Three-day treatment with imipenem for unexplained fever during prolonged neutropaenia in haematology patients receiving fluoroquinolone and fluconazole prophylaxis: a prospective observational safety study.
BACKGROUND
Guidelines advocate >7d of broad-spectrum antibiotics for unexplained fever (UF) during neutropaenia. However, effective antimicrobial prophylaxis reduces the incidence of gram-negative infections, which may allow shorter treatment. This study evaluates the safety of discontinuing empirical broad-spectrum antibiotics if no microbial source is documented after an initial work-up of 72 h.


METHODS
Prospective observational study at a tertiary-care haematology-unit in patients suffering from haematologic malignancies and treatment-induced prolonged neutropaenia of 10d. Oral fluoroquinolone and fluconazole prophylaxis was given from day 1. Fever was empirically treated with imipenem which was discontinued after 72 h if, following a standardised protocol, no infectious aetiology was documented. Duration of fever, antimicrobial therapy and overall mortality were registered.


RESULTS
One hundred and sixty six patients were evaluated during 276 neutropaenic episodes. One hundred and thirty six patients (82.5%) experienced 1 febrile episode. A total of 317 febrile episodes were observed, of which 177 (56%) were diagnosed as UF. In 135 febrile episodes (43%), a probable/definite infectious origin was documented. Mean duration of fever in neutropaenic periods with 1 febrile episode was 5d, and mean time of treatment with imipenem was 4.7d. In patients without documented infection, mean time of imipenem treatment was only 3.7d. Overall mortality 30 d after neutrophil recovery was 3.6% (6/166); no patient died from untreated bacterial infection.


CONCLUSIONS
Discontinuation of broad-spectrum antibiotics during neutropaenia in haematology patients on fluoroquinolone and fluconazole prophylaxis is safe, provided that no infectious aetiology is established after 72 h.
Slobbe
Lennert
L
Department of Internal Medicine, Division of Infectious Diseases, 's Gravendijkwal 230, Erasmus MC, Rotterdam, The Netherlands.
Waal
Loes van der
Lv
Jongman
Lydia R
LR
Lugtenburg
Pieternella J
PJ
Rijnders
Bart J A
BJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D019072:Antibiotic Prophylaxis; D000935:Antifungal Agents / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000009:adverse effects; D003091:Colistin / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D005260:Female; D005335:Fever of Unknown Origin / Q000188:drug therapy* / Q000209:etiology; D015725:Fluconazole / Q000008:administration & dosage; D024841:Fluoroquinolones / Q000008:administration & dosage; D019337:Hematologic Neoplasms / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D015378:Imipenem / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced*; D011446:Prospective Studies; D028761:Withholding Treatment; D055815:Young Adult
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D000970:Antineoplastic Agents; D024841:Fluoroquinolones; D015378:Imipenem; D015725:Fluconazole; D003091:Colistin