Is There Evidence on the Optimal Duration of Aminoglycoside Therapy in β-Lactam/Aminoglycoside Combination Regimens Used for the Treatment of Gram-Negative Bacterial Infections? A Systematic Review

Background

The optimal duration of therapy of aminoglycosides in combination regimens is expected to be different from that of monotherapy regimens, and shorter durations could help minimize toxicity without compromising efficacy. The aim of this review was to assess the evidence for the optimal duration of aminoglycosides in β-lactam/aminoglycoside combinations used for the treatment of Gram-negative bacterial infections.

Materials and Methods

PubMed, Cochrane, Embase, Scopus, Web of Science, and CINHAL databases were searched. Covidence software was used for article screening and management. Studies were included if they clearly reported the duration of therapy of aminoglycosides in β-lactam/aminoglycoside combinations used against Gram-negative bacteria. The protocol is registered with PROSPERO (CRD42023392709).

Results

A total of 45 β-lactam/aminoglycoside combination courses from 32 articles were evaluated. The duration of therapy of aminoglycosides in combinations regimens ranged from 1 to 14 days, varying with the type of infection treated. In half (51.1%; (23/45) of the combinations, aminoglycosides were administered for a duration ranging from 6 to 9 days. In 26.7% (12/45) of the combinations, the duration of aminoglycoside therapy was ≤ 5 days. In the remaining 22.2% (10/45) of these combinations, the aminoglycosides were administered for a duration of ≥ 10 days. Aminoglycosides were administered for a longer duration of 7-14 days in 12 (75%) of the 16 combination courses that induced toxicity.

Conclusions

Long duration of aminoglycoside use is associated with increased risk of toxicity. However, there is a lack of evidence on defining an optimal duration of aminoglycoside therapy in β-lactam/aminoglycoside combination regimens that ensures clinical efficacy outcomes whilst minimizing toxicity outcomes.