Synergistic effect of a novel focal hyperthermia on the efficacy of rifampin in staphylococcal experimental foreign-body infection.
This study was designed to evaluate the efficacy of focal hyperthermia and rifampin in vitro and in vivo using a rabbit model of foreign-body infection by methicillin-resistant Staphylococcus aureus (MRSA). In vitro studies demonstrated bacterial re-growth and development of rifampin resistance after 24 h with rifampin alone, which was prevented under hyperthermic conditions. For the in vivo studies, rifampin was administered intraperitoneally every 12 h for 7 days to rabbits with MRSA-containing cages implanted into their flanks. When combined with hyperthermia at 39 degrees C, 41 degrees C and 43 degrees C, rifampin significantly reduced in-cage bacterial counts by > 3.0 log(10) colony forming units/ml compared with rifampin alone. Eradication of cage-associated infection was achieved more effectively when rifampin was combined with hyperthermia, with cure rates of 70-95% on day 10. Focal hyperthermia combined with rifampin prevented the emergence of rifampin resistance and maintained rifampin efficacy. These findings might have implications for orthopaedic surgery.
Zou
G-Y
GY
Department of Orthopaedic Surgery, The Sixth Affiliated People's Hospital, Shanghai Jiaotong University, Shanghai, China.
Shen
H
H
Jiang
Y
Y
Zhang
X-L
XL
D000818:Animals; D000904:Antibiotics, Antitubercular / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018441:Biofilms / Q000187:drug effects; D015169:Colony Count, Microbial; D015194:Diffusion Chambers, Culture; D004195:Disease Models, Animal; D015745:Granuloma, Foreign-Body / Q000188:drug therapy* / Q000209:etiology; D006979:Hyperthermia, Induced; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D008297:Male; D016106:Methicillin Resistance / Q000187:drug effects*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D011817:Rabbits; D012293:Rifampin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013203:Staphylococcal Infections / Q000150:complications / Q000188:drug therapy*; D016896:Treatment Outcome
D000904:Antibiotics, Antitubercular; D012293:Rifampin