Invasive aspergillosis in liver transplant recipients in the 1990s

Invasive aspergillosis occurred in 26 liver transplant recipients since 1990 at five liver transplant centers. The median time to onset was 17 days after transplantation. Twenty-seven percent of the patients had undergone retransplantation. Invasive aspergillosis occurred significantly earlier after transplantation in smokers than in nonsmokers (P=0.017). Patients with late-onset aspergillosis (occurring after posttransplant day 90) were more likely to have had prior cytomegalovirus infection than those with early- onset aspergillosis (occurring within 90 days of transplantation) (67% vs. 10%, respectively, P=0.013). Only 8% of the patients had received additional corticosteroids or OKT3, which suggests that augmented immunosuppression may not be a relevant risk factor for invasive aspergillosis in the 1990s due to less frequent use of these agents. The median serum bilirubin level of the patients was 21.8 mg/dl, 85% of the patients had renal insufficiency, and 54% were on dialysis before the onset of invasive aspergillosis, which suggest that overall severity of illness, including poorly functioning hepatic allograft and renal failure may be the major determinants of disease occurrence. Overall mortality was 92% (24/26). No difference in mortality could be shown for the patients who received amphotericin B versus liposomal amphotericin B preparations (100% vs. 89%); however, the mean time to death after the initiation of therapy was 20 days in patients who received amphotericin B and 43 days in those who received liposomal amphotericin B preparations

Practice guidelines for diseases caused by Aspergillus

Aspergillosis comprises a variety of manifestations of infection. These guidelines are directed to 3 principal entities: invasive aspergillosis, involving several organ systems (particularly pulmonary disease); pulmonary aspergilloma; and allergic bronchopulmonary aspergillosis. The recommendations are distilled in this summary, but the reader is encouraged to review the more extensive discussions in subsequent sections, which show the strength of the recommendations and the quality of the evidence, and the original publications cited in detail. Invasive aspergillosis. Because it is highly lethal in the immunocompromised host, even in the face of therapy, work-up must be prompt and aggressive, and therapy may need to be initiated upon suspicion of the diagnosis, without definitive proof (BIII). Intravenous therapy should be used initially in rapidly progressing disease (BIII). The largest therapeutic experience is with amphotericin B deoxycholate, which should be given at maximum tolerated doses (e.g., 1-1.5 mg/kg/d) and should be continued, despite modest increases in serum creatinine levels (BIII). Lipid formulations of amphotericin are indicated for the patient who has impaired renal function or who develops nephrotoxicity while receiving deoxycholate amphotericin (AII). Oral itraconazole is an alternative for patients who can take oral medication, are likely to be adherent, can be demonstrated (by serum level monitoring) to absorb the drug, and lack the potential for interaction with other drugs (BII). Oral itraconazole is attractive for continuing therapy in the patient who responds to initial iv therapy (CIII). Therapy should be prolonged beyond resolution of disease and reversible underlying predispositions (BIII). Adjunctive therapy (particularly surgery and combination chemotherapy, also immunotherapy), may be useful in certain situations (CIII). Aspergilloma. The optimal treatment strategy for aspergilloma is unknown. Therapy is predominantly directed at preventing life-threatening hemoptysis. Surgical removal of aspergilloma is definitive treatment, but because of significant morbidity and mortality it should be reserved for high-risk patients such as those with episodes of life-threatening hemoptysis, and considered for patients with underlying sarcoidosis, immunocompromised patients, and those with increasing Aspergillus-specific IgG titers (CIII). Surgical candidates would need to have adequate pulmonary function to undergo the operation. Bronchial artery embolization rarely produces a permanent success, but may be useful as a temporizing procedure in patients with life-threatening hemoptysis. Endobronchial and intracavitary instillation of antifungals or oral itraconazole may be useful for this condition. Since the majority of aspergillomas do not cause life-threatening hemoptysis, the morbidity and cost of treatment must be weighed against the clinical benefit. Allergic bronchopulmonary aspergillosis (APBA). Although no well-designed studies have been carried out, the available data support the use of corticosteroids for acute exacerbations of ABPA (AII). Neither the optimal corticosteroid dose nor the duration of therapy has been standardized, but limited data suggest the starting dose should be 0.5 mg/kg/d of prednisone. The decision to taper corticosteroids should be made on an individual basis, depending on the clinical course (BIII). The available data suggest that clinical symptoms alone are inadequate to make such decisions, since significant lung damage may occur in asymptomatic patients. Increasing serum IgE levels, new or worsening infiltrate on chest radiograph, and worsening spirometry suggest that corticosteroids should be used (BII). Multiple asthmatic exacerbations in a patient with ABPA suggest that chronic corticosteroid therapy should be used (BIII). Itraconazole appears useful as a corticosteroid sparing agent (BII). Although the frequency of these diseases in on the rise, there is a paucity of randomized comparative trials involving these entities; therefore, the recommendations represent a compromise and consensus among students of these diseases (i.e., the authors). They have synthesized the recommendations from published and personal experience, including case series, open trilas, and any comparative trials, as indicated

Infective endocarditis: a survey of cases in the South-East region of Scotland, 1969-72.

The incidence and characteristics of infective endocarditis were studied in a defined community over a four-year period. Seventy-eight cases were found, giving an incidence of 16 cases permillion per year. The commonest presenting features were those of infection; 53% had cardiac failure and 37% evidence of emboli when first seen. Twenty-three cases occurred on rheumatic heart valves, 13 on valvular prostheses, and 19 in previously normal hearts. Streptococcus viridans was the commonest organism, but there was a relatively high incidence of staphylococcal infection. Only four cases were preceded by dental manipulation, and no source for the infection was found in 46 patients. The mortality rate was 46%, cardiac failure and embolic phenomena accounting for 65% of deaths. It is unlikely that earlier diagnosis or cardiac surgery would have reduced the mortality appreciably