Long-term Use of Tedizolid as Suppressive Therapy for Recurrent Methicillin-Resistant Staphylococcus aureus Graft Infection

To the Editor— Tedizolid is an oxazolidinone antibiotic recently approved by the Food and Drug Administration (FDA) for acute bacterial skin and skin structure infections (ABSSSIs). Initial phase I and II studies have suggested that tedizolid may offer an improved safety profile over linezolid (at the approved dose) with less likelihood of hematological and neurological toxicities and fewer drug-drug interactions [1, 2]. However, phase III studies (ESTABLISH-1/2) in ABSSSIs [3, 4] were designed to use this drug for only 6 days; thus, the long-term toxicity of this antibiotic is unknown. Furthermore, recent data using the FDA adverse event reporting system suggested that linezolid and tedizolid had similar rates of thrombocytopenia [5]. Tedizolid is an attractive agent to treat infections that require prolonged treatment due to its excellent oral bioavailability and once daily administration. Here, we report a patient who received tedizolid for 18 months, as suppressive therapy for recurrent methicillin-resistant Staphylococcus aureus (MRSA) infection of an infected endovascular graft.

The patient is a 69 year-old man with a history of severe peripheral vascular disease who underwent right to left femoropopliteal bypass for limb ischemia. One month after surgery, he developed MRSA bacteremia due to an infected graft with a small abscess (first episode). Transesophageal echo was negative for vegetations and a decision to retain the graft was made due to high perioperative risk. After 6 weeks of therapy with vancomycin and rifampin, the patient was placed on suppressive therapy with sulfamethoxazole/trimethoprim (SMX/TMP; TMP dose 160 mg oral twice daily). However, the patient developed acute kidney injury and hyperkalemia, which prompted to the reduction of SMX/TMP to once daily. After 4 weeks of SMX/TMP, a second episode of bacteremia occurred, which was successfully treated with 6 weeks of ceftaroline (600 mg intravenously q8h). After completion of therapy, the patient was placed on tedizolid (200 mg orally daily) due to limited oral options because the organism was resistant to fluoroquinolones and tetracycline.

Table 1 shows a summary of basic laboratory values after initiation of tedizolid. Two additional recurrences of MRSA bacteremia were documented at 9.5 and 18 months (3rd and 4th recurrence, respectively) after initiation of tedizolid therapy. The isolate recovered from the third episode showed an elevated minimum inhibitory concentration to ceftaroline but retained susceptibility to linezolid (Table S1). For both episodes, the patient was successfully treated with a combination of daptomycin (8 mg/kg IV daily) plus ceftaroline (600 mg IV q8h) for 6 weeks. The graft was partially replaced after the fourth episode. Oral tedizolid suppressive therapy was restarted after parenteral therapy in each recurrence. No evidence of hematological or neurological toxicity has been identified after monthly evaluations for a total of 18 months.

Table 1.

Basic Hematological Counts After Initiation of Tedizolid

Months after initiation	0	2	4	6	8	9	11	13	15	17	18
WBC (k/µL)	7.2	8.5	7.7	8.6	11.5	7.8	7.7	8.0	8.8	8.6	12.7
Hgb (gm/dL)	7.8	8.4	12.3	12.0	12.4	12.9	12.5	7.6	10.3	11.7	10.9
Ht (%)	27.1	28.4	38.2	36.7	38.6	39.8	38.3	22.9	32.9	36.0	35.5
Platelet (k/µL)	261	330	210	201	254	234	186	157	307	314	360

Abbreviations: Hgb, hemoglobin; Ht, hematocrit; WBC, white blood cell counts.

The median duration of tedizolid use was 91 days in the largest series of 25 patients with nontuberculous mycobacterial infection [6]. Neuropathy developed in 5 patients, and only 1 patient developed thrombocytopenia. Of note, 4 of the 5 patients who developed neuropathy were receiving ethambutol, and 1 patient had a preexisting neuropathy due to prior linezolid therapy. The use of tedizolid for 18 months has no precedent, and our experience support the safety of this compound for prolonged courses of therapy. Larger studies are warranted to evaluate the efficacy and safety of tedizolid.

Note

Potential conflicts of interest. C. A. A. reports research grants from Merck and the Medicines Company. All other authors report no potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.