Thrombocytopenia Can be Avoided By Monitoring Linezolid Blood Levels – Enabling Long-Term Linezolid
Use for the Successful Treatment of Refractory Pyogenic Spondylodiscitis
Medicalhistory

A male in his 50s (height 172 cm, weight 78 kg, S-cr 0.34 mg/dL) was
hospitalized with fever and a diagnosis of pyogenic spondylodiscitis.

Day 1

During incisional drainage, Methicillin-resistant Staphylococcus
epidermidis (MRSE) was detected in the incision. Treatment with 600
mg of intravenous linezolid (LZD) two times per day started.
(LZD MIC ≤ 1).
Patient was placed on a continuous rotation of MRSA antibiotics due toLZD-induced thrombocytopenia, but no improvement was observed.
Patient switched to LZD with reduced dosage of 600 mg once per day.

Day 138

Day 148

MRSE detected at drainage incision
Support started

Transfer

Body temp (˚C)

LZD blood concentration was measured due to thrombocytopenic
tendency and found an AUC24 of 299.7 μg-h/mL, which was high despite
the dosage reduction.
- Average AUC24 for a healthy adult on twice daily 600 mg: 220 μg-h/mL- When AUC24 ≥ 280 μg-h/mL, risk of thrombocytopenia is 50%

Targetrange

Pea F et al. J. Antimicrob. Chemother. 2012, 67: 2034-42.

Day 203

An LZD blood concentration test showed AUC24 was 127.2 µg-h/mL,
within effective range (AUC24/MIC ≥ 100), so the same dosage wascontinued.
The patient was transferred to another hospital with nothrombocytopenia with the same LZD dosage.

- When LZD is administered for 14 days or longer, thrombocytopenia risk increases.
- The LZD package insert states no dosage adjustments are required for patients with
impaired renal function.
- However, some reports suggest dosages should be adjusted for patients with impaired renalfunction.
Matsumoto K et al. Int. J. Antimicrob. Agents 2014, 44:242-7.
- In this case study, LZD blood concentration was high despite normal renal function. Dosage
adjustment made it possible to avoid thrombocytopenia, continue long-term LZD
administration, and provide successful treatment.

Beware of thrombocytopenia when administering LZD.
When long-term administration is necessary, it is possible to avoid
thrombocytopenia with proactive therapeutic drug monitoring (TDM)

Intravenous LZD reduced
to 600 mg 1 time/day

AUC24 high,dosagereducedTarget range
reached,dosagecontinued

A*: VCM 1000 mg 2 times/day; B*: VCM 1250 mg 2 times/day
LZD: Linezolid, DAP: Daptomycin, VCM: Vancomycin, TZD: Tedizolid
30Day 148
IV 600mg 1/day
AUC24=299.7(μg・h/mL)

2520
151050048

concentration (µg-h/mL)
Blood血中濃度（μg/mL）

Day 188

Continuous rotation of MRSA
antibiotics due to LZD-induced
thrombocytopenia

concentration (µg-h/mL)
Blood血中濃度（μg/mL）

Day 184→ Intravenous LZD dosage was reduced to 400 mg once daily.
→ Patient was then switched to oral medication at the same dosage.
→ Oral LZD was reduced to 300mg.

12 16 20 24 (h)30Day 188
Oral 300mg 1/day

2520

AUC24=127.2(μg・h/mL)

15
10
50048

12 16 20 24 (h)Daisho T et al. J. Orthop. Sci. 2021 (Epub ahead of print)

AMR Alliance Japan requested this case report as a part of a project to compile examples of antimicrobial stewardship and cases with and without the use of antibiotics.
For more information, please contact AMR Alliance Japan. Grand Cube, 3rd Floor, 1 -9 -2 Otemachi Financial City, Otemachi, Chiyoda-ku, Tokyo 100 0004 Tel: 03-4243-7156 Fax: 03-4243-7378 E-mail: info@hgpi.org