5PSQ-077 Microbiological contamination following the use of two compounded formulations of tacrolimus eye drops

<h3>Background and Importance</h3> Tacrolimus eye drops are sterile formulations prepared in hospital pharmacy departments. The classic formulation (F1) contains ethanol as a solubiliser, which may potentially cause irritation to the ocular surface. A novel ethanol-free formulation (F2) has been developed using cyclodextrin. While cyclodextrins are not toxic to the ocular surface, they are sugars, which could increase microbiological contamination by acting as a growth medium. <h3>Aim and Objectives</h3> To determine microbial contamination derived from the use of both formulations. <h3>Material and Methods</h3> F1 is tacrolimus 0.03% eye drops, it was prepared using Prograf ampoules (containing ethanol as excipient) and Liquifilm. F2 is tacrolimus 0.015% eye drops; it was prepared from tacrolimus raw material and 40% hydroxypropyl-beta-cyclodextrin (HPβCD) solubilised in Liquifilm. Both were prepared under sterile conditions. Microbiological controls were negative. Two bottles of each formulation were dispensed per patient, who were instructed to use one bottle/week and to store them in the refrigerator. Containers were returned and analysed in pairs as they were dispensed. 250 µL of each of the two containers of TE were instilled into an 8 mL brain-heart infusion (BHI) tube and into a 5 mL thioglycolate (TG) tube. The same procedure was done for TCD. The BHI broth was incubated for 14 days at room temperature, while the TG broth was incubated for 4 days at 37°C, both in aerobiosis. Those that developed appreciable turbidity during incubation were subcultured to AS-CHOCO and Sabouraud, incubated in aerobiosis for 24 hours at 37°C. Identification was made with MALDI-TOF MS. <h3>Results</h3> A total of 45 patients returned their used containers (180). After analysis, 16 samples of F1 and 12 for F2 were positive. The following microorganisms were isolated and identified: Acinetobacter sp. (n=1), Bacillus sp. (n=3), Chryseobacterium indologenes (n=1), Elizabethkingia miricola (n=2), Enterococcus faecalis (n=1), Pantoea agglomerans (n=2), Pseudomonas sp. (n=5), Raoultella ornithinolytica (n=1), Serratia liquefaciens (n=4), Serratia grimesii (n=2), Serratia proteamaculans (n=2), Serratia marcenses (n=1), Stenotrophomonas maltophilia (n=5), Rahnella aquatilis (n=2). No evidence of infection was observed. <h3>Conclusion and Relevance</h3> Both tacrolimus formulations were similarly contaminated due to improper manipulation by the patient. The incorporation of cyclodextrins is expected to mitigate ocular irritation while maintaining an equivalent risk of microbial contamination. <h3>References and/or Acknowledgements</h3> <h3>Conflict of Interest</h3> No conflict of interest