In vitro performances of novel co-spray-dried azithromycin/rifampicin microparticles for Rhodococcus equi disease treatment

• Published in: Scientific reports 2018-08, Vol.8 (1), p.12149-11, Article 12149
• Main Authors: Rampacci, Elisa, Marenzoni, Maria Luisa, Chiaradia, Elisabetta, Passamonti, Fabrizio, Ricci, Maurizio, Pepe, Marco, Coletti, Mauro, Giovagnoli, Stefano
• Format: Article
• Language: English
• Subjects: 13/106; 631/154/1438; 631/326/22/1290; 639/925/930/12; 692/699/255/1318; Actinomycetales Infections - drug therapy; Actinomycetales Infections - microbiology; Animals; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Antibacterial activity; Antibiotics; Azithromycin; Azithromycin - pharmacology; Azithromycin - therapeutic use; Bioavailability; Cytotoxicity; Drug Combinations; Drug Compounding - methods; Drug interaction; Drug Synergism; Drying; Humanities and Social Sciences; Humans; Microbial Sensitivity Tests; Microparticles; Minimum inhibitory concentration; multidisciplinary; Powder; Powders; Rhodococcus equi; Rhodococcus equi - drug effects; Rhodococcus equi - pathogenicity; Rifampin; Rifampin - pharmacology; Rifampin - therapeutic use; Science; Science (multidisciplinary); THP-1 Cells; Toxicity Tests; Zoonoses - drug therapy; Zoonoses - microbiology
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-30715-z

This work was aimed at providing clues on the in vitro performances of novel azithromycin/rifampicin combinations, in the form of co-spray-dried microparticles (AZM/RIF MP), against Rhodococcus equi , an animal and emerging human pathogen found responsible for worrying zoonosis. Various AZM/RIF combinations were spray-dried and characterized for their morphology and size. Susceptibility studies included determination of MIC, MBC, Fractional Inhibitory/Bactericidal Concentration Indexes and intracellular activity in R . equi -infected THP-1 cells. Cytotoxicity was tested on BEAS-2B cells through MTT assay and combination index assessment for drug interaction. Spray-dried MP were collapsed and 3–10 times smaller than commercial powders. Drug combinations showed an enhancement of in vitro antibacterial activity with a remarkable synergistic bactericidal effect. Azithromycin MP and AZM/RIF MP 2:1 led to a CFU reduction of >90% up to 4 days after treatment at all tested concentrations (p = 0.001) but AZM/RIF MP 2:1 were at least four-fold more potent than AZM MP alone. IC 50 values of >100 mg/L supported low cytotoxicity of drug combinations and the combination index suggested an antagonistic toxic effect. Co-spray-drying enhanced powder dispersibility and solubility, which may improve bioavailability as well as provide administration alternatives. The novel AZM/RIF MP combinations could result a valid platform to develop new treatment strategies against R . equi infections in animals and humans.