title: Randomized trial of the addition of gram-positive prophylaxis to standard antimicrobial prophylaxis for patients undergoing autologous bone marrow transplantation.
abstract: The purpose of the study reported here was to investigate the impact of prophylaxis against gram-positive infections in patients undergoing high-dose chemotherapy and autologous bone marrow transplantation in a randomized trial. Forty-three patients undergoing high-dose chemotherapy with autologous bone marrow transplant were enrolled in a nonblinded randomized trial to receive or not to receive prophylaxis for gram-positive infections with 10(6) U of penicillin intravenously (i.v.) every 6 h (q6h) (if penicillin allergic, 750 mg of vancomycin i.v. q12h) in addition to standard antimicrobial prophylaxis with 400 mg of norfloxacin orally three times a day, 200 mg of fluconazole orally once a day, and 5 mg of acyclovir per kg of body weight i.v. q12h. The patients were being treated for germ cell cancer (n = 15), breast cancer (n = 16), Hodgkin's disease (n = 3), non-Hodgkin's lymphoma (n = 4), acute myeloid leukemia (n = 1), acute lymphoblastic leukemia (n = 1), and ovarian cancer (n = 3). The trial was stopped because of excess morbidity in the form of streptococcal septic shock in the group not receiving gram-positive prophylaxis. There were significantly fewer overall infections (10 versus 3; P = 0.016) and streptococcal infections (9 versus 1; P = 0.0078) in the group receiving gram-positive prophylaxis. There were no significant differences in the numbers of deaths, duration of broad-spectrum antibiotics, or incidence of neutropenic fever between the two groups. Prophylaxis for gram-positive infections with penicillin or vancomycin is effective in reducing the incidence of streptococcal infections in patients undergoing high-dose chemotherapy and autologous bone marrow transplant. However, this approach may carry a risk of fostering resistance among streptococci to penicillin or vancomycin.
authors.affiliation: Bone Marrow Transplant Program, Indiana University School of Medicine, Indianapolis.
authors.forename: E R
authors.initials: ER
authors.lastname: Broun
authors.forename: J L
authors.initials: JL
authors.lastname: Wheat
authors.forename: P H
authors.initials: PH
authors.lastname: Kneebone
authors.forename: K
authors.initials: K
authors.lastname: Sundblad
authors.forename: R A
authors.initials: RA
authors.lastname: Hromas
authors.forename: G
authors.initials: G
authors.lastname: Tricot
mesh_terms: D000212:Acyclovir / Q000627:therapeutic use; D000328:Adult; D016470:Bacteremia / Q000382:microbiology / Q000517:prevention & control; D016026:Bone Marrow Transplantation; D005260:Female; D005334:Fever / Q000517:prevention & control; D015725:Fluconazole / Q000627:therapeutic use; D016908:Gram-Positive Bacterial Infections / Q000382:microbiology / Q000517:prevention & control*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications / Q000628:therapy; D009643:Norfloxacin / Q000627:therapeutic use; D010406:Penicillins / Q000008:administration & dosage / Q000627:therapeutic use*; D011292:Premedication; D013290:Streptococcal Infections / Q000382:microbiology / Q000517:prevention & control; D014640:Vancomycin / Q000627:therapeutic use
chemical_list: D010406:Penicillins; D014640:Vancomycin; D015725:Fluconazole; D009643:Norfloxacin; D000212:Acyclovir