What is the concern with Patient CK's current regimen of daptomycin (cubicin) 1000 mg per day, given her last creatine kinase (CK) level was 491 and her last reading on 4/16 was 67, indicating impaired renal function or other potential issues?

From the Guidelines

I strongly recommend discontinuing daptomycin immediately due to the significantly elevated CK level of 491, which indicates muscle toxicity. Although the most recent CK reading from 4/16 was 67 (within normal range), the current elevation represents a serious adverse effect of daptomycin therapy 1. After stopping daptomycin, an alternative antibiotic should be selected based on the infection being treated and antimicrobial susceptibility results. The patient should be monitored with serial CK measurements until levels normalize, and assessed for symptoms of muscle pain, weakness, or dark urine which could indicate rhabdomyolysis.

Key Considerations

• Daptomycin-induced muscle toxicity occurs because the medication can directly damage skeletal muscle cell membranes, leading to elevated CK levels and potential myopathy 1.
• This risk increases with higher doses and when used concurrently with statins or other medications that can cause muscle toxicity.
• Adequate hydration should be maintained to protect renal function while the elevated CK resolves.

Alternative Treatment Options

• High-dose daptomycin at 8-12 mg/kg daily may be used to treat VRE-BSI, but with close monitoring of CK levels 1.
• Alternative antibiotics such as linezolid, tigecycline, or fosfomycin may be considered based on the infection being treated and antimicrobial susceptibility results.
• Combination antimicrobial therapy may be considered in severely ill patients or those who fail treatment with traditional options 1.

From the FDA Drug Label

In patients who receive daptomycin for injection, CPK levels should be monitored weekly, and more frequently in patients who received recent prior or concomitant therapy with an HMG-CoA reductase inhibitor or in whom elevations in CPK occur during treatment with daptomycin for injection Daptomycin for injection should be discontinued in patients with unexplained signs and symptoms of myopathy in conjunction with CPK elevations to levels >1,000 U/L (~5× ULN), and in patients without reported symptoms who have marked elevations in CPK, with levels >2,000 U/L (≥10 × ULN)

The patient's CK level is 491, and they are currently taking daptomycin 1000 mg a day.

• The patient's CK level is below the threshold for discontinuation of daptomycin (>1,000 U/L or >2,000 U/L).
• However, the patient's CK level should be monitored weekly or more frequently if necessary, as per the guidelines.
• It is essential to continue monitoring the patient's CK levels and watch for signs and symptoms of myopathy, as daptomycin can cause elevations in CPK 2.

From the Research

Patient CK Levels and Daptomycin Therapy

• Patient CK was 491, and the patient is currently taking daptomycin 1000 mg a day, with the last reading on 4/16 being 67.
• The significant decrease in CK levels from 491 to 67 suggests that the patient's muscle injury may be resolving 3.

Daptomycin-Induced Muscle Injury

• Daptomycin has been associated with muscle pain and elevated creatine kinase (CK) levels, indicating muscle injury 4.
• A study found that withholding one dose of daptomycin during treatment may allow patients with asymptomatic, elevated CK concentrations to continue therapy with CK level normalization 3.
• Another study suggested that high-dose daptomycin is increasingly used in patients with bone and joint infection, raising concerns about a higher risk of adverse events, including daptomycin-induced eosinophilic pneumonia and myotoxicity 5.

Management of Daptomycin-Induced Muscle Injury

• The current package labeling recommends discontinuation of daptomycin with significant myopathy symptoms in association with a CK elevation >1000 U/L or in patients without muscle pain and a CK >10 times normal 4.
• A study recommended that patients receiving statins who start daptomycin therapy should continue statin but with weekly monitoring of CPK levels 6.
• Daptomycin exposure has been identified as a risk factor for daptomycin-induced eosinophilic pneumonia and muscular toxicity, and therapeutic drug monitoring (TDM) and model-informed precision dosing may help optimize the efficacy and safety of daptomycin treatment 5.