Reduction in mortality from gram-negative sepsis in neutropenic patients receiving trimethoprim/sulfamethoxazole therapy.

The causes of death were reviewed in 53 patients from two prospective randomized trials on the efficacy of trimethoprim/sulfamethoxazole as prophylaxis of gram-negative bacillary infection in granulocytopenic patients. Twenty-nine deaths occurred in patients treated with TMP/SMX prophylaxis while 24 occurred in patients who served as controls in the first trial. The two groups were similar, with the exception that more patients in the TMP/SMX group had acute leukemia (82 versus 50%; P less than 0.02). Microbiologically documented gram-negative rod infection preceeded death in 8/24 control patients as compared to 2/29 TMP/SMX recipients (P less than 0.02). This decrease in gram-negative related deaths was most pronounced in the patients with acute leukemia. Fatal gram-negative rod infection occurred in 7/12 control leukemic patients as compared to 2/24 TMP/SMX treated patients. Despite the reduction in numbers of gram-negative rod-related deaths, infectious deaths accounted for 16/24 and 15/29 patients in control and TMP/SMX treated patients, respectively. Similar numbers of fungal, viral, and gram-positive bacterial infections occurred in each group. Fever with pulmonary infiltrates but without proven etilogic agents were included in the category of "clinically documented infections;" 6/7 patients with fever and undiagnosed pulmonary infiltrates were in the TMP/SMX group. Prophylactic administration or oral trimethoprim/sulfamethoxazole reduces the frequency of fatal gram-negative rod infections in neutropenic patients.

A prospective controlled investigation of prophylactic trimethoprim/sulfamethoxazole in hospitalized granulocytopenic patients.

Oral trimethoprim/sulfamethoxazole (TMP/SMZ) therapy was investigated in the prophylaxis of infections in granulocytopenia. Hospitalized granulocytopenic patients were allocated at random to receive TMP/SMZ (group 1) or to a control group (group 2). The percentage of febrile granulocytopenic days was significantly reduced in group 1, 19 per cent compared to 39 per cent in group 2 (P less than 0.01). In group 1, there were no bacteremias in 59 episodes of granulocytopenia (909 days). In group 2, there were nine bacteremias in 52 episodes of granulocytopenia (796 days)(P = 0.001). Disseminated candidiasis developed in two patients in each group. Candida occurred in similar numbers in surveillance cultures in both groups; Staphylococcus aureus and Pseudomonas aeruginosa were slightly decreased, and Enterobacteriaceae resistant to TMP slightly increased in group 1. This study suggest that oral prophylactic TMP/SMZ therapy is an effective, well tolerated, easily administered alternative to "gut sterilization" with nonabsorbable antibiotics.

Granulocytopenia in hospitalized patients: I. Prognostic factors and etiology of fever.

The clinical course of 126 hospitalized patients during 192 episodes of granulocytopenia and fever was studied. Fever was a regular accompaniment of granulocytopenia, occurring in 94 per cent of granulocytopenic episodes. The mean duration of granulocytopenia (less than 1,000/mm3) was 18 days, with fever (temperature greater than 38 degrees C) being present during 44 per cent of those days. Fever was present during 69 per cent of days with a granulocyte count less than 10/mm3. A presumed infection was present in 86 of 128 febrile granulocytopenic episodes in adults and in 19 of 64 febrile granulocytopenic episodes in children. A fungal infection was found in 11 patients; a viral infection in 23 patients. Bacteremia occurred during 44 granulocytopenic episodes with 16.8 bacteremias/1,000 days of granulocytopenia in adults and 12.7 bacteremias/1,000 days in children. The mortality was 33 per cent per granulocytopenic episode in adults and only 8 per cent per episode in children.

Clinical evaluation of amikacin in treatment of infections due to gram-negative aerobic bacilli.

The efficacy and safety of amikacin were evaluated in 42 patients with infections presumed to be due to gram-negative rods. The dosage of 7.5 mg of amikacin/kg every 12 hr was administered intramuscularly to 32 patients and intravenously to seven patients; three patients with renal impairment were given a modified regimen. The duration of treatment was three to 51 days (mean, 9.6 days). Of 19 patients with acute pyelonephritis, five had positive blood culture results. Ten patients had chronic urinary infection, and isolates of Pseudomonas aeruginosa from four of these patients acquired resistance to amikacin during therapy. Of seven patients with gram-negative bacteremia from sources other than the urinary tract, four showed satisfactory and three had less than optimal responses to therapy with amikacin. Two patients with chronic osteomyelitis or soft tissue infection improved but subsequently relapsed. Two patients with acute febrile illness, in whom the etiologic agent was unidentified, recovered. Serial audiograms revealed no change in 26 of 27 patients; one had a significant deterioration in hearing. A transient rise in the level of serum creatinine was noted in three patients. Serial tests of liver function revealed no abnormalities.