Oral minocycline-minocycline

Multicenter randomised controlled clinical trial to compare antimicrobial oral treatment with minocycline plus rifampicin to oral treatment with linezolid for complicated skin and soft tissue infections (cSSTI) due to MRSA.

Bayliss MAJ, Rigdova K, Kyriakides M, Grier S, Lovering AM, Williams H, Griffith DC, MacGowan A.: Development, validation and application of a novel HPLC-MS/MS method for the measurement of minocycline in human plasma and urine. J Pharm Biomed Anal. 2019 May 30;169:90-98

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The study Pharmacodynamics of minocycline against Staphylococcus aureus studied in an in vitro pharmacokinetic model of infection by AR Noel, KE Bowker, S Tomaselli, AP MacGowan, WW Hope has been presented at ICAAC 2013. This PK/PD study will support the clinical study of WP3.

Background: Minocycline (MIN) is a widely used oral therapy for mild to moderate MRSA infection which can be safely treated with non-parenteral antibiotics. Despite a long tradition of use to treat Staphylococcal infection, there is little data to support present dosing regimens and no data on the risks of emergence of resistance. Clinical breakpoints, both in Europe and USA, are based on historic data. Our objective was to provide modern information on the pharmacodynamic index size for minocycline and S.aureus with a view to re-assessing established clinical breakpoints and potential dose regimens. Methods: An in vitro dilutional pharmacokinetic model was used to perform a series of dose ranging studies against 4 strains of S.aureus (MIN MIC 0.19-0.5mg/L, all susceptible by EUCAST breakpoints S≥0.5mg/L). Antibacterial effect was measured by changes in viable count over 72h and changes in population profile by recovery on MICx4 or MICx8 plates after 24, 48 and 72h MIN exposure. Results: The fAUC/MIC at 24h for static and -1 log reductions in viable count were 11.5±6.1 and 18.1±8.1 respectively. For -2 log reduction in viable count, the fAUC/MIC was >200 for two strains, and 33.1 and 42.8 for the two others. fAUC/MIC targets were modestly increased after 72h being 12.9±2.9, static effect; 17.7±5.2, -1 log drop; 2 log drop values were >75, and 32.1 and 18.2 for the other two strains. There were no changes in population profiles indicated by growth on MICx4 or MICx8 plates at 24, 48 or 72h. Conclusions: A suitable fAUC/MIC target related to static -1 log drop for MIN is 10-15. This target was not associated with any change in population profiles and would suggest a clinical breakpoint of S≤0.25-0.5mg/L for a dose of 100mg 12 hrly.