Letter to the Editor
Fluoroquinolone therapy could influence the clinical signs of pulmonary coccidioidomycosis
La terapia con fluoroquinolonas podría influir en las manifestaciones clínicas de la coccidioidomicosis pulmonar
René Agustín Flores-Franco
Instituto Mexicano del Seguro Social (IMSS), Hospital General Regional de Zona 1, Unidad “Morelos”, Departamento de Medicina Interna, Av. Universidad y García Conde, Col. Centro, C.P. 3100 Chihuahua, Chih, Mexico
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Antifungal prophylaxis in solid organ transplant recipients” [Rev Iberoam Micol. 33 (4) (2016) 187–195]" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:1 [ "paginaInicial" => "60" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Fe de errores: «EPICO 3.0. Profilaxis antifúngica en el paciente trasplantado de órgano sólido» <[Rev Iberoam Micol. 33 (4) (2016) 187–195]>" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Rafael Zaragoza, José María Aguado, Ricard Ferrer, Alejandro H. 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"apellidos" => "Rodríguez" ] 4 => array:2 [ "nombre" => "Emilio" "apellidos" => "Maseda" ] 5 => array:2 [ "nombre" => "Pedro" "apellidos" => "Llinares" ] 6 => array:2 [ "nombre" => "Santiago" "apellidos" => "Grau" ] 7 => array:2 [ "nombre" => "Patricia" "apellidos" => "Muñoz" ] 8 => array:2 [ "nombre" => "Jesús" "apellidos" => "Fortún" ] 9 => array:2 [ "nombre" => "Mercedes" "apellidos" => "Bouzada" ] 10 => array:2 [ "nombre" => "Juan Carlos" "apellidos" => "del Pozo" ] 11 => array:2 [ "nombre" => "Rafael" "apellidos" => "León" ] 12 => array:1 [ "colaborador" => "EPICO Project Group" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1130140617300098?idApp=UINPBA00004N" "url" => "/11301406/0000003400000001/v2_201704050141/S1130140617300098/v2_201704050141/en/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S1130140616300547" "issn" => "11301406" "doi" => "10.1016/j.riam.2016.05.002" "estado" => "S300" "fechaPublicacion" => "2017-01-01" "aid" => "407" "copyright" => "Asociación Española de Micología" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "cor" "cita" => "Rev Iberoam Micol. 2017;34:57-8" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 1377 "formatos" => array:3 [ "EPUB" => 36 "HTML" => 1080 "PDF" => 261 ] ] "es" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Carta a los Directores</span>" "titulo" => "Mucormicosis renal grave en un paciente crítico" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "57" "paginaFinal" => "58" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Isolated renal mucormycosis in a critically ill patient" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figura 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 749 "Ancho" => 1000 "Tamanyo" => 297819 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Elementos fúngicos compatibles con un diagnóstico de mucormicosis. Se observan hifas anchas y ramificadas en ángulo recto. El parénquima renal, que presenta una pielonefritis crónica granulomatosa, está necrosado (tinción de PAS, ×40).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Montserrat Vallverdú Vidal, Silvia Iglesias Moles, Meritxell Palomera Fernandez, Mercedes Palomar Martinez" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Montserrat" "apellidos" => "Vallverdú Vidal" ] 1 => array:2 [ "nombre" => "Silvia" "apellidos" => "Iglesias Moles" ] 2 => array:2 [ "nombre" => "Meritxell" "apellidos" => "Palomera Fernandez" ] 3 => array:2 [ "nombre" => "Mercedes" "apellidos" => "Palomar Martinez" ] ] ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1130140616300547?idApp=UINPBA00004N" "url" => "/11301406/0000003400000001/v2_201704050141/S1130140616300547/v2_201704050141/es/main.assets" ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Fluoroquinolone therapy could influence the clinical signs of pulmonary coccidioidomycosis" "tieneTextoCompleto" => true "saludo" => "<span class="elsevierStyleItalic">Dear Editors</span>," "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "58" "paginaFinal" => "59" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "René Agustín Flores-Franco" "autores" => array:1 [ 0 => array:3 [ "nombre" => "René Agustín" "apellidos" => "Flores-Franco" "email" => array:1 [ 0 => "rflores99@prontomail.com" ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Instituto Mexicano del Seguro Social (IMSS), Hospital General Regional de Zona 1, Unidad “Morelos”, Departamento de Medicina Interna, Av. Universidad y García Conde, Col. Centro, C.P. 3100 Chihuahua, Chih, Mexico" "identificador" => "aff0005" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "La terapia con fluoroquinolonas podría influir en las manifestaciones clínicas de la coccidioidomicosis pulmonar" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Symptoms of coccidioidomycosis can frequently be mistaken with those of community-acquired pneumonia (CAP) and even be treated initially with antibacterials. Coccidioidal pneumonia is not an infrequent presentation and studies carried out in endemic zones of the United States have shown that 15% of CAP have a positive serology for <span class="elsevierStyleItalic">Coccidioides</span>,<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a> a reason why the most recent CAP management guidelines recommend thinking about coccidioidomycosis in those cases from endemic areas.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> There are no definitive studies regarding the possible influence of CAP's empiric therapy in the presentation of an unsuspected coccidioidomycosis. On the other hand, seeing that many cases of coccidioidal pneumonia present a spontaneous resolution of the signs and symptoms, a patient with unsuspected coccidioidomycosis receiving antibacterials could seem to respond satisfactorily. We herein expose (see <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>) the experience with the use of empiric antibacterials for CAP in five consecutive cases from our endemic area which were confirmed later on as pulmonary coccidioidomycosis.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0010" class="elsevierStylePara elsevierViewall">The pneumonic presentation of coccidioidomycosis is not infrequent and it has been reported as high as up to 44% of clinical forms among the Hispanic population.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a> Considering this scenario we must not be surprised if many cases are initially treated as CAP.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Because of their wide antibacterial spectrum, fluoroquinolones have been recommended as first line medications during the empiric treatment of CAP in adults, mainly if associated comorbidities exist.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> All of our patients were exposed to fluoroquinolones. Although lacking of an intrinsic antimycotic activity per se, fluoroquinolones can influence the growth of pathogenic fungi by inhibiting the enzymatic topoisomerase II and topoisomerase IV pathways or, influence their clinical manifestations on inhibiting the production of pro-inflammatory cytokines by the mononuclear cells.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1,2</span></a> This latter could also favor the induction of self-limited clinical forms on coccidioidomycosis as occurred in cases 4 and 5.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The co-infection with other microorganisms such as <span class="elsevierStyleItalic">Mycobacterium tuberculosis</span> could also explain our results. Those antibacterials with antituberculosis activity such as fluoroquinolones theoretically could alleviate the symptoms caused by the tuberculosis component. However, although our search for <span class="elsevierStyleItalic">M. tuberculosis</span> was not exhaustive in some of our cases, the progression of symptomatology after initiating the specific antimycotic treatment conduced convincingly toward its improvement discarding any possibility of comorbidity with tuberculosis.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Spontaneous remission of coccidioidomycosis is a frequent described phenomenon and undoubtedly could explain in part the evolution of our patients. In Valdivia's and colleagues cohort<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a> the majority of those patients initially diagnosed as bacterial CAP and who subsequently developed coccidioidomycosis were treated only with one or several cycles of antibacterials and everyone benefited from them. Unfortunately it was not mentioned which antibiotics were used.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The main repercussion an antimicrobial treatment indicated for bacterial CAP that may influence the clinical presentation of coccidioidomycosis would have is the delay in the diagnosis and, consequently, the consumption of unnecessary resources as we observed in case 1. Waiting for more information obtained from blinded trials, the clinician must be alert on how the use of antibacterials in CAP, especially the fluoroquinolones, could influence the clinical manifestations of coccidioidomycosis, contributing to the delay in the correct diagnosis and, consequently, in its treatment.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => 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:3 [ "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">DM: diabetes mellitus; F: female; M: male.</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">Case<br>Gender<br>(F/M) \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 (years) \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">Comorbidities \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">Symptoms presentation \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">Rx/CT \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">Initial antimicrobial treatment \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">Progress \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">Outcome \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">Case 1<br>F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><br>57 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><br>DM \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1-Month of cough, dyspnea, fever, significant weight loss, other constitutional symptoms \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Right lobar pneumonia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 days of moxifloxacin 400<span class="elsevierStyleHsp" style=""></span>mg IV o.d. and cefotaxime 1<span class="elsevierStyleHsp" style=""></span>g IV t.i.d. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Partial improvement in her general symptoms, gas exchange and leukocyte count \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">After initial antimicrobial withdraw her symptoms were exacerbated.<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">*</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">†</span></a> Amphotericin-B therapy was required \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">Case 2<br>F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><br>71 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><br>DM \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3-Weeks of cough, chest pain, fever, fatigue, night sweats \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Left lobar pneumonia. Multiple disseminated nodules \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7 days of moxifloxacin 400<span class="elsevierStyleHsp" style=""></span>mg IV o.d. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Gas exchange and leukocyte count improved, periods between fever peaks were more spaced \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Amphotericin-B therapy was required<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">†</span></a> \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">Case 3<br>M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><br>42 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><br>– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2-Weeks of dyspnea, cough, chest pain, fever, night sweats, malaise \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Left lobar pneumonia. Pleural effusion. Multiple disseminated nodules \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 days of ceftriaxone 1<span class="elsevierStyleHsp" style=""></span>g IM b.i.d. followed by 7 days of moxifloxacin 400<span class="elsevierStyleHsp" style=""></span>mg orally o.d. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Developed a cutaneous hypersensitivity reaction to ceftriaxone \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Symptoms improved significantly but the changes on a control chest X ray persisted.<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">†</span></a> Itraconazole therapy was required \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">Case 4<br>M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><br>34 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><br>DM \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1-Month of cough, progressive dyspnea, fever, sweating, significant weight loss \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Diffuse infiltration. Multiple disseminated nodules \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2-Weeks of moxifloxacin 400<span class="elsevierStyleHsp" style=""></span>mg orally o.d. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Symptoms improved until reaching an asymptomatic state \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Antimycotic therapy was not required<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">‡</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">¶</span></a> \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">Case 5<br>F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><br>73 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><br>– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2-Months of symptomatic right sided pleural effusion, fever, night sweats, malaise \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Right sided pleural effusion \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2-Weeks of ciprofloxacin 500<span class="elsevierStyleHsp" style=""></span>mg orally b.i.d. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Reach an asymptomatic state without recurrence of pleural effusion \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Antimycotic therapy was not required<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">§</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">¶</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1386716.png" ] ] ] "notaPie" => array:5 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "*" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">In case 1 it was decided to substitute the initial antimicrobial scheme to one with a wider coverage including staphylococci.</p>" ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "†" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">In cases 1, 2, and 3, a bronchoscopy finally revealed the presence of <span class="elsevierStyleItalic">Coccidioides</span> spherules.</p>" ] 2 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "‡" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">In case 4 a polymerase chain reaction (PCR) testing for <span class="elsevierStyleItalic">Coccidioides</span> on bronchoscopic biopsy resulted positive.</p>" ] 3 => array:3 [ "identificador" => "tblfn0020" "etiqueta" => "§" "nota" => "<p class="elsevierStyleNotepara" id="npar0020">In case 5 a PCR testing for <span class="elsevierStyleItalic">Coccidioides</span> on pleural biopsy resulted positive and a serologic testing confirmed high titers of IgM and IgG antibodies to <span class="elsevierStyleItalic">Coccidioides</span> antigens.</p>" ] 4 => array:3 [ "identificador" => "tblfn0025" "etiqueta" => "¶" "nota" => "<p class="elsevierStyleNotepara" id="npar0025">PCR testing for <span class="elsevierStyleItalic">M. tuberculosis</span> was performed in biopsies from cases 4 and 5 and resulted negative.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Coccidioidomycosis case-series under fluoroquinolone therapy.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Direct effects of non-antifungal agents used in cancer chemotherapy and organ transplantation on the development and virulence of <span class="elsevierStyleItalic">Candida</span> and <span class="elsevierStyleItalic">Aspergillus</span> species" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "S.C.A. Chen" 1 => "R.E. Lewis" 2 => "D.P. Kontoyiannis" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Virulence" "fecha" => "2001" "volumen" => "2" "paginaInicial" => "280" "paginaFinal" => "295" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21701255" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0035" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Immunomodulatory activities of fluoroquinolonas" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "A. 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Dean" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1086/511159" "Revista" => array:7 [ "tituloSerie" => "Clin Infect Dis" "fecha" => "2007" "volumen" => "44" "numero" => "Suppl. 2" "paginaInicial" => "S27" "paginaFinal" => "S72" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17278083" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0045" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epidemiological profile of coccidioidomycosis infection in a predominantly Hispanic population" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M.A. Pena-Ruiz" 1 => "Z.D. Mulla" 2 => "A. Escobar" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "South Med J" "fecha" => "2006" "volumen" => "99" "paginaInicial" => "1033" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0050" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Coccidioidomycosis as a common cause of community-acquired pneumonia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L. Valdivia" 1 => "D. Nix" 2 => "M. Wright" 3 => "E. Lindberg" 4 => "T. Fagan" 5 => "D. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 7 | 5 | 12 |
| 2024 September | 19 | 4 | 23 |
| 2024 August | 10 | 3 | 13 |
| 2024 July | 16 | 4 | 20 |
| 2024 June | 8 | 4 | 12 |
| 2024 May | 6 | 4 | 10 |
| 2024 April | 8 | 25 | 33 |
| 2024 March | 12 | 10 | 22 |
| 2024 February | 9 | 3 | 12 |
| 2024 January | 7 | 3 | 10 |
| 2023 December | 10 | 2 | 12 |
| 2023 November | 14 | 4 | 18 |
| 2023 October | 14 | 2 | 16 |
| 2023 September | 7 | 1 | 8 |
| 2023 August | 9 | 1 | 10 |
| 2023 July | 7 | 5 | 12 |
| 2023 June | 8 | 0 | 8 |
| 2023 May | 9 | 3 | 12 |
| 2023 April | 11 | 2 | 13 |
| 2023 March | 9 | 1 | 10 |
| 2023 February | 7 | 11 | 18 |
| 2023 January | 12 | 2 | 14 |
| 2022 December | 13 | 10 | 23 |
| 2022 November | 14 | 7 | 21 |
| 2022 October | 8 | 6 | 14 |
| 2022 September | 11 | 15 | 26 |
| 2022 August | 8 | 12 | 20 |
| 2022 July | 8 | 9 | 17 |
| 2022 June | 8 | 8 | 16 |
| 2022 May | 12 | 7 | 19 |
| 2022 April | 15 | 11 | 26 |
| 2022 March | 16 | 8 | 24 |
| 2022 February | 11 | 9 | 20 |
| 2022 January | 15 | 8 | 23 |
| 2021 December | 19 | 7 | 26 |
| 2021 November | 23 | 7 | 30 |
| 2021 October | 13 | 12 | 25 |
| 2021 September | 6 | 10 | 16 |
| 2021 August | 10 | 7 | 17 |
| 2021 July | 7 | 11 | 18 |
| 2021 June | 13 | 10 | 23 |
| 2021 May | 9 | 8 | 17 |
| 2021 April | 30 | 36 | 66 |
| 2021 March | 16 | 17 | 33 |
| 2021 February | 11 | 9 | 20 |
| 2021 January | 9 | 10 | 19 |
| 2020 December | 10 | 10 | 20 |
| 2020 November | 9 | 8 | 17 |
| 2020 October | 12 | 4 | 16 |
| 2020 September | 9 | 15 | 24 |
| 2020 August | 8 | 4 | 12 |
| 2020 July | 6 | 4 | 10 |
| 2020 June | 10 | 10 | 20 |
| 2020 May | 17 | 15 | 32 |
| 2020 April | 7 | 5 | 12 |
| 2020 March | 12 | 9 | 21 |
| 2020 February | 8 | 16 | 24 |
| 2020 January | 6 | 5 | 11 |
| 2019 December | 12 | 4 | 16 |
| 2019 November | 14 | 9 | 23 |
| 2019 October | 5 | 6 | 11 |
| 2019 September | 6 | 10 | 16 |
| 2019 August | 11 | 21 | 32 |
| 2019 July | 7 | 15 | 22 |
| 2019 June | 14 | 28 | 42 |
| 2019 May | 65 | 32 | 97 |
| 2019 April | 23 | 17 | 40 |
| 2019 March | 3 | 7 | 10 |
| 2019 February | 7 | 10 | 17 |
| 2019 January | 4 | 3 | 7 |
| 2018 December | 1 | 11 | 12 |
| 2018 November | 2 | 6 | 8 |
| 2018 October | 6 | 11 | 17 |
| 2018 September | 1 | 0 | 1 |
| 2018 August | 4 | 11 | 15 |
| 2018 July | 0 | 3 | 3 |
| 2018 June | 0 | 7 | 7 |
| 2018 May | 3 | 13 | 16 |
| 2018 April | 6 | 3 | 9 |
| 2018 March | 5 | 2 | 7 |
| 2018 February | 7 | 4 | 11 |
| 2018 January | 7 | 2 | 9 |
| 2017 December | 4 | 1 | 5 |
| 2017 November | 5 | 5 | 10 |
| 2017 October | 11 | 2 | 13 |
| 2017 September | 1 | 12 | 13 |
| 2017 August | 10 | 0 | 10 |
| 2017 July | 11 | 4 | 15 |
| 2017 June | 12 | 6 | 18 |
| 2017 May | 16 | 9 | 25 |
| 2017 April | 29 | 3 | 32 |
| 2017 March | 2 | 0 | 2 |
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