Treatment of meningitis caused by vancomycin-resistant Enterococcus faecium: high-dose and combination daptomycin therapy.
OBJECTIVE
To report 3 successful treatments of vancomycin-resistant Enterococcus faecium meningitis in adults using daptomycin and either linezolid or gentamicin.


METHODS
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. Threeto four-week treatment regimens with daptomycin 6-12 mg/kg and either gentamicin or linezolid led to clinical resolution and microbiological clearance of infection.


CONCLUSIONS
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.
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California-San Diego, La Jolla, CA, USA. jenle@ucsd.edu
Jennifer
J
Le
P Brandon
PB
Bookstaver
Celeste N
CN
Rudisill
Mohamed G
MG
Hashem
Raza
R
Iqbal
Charles L
CL
James
George
G
Sakoulas
D000081:Acetamides / Q000008:administration & dosage / Q000627:therapeutic use*; D000368:Aged; D017576:Daptomycin / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D016984:Enterococcus faecium / Q000187:drug effects*; D005839:Gentamicins / Q000008:administration & dosage / Q000627:therapeutic use*; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy*; D006801:Humans; D000069349:Linezolid; D008297:Male; D016920:Meningitis, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D008875:Middle Aged; D023303:Oxazolidinones / Q000008:administration & dosage / Q000627:therapeutic use*; D014640:Vancomycin / Q000494:pharmacology*; D020713:Vancomycin Resistance / Q000187:drug effects
D000081:Acetamides; D005839:Gentamicins; D023303:Oxazolidinones; D014640:Vancomycin; D000069349:Linezolid; D017576:Daptomycin