title: Successful treatment of methicillin-resistant Staphylococcus aureus osteomyelitis with combination therapy using linezolid and rifampicin under therapeutic drug monitoring.
abstract: Linezolid is an effective antibiotic against most gram-positive bacteria including drug-resistant strains such as methicillin-resistant Staphylococcus aureus. Although linezolid therapy is known to result in thrombocytopenia, dosage adjustment or therapeutic drug monitoring of linezolid is not generally necessary. In this report, however, we describe the case of a 79-year-old woman with recurrent methicillin-resistant S. aureus osteomyelitis that was successfully treated via surgery and combination therapy using linezolid and rifampicin under therapeutic drug monitoring for maintaining an appropriate serum linezolid concentration. The patient underwent surgery for the removal of the artificial left knee joint and placement of vancomycin-impregnated bone cement beads against methicillin-resistant S. aureus after total left knee implant arthroplasty for osteoarthritis. We also initiated linezolid administration at a conventional dose of 600 mg/h at 12-h intervals, but reduced it to 300 mg/h at 12-h intervals on day 9 because of a decrease in platelet count and an increase in serum linezolid trough concentration. However, when the infection exacerbated, we again increased the linezolid dose to 600 mg/h at 12-h intervals and performed combination therapy with rifampicin, considering their synergistic effects and the control of serum linezolid trough concentration via drug interaction. Methicillin-resistant S. aureus infection improved without reducing the dose of or discontinuing linezolid. The findings in the present case suggest that therapeutic drug monitoring could be useful for ensuring the therapeutic efficacy and safety of combination therapy even in patients with osteomyelitis who require long-term antibiotic administration.
authors.affiliation: Department of Clinical Infectious Diseases, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Ashizawa
authors.affiliation: Department of Medical Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tsuji
authors.affiliation: Department of Clinical Infectious Diseases, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Koyomi
authors.initials: K
authors.lastname: Kawago
authors.affiliation: Department of Clinical Infectious Diseases, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Higashi
authors.affiliation: Department of Clinical Infectious Diseases, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Tashiro
authors.affiliation: Department of Orthopedic Surgery, Faculty of Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Nogami
authors.affiliation: Department of Orthopedic Surgery, Faculty of Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Gejo
authors.affiliation: Department of Clinical Infectious Diseases, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Munetoshi
authors.initials: M
authors.lastname: Narukawa
authors.affiliation: Department of Orthopedic Surgery, Faculty of Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Tomoatsu
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Department of Clinical Infectious Diseases, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan. Electronic address: yamamoto@med.u-toyama.ac.jp.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yamamoto
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007717:Knee / Q000382:microbiology / Q000473:pathology; D000069349:Linezolid / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D055624:Methicillin-Resistant Staphylococcus aureus; D010019:Osteomyelitis / Q000188:drug therapy* / Q000382:microbiology; D010329:Patella / Q000382:microbiology / Q000473:pathology; D012293:Rifampin / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D000069349:Linezolid; D012293:Rifampin
keywords: Co-administration; Linezolid; Methicillin-resistant Staphylococcus aureus; Osteomyelitis; Rifampicin; Therapeutic drug monitoring