Infection: aminoglycosides: once-daily treatment is more effective and less toxic than multiple daily doses.

Clinical bottom line (level 1a)

  1. Non-neutropenic adults with an infection who are given once-daily aminoglycosides, are more likely to have clinical effectiveness than those given multiple daily dose aminoglycosides.
  2. Patients given once -daily aminoglycosides are less likely to have nephrotoxicity.
  3. There is no clear difference in ototoxicity.
Ferriols-Lisart and Alos-Alminana: American Journal of Health-Systmes and Pharmacology 1996; 53: 1141-1150
Expires May 2003

The study

Systematic review of randomised controlled trials of
  • Patients: non-neutropenic adult patients with clinical or bacteriologic symptoms of infection
  • Intervention: several times daily aminoglycosides compared with once daily aminoglycosides
  • Outcome: clinical effectiveness and toxicity (nephrotoxicity and ototoxicity)


    • Articles found in English using MEDLINE, January 1988 to October 1995 (search terms: aminoglycoside, netilmicin, amikacin, gentamicin, tobramycin, once-daily, single daily dose ) and additional studies were identified from relevant review articles and references in the retrieved articles

    Selection criteria: as above
    Appraisal criteria: reviewed independently by two blinded authors. Details in text
    Articles excluded if: editorials, reviews, animal studies or case reports; control group was inadequate (different aminoglycoside to experimental group); conducted in vitro or in some other experimental model; data not sufficient for analysis

    Eighteen studies involving 2317 patients were included.
    There was no significant heterogeneity.

    The evidence

    Outcome Time to outcome CER OR
    (95% CI)    		 NNH
    (95% CI)
    clinical effectiveness unknown 168/933
    (82%)    		 1.47
    (1.13 to 1.94)     		20
    (13 to 58)
    nephrotoxicity unknown 168/933
    (82%)    		 0.60
    (0.40 to 0.86)     		11
    (6 to 43)
    ototoxicity unknown 168/933
    (82%)    		 0.56
    (0.26 to 1.16)     		10
    (NNT = 48 to infinity;
    NNH = 4 to infinity)

    • Confining the analysis to high quality trials led to a reduction in the estimate of effectiveness.

    Citation

    1. Ferriols-Lisart R, and Alos-Alminana M: Effectiveness and safety of once-daily aminoglycosides: A meta-analysis. American Journal of Health-Systmes and Pharmacology 1996; 53: 1141-1150
    Contributor: Clare Wotton and Musab Hayatli, May 2000
    Reviewer: Dirk Stengel

    Clinical Question.
    Patient infection
    Intervention or Exposure several times daily aminoglycosides
    Comparison once daily aminoglycosides
    Outcome effectiveness and toxicity