Case discussion

A swollen face

Patients with allogeneic bone marrow transplantations are sensitive to opportunistic infections (Table 1).

Among the fungal pathogens, Candida spp. and Aspergillus spp. are the most important contributing to significant morbidity and mortality in these immune compromised patients and all allogeneic stem cell recipients should receive fluconazole to prevent systemic infection with susceptible yeasts during neutropenia (AI). The recommended dose is 400 mg/day, either orally or intravenously given (AI). Overall, antifungal prophylaxis is recommended at least until day +75. If immunosuppression is given after day +75, antifungal prophylaxis should be considered.

Posaconazol can be recommended for primary prophylaxis of aspergillosis after bone marrow transplantation if the patient is receiving immunosuppression for an acute graft-versus-host reaction.

Invasive or systemic mould infections in stem cell recipients most frequently result from inhaled spores colonising the nasal sinus and the respiratory tract. Risk factors for mould infections after stem cell transplantation are graft-versus-host disease, prolonged immunosuppression and a history of prolonged neutropenia under prior chemotherapy.

Diagnosis of infection with invasive moulds remains problematic. Biopsy evidence of tissue invasion is preferred but not easily obtained in immunosuppressed patients who are often thrombocytopenic. These organisms are ubiquitous in the environment so that a culture that yields one of these moulds from sputum or bronchoalveolar lavage fluid may merely reflect contamination or colonization. The laboratory should be able to identify the specific species of Aspergillus and at least the genus of non-Aspergillus moulds. This allows the clinician to choose the appropriate antifungal agent.

As early treatment is the goal in fungal infection, pre-emptive treatment based on 2 times weekly galactomannan testing in blood samples and high-resolution CT-scan is standard of care.

The treatment of mould infections has changed markedly in recent years. Previously, amphotericin B and itraconazole were the only available agents, but many non-Aspergillus moulds were resistant to these agents and the mortality rate for aspergillosis remained over 80% for the highest risk groups. Voriconazole has become the agent of choice for invasive aspergillosis, based on superior outcomes in a controlled, randomized, blinded treatment trial that compared voriconazole with amphotericin B. Voriconazole is also effective for the treatment of infections with Scedosporium, Fusarium, and other moulds.. However, the zygomycetes are resistant to voriconazole and must be treated with amphotericin B.

The echinocandins are useful in the treatment of aspergillosis. They are most useful as second-line therapy and have not been studied as first-line therapy for invasive aspergillosis. Echinocandins are often combined with other agents, such as voriconazole, to treat seriously ill patients with aspergillosis . However, there are no controlled clinical trials showing that combination therapy is beneficial.

Table 1. Predominance of opportunistic infections after allogeneic bone marrow transplantation.

Free full text links:

Krüger WH, Bohlius J, Cornely OA, Einsele H, Hebart H, Massenkeil G, Schüttrumpf S, Silling G, Ullmann AJ, Waldschmidt DT, Wolf HH. Antimicrobial prophylaxis in allogeneic bone marrow transplantation. Guidelines of the infectious diseases working party (AGIHO) of the german society of haematology and oncology. Ann Oncol.2005; 16: 1381-90.

Cornely OA, Maertens J, Winston DJ, Perfect J, Ullmann AJ, Walsh TJ, Helfgott D, Holowiecki J, Stockelberg D, Goh YT, Petrini M, Hardalo C, Suresh R, Angulo-Gonzalez D. Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia.New Engl JMed. 2007;356(4):348-59.

Kauffman CA. Fungal infections. Proc Am Thorac Soc.2006; 3: 35-40.

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