Oral enoxacin for infection prevention in adults with acute nonlymphocytic leukemia. The Enoxacin Prophylaxis Study Group

Abstract

A randomized, double-blind, placebo-controlled trial was conducted in eight hematologic units to determine the efficacy and safety of oral enoxacin for infection prevention in adult patients with acute nonlymphocytic leukemia. One hundred nineteen patients undergoing remission induction or consolidation chemotherapy were enrolled; 62 of them received enoxacin (400 mg orally every 12 h). Patients received antifungal prophylaxis with oral mycostatin (1,000,000 U four times daily) or clotrimazole (1 troche five times daily). Analysis was performed on an intent-to-treat basis. There was no significant difference between groups in race, age, or type and stage of leukemia, but there were more males in the placebo group (P = 0.073 [Fisher's exact test]). Fewer enoxacin patients had gram-negative bacteremia (1 versus 14 [P < 0.001]), gram-negative infection at any site (2 versus 19 [P < 0.001]), or bacterial and/or fungal infection (17 versus 26 [P = 0.056]). There was no significant difference in the number of patients with gram-positive infection at any site (12 versus 16), gram-positive bacteremia (9 versus 10), deep fungal infection (6 versus 2), death (2 versus 3), other antimicrobial therapy required (48 versus 48), therapy with amphotericin B (15 versus 7 [P = 0.105]), any adverse event (45 versus 36), or any study drug-associated adverse events (13 versus 6). Logistic regression confirmed (odds ratios and 95% confidence intervals are given in parentheses) that enoxacin reduced the risk of gram-negative infection (0.07; 0.01 to 0.30), especially gram-negative bacillary bacteremia (0.05; 0.01 to 0.37), without altering the risk of gram-positive bacterial (0.63; 0.26 to 1.5), deep fungal (2.57; 0.47 to 13.9), or Clostridium difficile (1.16; 0.3 to 4.56) infection. The median time to the onset of fever of more than or equal 102.8 F (39.3 degree C) was 32 days for the enoxacin group versus 15 days for patients receiving placebo (P=0.0007 [Wilcoxon test]). In patients with acute nonlymphocytic leukemia, oral enoxacin prevents gram-negative infections, delays the onset of fever, does not alter the incidence of gram-positive or proven deep fungal infections, and is well tolerated.

Antibiotic prophylaxis in neutropenic patients

“…2,3,12,18,19 Seven documented infections were observed in 1250 patients who were randomized to receive prophylaxis in those studies, and there were 5 infections in 1279 patients who were randomized to receive either placebo or no treatment (RR, 1.44; 95% CI, 0.45-4.63). In the 2 new and larger studies 2,3 no Clostridium difficile infections were detected.…”

“…We have updated our meta-analysis 1 with data from recent trials 2,3 and divided the trials [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] according to the type of patient (Fig. 1).…”

Reply from Jose A Pérez Simón on behalf of the authors

“…In this sense, avoiding or delaying fever episodes would be expected to result in proportionate reductions in fever-associated morbidity. [9][10][11] We believe that Nucci et al's statement that 'this strategy should be strongly discouraged' is not supported by any study with a design similar to the present one and it would be more correct, as we mentioned, to state that 'this prophylactic strategy should be confirmed in a larger series of closely monitored patients'.…”

Levofloxacin prophylaxis to prevent bacterial infection in chemotherapy-induced neutropenia in acute leukemia

“…Prolonged neutropenia (>7 days) is a recognized factor for febrile neutropenia 6 . Only 14 patients had prolonged neutropenia.…”

“…Use of fluroquinolone extended spectrum to Gram positive bacteria e.g. levofloxacin or addition of antibiotic effective against Gram positive bacteria reported to reduce the Gram positive septicemia 5,6 . Though there is a concern about the emergence or drug resistant bacteria with the prophylaxis of these antibiotics 7,8 .…”