Treatment of Meningitis Caused by Vancomycin-Resistant Enterococcus faecium: High-Dose and Combination Daptomycin Therapy

• Published in: The Annals of pharmacotherapy 2010-12, Vol.44 (12), p.2001-2006
• Main Authors: Le, Jennifer, Bookstaver, P Brandon, Rudisill, Celeste N, Hashem, Mohamed G, Iqbal, Raza, James, Charles L, Sakoulas, George
• Format: Article
• Language: English
• Subjects: Acetamides - administration & dosage; Acetamides - therapeutic use; Aged; Biological and medical sciences; Daptomycin - administration & dosage; Daptomycin - therapeutic use; Drug Therapy, Combination; Enterococcus; Enterococcus faecium; Enterococcus faecium - drug effects; Gentamicins - administration & dosage; Gentamicins - therapeutic use; Gram-Positive Bacterial Infections - drug therapy; Humans; Linezolid; Male; Medical sciences; Meningitis, Bacterial - drug therapy; Meningitis, Bacterial - microbiology; Middle Aged; Oxazolidinones - administration & dosage; Oxazolidinones - therapeutic use; Pharmacology. Drug treatments; Staphylococcus; Vancomycin - pharmacology; Vancomycin Resistance - drug effects
• ISSN: 1060-0280; 1542-6270
• DOI: 10.1345/aph.1P333

Objective: To report 3 successful treatments of vancomycin-resistant Enterococcus faecium meningitis in adults using daptomycin and either linezolid or gentamicin. Case Summary: Three case reports involving males (aged 58-78 years) are presented; in each case (trigeminal nerve microvascular decompression and subdural hygroma; paraspinal abscess; and hydrocephalus with subsequent craniotomy and ventriculo-peritoneal shunt placement) CSF examination revealed vancomycin-resistant Enterococcus (VRE) susceptible to daptomycin, gentamicin, and/or linezolid. Three- to four-week treatment regimens with daptomycin 6-12 mg/kg and either gentamicin or linezolid led to clinical resolution and microbiological clearance of infection. Discussion: Daptomycin has previously been shown to be successful in treating methicillin-resistant Staphylococcus aureus–associated meningitis and other serious VRE and enterococcal infections. Higher than approved doses of daptomycin were used in 2 cases where in theory higher CSF concentrations would thus be obtained. Gentamicin and linezolid were added to daptomycin therapy based on in vitro data synergy results and because of documented successful treatment for VRE meningitis, respectively. Conclusions: The difficulty in treating VRE CSF infections involves both drug kinetics and microbial resistance factors, as well as external factors such as foreign bodies like shunts. This report highlighted 3 cases where daptomycin use in concert with either gentamicin or linezolid was successful in treating this infection. Additional controlled trials will be helpful in identifying the best strategies when using daptomycin to treat CSF infections.