Sequential prophylactic oral and empiric once-daily parenteral antibiotics for neutropenia and fever after high-dose chemotherapy and autologous bone marrow support.
OBJECTIVE
We studied the effectiveness of prophylactic oral ciprofloxacin and rifampin on fever prevention in patients undergoing autologous bone marrow transplantation (ABMT) for breast cancer. Furthermore, we evaluated the toxicity and efficacy of empiric once-daily vancomycin and tobramycin for febrile neutropenia.


METHODS
Ninety-nine assessable women received prophylactic ciprofloxacin and rifampin after high-dose chemotherapy (HDC) for advanced or high-risk primary breast cancer supported with either bone marrow and peripheral-blood progenitor cells (PBPCs) or bone marrow purged with chemotherapy and monoclonal antibodies. Neutropenic fever was treated with empiric once-daily vancomycin and tobramycin. Patients were compared with historic controls treated with the identical HDC and bone marrow support regimen.


RESULTS
In patients treated with bone marrow and PBPCs, the incidence of fever during neutropenia was reduced by ciprofloxacin and rifampin from 98% to 57%. Documented infections were reduced from 42% to 13% (P < .01) and bacteremia from 18% to 0% (P < .001). In purged bone marrow recipients, the overall infection rate decreased from 74% to 17% (P < .001), and bacteremia from 29% to 7%. (P = .02). No patient developed breakthrough bacteremia or sepsis syndrome while on study. Serum creatinine level greater than 1.8 g/dL was noted in 7% of controls and 10% of study patients. Increased ototoxicity was not encountered with the higher peak concentrations of vancomycin and tobramycin.


CONCLUSIONS
The therapeutic strategy of ciprofloxacin and rifampin followed by once-daily vancomycin and tobramycin markedly reduced the incidence of infection and virtually eliminated bacteremia in both purged and nonpurged bone marrow recipients. Once-daily vancomycin and tobramycin was safe and effective and, because of the ease of use, facilitates outpatient management of ABMT patients.
Gilbert
C
C
Duke University Bone Marrow Transplant Program, Duke University Medical Center, Durham, NC 27710.
Meisenberg
B
B
Vredenburgh
J
J
Ross
M
M
Hussein
A
A
Perfect
J
J
Peters
W P
WP
D000284:Administration, Oral; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D001424:Bacterial Infections / Q000209:etiology / Q000517:prevention & control*; D016465:Bone Marrow Purging; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D001943:Breast Neoplasms / Q000628:therapy*; D002939:Ciprofloxacin / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005334:Fever / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D007275:Injections, Intravenous; D008875:Middle Aged; D009503:Neutropenia / Q000209:etiology / Q000517:prevention & control*; D012293:Rifampin / Q000627:therapeutic use; D033581:Stem Cell Transplantation; D014031:Tobramycin / Q000627:therapeutic use; D014640:Vancomycin / Q000627:therapeutic use
D002939:Ciprofloxacin; D014640:Vancomycin; D012293:Rifampin; D014031:Tobramycin