Tedizolid: a service evaluation in a large UK teaching hospital

Abstract

Tedizolid is a new oxazolidinone antibiotic with little real-life data on use outside of skin and soft tissue infections. There is a paucity of safety evidence in courses greater than 6 days. Our centre uses tedizolid predominantly when linezolid-associated adverse events have occurred. This service evaluation describes our experience to date. We performed a retrospective service evaluation by reviewing case notes, prescription charts, and laboratory system results for each patient prescribed tedizolid at our hospital and recording patient demographics, clinical details, and outcomes. Sixty patients received tedizolid between May 2016 and November 2018. Most were treated for bone or joint infections and had stopped linezolid prior to tedizolid prescription. Mean length of tedizolid therapy was 27 days. Haematological adverse effects were infrequent. Most patients (72%) finished the course and their clinical condition improved during treatment (72%). Adverse events were common, but often not thought to be tedizolid related. Tedizolid appears to be safe in prolonged courses within this context. It may be suitable for longer-term antibiotic therapy within a complex oral and parenteral outpatient antibiotic therapy (COPAT) service. Patients who do not tolerate linezolid can be safely switched to tedizolid if appropriate.

Appendix

Patient characteristics

Twenty-two patients (37%) were taking either a monoamine oxidase inhibitor or another drug contraindicated during linezolid therapy according to the UK SPC.

Linezolid before tedizolid

Of the 49 patients who received linezolid prior to tedizolid, almost all (47, 96%) received linezolid via the oral route prior to tedizolid prescription, whilst two patients received intravenous and then oral linezolid.

Combination antibiotic therapy

Those on combination antibiotic therapy (Appendix Table 5) tended to have shorter courses of tedizolid; mean length = 24 days (median 18 days) with combination versus mean length = 30 days (median 27 days) with monotherapy. Furthermore, those on combination therapy tended to be less likely to finish their course with 61% of those on combination therapy finishing the planned course versus 85% of those on monotherapy.

Table 5 Antibiotics used alongside tedizolid

Table 6 Microbiology

Deterioration on tedizolid

Six patients (10%) clinically deteriorated whilst prescribed tedizolid; one had a diagnosis of cerebral aspergillosis, in which tedizolid was prescribed due to concern about superadded bacterial infection; this patient subsequently died. An elderly patient with comorbidities of six organ systems, who was being treated for prosthetic joint infection, declined generally; antibiotic therapy was subsequently withdrawn prior to death. Both deaths were not considered to be tedizolid related.

Another patient stopped their analgesia (described below). Of the other three patients who clinically deteriorated whilst taking tedizolid, one had diabetic foot infection and was switched to co-trimoxazole. Another patient with diabetic foot infection (and osteomyelitis) subsequently required amputation. Finally, a patient with complex discitis, bacteraemia, splenic abscess, and endocarditis was switched back to intravenous antibiotics due to a lack of clinical improvement and increasing inflammatory markers, despite the splenic abscess decreasing in size on tedizolid.

Further adverse events

Ten patients (17%) required admission to hospital or surgery within 30 days of stopping tedizolid: three readmissions were for surgery; one was admitted for pain control (she had stopped all of her analgesics and requested a switch to IV teicoplanin, which she had previously been on); two were readmitted with nausea and vomiting or anorexia (one of these was diagnosed with norovirus and the other had been discharged on linezolid which was felt to be the likely cause); one was admitted feeling generally unwell and was found to have a hospital-acquired pneumonia; one was admitted due to adverse effects of oral moxifloxacin and infection; two were admitted due to deterioration, one with worsening foot pain and increased discharge and the other with a worsening infection despite clinically improving on a short course of tedizolid, having been discharged from hospital on clindamycin prior to this; and one was admitted for a seizure (thought to be unrelated). No readmission was felt, therefore, to be related directly to tedizolid.

Thirteen patients (25%) required ongoing antimicrobial therapy after tedizolid (without admission or surgery): six of these had complex prosthetic joint infections where prolonged antibiotic therapy would be expected; four had diabetic foot infections which included one patient who deteriorated on tedizolid and was switched to co-trimoxazole; one patient had a complex shoulder infection for who prolonged antibiotic therapy was planned after initial tedizolid; and two patients were switched to IV teicoplanin, one with discitis, endocarditis, bacteraemia, and a splenic abscess (as discussed above) and the other is the patient who stopped their analgesia (see above and below).

Two patients required blood transfusions whilst on therapy (3%) and one had severe anaemia which limited linezolid therapy but then improved on tedizolid—this was felt to be multifactorial (her Hb was 72 g/L at the start of linezolid therapy) and was not considered to be tedizolid related. The other patient was transfused due to a low Hb (68 g/L) following linezolid therapy. Three patients were taking oral iron supplements (5%) and 1 was on erythropoietin injections, with chronic kidney disease requiring haemodialysis (2%).

Early cessation of tedizolid

Of the 15 patients who stopped tedizolid early, the reason for stopping was not considered to be due to tedizolid in 6 patients. One patient, who stopped tedizolid due to fatigue, had stopped taking analgesia just prior to this and was felt to be exhausted by severe pain. Another patient stopped because they felt they had been on antibiotics for long enough. Two patients who stopped due to joint pains (one also had tendonitis) were also taking ciprofloxacin concomitantly, which was felt to be the more likely cause. One patient was mistakenly prescribed tedizolid by a junior doctor and was switched to linezolid when this was identified. Another patient stopped tedizolid after being admitted to another hospital that did not have tedizolid on their formulary. In 2 patients, it was unclear whether tedizolid was given to planned completion or not—these were recorded as unclear. In one of these, tedizolid was given for a week (confirmed by pharmacy), but at the follow-up appointment, the clinical notes simply stated, “To continue moxifloxacin”. In the other case, the notes stated: “has probably had enough”, but it was unclear whether this was felt to be due to adverse effects or because the infection was treated.

Details of adverse effects

Whilst many patients had a documented adverse effect that could have conceivably been due to tedizolid, in particular nausea, fatigue, and loose stools, many were not subsequently thought to be tedizolid associated. One patient with nausea, for example, required admission to hospital, but was diagnosed with norovirus infection. Another patient reported shortness of breath but was also prescribed ciprofloxacin. A patient who also complained of shortness of breath only did so at one clinic review, but not subsequently during prolonged therapy. The dry mouth and dizziness described by one patient resolved despite continuing therapy. One of two patients who developed acute kidney injury (AKI) was also prescribed multiple nephrotoxic medications, whilst in another patient, it was unclear whether AKI was related to underlying infection or antibiotic therapy. A patient with anaemia received a treatment break for 40 days during which their haemoglobin recovered from 70 to 121 g/L with oral iron. This patient then tolerated prolonged courses of tedizolid (107 and 78 days) without a clinically important decline in haemoglobin. The patient with thrombocytopenia had a platelet count of 74 × 10^9/L on stopping linezolid that remained low (75 × 10^9/L) whilst taking tedizolid without further deterioration.

Of the other documented adverse effects, one patient complained of loose stools, but the sample provided was fully formed. The same patient also stopped tedizolid due to palpitations (she was also prescribed ciprofloxacin, which was felt to be the probable cause); on restarting tedizolid, she had no further adverse effects. A patient who reported loose stools described as “loose to normal” had resolved fully at follow-up 1 week later. Another patient developed hyponatraemia (sodium = 119 mmol/L at nadir), which resulted in tedizolid cessation, but then tolerated it for 63 days without hyponatraemia. The cough that one patient complained of was thought to be a viral upper respiratory tract infection and not antibiotic related. The documented case of leukopenia (nadir 3.4 × 10⁹/L) resolved without stopping tedizolid (to 4.5 × 10⁹/L). One patient had a seizure on the last day of tedizolid, but this was not felt to be antibiotic related. The abdominal pain one patient developed while prescribed tedizolid was also not thought to be antibiotic related. One patient suffered from weakness and falls, thought to be due to poor oral fluid intake. Malaise reported by one patient at the beginning of tedizolid therapy improved during treatment and was felt to be infection related. Finally, the paraesthesia reported by one patient was not felt to be clinically significant; the onset of subsequent visual disturbance in the same patient occurred 1 week after stopping tedizolid.