Use of Liposomal Gentamicin for Treatment of 5 Foals with Experimentally Induced Rhodococcus equi Pneumonia

Abstract

BackgroundAdverse effects of, and bacterial resistance to, macrolides used to treat Rhodococcus equi infections have prompted search for clinically effective alternative antimicrobials. Liposomal gentamicin (LG) is effective against R. equi in vitro and decreases tissue concentrations of R. equi in experimentally infected mice. Effectiveness of LG treatment of foals with R. equi pneumonia, however, has not been described.HypothesisLiposomal gentamicin is safe and effective for treating foals with R. equi pneumonia.AnimalsTen foals with experimentally induced R. equi pneumonia.MethodsPilot treatment trial. Foals with pneumonia induced by intrabronchial instillation of R. equi were randomly allocated to receive either clarithromycin combined with rifampin (CLR + RIF) PO or LG IV, and followed by daily physical examinations and weekly thoracic ultrasonography and serum creatinine concentration determinations until the resolution of clinical signs. Treatment success was defined as the resolution of clinical signs and ultrasonographically identified pulmonary abscesses.ResultsAll 10 foals were successfully treated. Two of 5 foals treated with LG developed azotemia within 1 week; LG was discontinued and treatment switched to CLR + RIF for these foals. None of the CLR + RIF treated foals developed azotemia.Conclusions and Clinical ImportanceLiposomal gentamicin IV can be effective for treatment of R. equi pneumonia, but nephrotoxicity indicates that an alternative dosing interval or route (such as nebulization) will be needed before LG is adequately safe for clinical use. Larger comparative trials will be needed to evaluate the relative efficacy of a safer LG dosage regimen.

Rhodococcus equifoal pneumonia: Update on epidemiology, immunity, treatment and prevention

“…113 Liposomal gentamicin sulfate reached therapeutic concentrations in BAL cells and PELF but its use resulted in evidence of nephrotoxicity in some foals. 138,139 More work is needed to evaluate the efficacy and risks of nebulised gentamicin against R. equi but this approach might be a good alternative for treating foals infected with macrolide-resistant strains. 115 Adjunct therapy using streptolysin O (SLO), a virulence factor of streptococci which binds to cholesterol in cell membranes creating cellular pores, in combination with clarithromycin and rifampin decreased bacterial counts and gross pathological findings in the lungs of foals experimentally infected with R. equi.…”

“…Moreover, the combination of azithromycin‐doxycycline was not inferior to azithromycin‐rifampin and resulted in > 95% treatment success in foals with mild to moderate bronchopneumonia 113 . Liposomal gentamicin sulfate reached therapeutic concentrations in BAL cells and PELF but its use resulted in evidence of nephrotoxicity in some foals 138,139 . More work is needed to evaluate the efficacy and risks of nebulised gentamicin against R. equi but this approach might be a good alternative for treating foals infected with macrolide‐resistant strains 115 …”

Current Trends in Understanding and Managing Equine Rhodococcosis

“…Another alternative recently checked for antirhodococcal potential in foals was liposomal gentamicin, which exceeds MIC 90 for Rhodococcus in bronchoalveolar fluid for over 48 h. Its main disadvantage is a wildly described nephrotoxicity, which considerably shortens the time of safe use. However, long antimicrobial activity in the affected tissues may be a key to modify the administration protocol and its effective use in the future [ 49 ].…”

A Novel Screening Strategy Reveals ROS-Generating Antimicrobials That Act Synergistically against the Intracellular Veterinary Pathogen Rhodococcus equi

“…Accordingly, gentamicin encapsulated in liposomes efficiently eradicated R. equi in a mouse model of infection [32]. Unfortunately, liposomal gentamicin caused nephrotoxicity in foals [33], abolishing the potential veterinary use of this particular encapsulated antibiotic. Nevertheless, the use of liposomal antibiotics for the treatment of infections caused by intracellular pathogens is now widely recognized as an important and safe therapeutic strategy to increase the internalization of highly effective antibiotics with poor cellular uptake [34].…”