threatening piperacilin-induced inmune haemolysis in a patient with cystic fibrosis.
BMJ Case Rep, (2013),
[5]
J.F. Roehmel, C. Schwarz, A. Mehl, P. Stock, D. Staab.
Hypersensitivity to antibiotics in patients with cystic fibrosis.
J Cyst Fibros, 13 (2014), pp. 205-211
[6]
J.K. Block, K.L. Vandemheen, E. Tullis, D. Fergusson, S. Doucette, D. Haase, et al.
Predictors of pulmonary exacerbations in patients with cystic fibrosis infected with multi-resistant bacteria.
Thorax, 61 (2006), pp. 969-974

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.

Copyright © 2015. SEPAR
Archivos de Bronconeumología
Article options
Tools

Are you a health professional able to prescribe or dispense drugs?