Activity of Omadacycline in Rat Methicillin-Resistant Staphylococcus aureus Osteomyelitis

Abstract

Omadacycline, vancomycin and rifampin as well as rifampin combination therapies were evaluated in an experimental rat model of MRSA osteomyelitis. All treatment groups had less MRSA recovered than saline-treated animals. Emergence of rifampin resistance was observed in 3 of 16 animals with rifampin monotherapy, and none with rifampin combination therapy. After treatment, the median tibial bacterial load was 6.04, 0.1, 4.81 and 5.24 log 10 cfu/g for saline-, rifampin-, vancomycin- and omadacycline-treated animals. Omadacycline or vancomycin administered with rifampin yielded no detectable MRSA. Omadacycline, administered with rifampin, deserves evaluation in humans as a potential treatment for osteomyelitis.

Can intracellular Staphylococcus aureus in osteomyelitis be treated using current antibiotics? A systematic review and narrative synthesis

“…Furthermore, newer antibiotics that did not appear in our search at the time of the study should be evaluated for their potential intracellular effectiveness. For example, omadacycline, a novel tetracycline, seems to be effective against MRSA in osteomyelitis in a mouse model 188 and intracellularly against Legionella pneumophila, 189 even though its effectiveness seems to be pH dependent. 190 …”

The Application of Rat Models in Staphylococcus aureus Infections

“…In addition, many researchers have used rat models to explore the therapeutic effect of antibiotics on MRSA-induced osteomyelitis [ 52 , 53 , 54 ]. For instance, Karau et al compared the efficacy of rifabutin, rifapentine, and rifampin, alone or in combination with vancomycin, in the treatment of foreign body osteomyelitis in rats [ 52 ].…”

“…This suggests that rifapentine and/or rifabutin might be an alternative to rifampin in the clinical management of S. aureus -caused periprosthetic joint infections. Karau et al reported that omadacycline exhibited activity in a rat model of chronic osteomyelitis induced by MRSA when it was administered alone, and higher activity when administered with rifampin [ 53 ]. Zhou et al found that the combination of erythromycin and curcumin was able to inhibit the growth of MRSA and reduce bone infections in rats [ 54 ].…”