Daptomycin (Cubicin)

Clinical Indications

Inpatient Complicated Skin and Soft Tissue Infection (cSSTI) Due to Staphylococcus Aureus (see Cellulitis, [[Cellulitis]])

  • Definition of cSSTI
    • Cellulitis
    • Deeper Soft Tissue Infection
    • Infected Ulcers/Burns
    • Major Abscess
    • Surgical/Traumatic Wound Infection
  • Recommendations
    • One of the Recommended Agents for the Treatment of Inpatient cSSTI Due to Methicillin-Resistant Staphylococcus Aureus (MRSA) (Infectious Diseases Society of America 2011 Guidelines for the Treatment of MRSA) (Clin Infect Dis, 2011) [MEDLINE]

Uncomplicated/Complicated Bacteremia Due to Staphylococcus Aureus

  • Definition of Uncomplicated Bacteremia
    • Positive Blood Cultures for MRSA
    • Exclusion of Endocarditis
    • No Implanted Prosthetics
    • Follow-Up Negative Blood Cultures 2-4 Days After Initial Set
    • No Metastatic Foci of Infection
    • Defervescence within 72 hrs of Initiating Effective Therapy
  • Definition of Complicated Bacteremia
    • Patients with Positive Blood Cultures for MRSA Who Do Not Meet the Criteria for Uncomplicated Bacteremia
  • Recommendations
    • One of the Recommended Agents for the Treatment of Bacteremia Due to Methicillin-Resistant Staphylococcus Aureus (MRSA) (Infectious Diseases Society of America 2011 Guidelines for the Treatment of MRSA) (Clin Infect Dis, 2011) [MEDLINE]

Native Valve Infective Endocarditis Due to Staphylococcus Aureus (see Endocarditis, [[Endocarditis]])

  • Recommendations
    • One of the Recommended Agents for the Treatment of Native Valve Infective Endocarditis Due to Methicillin-Resistant Staphylococcus Aureus (MRSA) (Infectious Diseases Society of America 2011 Guidelines for the Treatment of MRSA) (Clin Infect Dis, 2011) [MEDLINE]

Microbial Coverage

Staphylococcus Aureus (see Staphylococcus Aureus, [[Staphylococcus Aureus]])

  • Methicillin-Sensitive Staphylococcus Aureus (MSSA)
  • Methicillin-Resistant Staphylococcus Aureus (MRSA)

Streptococcus (see Streptococcus, [[Streptococcus]])

  • xxxx

Enterococcus (see Enterococcus, [[Enterococcus]])

  • Vancomycin-Resistant Enterococcus (VRE) (see Enterococcus, [[Enterococcus]])

Pharmacology

  • Cyclic Lipopeptide
    • Mechanism: calcium-dependent depolarization of bacterial cell wall (due to the lipophilic tail of the drug inserting itself into the bacterial membrane, forming a channel in the membrane -> potassium efflux)
      • Bactericidal

Metabolism

  • Renal: 80% excreted unchanged via kidneys
  • Pharmacokinetics
    • Elimination Half-Life: 8 hrs

Drug Penetration

  • Cerebrospinal Fluid (CSF): poor, even with meningeal inflammation

Administration

  • IV (Complicated Skin/Skin Structure Infections): 4 mg/kg IV qday
  • IV (Bacteremia/Endocarditis): 6 mg/kg IV qday

Dose Adjustment

  • Hepatic: none (for mild-moderate liver disease)
  • Renal
    • CrCl <30 ml/min: decrease dosing frequency to q48 hrs
    • Hemodialysis: give dose after hemodialysis

Drug Interactions

  • HMG-CoA Reductase Inhibitors (see HMG-CoA Reductase Inhibitors, [[HMG-CoA Reductase Inhibitors]]): concomitant use increases risk of creatine kinase elevation and myopathy

Adverse Effects

Gastrointestinal Adverse Effects

Hematologic Adverse Effects

  • Neutropenia (see Neutropenia, [[Neutropenia]])
    • Epidemiology: associated with prolonged daptomycin administration
    • Treatment: reversible with discontinuation of daptomycin

Pulmonary Adverse Effects

Rheumatologic/Orthopedic Adverse Effects

  • Muscle-Related Complications: usually begin within one week of starting therapy
    • Elevated Creatine Kinase (see Serum Creatine Kinase, [[Serum Creatine Kinase]]): occurs in 2.8% of cases
    • Myopathy (see Myopathy, [[Myopathy]]): symptomatic myopathy occurs in 0.2% of cases
    • Myalgias (see Myalgias, [[Myalgias]])
    • Rhabdomyolysis (see Rhabdomyolysis, [[Rhabdomyolysis]]): case reports
    • Treatment: discontinue daptomycin -> symptoms usually resolve in 2-3 days
      • Creatine kinase elevation may persist for up to 2 wks

Other Adverse Effects

  • Injection Site Reaction: occurs in 6% of cases

References

  • Two cases of daptomycin-induced eosinophilic pneumonia and chronic pneumonitis. Clin Infect Dis. 2010 Mar 1;50(5):737-40. doi: 10.1086/650487 [MEDLINE]