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: T Saito, N Shime, K Itoh, N Fujita, Y Saito, M Shinozaki, K Shibuya, K Makimura, S Hashimoto
• Journal: Infection (Infection) Vol. 37 Issue 6 Pg. 547-50 (Dec 2009) ISSN: 1439-0973 [Electronic] Germany
• PMID: 19730788 (Publication Type: Case Reports, Journal Article)

Chemical References

• Antifungal Agents
• Immunosuppressive Agents
• Mannans
• beta-Glucans
• galactomannan
• Trimethoprim, Sulfamethoxazole Drug Combination
• Prednisolone
• Galactose

Topics

• Antifungal Agents (therapeutic use)
• Aspergillosis (diagnosis, microbiology, pathology)
• Aspergillus (isolation & purification)
• Brain (microbiology)
• Fatal Outcome
• Female
• Galactose (analogs & derivatives)
• Heart (microbiology)
• Humans
• Immunosuppressive Agents (adverse effects, therapeutic use)
• Intensive Care Units
• Lung (microbiology)
• Mannans (blood)
• Middle Aged
• Pneumocystis carinii (isolation & purification)
• Pneumonia, Pneumocystis (diagnosis, drug therapy, microbiology)
• Prednisolone (adverse effects, therapeutic use)
• Trimethoprim, Sulfamethoxazole Drug Combination (therapeutic use)
• beta-Glucans (blood)