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Legionella infections are getting increasingly important as causes of severe pneumonias or of acute respiratory insufficiency. Consumptive or immunosuppressive underlying diseases such as diabetes mellitus, cardiac insufficiency, alcohol-induced liver damage, malignant tumours or drug-induced immunosuppression after organ transplantation, are among the risk factors. Diagnosis is based on direct identification of the pathogen from body secretions by means of direct immunofluorescence. The serological immunoresponse often takes place long after outbreak of the disease or fails entirely to appear and is therefore only suitable for retrospective confirmation. Therapy of choice is an intravenous administration of erythromycin. There are now increasing pointers to the efficiency of fluoroquinolone antibiotics, such as ciprofloxacin. We report on the course of a severe case of legionnaire's disease with multiple organ failure occurring in a patient after bone marrow depression induced by anti-inflammatory drugs. Treatment erythromycin resulted in a marked cholestasis, so that antibiotic treatment was changed to ciprofloxacin. This therapy as well as the supportive intensive-care treatment eventually led to the patient's complete recovery. Based on the case report, fundamental aspects of diagnostics, antibiotic treatment, intensive-care treatment and prognosis of severe cases of legionellosis are discussed.

The high incidence of opportunistic pulmonary infections in fludarabine-treated patients at Walter Reed Army Medical Center (WRAMC) and in the literature are described. A CancerLit search of fludarabine from June 1983-April 1994 with subsequent cross referencing and a retrospective review of all patients receiving fludarabine at WRAMC was performed. A total of 2,269 patients with low-grade lymphoid malignancies who received 7,547 + cycles of fludarabine were identified from the literature. Seventy-three (3.2%) of these patients developed opportunistic infections. Seventy-one (97%) of these infections occurred in patients who were pretreated with alkylator regimens or corticosteroids. Forty-five (2%) of these were of respiratory origin and associated with a 56% mortality rate. In contrast, 6 of the 21 patients (29%) treated with fludarabine at WRAMC developed opportunistic pulmonary infections which included three Pneumocystis carinii (PCP), one PCP/disseminated Candidiasis, one Mycobacterium avium intracellulare, and one Aspergillus niger pneumonia. These infections developed during and after treatment with fludarabine in alkylator-resistant patients who had received corticosteroids before (n = 6), during (n = 1), or after (n = 4) fludarabine therapy. Lack of PCP prophylaxis was the only significant (P = .018) variable that differentiated patients who developed opportunistic pulmonary infections. Corticosteroid treatment before, during, or after fludarabine treatment in patients with alkylator-resistant, low-grade lymphoid malignancies who have not received PCP prophylaxis is associated with an increased risk of opportunistic pulmonary infections. Aggressive work-up of pulmonary syndromes and PCP prophylaxis in these patients should be considered during and after treatment with fludarabine.

Cladribine is an effective therapy for hairy cell leukaemia (HCL), but the standard regime is frequently complicated by neutropenic fever and prolonged T-cell depression. We studied 102 patients with active HCL following treatment with various doses of cladribine given for 7 d. Two patients received 1 mg cladribine/m2/d without toxicity or effect. Eight subsequent patients received 2 mg cladribine/m2/d, and normalized cytopenia as quickly as 94 control patients receiving a standard dose (3.4 mg/m2 or 0.085 mg/kg), with significantly less lymphopenia and a similar complete remission rate.

Temporal arteritis is a systemic necrotizing vasculitis for which the only effective treatment is systemic corticosteroids. A review of the literature suggests that there is a significant mortality rate in untreated patients but that those patients who receive adequate corticosteroid treatment rarely experience a reduced life expectancy. I had the opportunity to evaluate a patient with temporal arteritis who eventually died from disseminated aspergillosis 6 weeks after beginning corticosteroid treatment. A high index of suspicion for infections with opportunistic organisms should be maintained in patients with temporal arteritis receiving corticosteroids.

On account of its high mortality, pneumonia is a particularly feared infectious complication in granulocytopenic patients. One of the main reasons for the fatal outcome is the increasing rate of pulmonary mycoses. Fungal infections offer considerable problems concerning diagnostics and therapy. To improve the prognosis of pulmonary mycoses undelayed diagnostics--even by more invasive methods like bronchoalveolar lavage--and immediate start of antifungal treatment (Amphotericin B/5-Flucytosine are still considered as standard therapy) is necessary. A further problem are gram positive organisms, insufficiently prevented by the standard prophylactic regimens. Particularly pneumonia by Staphylococcus aureus and Viridans-Streptococci may show lethal outcome. The initial treatment with glycopeptides is discussed. Treatment of infections by gram negative organisms however, is less controversial. Finally pneumonias in granulocytopenic patients present serious problems in diagnostics and therapy requiring interdisciplinary co-operation of hematology, radiology, pneumology and microbiology.

The influence of neuroleptic drugs on body temperature regulation is well established. Even with atypical neuroleptic drugs such as clozapine, hyperthermia has been observed as well as the malignant neuroleptic syndrome. It is likely that the influence of clozapine affects the immune response. A case is reported in which afebrile angina tonsillaris and endocarditis developed, as a result of high-dosage therapy with clozapine over several years. Besides the special features of the course, differential diagnosis, therapy and possible influence on the body temperature and the immune response are discussed.

Both recombinant interferon alpha and deoxycoformycin (dCF) are effective in the treatment of hairy cell leukaemia. In an attempt to reduce the complications from dCF therapy, a pilot study of the Eastern Cooperative Oncology Group (ECOG) first treated patients with interferon to improve peripheral blood cell counts before dCF treatment began. Thirty-four patients were treated for 3 months with recombinant interferon alpha-2a (rIFN alpha-2a), 3 x 10(6) IU subcutaneously three times a week for 3 months, and then by dCF, 4 mg/m2 intravenously every 2 weeks for a maximum of 12 months. The overall response rate was 94% (32/34); 76% of patients (26/34) had complete response (CR) (90% confidence interval, 62-88%) and 18% (6/34) partial response. One patient was found to have a Mycobacterium avium infection while receiving rIFN alpha-2a. Without specific antimycobacterial therapy and with continued administration of rIFN alpha-2a and dCF, the infection resolved and he achieved CR. Three patients had culture-negative febrile episodes during the dCF phase of treatment. Non-disseminated herpes zoster developed in four patients, but three of the episodes occurred only after treatment was discontinued. Sequential administration of rIFN alpha-2a and dCF resulted in fewer infections (P = 0.027) than in ECOG's previous study of dCF used alone. Two patients died, one of combined hairy cell leukaemia and non-Hodgkin's lymphoma of intermediate histologic type 17 months after entry into the study and the other of cardiac arrest 20 months after entry. Thirty-two patients were alive with a median follow-up of 21 months (range 13-31 months). This combination produces durable CRs with a low incidence of infection.

In a patient with rheumatoid arthritis pancytopenia and Pneumocystis carinii pneumonia occurred during low dose methotrexate therapy. This case emphasizes the potential development of opportunistic infections even with low dose methotrexate. Pneumocystis carinii pneumonia resembles methotrexate induced pneumonitis. Therefore opportunistic infections should be considered before a definite diagnosis of methotrexate induced pneumonitis is made.

Opportunistic infections occur in patients with rheumatic diseases treated with low dose methotrexate (MTX) with or without other immunosuppressants. Our case report illustrates a fatal case of Pneumocystis carinii pneumonia in a patient with rheumatoid arthritis treated with low dose MTX and glucocorticoid. A review of the literature reveals other opportunistic infections such as Cryptococcus, Nocardia, and herpes zoster presenting in such patients. These occurrences suggest that MTX should be used cautiously in patients with rheumatic disease receiving concomitant medical therapy.

The clinical courses of 26 patients with severe neutropenia after application of cytostatic agents are demonstrated. The symptomatology reaches from complete freedom of complaints to severe and most severe clinical appearances. In all 7 asymptomatic patients a complete remission of the changes of the blood picture occurred. Patients with lacking or partial remission of the blood picture after severe neutropenia induced by cytostatic agents have in general a bad prognosis quoad vitam. Infections are the most important complication of a severe neutropenia. Conclusions for the clinical practice concerning the prophylaxis and the early recognition of severe neutropenias as well as of neutropenic complications are derived. Irreversible lesions of the bone marrow by cytostatic agents are notifiable unwished effects of drugs.

The relative risks of non-specific upper respiratory tract infections were studied in two well matched groups of military recruits to see whether dapsone-pyrimethamine (Maloprim) given as antimalarial prophylaxis was associated with immunosuppression. Mean risks of upper respiratory tract infection were 64% higher in the study group than in the controls, the largest monthly differences being recorded in the months of harder training. These findings were unlikely to have been due solely to harder training in the study group, as concurrently measured sprains (arguably more likely to have been affected) were increased by only 19%. A more likely explanation was some degree of immunosuppression, physical stress possibly having a synergistic effect. These findings suggest that travellers taking dapsone-pyrimethamine as antimalarial prophylaxis may be rendered more susceptible to commoner infections, especially when engaged in increased physical activity.

Twenty patients with disseminated cancer both untreated and previously treated received bialkylator chemotherapy, thiotepa, and cyclophosphamide and reinfusion of cryopreserved autologous bone marrow (ABMR). The cyclophosphamide dose was constant at 7.5 g/m2 over three days, while thiotepa was started at 1.8 mg/kg for three days in escalating dose by a modified Fibonacci schema to 7 mg/kg. The median time to recovery of more than 500 granulocytes and more than 50,000 platelets/microL was 18 and 27 days, respectively. Four patients died as a consequence of severe, overwhelming infections or progressive disease during their period of aplasia. Of the 18 evaluable patients, a complete response (CR) was achieved in three patients and a partial response (PR) in ten patients for an overall response rate of 72%. The median duration of response was 14 weeks. Other nonhematologic toxicities included nausea/vomiting, diarrhea, stomatitis, skin rash, and cardiomyopathy. The maximum tolerated dose (MTD) of thiotepa was 700 mg/m2 or 6 mg/kg for three doses. Although there are substantial toxicities associated with this regimen, high-dose thiotepa and cyclophosphamide produce high response rates in patients with disseminated cancer.