Letter to the Editor
Daptomycin associated eosinophilic pneumonia
Neumonitis eosinofílica por daptomicina
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It can be primary (idiopathic) or secondary; secondary causes include treatment with daptomycin, a lipopeptide used to treat Gram-positive bacterial infections.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Here we present a case of AEP secondary to daptomycin treatment.</p><p id="par0010" class="elsevierStylePara elsevierViewall">This case involves a 92-year-old man, allergic to penicillin, hypertensive, diabetic and with chronic kidney disease. He was admitted to our center with acute cholecystitis and bacteremia due to <span class="elsevierStyleItalic">Enterobacter aerogenes</span>, and ciprofloxacin treatment was started. On the sixth day he started with a fever accompanied with shivering and feeling generally unwell. New blood cultures were obtained, and the physical examination revealed phlebitis in the inner elbow area of the left arm, so vancomycin was added to the initial antibiotic therapy. This was maintained when growth was seen in blood cultures of <span class="elsevierStyleItalic">Staphylococcus aureus</span> oxacillin sensitive (SAMS), with a MIC for vancomycin by E-test® of 1.5 mg/d. Despite antibiotic therapy, the patient continued with feverish peaks and growth of oxacillin-susceptible <span class="elsevierStyleItalic">S. aureus</span> in control cultures at 72 h, so the regimen was changed to daptomycin 10 mg/kg/day plus fosfomycin 2 g/6 h and complementary studies were requested. Henceforth he presented favorable clinical and laboratory progress, with negative control blood cultures, the echo-Doppler showing no signs of suppurative thrombophlebitis and the echocardiogram with no vegetations. So fosfomycin was suspended after one week, and the daptomycin was maintained.</p><p id="par0015" class="elsevierStylePara elsevierViewall">On the twelfth day of treatment with daptomycin, he began to present febrile peaks, associated with dyspnea and respiratory failure, without locating a focus and with negative successive cultures. An urgent CT scan was performed, which showed patchy consolidation areas associated with a reticular pattern in the middle lobe and lingula. With the suspicion of eosinophilic pneumonitis secondary to daptomycin, this drug was discontinued and a systemic corticosteroid was started. The patient remained afebrile from that moment forward, with progressive improvement in respiratory dynamics in the first 24 h, as well as radiological resolution of the infiltrates after one week. A bronchoscopy was not performed due to the patient's comorbidities, but he presented peripheral eosinophilia.</p><p id="par0020" class="elsevierStylePara elsevierViewall">AEP was first described in 1989, but it was in 1994 that Allen et al. established the diagnostic criteria for this syndrome: fever of at least 5 days, hypoxemia, diffuse alveolar or alveolar-interstitial infiltrates, and eosinophilia greater than 25% on BAL.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> It is characterised by a condition which develops within one month (usually less than a week) of a non-productive cough (95%), dyspnea (92%), fever (88%), malaise, night sweats, chills and pleuritic pain.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> The physical examination shows tachypnea and bibasal crackles. The laboratory tests usually show leucocytosis with neutrophilia, with subsequent appearance of peripheral eosinophilia; it can be associated with elevated CRP, IgE and/or ESR. In imaging it usually presents reticular or ground-glass opacities, predominantly in an apical location (50% of cases), and it can be migratory in up to 25%.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The aetiology can be primary (idiopathic), or secondary with the focus being placed on exposure to antibiotics (daptomycin, minocycline, nitrofurantoin), steroidal anti-inflammatory drugs (sulfasalazine, mesalazine), and anti-seizural drugs.</p><p id="par0030" class="elsevierStylePara elsevierViewall">According to papers published to date, daptomycin is one of the main causes of secondary AEP.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Since the approval for its use in soft tissue Gram-positive bacterial infections in September 2003, and the subsequent extension in 2006 to bacteremia by <span class="elsevierStyleItalic">S. aureus</span> its prescription has continued to expand. The first cases are reported in 2007<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> and since then 51 cases have been published. The diagnostic criteria according to the FDA guidelines are presented in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The pathophysiology is unclear; one theory is based on the accumulation of daptomycin hindering the production of surfactant causing damage and inflammation in the lung epithelium; another theory is that the detection of an antigen by alveolar macrophages leads to the recruitment of T-Helper 2 Lymphocytes, thus releasing IL-5 that promotes the production and migration of eosinophils to the lung.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Daptomycin AEP is a rare but serious entity. Its incidence continues to increase over the last few years, in parallel with the increase in the use of daptomycin. It is important to know about this adverse effect, since the diagnosis requires clinical suspicion, and it is essential to suspend the drug for its resolution.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Fernández-González R, Díaz López MD, Lorenzo Vizcaya AM, González Noya A. Neumonitis eosinofílica por daptomicina. Med Clin (Barc). 2021;156:148–149.</p>" ] ] "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">BAL: bronchoalveolar lavage; FDA: Food and Drug Administration; X-ray: radiography; CT: computed tomography; NIMV: non-invasive mechanical ventilation.</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="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Definitive \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Probable \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Possible \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Unlikely \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Concurrent exposure to daptomycin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Concurrent exposure to daptomycin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Concurrent exposure to daptomycin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">All other cases that did not meet criteria \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Dyspnea with increased oxygen requirement or NIMV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Dyspnea with increased oxygen requirement or NIMV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">New infiltrates on chest X-ray or CT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">New infiltrates on chest X-ray or CT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">New infiltrates on chest X-ray or CT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Clinical improvement following daptomycin withdrawal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BAL > 25% eosinophils \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BAL < 25% eosinophils or peripheral eosinophilia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Clinical improvement following daptomycin withdrawal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Clinical improvement following daptomycin withdrawal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fever \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2514277.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Diagnostic criteria for eosinophilic pneumonitis associated with the use of daptomycin according to the FDA guidelines.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "FDA Drug And Safety Communication: Eosinophilic pneumonia associated with the use of Cubicin (daptomycin). 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"fecha" => "2016" "volumen" => "5" "paginaInicial" => "55" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27999664" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000015600000003/v1_202102051000/S2387020620306422/v1_202102051000/en/main.assets" "Apartado" => array:4 [ "identificador" => "43309" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23870206/0000015600000003/v1_202102051000/S2387020620306422/v1_202102051000/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020620306422?idApp=UINPBA00004N" ]
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