We reviewed 55 cases of streptococcal bacteremia in adult patients who received cytotoxic chemotherapy for treatment of acute leukemia. Viridans group streptococci were the most frequent species isolated (45 isolates). Hemolytic streptococci (four isolates), pneumococci (three isolates), and enterococci (three isolates) were infrequent. Clinical features of streptococcal bacteremia included fever, upper and lower respiratory infection, respiratory distress syndrome, soft tissue infection, and septic shock. Forty patients who had only streptococci, but no other organisms isolated from their blood, were compared with 36 cases of gram-negative bacillary bacteremia that occurred during the same study period within the same population at risk. The comparison showed that patients with streptococcal bacteremia had more often received high dose cytosine arabinoside as part of their chemotherapy (17 vs. five), had a longer mean duration of fever (11 vs. seven days, p less than 0.01) needed slightly more days of antibacterial therapy (15 vs. 12 days, p = 0.07, not significant), and were more likely to have been treated with newer quinolones for infection prevention (30 vs. eight). No differences between both groups were found for age, underlying disease, remission status, duration of severe granulocytopenia, and number of superinfections. The overall mortality was 18% in streptococcal bacteremia and 17% in gram-negative bacillary bacteremia. Streptococci, especially viridans group streptococci, should now be regarded as frequent causes of serious life-threatening infections following aggressive chemotherapy in patients with hematologic malignancies.

The incidence of invasive fungal infections after bone marrow transplantation (BMT) was analyzed in 303 consecutive marrow graft recipients (allogeneic n = 271, autologous n = 27, syngeneic n = 5). All patients received inhalations with amphotericin B (10 mg twice daily) during neutropenia. The overall incidence of invasive fungal infections within the first 120 days after transplant was 3.6% (11/303; aspergillosis: 6; yeast infection: 5). Four of the 11 cases occurred early, and seven cases were observed after neutrophil recovery and discontinuation of amphotericin B inhalation treatment. Late infection was significantly associated with the development of acute graft-versus-host disease. Four of the 11 infections (early 2/4; late: 2/7) were observed in patients with a history of previous fungal infection. Other patient and treatment characteristics were not helpful in defining potential risk factors. In particular, the incidence of invasive fungal infections did not differ between patients with more or less strict reverse isolation measures. Occasional side effects such as initial mild cough and bad taste were rare, usually disappeared during continued administration, and were in no case the reason for discontinuation of treatment. These data suggest that aerosolized amphotericin B may be a useful, convenient, and efficient prophylactic antifungal regimen in BMT.

The optimum treatment conditions of interferon (IFN) a therapy in chronic myeloid leukemia (CML) are still controversial. To evaluate the role of hydroxyurea (HU) for the outcome of IFN therapy, we conducted a randomized trial to compare the combination of IFN and HU vs HU monotherapy (CML-study II). From February 1991 to December 1994, 376 patients with newly diagnosed CML in chronic phase were randomized. In all, 340 patients were Ph/BCR-ABL positive and evaluable. Randomization was unbalanced 1:2 in favor of the combination therapy, since study conditions were identical to the previous CMLstudy I and it had been planned in advance to add the HU patients of study I (n ¼ 194) to the HU control group. Therefore, a total of 534 patients were evaluable (226 patients with IFN/HU and 308 patients with HU). Analyses were according to intention-to-treat. Median observation time of nontransplanted living patients was 7.6 years (7.9 years for IFN/HU and 7.3 years for HU). The risk profile (new CML score) was available for 532 patients: 200 patients (38%) were low, 239 patients (45%) intermediate, and 93 patients (17%) high risk. Complete hematologic response rates were higher in IFN/HU-treated patients (59 vs 32%). Of 169 evaluable IFN/HU-treated patients (75%), 104 patients (62%) achieved a cytogenetic response that was complete in 12% (n ¼ 21), major in 14% (n ¼ 24), and at least minimal in 35% (n ¼ 59). Of the 534 patients, 105 (20%) underwent allogeneic stem cell transplantation in first chronic phase. In the low-risk group, 65 of 200 patients were transplanted (33%), 30 (13%) in the intermediate-risk group, and nine (10%) in the high-risk group. Duration of chronic phase was 55 months for IFN/HU and 41 months for HU (Po0.0001). Median survival was 64 months for IFN/HU and 53 months for HU-treated patients (P ¼ 0.0063). We conclude that IFN in combination with HU achieves a significant long-term survival advantage over HU monotherapy. In view of the data of CML-study I, these results suggest that IFN/HU is also superior to IFN alone. HU should be combined with IFN in IFN-based therapies and for comparisons with new therapies.

In a prospective, randomized trial, netilmicin given once daily (OD) was compared in terms of efficacy and safety with the conventional 8-hourly dosing regimen (TD), both in combination with a broad spectrum beta-lactam, as initial empirical therapy for febrile neutropenic patients; the total daily dosage of netilmicin in each group was 6 mg/kg body weight. Twenty-nine of the 116 (25%) evaluable patients had microbiologically documented septicaemia, most of which were caused by Gram-positive bacteria, 41 (35%) had microbiologically documented infection without bacteraemia and 46 (40%) had possible infection. Highest peak serum concentrations of netilmicin in the OD group were significantly higher and trough serum concentrations significantly lower than in the TD group. A multivariate analysis revealed that neither the dosage regimen nor the peak serum concentration of netilmicin were determinants of a favourable outcome. The response rates of both groups to the initial treatment regimens were comparable and increased similarly following modification of the initial therapy. Response rates were particularly poor in patients with lower respiratory tract infection and in those who remained neutropenic throughout the course of treatment. The incidence of nephrotoxicity was low and did not differ significantly between groups. Once-daily dosing of netilmicin appears to be as effective and as safe as thrice-daily dosing, but is unlikely to further improve the response of febrile neutropenic patients to empirical therapy.

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