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]

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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]])

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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

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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

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Adverse Effects

Gastrointestinal Adverse Effects

• Constipation (see Constipation, [[Constipation]])
• Nausea (see Nausea and Vomiting, [[Nausea and Vomiting]])

Hematologic Adverse Effects

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

Pulmonary Adverse Effects

• Drug-Induced Pulmonary Eosinophilia (see Drug-Induced Pulmonary Eosinophilia, [[Drug-Induced Pulmonary Eosinophilia]])

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

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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]