Effectiveness and tolerability of prolonged linezolid treatment for chronic osteomyelitis: a retrospective study.
BACKGROUND
Linezolid is an oxazolidinone agent which is apparently well designed for treating chronic osteomyelitis, but data on effectiveness and tolerability as prolonged therapy is currently lacking.


OBJECTIVE
The purpose of this study was to assess the effectiveness and tolerability of linezolid in the treatment of chronic osteomyelitis.


METHODS
The charts of hospitalized patients who had been treated with linezolid for >4 weeks because of chronic osteomyelitis and were followed up for > or =12 months after the end of treatment were retrospectively reviewed for clinical outcome and tolerability. Cure was defined as the absence of clinical, biological, or radiological evidence of infection throughout the posttreatment follow-up. Linezolid tolerability was assessed on the basis of hematologic properties during treatment.


RESULTS
Of the 66 patients included, all were white (mean [SD] age, 67.7 [18.1] years; 41 men and 25 women; mean [SD] weight, 80.7 [18.6] kg). Thirty-seven (56.1%) patients had infection due to implants including 27 prosthetic joints. Pathogens were predominantly methicillin-resistant staphylococci (49/72 strains, 68.1 %). Every patient was administered N linezolid (600 mg BID) treatment for 6 to 8 days as inpatients, and then, as outpatients, they were switched to PO treatment. Fifty (75.8%) patients received a combination of linezolid and other antimicrobial agents, including rifampin (32 [48.5%]). Surgery was performed in 52 (78.8%) patients. The median hospital stay was 14 days (mean [SD], 19 [11.4] days [range, 7-70 days] ). The median duration of treatment was 13 weeks (mean [SD], 14.3 [8.2] weeks [range, 5-36 weeks]). At the end of treatment, 56 (84.8%) patients were cured, and during the post-treatment follow-up (median duration, 15 months [range, 12-36 months]), 4 relapses occurred, resulting in an overall successful cure for 52 (78.8%) patients. Reversible anemia was reported in 21 patients (31.8%), of whom 16 (24.2%) required blood transfusions. Median time from treatment initiation to anemia onset was 7.3 weeks (range, 4-12 weeks). Peripheral neuropathy was reported in 6 (9.1%) patients, of whom 4 remained symptomatic for up to 24 months after linezolid discontinuation. Other reported adverse events included nausea (6 [9.1%]), diarrhea (1 [1.5%]), and headache (2 [3.0%]), although none of these patients discontinued treatment.


CONCLUSIONS
In this retrospective chart review, treatment with linezolid as monotherapy or in combination with antimicrobials and/or surgery was associated with cure of chronic osteomyelitis in 84.8% of subjects at 12 weeks after the end of treatment and 78.8% at follow-up. Adverse events were reported in 51.5% of subjects, and 34.8% of subjects discontinued the study because of adverse events. The potential for severe complications justifies close monitoring of these patients.
Senneville
Eric
E
Infectious Diseases Department, Dron Hospital of Tourcoing, Tourcoing, France. Electronic address: esenneville@ch-tourcoing.fr.
Legout
Laurence
L
Infectious Diseases Department, Dron Hospital of Tourcoing, Tourcoing, France.
Valette
Michel
M
Infectious Diseases Department, Dron Hospital of Tourcoing, Tourcoing, France.
Yazdanpanah
Yazdan
Y
Infectious Diseases Department, Dron Hospital of Tourcoing, Tourcoing, France.
Beltrand
Eric
E
Department of Orthopedic Surgery, Dron Hospital of Tourcoing, Tourcoing, France.
Caillaux
Michèle
M
Microbiology Laboratory, Dron Hospital of Tourcoing, Tourcoing, France.
Migaud
Henri
H
Department of Orthopedic Surgery, CHRU, Lille, France.
Mouton
Yves
Y
Infectious Diseases Department, Dron Hospital of Tourcoing, Tourcoing, France.
D000081:Acetamides / Q000009:adverse effects / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000139:chemically induced; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D002908:Chronic Disease; D005260:Female; D006801:Humans; D000069349:Linezolid; D008297:Male; D008875:Middle Aged; D010019:Osteomyelitis / Q000188:drug therapy*; D023303:Oxazolidinones / Q000009:adverse effects / Q000627:therapeutic use*; D012189:Retrospective Studies
D000081:Acetamides; D000890:Anti-Infective Agents; D023303:Oxazolidinones; D000069349:Linezolid