Critical care of the hematopoietic stem cell transplant recipient

Bacterial pneumonia

Bacterial pneumonia may occur at any time in the posttransplantation period but is particularly prevalent during the preengraftment period of profound neutropenia. Gram-negative pathogens, including Pseudomonas aeruginosa, predominate during this time. Legionella species are an important cause of nosocomial pneumonia in some centers.

Bacterial pneumonia is commonly heralded by fever, but respiratory symptoms and signs may be absent in the neutropenic host. Presumably because of the paucity of neutrophils, chest x-ray abnormalities may be subtle or absent as well. In one series, the use of high-resolution computed tomography (CT) imaging revealed evidence of pneumonia in more than 50% of febrile neutropenic patients with normal chest radiographs. Broad-spectrum antibiotics (with anti- Pseudomonas activity) should be initiated expeditiously in all suspected cases of bacterial pneumonia and in febrile, neutropenic patients without an identified site of infection. In choosing an antibiotic regimen, clinicians must be cognizant of the particular epidemiologic and susceptibility patterns in their hospital- and patient-associated risk factors that might increase the risk of highly resistant pathogens such as methicillin-resistant Staphylococcus aureus, extended-spectrum beta-lactamase-producing Enterobacteriaceae, and carbapenemase-producing organisms.

Aspergillus

Although the incidence of invasive aspergillosis has declined significantly with widespread implementation of azole prophylaxis, it remains one of the most devastating complications of HSCT and one of the leading causes of infectious death in this group. Allogeneic transplant recipients in particular are at increased risk for invasive aspergillosis caused by neutropenia during the preengraftment phase and the administration of immunosuppressive agents to both prevent and treat GVHD. The reported frequency of invasive aspergillosis in the allogeneic population varies between 5% and 15% compared with 0%–8% among autologous HSCT recipients.

Invasive aspergillosis is confined to the lungs in the majority of cases, but sinusitis and central nervous system involvement also occur with some frequency. Cough and dyspnea are the most common presenting symptoms. Pleuritic chest pain and hemoptysis are important, albeit nonspecific, clues to the presence of invasive aspergillosis, reflecting the tendency of the organism to invade blood vessels and cause pulmonary infarction. Fever may be absent in up to two-thirds of patients.

Initial radiographic findings include single or multiple nodules, cavities, and subsegmental or segmental consolidation. CT imaging is more sensitive in detecting abnormalities and can do so at an earlier stage of infection. A highly characteristic CT finding is the halo sign, a rim of low attenuation representing edema or hemorrhage that surrounds a pulmonary nodule. In one study, the halo sign was present in over 90% of neutropenic patients with invasive pulmonary aspergillosis when CT scans were performed at the onset of fever.

Establishing a definitive diagnosis of invasive pulmonary aspergillosis remains difficult, and up to 30% of cases are unrecognized antemortem. The recovery of Aspergillus species on cultures of bronchoalveolar lavage fluid is highly suggestive of invasive infection in the HSCT population, but sensitivity is only 27%–57%, with the lowest yields reported for peripheral nodular lesions. ^, Transthoracic fine-needle aspiration of accessible focal lesions has a yield of 50%–67%, but performance of this procedure is often precluded by the presence of severe thrombocytopenia. ^, An enzyme-linked immunosorbent assay that detects galactomannan, a fungal cell wall component released during invasive disease, has been introduced into clinical practice as a diagnostic tool, albeit with its own limitations. Among HSCT patients with proven or probable cases of invasive aspergillosis included in a meta-analysis, the pooled sensitivity, specificity, and positive and negative predictive values of serum galactomannan testing were 82%, 86%, 65%, and 65%, respectively. Galactomannan testing of bronchoalveolar lavage (BAL) fluid appears to offer greater sensitivity than the serum assay, without sacrificing specificity. ^{, ,} Current practice guidelines from the Infectious Disease Society of America endorse the use of both serum and BAL galactomannan assays in the diagnosis of invasive aspergillosis in the HSCT population (strong recommendation; moderate-quality evidence).

Voriconazole is the treatment of choice for invasive aspergillosis, based on demonstration of superior efficacy and less toxicity compared with amphotericin B. A multicenter registry of HSCT recipients documented partial or complete response at 12 weeks in 64% of patients with invasive aspergillosis, the majority of whom were treated with voriconazole either alone or in combination with an echinocandin. The mortality rate at this time point was 36%, a dramatic reduction from rates in excess of 80% reported in the 1990s. Liposomal amphotericin B and isavuconazole are alternative options for patients in whom voriconazole is contraindicated or not tolerated. The echinocandins (caspofungin, micafungin), used either alone or in combination with another antifungal agent, are considered to be salvage therapy for severe or refractory cases. Surgical resection of localized disease is sometimes used as an adjunct to antifungal therapy in refractory cases or in the setting of massive hemoptysis.