Daptomycin/vancomycin

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An event is serious (based on the ICH definition) when the patient outcome is:

• * death

• * life-threatening

• * hospitalisation

• * disability

• * congenital anomaly

• * other medically important event

An 80-year-old man developed resting myoclonus following treatment with daptomycin. Additionally, he developed progressive deterioration of kidney function and pharmacodermia during treatment with vancomycin [not all routes and outcomes stated; time to reaction onset not stated].

The man, who had insulin-dependent type 2 diabetes mellitus, hypertension, chronic kidney failure, ischaemic heart disease, ophthalmoplegia because of the third right cranial pair palsy, prostate adenocarcinoma (controlled with unspecified hormone therapy), atrial fibrillation and permanent VVI pacemaker for sinus node disease, had been receiving cilostazol, thioctic acid, amlodipine, melatonin, pantoprazole, rivaroxaban, tamsulosin, ezetimibe, fenofibrate and insulin detemir. He was admitted to a hospital in Argentina for COVID-19 pneumonia, requiring management in the ICU without any need for mechanical ventilation. Subsequently, he developed prolonged febrile syndrome, but no isolated germs were detected during microbiological studies. Initially, he was presumed to have developed hospital pneumonia, for which he received vancomycin and meropenem for 7 days. After completion of the antibiotic regimen, febrile syndrome persisted. After ruling out other causes of hyperthermia, transesophageal echocardiogram was performed on day 41 of admission, which demonstrated a 3mm vegetation on the aortic valve. He was diagnosed with infective endocarditis of the native aortic valve, but no germs were identified. He started receiving empiric treatment with vancomycin 1g every 12h and cefepime. Because of the need of prolonged IV antibiotic treatment along with empirical coverage, vancomycin was replaced with IV infusion of daptomycin 10 mg/kg every 24h (dose: 900 mg every 24h). Six days after the initiation of daptomycin, he presented with myoclonus in the limbs (at rest). Metabolic causes were ruled out based on laboratory tests.

Daptomycin-related resting myoclonus was suspected. The man's daptomycin therapy was changed back to vancomycin, following which remission of the tremor was noted. A progressive deterioration of the kidney function and pharmacodermia in the dorsum and lower and upper limbs was detected in the setting of the supratherapeutic plasma levels of vancomycin at 26.3 µg/mL. Hence, vancomycin was again stopped.

After 5 days, daptomycin was restarted. After the first daptomycin infusion, the man presented with myoclonus in the lower and upper limbs, which later became generalised. Physical examination revealed that he was awake and oriented in the three spheres. His cranial nerves, osteotendinous reflexes and strength were preserved. At night, involuntary movements persisted, making sleep difficult. Serial electroencephalograms demonstrated no significant alterations, and his movements were considered asterixis related to daptomycin-induced myoclonus. Daptomycin was stopped. During the following week, a gradual improvement was observed. Thereafter, he completed 4 weeks of antibiotic treatment with cefepime and linezolid. He was maintained on chronic suppressive antibiotic therapy with ciprofloxacin and minocycline. Causality analysis was conducted using Naranjo scale, which yielded a score of 7 for the reaction to vancomycin and 8 for the reaction to daptomycin. These values corresponded to probable causality between daptomycin and myoclonus; and vancomycin and progressive deterioration of kidney function and pharmacodermia.