Once versus multiple daily dosing of aminoglycosides for patients with febrile neutropenia: a systematic review and meta-analysis

• Published in: Journal of antimicrobial chemotherapy 2011-02, Vol.66 (2), p.251-259
• Main Authors: MAVROS, Michael N, POLYZOS, Konstantinos A, RAFAILIDIS, Petros I, FALAGAS, Matthew E
• Format: Article
• Language: English
• Subjects: Aminoglycosides - administration & dosage; Aminoglycosides - adverse effects; Aminoglycosides - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antimicrobial agents; Bacterial infections; Biological and medical sciences; Clinical trials; Drug Administration Schedule; Drug dosages; Drug therapy; Fever - drug therapy; Fever - microbiology; Fever - mortality; Hematologic and hematopoietic diseases; Humans; Medical sciences; Neutropenia - drug therapy; Neutropenia - microbiology; Neutropenia - mortality; Other diseases. Hematologic involvement in other diseases; Patients; Pharmacology. Drug treatments; Product safety; Systematic review; Treatment Outcome
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkq451

Once daily dosing (ODD) of aminoglycosides has become a standard of care for most patient populations. However, the use of ODD of aminoglycosides has not been clarified in febrile neutropenia. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) that compared the effectiveness and safety of ODD versus multiple daily dosing (MDD) of aminoglycosides in patients with febrile neutropenia. We searched the PubMed, Scopus, Cochrane Central Register of Trials and clinicaltrials.gov databases up to July 2010. A total of five and eight RCTs were included in the effectiveness and safety analyses, respectively. We observed a trend towards better effectiveness of the ODD regimen in the clinically evaluable population {five RCTs, 403 patient-episodes, risk ratio (RR)  = 1.18 [95% confidence interval (95% CI): 0.98, 1.42]}, but not in the microbiologically evaluable population [three RCTs, 119 patient-episodes, RR = 1.11 (95% CI: 0.84, 1.48)]. The occurrence of nephrotoxicity was similar between the two groups [seven RCTs, 1643 patient-episodes, RR = 0.74 (95% CI: 0.36, 1.50)], as was ototoxicity [six RCTs, 862 patient-episodes, RR = 1.05 (95% CI: 0.51, 2.19)]. There was no difference in mortality [four RCTs, 403 patient-episodes, RR = 0.77 (95% CI: 0.21, 2.78)]. Although the generalization of our findings may be restricted by the relatively small sample size and other methodological limitations of the included RCTs, ODD appears to be at least as effective and as safe as MDD in patients with febrile neutropenia. RCTs comparing ODD versus MDD in patients with bacteraemia and profound or prolonged neutropenia would be of additional value.