Double-blind comparison of teicoplanin versus vancomycin in febrile neutropenic patients receiving concomitant tobramycin and piperacillin: effect on cyclosporin A-associated nephrotoxicity

Abstract

A prospective, randomized, and double-blind study comparing teicoplanin with vancomycin in the initial management of febrile neutropenic patients was conducted. Teicoplanin was administered at 6 mg per kg of body weight every 24 h (q24h) intravenously (i.v.) after initial loading at 6 mg/kg ql2h for three doses. Vancomycin was administered at 15 mg/kg ql2h i.v. Patients also received piperacillin (3 g q4h i.v.) and tobramycin (1.5 to 2.0 mg/kg q8h i.v.). Of 53 patients enrolled, 50 were judged to be evaluable. Among these, 25 received teicoplanin and 25 received vancomycin. At enrollment, both groups were comparable in age, sex, renal function, underlying hematologic condition, and concurrent therapy. Both groups had similar sites of infection and microbial pathogens. Empirical antimicrobial therapy resulted in the cure of or improvement in 23 (92%) teicoplanin patients and 21 (84%) vancomycin patients (P = 0.67). Failures occurred with two vancomycin patients but no teicoplanin patients. Clinical response was indeterminate for two patients in each group. Adverse reactions occurred significantly more often in the vancomycin group than in the teicoplanin group (P = 0.01), and these reactions required the termination of the study regimens of 6 vancomycin versus 0 teicoplanin patients (P = 0.02). Nephrotoxicity was observed more frequently in the vancomycin group (10 versus 2 patients; P = 0.02). Subgroup analysis revealed a significant deterioration of renal function when vancomycin and cyclosporin A, but not teicoplanin and cyclosporin A, were used concurrently (P = 0.02). Among patients who received vancomycin and amphotericin B or teicoplanin and amphotericin B concurrently, deterioration in renal function was equivalent in both groups. Teicoplanin in the dosage employed was tolerated better than vancomycin in the empirical treatment of fever and neutropenia in our patient population.

Effects of teicoplanin and those of vancomycin in initial empirical antibiotic regimen for febrile, neutropenic patients with hematologic malignancies. Gimema Infection Program

“…Our data do not confirm either the higher rate of nephrotoxicity (6%) attributable to vancomycin previously reported in neutropenic patients receiving an empirical antibiotic regimen (5) or the less nephrotoxic potential suggested for teicoplanin when both glycopeptide antibiotics were combined with tobramycin and piperacillin in neutropenic patients (13). However, it is worthy of note that in the small study by Kureishi et al (13) teicoplanin was less nephrotoxic than vancomycin, especially in the subgroup of patients who concurrently received cyclosporin A; this was not the case for our patients. The very low rate of nephrotoxicity documented in our patients might be related to inadequate concentrations of aminoglycosides in serum, because an assay of serum for the recommended peak and trough levels was not routinely performed.…”

“…Teicoplanin, an antibiotic administered once daily with activity against strains of enterococci resistant to vancomycin, seems to be less toxic (13,21) and is easier to administer. Both vancomycin (12,22) and teicoplanin (4, 14,16), when used in initial, combined therapy, have proved to be efficacious in the treatment of neutropenic patients with gram-positive bacteremias; however, comparative studies able to establish which glycopeptide antibiotic may be the better choice in febrile, neutropenic patients are lacking.…”

Meta-analysis of Randomized Controlled Trials of Vancomycin for the Treatment of Patients With Gram-Positive Infections: Focus on the Study Design

“…77 In trials studying febrile neutropenic patients, vancomycin and comparator antibiotics were included in the first-line empirical regimen in 7 trials, 32,54,61,62,64,67,69 in 2 trials they were administered after treatment failure of the initial regimen (usually a ␤-lactam with or without an aminoglycoside) was encountered, 59,71 and in the remaining 3 randomization was performed after the VANCOMYCIN FOR GRAM-POSITIVE INFECTIONS: A META-ANALYSIS isolation of gram-positive cocci. 55,57,73 Finally, 1 trial did not report the time of randomization.…”

“…a These numbers correspond to 2 different randomized controlled trials that were published as one in Clinical Infectious Diseases. 50 45 2005 Corey et al, 39 2010 D'Antonio et al, 55 2004 Florescu et al, 44 2008 Gilbert et al, 72 1991 Jaksic et al, 32 2006 Kureishi et al, 69 1991 Lin et al, 27 2008 Noel et al, 43 2008 Noel et al, 42 2008 Rolston et al, 66 1994 Rolston et al, 58 1999 Rubinstein et al, 38 2001 Rubinstein et al, 50 2011 (0015) …”

Tratamento ambulatorial da neutropenia febril

“…Embora os Estados Unidos da América não tenham autorizado o uso desta droga, é uma alternativa em substituição ao uso de vancomicina 57,58 . Além disso, a facilidade posológica e a baixa taxa de eventos adversos merecem ser consideradas para a aplicação de teicoplanina em ambiente de ambulatorial considerado hospital-dia 59 .…”