Efficacy of linezolid in the treatment of mediastinitis due to methicillin-resistant Staphylococcus aureus: an experimental study.
BACKGROUND
The treatment of postoperative mediastinitis is very important because of its high morbidity, mortality, and increased hospital stay and hospital costs. The aims of our research were to investigate whether linezolid alone can be an effective treatment agent for methicillin-resistant Staphylococcus aureus (MRSA) mediastinitis, and to determine whether linezolid can provide synergistic activity when given in combination with rifampin.


METHODS
A partial upper median sternotomy was performed on 70 rats. The animals were divided into seven groups: an uncontaminated control group; an untreated contaminated group; three contaminated groups that received antibiotic therapy with either 25 or 50 mg/kg linezolid twice a day, or rifampin 5 mg/kg twice a day; and two contaminated groups that received a combination therapy consisting of 25 or 50 mg/kg linezolid and rifampin 5 mg/kg twice a day. The antibiotic treatment lasted 7 days. Tissue samples from the upper ends of the sternum and swab specimens of the upper mediastinum were obtained and evaluated microbiologically.


RESULTS
The 25-mg/kg dose of linezolid, either alone or combined with rifampin, was not effective in reducing the bacterial counts in mediastinum and sternum. Quantitative bacterial cultures of mediastinum and sternum were significantly lower in the groups receiving 50 mg/kg linezolid alone or in combination with rifampin compared with the control. Adding of rifampin to linezolid therapy did not result in a significant change in bacterial counts versus linezolid alone.


CONCLUSIONS
A high dose of linezolid should be considered as a possible therapeutic agent for the treatment of post-sternotomy infection caused by MRSA.
Sacar
Mustafa
M
Department of Cardiovascular Surgery, Pamukkale University Faculty of Medicine, Kinikli Kampusu, Kinikli 20070 Denizli, Turkey. mustafasacar@hotmail.com
Sacar
Suzan
S
Kaleli
Ilknur
I
Cevahir
Nural
N
Teke
Zafer
Z
Kavas
Semra Toprak
ST
Asan
Ali
A
Aytekin
Faruk Onder
FO
Baltalarli
Ahmet
A
Turgut
Huseyin
H
D000081:Acetamides / Q000008:administration & dosage*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D000069349:Linezolid; D008297:Male; D008480:Mediastinitis / Q000188:drug therapy*; D016106:Methicillin Resistance / Q000187:drug effects*; D023303:Oxazolidinones / Q000008:administration & dosage*; D051381:Rats; D012293:Rifampin / Q000627:therapeutic use; D013203:Staphylococcal Infections / Q000188:drug therapy; D013211:Staphylococcus aureus / Q000187:drug effects*; D013530:Surgical Wound Infection / Q000188:drug therapy*
D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D000069349:Linezolid; D012293:Rifampin