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with fine peripheral enhancement&#44; central necrosis&#44; and a perilesional halo of edema&#44; consistent with abscesses&#46; The ophthalmologic examination revealed severe right endophthalmitis&#44; requiring vitrectomy&#46; Cerebrospinal fluid and blood were positive for galactomanan antigen&#46; After vitrectomy&#44; the vitreous humor showed abundant septate hyphae&#59; <span class="elsevierStyleItalic">A&#46; fumigatus</span> was cultured&#46; The pleural effusion was not loculated&#44; and had a purulent appearance with pH 7&#46;34&#44; leukocytes 3&#46;6&#215;10<span class="elsevierStyleSup">3</span>&#47;&#956;l &#40;69&#37; segments&#44; 31&#37; lymphocytes&#41;&#44; glucose 87<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#44; total proteins 3&#46;6<span class="elsevierStyleHsp" style=""></span>g&#47;dl&#44; C-reactive protein 3&#46;08<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#44; procalcitonin 0&#46;3<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#44; LDH 894<span class="elsevierStyleHsp" style=""></span>IU&#47;l&#44; adenosine deaminase 8<span class="elsevierStyleHsp" style=""></span>U&#47;l&#44; interleukin-6 70<span class="elsevierStyleHsp" style=""></span>393<span class="elsevierStyleHsp" style=""></span>pg&#47;ml&#46; Fungal hyphae were observed and <span class="elsevierStyleItalic">A&#46; fumigatus</span> was obtained on culture&#46; A thyroid abscess was aspirated&#44; and hyphae were observed&#46; Enterococcus faecalis was isolated from culture of the foreskin&#44; and trimethoprim&#8211;sulfamethoxazole sensitive Stenotrophomonas maltophilia from 2 sputum cultures&#44; obtained 2 months after admission&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The clinical situation was interpreted as T-cell acute lymphoblastic leukemia with late post-chemotherapy bone marrow aplasia and disseminated aspergillosis &#40;<span class="elsevierStyleItalic">A&#46; fumigatus</span>&#41; during the reinduction phase&#44; with ophthalmic&#44; cerebral&#44; pulmonary&#44; pleural &#40;empyema&#41;&#44; hepatic&#44; and thyroid involvement with bacterial co-infections&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">During admission&#44; the patient received various courses of antifungals &#40;amphotericin&#44; voriconazole &#91;up to 9<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;12<span class="elsevierStyleHsp" style=""></span>h depending on blood levels&#44; as well as 8 intravitreal doses&#93;&#44; AmBisome<span class="elsevierStyleSup">&#174;</span> and caspofungin&#41;&#44; antibacterials &#40;meropenem&#44; vancomycin&#44; linezolid&#44; cotrimoxazole&#44; levofloxacin&#44; amikacin&#44; and clindamycin&#41;&#44; and dexamethasone&#44; and a chest tube was placed &#40;16F&#44; 3 days then resolution&#41;&#46; The patient progressed slowly&#44; except for the pleural involvement&#44; until voriconazole was administered at doses much higher than recommended in the package insert&#44; and plasma levels within the therapeutic range were achieved&#46; The patient was discharged after 3 months&#44; having remained afebrile for the last month&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">A diagnosis of fungal pleural empyema poses a clinical dilemma that is especially worrying in the setting of severely immunocompromised cancer patients&#46; Our patient met the criteria for diagnosis of proven invasive fungal disease&#44;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">4</span></a><span class="elsevierStyleItalic">A&#46; fumigatus</span> on this occasion&#44; and is one of the few cases in which pleural fluid has been infected by <span class="elsevierStyleItalic">Aspergillus</span> in an immunocompromised patient&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">5</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">A recent study reported a high percentage &#40;16&#37;&#59; 111&#47;708&#41; of cultures positive for fungi in pleural fluid from cancer patients&#46; This appears to be due to a higher incidence of invasive fungal infection in cancer patients&#44; and improved detection of fungi by microbiological techniques&#46; <span class="elsevierStyleItalic">Aspergillus</span> spp&#46; were&#44; in terms of percentages&#44; the predominant microorganism in leukemia patients &#40;the disease presented by our patient&#41;&#44; suggesting that the type of cancer may be one of the risk factors for developing <span class="elsevierStyleItalic">Aspergillus</span> empyema&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Voriconazole is the recommended antifungal for the treatment of invasive aspergillosis in most patients&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">7</span></a> Although this drug achieves high concentrations in pleural fluid&#44;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">8&#44;9</span></a> pleural empyemas caused by Aspergillosis are usually treated with a combination of various antifungals<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">5</span></a> due to the high mortality rate &#40;34&#37;&#8211;75&#37;&#44; depending on when it is evaluated&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">1&#44;6</span></a> Intrapleural administration has been described in isolated cases&#44;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">1&#44;10</span></a> and more studies are required to support this strategy&#46; Treatment for all empyemas requires chest drainage&#44; and if the patient presents life-threatening hemoptysis&#44; lung resection surgery should be considered&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">11</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">In summary&#44; in an immunocompromised cancer patient with pleural empyema&#44; cultures in the appropriate media should be performed to rule out fungal infection&#46; Treatment must consist of chest drainage and the long-term administration of a combination of various antifungals&#44; including voriconazole&#44; since mortality in these infections is high&#46;</p></span>"
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Scientific Letter
Aspergillus fumigatus Empyema
Empiema por Aspergillus fumigatus
Lucía Ferreiroa,b,
Corresponding author
lferfer7@gmail.com

Corresponding author.
, M. Luisa Pérez del Molinoc, Marta Sonia González-Pérezd, Luis Valdésa,b
a Servicio de Neumología, Complejo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, La Coruña, Spain
b Grupo Interdisciplinar de Investigación en Neumología, Instituto de Investigaciones Sanitarias de Santiago (IDIS), Santiago de Compostela, La Coruña, Spain
c Servicio de Microbiología, Complejo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, La Coruña, Spain
d Servicio de Hematología, Complejo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, La Coruña, Spain
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treated in our hospital&#46; This was a 19-year-old man who had been diagnosed 7 months previously with intermediate-risk cortical phenotype T-cell acute lymphoblastic leukemia&#46; He received induction&#44; consolidation and reinduction therapies&#44; according to standard protocols&#44; and achieved complete remission&#46; Complications associated with the various treatments included vitamin K deficiency&#44; hypofibrinogenemia&#44; pancytopenia &#40;with hemolytic anemia requiring transfusions&#41;&#44; hyperglycemia&#44; and hypertransaminasemia&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Thirty days after reinduction therapy&#44; he was admitted to the hematology department for loss of vision in the right eye&#44; odynophagia&#44; and fever&#46; Vital signs showed temperature 37&#46;5<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; blood pressure 110&#47;60<span class="elsevierStyleHsp" style=""></span>mmHg and heart rate 100<span class="elsevierStyleHsp" style=""></span>bpm&#46; Breathing at rest was normal&#44; and notable findings on physical examination included pallor of the skin and mucosa&#44; Cushingoid facies&#44; bronchial breath sounds in the base of the left hemithorax&#44; with crackles reaching the middle field&#44; edema of the lower limbs&#44; and exudative ulceration of the foreskin&#46; Abdominal examination was normal and no peripheral lymphadenopathies were palpated&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The most relevant additional examinations included blood tests&#58; hemoglobin 8&#46;2<span class="elsevierStyleHsp" style=""></span>g&#47;dl&#44; hematocrit 24&#46;9&#37;&#44; leukocytes 1&#215;10<span class="elsevierStyleSup">3</span>&#47;&#956;1 &#40;62&#37; neutrophils&#44; 35&#37; lymphocytes&#41;&#44; platelets 24&#215;10<span class="elsevierStyleSup">3</span>&#47;&#956;l&#44; total proteins 4&#46;5<span class="elsevierStyleHsp" style=""></span>g&#47;dl&#44; GOT 117<span class="elsevierStyleHsp" style=""></span>IU&#47;l&#44; 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LDH 894<span class="elsevierStyleHsp" style=""></span>IU&#47;l&#44; adenosine deaminase 8<span class="elsevierStyleHsp" style=""></span>U&#47;l&#44; interleukin-6 70<span class="elsevierStyleHsp" style=""></span>393<span class="elsevierStyleHsp" style=""></span>pg&#47;ml&#46; Fungal hyphae were observed and <span class="elsevierStyleItalic">A&#46; fumigatus</span> was obtained on culture&#46; A thyroid abscess was aspirated&#44; and hyphae were observed&#46; Enterococcus faecalis was isolated from culture of the foreskin&#44; and trimethoprim&#8211;sulfamethoxazole sensitive Stenotrophomonas maltophilia from 2 sputum cultures&#44; obtained 2 months after admission&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The clinical situation was interpreted as T-cell acute lymphoblastic leukemia with late post-chemotherapy bone marrow aplasia and disseminated aspergillosis &#40;<span class="elsevierStyleItalic">A&#46; fumigatus</span>&#41; during the reinduction phase&#44; with ophthalmic&#44; cerebral&#44; pulmonary&#44; pleural &#40;empyema&#41;&#44; hepatic&#44; and thyroid involvement with bacterial co-infections&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">During admission&#44; the patient received various courses of antifungals &#40;amphotericin&#44; voriconazole &#91;up to 9<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;12<span class="elsevierStyleHsp" style=""></span>h depending on blood levels&#44; as well as 8 intravitreal doses&#93;&#44; AmBisome<span class="elsevierStyleSup">&#174;</span> and caspofungin&#41;&#44; antibacterials &#40;meropenem&#44; vancomycin&#44; linezolid&#44; cotrimoxazole&#44; levofloxacin&#44; amikacin&#44; and clindamycin&#41;&#44; and dexamethasone&#44; and a chest tube was placed &#40;16F&#44; 3 days then resolution&#41;&#46; The patient progressed slowly&#44; except for the pleural involvement&#44; until voriconazole was administered at doses much higher than recommended in the package insert&#44; and plasma levels within the therapeutic range were achieved&#46; The patient was discharged after 3 months&#44; having remained afebrile for the last month&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">A diagnosis of fungal pleural empyema poses a clinical dilemma that is especially worrying in the setting of severely immunocompromised cancer patients&#46; Our patient met the criteria for diagnosis of proven invasive fungal disease&#44;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">4</span></a><span class="elsevierStyleItalic">A&#46; fumigatus</span> on this occasion&#44; and is one of the few cases in which pleural fluid has been infected by <span class="elsevierStyleItalic">Aspergillus</span> in an immunocompromised patient&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">5</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">A recent study reported a high percentage &#40;16&#37;&#59; 111&#47;708&#41; of cultures positive for fungi in pleural fluid from cancer patients&#46; This appears to be due to a higher incidence of invasive fungal infection in cancer patients&#44; and improved detection of fungi by microbiological techniques&#46; <span class="elsevierStyleItalic">Aspergillus</span> spp&#46; were&#44; in terms of percentages&#44; the predominant microorganism in leukemia patients &#40;the disease presented by our patient&#41;&#44; suggesting that the type of cancer may be one of the risk factors for developing <span class="elsevierStyleItalic">Aspergillus</span> empyema&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Voriconazole is the recommended antifungal for the treatment of invasive aspergillosis in most patients&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">7</span></a> Although this drug achieves high concentrations in pleural fluid&#44;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">8&#44;9</span></a> pleural empyemas caused by Aspergillosis are usually treated with a combination of various antifungals<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">5</span></a> due to the high mortality rate &#40;34&#37;&#8211;75&#37;&#44; depending on when it is evaluated&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">1&#44;6</span></a> Intrapleural administration has been described in isolated cases&#44;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">1&#44;10</span></a> and more studies are required to support this strategy&#46; Treatment for all empyemas requires chest drainage&#44; and if the patient presents life-threatening hemoptysis&#44; lung resection surgery should be considered&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">11</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">In summary&#44; in an immunocompromised cancer patient with pleural empyema&#44; cultures in the appropriate media should be performed to rule out fungal infection&#46; Treatment must consist of chest drainage and the long-term administration of a combination of various antifungals&#44; including voriconazole&#44; since mortality in these infections is high&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Ferreiro L&#44; P&#233;rez del Molino ML&#44; Gonz&#225;lez-P&#233;rez MS&#44; Vald&#233;s L&#46; Empiema por <span class="elsevierStyleItalic">Aspergillus fumigatus</span>&#46; Arch Bronconeumol&#46; 2017&#59;53&#58;399&#8211;400&#46;</p>"
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