Case report
Ceftazidime-induced thrombocytopenia
Trombocitopenia inducida por ceftazidima
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Domingo-Chiva, M. Díaz-Rangel, J.Á. Monsalve-Naharro, P. Cuesta-Montero, J.V. Catalá-Ripoll, E.M. García-Martínez" "autores" => array:6 [ 0 => array:4 [ "nombre" => "E." "apellidos" => "Domingo-Chiva" "email" => array:1 [ 0 => "estherdomingochiva@hotmail.com" ] "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" => "M." "apellidos" => "Díaz-Rangel" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "J.Á." "apellidos" => "Monsalve-Naharro" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "P." "apellidos" => "Cuesta-Montero" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 4 => array:3 [ "nombre" => "J.V." "apellidos" => "Catalá-Ripoll" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 5 => array:3 [ "nombre" => "E.M." "apellidos" => "García-Martínez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Farmacia Hospitalaria, Gerencia de Atención Integrada de Albacete, Albacete, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Anestesia, Reanimación y Terapéutica del Dolor, Gerencia de Atención Integrada de Albacete, Albacete, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Trombocitopenia inducida por ceftazidima" ] ] "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" => 1164 "Ancho" => 1600 "Tamanyo" => 99400 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Evolution over time of the platelet count in relation to the antibiotic treatment administered. Preoperative, immediate postoperative and admission (day 0) levels are shown. Cef: ceftazidime; Lev: levofloxacin; Imm. Postop. Immediate postoperative; Preop: preoperative; PT: piperaziline/tazobactam; TP: Platelet transfusion; Tobram: tobramycin.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Ceftazidime is a third generation cephalosporin that, because of its broad antibacterial spectrum, is frequently used in clinical practice to treat a variety of infections. Haematologic adverse drug reactions (ADR) are not a characteristic of ceftazidime, and the summary of product characteristics indicates that thrombocytopaenia is an uncommon ADR described in less than 1% of patients in clinical trials.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Case report</span><p id="par0010" class="elsevierStylePara elsevierViewall">We present the case of a 78-year-old man admitted to the Intensive Care Unit of the Anaesthesiology and Resuscitation Service for respiratory failure secondary to nosocomial pneumonia in the postoperative period of laparoscopic hepatic bisegmentectomy for hepatocarcinoma. He entered the Unit intubated and under mechanical ventilation, with an APACHE II score of 13. He was extubated at 24<span class="elsevierStyleHsp" style=""></span>h, although he continued to require non-invasive mechanical ventilation. At admission, empirical intravenous antibiotic therapy with piperacillin/tazobactam 4<span class="elsevierStyleHsp" style=""></span>g/0.5<span class="elsevierStyleHsp" style=""></span>g/6<span class="elsevierStyleHsp" style=""></span>h and levofloxacin 500<span class="elsevierStyleHsp" style=""></span>mg/12<span class="elsevierStyleHsp" style=""></span>h was started. At 48<span class="elsevierStyleHsp" style=""></span>h, the Microbiology Service reported significant growth of <span class="elsevierStyleItalic">Escherichia coli</span> and <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> in respiratory secretions obtained by tracheal aspirate. In view of worsening respiratory symptoms and chest X-ray, and since the emergency antibiogram showed sensitivity to ceftazidime but did not test the antibiotics initially administered, it was decided to substitute the initial antibiotic therapy with ceftazidime 2<span class="elsevierStyleHsp" style=""></span>g/8<span class="elsevierStyleHsp" style=""></span>h and tobramycin 500<span class="elsevierStyleHsp" style=""></span>mg/24<span class="elsevierStyleHsp" style=""></span>h.</p><p id="par0015" class="elsevierStylePara elsevierViewall">After the start of this new treatment, the patient presented progressive lowering of platelet count, which continued 3 days after suspension of tobramycin (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The patient continued to require non-invasive mechanical ventilation due to respiratory failure, although he showed no signs of sepsis and remained afebrile with normal procalcitonin levels and no coagulopathy or any other evidence of organic dysfunction associated with respiratory insufficiency. Thrombocytopenia was not accompanied by a decrease in red or white blood cells, and did not coincide with the addition of other drugs to the patient's treatment. In addition, platelet levels fell progressively to the point of requiring transfusion of platelets through a central venous line. Suspecting, due to the timing of symptom onset, that this was secondary ceftazidime, it was decided to suspend this drug after 7 days of treatment. Platelet levels began to rise, but taking into account the severity of the patient's condition and the improvement of the clinical picture with ceftazidime, it was re-started in order to prolong treatment. The reintroduction of ceftazidime again coincided with a new decrease in platelet count, so it was decided to replace it with imipenem. Withdrawal of ceftazidime was accompanied by a progressive improvement in platelet count (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">The patient made good progress, non-invasive mechanical ventilation was withdrawn, and he was discharged to the hospital ward. The case presented was reported to the Spanish Pharmacovigilance System by the Unit's pharmacist. Naranjo's algorithm,<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> we calculated that there was a probably causal association (8 points) between the drug and the adverse event (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0025" class="elsevierStylePara elsevierViewall">Thrombocytopenia is not an ADR commonly associated with cephalosporins. The product characteristics of ceftazidime list thrombocytopenia as an uncommon ADR, and although it has been reported with other cephalosporins of the same group, we found no reports of ceftazidime-induced thrombocytopenia in the literature.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3–5</span></a> The exact incidence of drug-induced thrombocytopenia (DIT) is not known, since case reporting is voluntary and no studies have explored this association. The estimated minimum incidence, based on several epidemiological studies in the US and Europe, is around 10 cases per million inhabitants per year. However, this could be much higher in specific populations, such as hospitalised patients, and an estimated 25% of critically ill patients develop DIT.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Thrombocytopenia can be caused by various diseases, including infection, sepsis, cancer, vitamin deficiencies, and microangiopathies; it can also be secondary to certain drugs, in which case, it can be caused by a direct toxic effect on the thrombopoietic mechanism in the bone marrow, resulting in decreased platelet production, or through immune-mediated mechanisms resulting in increased platelet destruction.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> The drugs most commonly associated with this ADR are cinchona alkaloids (quinine/quinidine), sulphonamides, NSAIDs, diuretics, anticonvulsants, tuberculostatics, heparin and linezolid.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">6,8</span></a> The most widely used laboratory test is determination of drug-dependent anti-platelet IgG antibodies in serum, however, this test is not available in hospitals, and has poor sensitivity.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> In our case, it was not performed due to unavailability in our centre. The diagnosis of DIT was established empirically based on the timing of administration of ceftazidime and onset of thrombocytopenia, and recurrence after re-exposure to the drug.</p><p id="par0035" class="elsevierStylePara elsevierViewall">In DIT, it is essential to identify and eliminate the causal agent rapidly before bleeding can occur. This calls for a thorough review of the drugs administered to the patient, and early suspension of the suspected culprit. However, deciding which drug or drugs to suspend often places clinicians in a dilemma. In our case, we were able to establish a clear temporal relationship with both onset after drug administration and recurrence after re-exposure.</p><p id="par0040" class="elsevierStylePara elsevierViewall">The spontaneous notification of suspicion of an ADR by the health professional, which in Spain is mandatory under the Royal Decree of Pharmacovigilance,<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> has proven to be the most effective method of identifying previously unknown risks associated with medicines. The Naranjo algorithm was developed to provide a causality assessment between an ADR and a drug.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> In this case, the Naranjo score was 8, indicating that thrombocytopenia was a probable ADR to ceftazidime. Using a 10-item questionnaire, this algorithm classifies ADRs by score as definite, probably, possible and doubtful.</p><p id="par0045" class="elsevierStylePara elsevierViewall">If DIT is suspected, the pharmacist can actively intervene by reviewing the prescribed medication and identifying the drug responsible. In this way it is possible to avoid the unnecessary withdrawal of other treatments that are unlikely to have caused thrombocytopenia.</p><p id="par0050" class="elsevierStylePara elsevierViewall">In conclusion, we would like to emphasize that ceftazidime-induced thrombocytopenia, given its potential severity, should always be considered, particularly when the symptoms cannot be explained by other causes. Pharmaceutical intervention may contribute to the management and/or resolution of DIT.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Ethical responsibilities</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Protection of human and animal rights</span><p id="par0055" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this study.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Data confidentiality</span><p id="par0060" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appears in this article.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Right to privacy and informed consent</span><p id="par0065" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appears in this article.</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conflict of interests</span><p id="par0070" class="elsevierStylePara elsevierViewall">None declared.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres945440" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec918127" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres945441" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec918126" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Case report" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Discussion" ] 7 => array:3 [ "identificador" => "sec0020" "titulo" => "Ethical responsibilities" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Protection of human and animal rights" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Data confidentiality" ] 2 => array:2 [ "identificador" => "sec0035" "titulo" => "Right to privacy and informed consent" ] ] ] 8 => array:2 [ "identificador" => "sec0040" "titulo" => "Conflict of interests" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2017-01-07" "fechaAceptado" => "2017-03-27" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec918127" "palabras" => array:6 [ 0 => "Ceftazidime" 1 => "Thrombocytopenia" 2 => "Blood dyscrasias" 3 => "Cephalosporins" 4 => "Pharmacovigilance" 5 => "Drug-related side effects and adverse reactions" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec918126" "palabras" => array:6 [ 0 => "Ceftazidima" 1 => "Trombocitopenia" 2 => "Discrasias sanguíneas" 3 => "Cefalosporinas" 4 => "Farmacovigilancia" 5 => "Efectos colaterales y reacciones adversas relacionados con medicamentos" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Ceftazidime is an antibiotic belonging to the group of third generation cephalosporins, frequently used in clinical practice for its broad antibacterial spectrum. A case report is presented on a 78-year-old man who entered the intensive care unit due to respiratory failure secondary to nosocomial pneumonia in the postoperative period of a laparoscopic hepatic bisegmentectomy for a hepatocarcinoma. It required invasive mechanical ventilation and was treated with ceftazidime, developing a progressive decrease in platelet count after the onset of this drug and after re-exposure to it, not coinciding with the introduction of other drugs. The adverse reaction was reported to the Spanish pharmacosurveillance system and according to the Naranjo algorithm the causal relationship was probable. Since no case of ceftazidime-induced thrombocytopenia was found in the literature, we consider knowledge of it relevant as an adverse effect to be taken into account given its potential severity, especially when it cannot be explained by other causes.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La ceftazidima es un antibiótico perteneciente al grupo de las cefalosporinas de tercera generación, de uso frecuente en la práctica clínica por su amplio espectro antibacteriano. Presentamos el caso de un varón de 78 años que ingresó en la unidad de cuidados intensivos por una insuficiencia respiratoria secundaria a una neumonía nosocomial en el postoperatorio de una bisegmentectomía hepática laparoscópica por un hepatocarcinoma. Precisó ventilación mecánica invasiva, y se trató con ceftazidima, desarrollando un descenso progresivo en la cifra de plaquetas tras el comienzo de este fármaco y tras la reexposición al mismo, no coincidiendo temporalmente con la introducción de otros fármacos. La reacción adversa fue comunicada al Sistema Español de Farmacovigilancia y según el algoritmo de Naranjo la relación de causalidad fue probable. Puesto que no se ha encontrado descrito en la literatura ningún caso de trombocitopenia inducida por ceftazidima se considera relevante su conocimiento para que sea una reacción adversa a tener en cuenta dada su potencial gravedad, especialmente cuando no sea explicable por otras causas.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Domingo-Chiva E, Díaz-Rangel M, Monsalve-Naharro JÁ, Cuesta-Montero P, Catalá-Ripoll JV, García-Martínez EM. Trombocitopenia inducida por ceftazidima. Rev Esp Anestesiol Reanim. 2017;64:590–593.</p>" ] ] "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" => 1164 "Ancho" => 1600 "Tamanyo" => 99400 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Evolution over time of the platelet count in relation to the antibiotic treatment administered. Preoperative, immediate postoperative and admission (day 0) levels are shown. Cef: ceftazidime; Lev: levofloxacin; Imm. Postop. Immediate postoperative; Preop: preoperative; PT: piperaziline/tazobactam; TP: Platelet transfusion; Tobram: tobramycin.</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:1 [ "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="" valign="top" scope="col" style="border-bottom: 2px solid black"> \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">Yes \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">No \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">NS \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">Score \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">Are there previous conclusive reports on this reaction? \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="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \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">Did the adverse event appear after the suspected drug was administered? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">+2 \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="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \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">Did the adverse reaction improve when the drug was discontinued or a specific antagonist was administered? \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="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \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></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Did the adverse reaction reappear when the drug was readministered? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">+2 \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="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \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">Are there alternative causes (other than the drug) that could on their own have caused the reaction? \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="char" valign="top">+2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \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">Did the reaction reappear when a placebo was given? \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="char" valign="top">+1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \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">Was the drug detected in the blood (or other fluids) in concentrations known to be toxic? \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="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \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">Was the reaction more severe when the close was increased or less severe when the dose was decreased? \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="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \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">Did the patient have a similar reaction to the same or similar drugs in any previous exposure? \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="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \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">Was the adverse event confirmed by any objective evidence? \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="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \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></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " colspan="3" align="left" valign="top">Total score</td><td class="td" title="table-entry " align="left" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">Score</span>:<br><span class="elsevierStyleHsp" style=""></span>Definite: 9 points or more.<br><span class="elsevierStyleHsp" style=""></span>Probable: 5–8<br><span class="elsevierStyleHsp" style=""></span>Possible: 1–4 points.<br><span class="elsevierStyleHsp" style=""></span>Doubtful: 0 points or less.</td><td class="td" title="table-entry " align="left" valign="top">Probable: \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1600640.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Causal relationship for this case report, according to the Naranjo algorithm.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a></p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Agencia Española del Medicamento. 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Sebesta" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Mil Med" "fecha" => "2012" "volumen" => "177" "paginaInicial" => "352" "paginaFinal" => "354" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22479926" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0075" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cefepime-associated thrombocytopenia in a critically ill patient" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "P.P. Lim" 1 => "C.P. Chong" 2 => "N.A. 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