TY - JOUR
T1 - Trimethoprim-Sulfamethoxazole Prophylaxis in Granulocytopenic Patients with Acute Leukemia
T2 - Evaluation of Serum Antibiotic Levels in a Randomized, Double-Blind, Placebo-Controlled Department of Veterans Affairs Cooperative Study
AU - Ward, T. T.
AU - Thomas, R. G.
AU - Fye, C. L.
AU - Arbeit, R.
AU - Coltman, C. A.
AU - Craig, W.
AU - Dana, B. W.
AU - Finegold, S. M.
AU - Lentino, J.
AU - Penn, R. L.
AU - Weinberg, J. B.
AU - Chow, B.
AU - Ochi, S.
N1 - Funding Information:
Received 4 May 1992; revised 21 April 1993. Financial support: This study was supported by the Cooperative Studies Program of the Medical Research Service of the Department of Veterans Affairs. * Participating investigators are listed at the end of the text. Reprints or correspondence: Dr. Thomas Ward, Infectious Disease Section (111F), DVA Medical Center, 3710 U.S. Veterans Road, Portland, Oregon 97207.
PY - 1993/9
Y1 - 1993/9
N2 - Despite widespread use of trimethoprim-sulfamethoxazole (TMP-SMZ) for prophylaxis in neutropenic patients, questions remain regarding its efficacy, toxicity, the risk of selection of resistant isolates, and the relation of its activity to selective decolonization vs. the attainment of direct inhibitory levels within blood and tissues. We evaluated the effect of TMP-SMZ (160/800 mg orally every 12 hours) in 42 adult granulocytopenic patients (<100 absolute neutrophils/mm3, mean duration 13.3 days) undergoing chemotherapy for acute leukemia at 11 participating Veterans Administration Medical Centers in a randomized, double-blind, placebo-controlled trial. No significant differences in survival, frequency of bacteremia, overall infections, use of systemic antimicrobial therapy, or adverse effects, including myelosuppression, were observed between patients receiving TMP-SMZ vs. those receiving placebo. All patients acquired trimethoprim-resistant organisms. Concentrations of trimethoprim in serum were significantly lower before febrile episodes than when patients were afebrile. These results suggest that the purpo rtedactivity of TMP-SMZ may be related to the serum concentration achieved. Moreover, the results highlight the need for additional study of the value of antibiotic prophylaxis in neutropenic patients.
AB - Despite widespread use of trimethoprim-sulfamethoxazole (TMP-SMZ) for prophylaxis in neutropenic patients, questions remain regarding its efficacy, toxicity, the risk of selection of resistant isolates, and the relation of its activity to selective decolonization vs. the attainment of direct inhibitory levels within blood and tissues. We evaluated the effect of TMP-SMZ (160/800 mg orally every 12 hours) in 42 adult granulocytopenic patients (<100 absolute neutrophils/mm3, mean duration 13.3 days) undergoing chemotherapy for acute leukemia at 11 participating Veterans Administration Medical Centers in a randomized, double-blind, placebo-controlled trial. No significant differences in survival, frequency of bacteremia, overall infections, use of systemic antimicrobial therapy, or adverse effects, including myelosuppression, were observed between patients receiving TMP-SMZ vs. those receiving placebo. All patients acquired trimethoprim-resistant organisms. Concentrations of trimethoprim in serum were significantly lower before febrile episodes than when patients were afebrile. These results suggest that the purpo rtedactivity of TMP-SMZ may be related to the serum concentration achieved. Moreover, the results highlight the need for additional study of the value of antibiotic prophylaxis in neutropenic patients.
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U2 - 10.1093/clinids/17.3.323
DO - 10.1093/clinids/17.3.323
M3 - Article
C2 - 8218671
AN - SCOPUS:0027249645
SN - 1058-4838
VL - 17
SP - 323
EP - 332
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 3
ER -