title: Disseminated aspergillosis following resolution of Pneumocystis pneumonia with sustained elevation of beta-glucan in an Intensive Care Unit: a case report.
abstract: Invasive aspergillosis is a major cause of morbidity and mortality in immunocompromised patients receiving intensive care. The double-sandwich ELISA for galactomannan is reported to have a high sensitivity (96.5%) for the detection of invasive aspergillosis when a cut-off value of 0.8 ng/ml is used. However, we have experienced a case of lethal disseminated aspergillosis in a patient that presented with a negative galactomannan (GM) test and persistent elevation of beta-D glucan (BG) levels. A 63-year-old female was admitted to our Intensive Care Unit (ICU) in acute respiratory failure and elevated BG. She had been receiving medication for Good-pasture syndrome based on anti-glomerular basement membrane antibodies and myeloperoxidase-antineutrophil cytoplasmic antibodies for 9 months and was receiving long-term prednisolone therapy (20 mg/day). On admission, her trachea was immediately intubated, and a PCR analysis of the bronchoalveolar lavage sample revealed Pneumocystis jiroveci. Trimethoprimsulfamethoxazole therapy was started for Pneumocystis pneumonia. The levels of BG remained elevated (> 100 pg/ml) during the treatment period despite the clinical resolution of Pneumocystis pneumonia, raising concerns of another complicated invasive fungal disease; consequently, fosfluconazole was administered empirically. The serum BG levels, however, did not decrease. Blood cultures did not detect a fungal infection. Serum GM levels measured by a double-sandwich ELISA on the 6th, 11th, and 24th days in the ICU were negative (< 0.2 ng/ml). The patient ultimately died of multiple organ failure on the 45th ICU day. Postmortem examination revealed a disseminated fungal infection with aggressive vascular invasion of the lungs, heart, and brain. In situ hybridization with a 568-bp probe of the alkaline proteinase sequence of Aspergillus fumigatus showed specific positive staining within the fungus present in the infected lung tissue, revealing that this patient may have had a systemic infection by A. fumigatus or A. flavus. This is a case of serum GM-negative disseminated aspergillosis pathologically proven by autopsy. Persistent elevated BG levels (> 100 pg/ml) refractory to trimethoprim-sulfamethoxazole and fosfluconazole may suggest possible Aspergillus infection and should prompt the initiation of empiric anti-aspergillosis therapies in patients at risk for fungal infection.
authors.affiliation: Division of Thoracic Surgery, Dept. of Thoracic and Cardiovascular Surgery, Kansai Medical University Hirakata Hospital, Shin-machi, Hirakata, Japan. saitotom@hirakata.kmu.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Saito
authors.forename: N
authors.initials: N
authors.lastname: Shime
authors.forename: K
authors.initials: K
authors.lastname: Itoh
authors.forename: N
authors.initials: N
authors.lastname: Fujita
authors.forename: Y
authors.initials: Y
authors.lastname: Saito
authors.forename: M
authors.initials: M
authors.lastname: Shinozaki
authors.forename: K
authors.initials: K
authors.lastname: Shibuya
authors.forename: K
authors.initials: K
authors.lastname: Makimura
authors.forename: S
authors.initials: S
authors.lastname: Hashimoto
mesh_terms: D000935:Antifungal Agents / Q000627:therapeutic use; D001228:Aspergillosis / Q000175:diagnosis* / Q000382:microbiology / Q000473:pathology; D001230:Aspergillus / Q000302:isolation & purification; D001921:Brain / Q000382:microbiology; D017809:Fatal Outcome; D005260:Female; D005690:Galactose / Q000031:analogs & derivatives; D006321:Heart / Q000382:microbiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D007362:Intensive Care Units; D008168:Lung / Q000382:microbiology; D008351:Mannans / Q000097:blood; D008875:Middle Aged; D045363:Pneumocystis carinii / Q000302:isolation & purification; D011020:Pneumonia, Pneumocystis / Q000175:diagnosis* / Q000188:drug therapy* / Q000382:microbiology; D011239:Prednisolone / Q000009:adverse effects / Q000627:therapeutic use; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use; D047071:beta-Glucans / Q000097:blood*
chemical_list: D000935:Antifungal Agents; D007166:Immunosuppressive Agents; D008351:Mannans; D047071:beta-Glucans; C012990:galactomannan; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D011239:Prednisolone; D005690:Galactose