Improving the Safety of Clinical Management of COVID-19 Patients Receiving Aminoglycosides and Parenteral Nutrition: Y-site Compatibility Studies

J Pharm Sci. 2023 Oct;112(10):2597-2603. doi: 10.1016/j.xphs.2023.08.007. Epub 2023 Aug 16.

Abstract

Purpose: Aminoglycosides (AMGs) are broad-spectrum bactericidal antibiotics that can resolve bacterial infections co-existing with COVID-19 or exploit their potential antiviral activities. Patients presenting the most severe forms of COVID-19 due to escalating catabolism and significant lean body mass loss often require the concomitant administration of parenteral nutrition (PN) and antibiotics. The Y-site administration is one of the approaches allowing the co-administration of two intravenous medications in patients with limited vascular access. Our study aimed to investigate the compatibility of AMGs and selected commercial PN admixtures enriched in omega-3 fatty acids.

Methods: Gentamycin (GM), amikacin (AM), and tobramycin (TM) solutions for infusion were combined with Nutriflex Omega Special (NOS) and Smofkabiven (SFK). Three different volume ratios were investigated: 1:2, 1:1, and 2:1, simulating Y-site administration. Samples underwent visual examination and determination of the lipid emulsion particle size, zeta potential, and pH immediately after preparation and after four hours of storage at room temperature (22 ± 2 °C) with sunlight exposure.

Results: GM and AM combined with NOS in all studied ratios met the set-up acceptance criteria. The addition of TM to NOS in a 2:1 volume ratio and all tested AMGs to SFK in all studied combinations significantly influenced the stability of the oil-water system leading to the appearance of globules larger than 5 µm exceeding the pharmacopeial limit of 0.05% immediately after preparation or after four hours of storage.

Conclusion: In conclusion, our study showed that NOS was less prone to destabilization of oil-in-water systems by AMGs than SFK. In justified clinical cases, due to the lack of appearance of precipitate or enlarged lipid droplets, the combined administration of GM and AM with the NOS could be considered, provided tested volume ratios of the drug and MCB in the infusion line are maintained. However, it should be noted that such an infusion may be associated with the risk of changes in the pharmacokinetics of the drug.

Keywords: Aminoglycosides; COVID-19; Nutriflex omega special; Smofkabiven; Y-site administration; compatibility tests.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoglycosides*
  • Anti-Bacterial Agents / therapeutic use
  • COVID-19*
  • Gentamicins
  • Humans
  • Parenteral Nutrition
  • Tobramycin
  • Water

Substances

  • Aminoglycosides
  • Anti-Bacterial Agents
  • Gentamicins
  • Tobramycin
  • Water