Daptomycin therapy for invasive Gram-positive bacterial infections in children.
BACKGROUND
Clinical improvement is often delayed among children with invasive infections caused by multidrug resistant Gram-positive bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) despite use of standard antimicrobial therapy. Daptomycin, a bactericidal lipopeptide antibiotic, may prove useful for treatment of these infections in children, but clinical experience is lacking.


METHODS
Retrospective review of medical records of hospitalized children who received daptomycin for treatment of invasive Gram-positive bacterial infections at Children's Medical Center Dallas from December 2003 to March 2007. Bacterial isolates were tested for susceptibility to daptomycin and characterized by pulsed-field gel electrophoresis and polymerase chain reaction for staphylococcal cassette chromosome mec A.


RESULTS
Sixteen children (10 male; median age, 6.5 years) received daptomycin. Fifteen (94%) children had invasive staphylococcal disease (14, MRSA, of which 13 were community-associated; 1, methicillin-susceptible S. aureus), and 1 had urinary tract infection caused by VRE. Twelve children with disseminated staphylococcal disease had bacteremia for 2-10 days despite therapy with 2 or more of the following: vancomycin, clindamycin, rifampin, aminoglycoside, or linezolid. The addition of daptomycin resulted in bacteriologic cure in 6 of 7 evaluable patients with persistent bacteremia. No adverse events were attributed to daptomycin. Overall, 14 patients improved and were discharged home, and 2 died of complications of their underlying medical conditions.


CONCLUSIONS
The majority of patients demonstrated clinical improvement after addition of daptomycin to conventional antimicrobial therapy. Further studies are needed to assess the pharmacokinetics, pharmacodynamics, safety, and effectiveness of daptomycin in infants and children.
Department of Pediatrics, University of Texas Southwestern Medical Center, Children's Medical Center Dallas, Dallas, TX 75390-9063, USA. monica.ardura@utsouthwestern.edu
Monica I
MI
Ardura
Asunción
A
Mejías
Kathy S
KS
Katz
Paula
P
Revell
George H
GH
McCracken
Pablo J
PJ
Sánchez
D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy / Q000382:microbiology; D002648:Child; D017576:Daptomycin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D016984:Enterococcus faecium / Q000187:drug effects; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D006760:Hospitalization; D006801:Humans; D008297:Male; D008712:Methicillin / Q000494:pharmacology; D016106:Methicillin Resistance / Q000235:genetics; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D013211:Staphylococcus aureus; D016896:Treatment Outcome; D020713:Vancomycin Resistance
D000900:Anti-Bacterial Agents; D017576:Daptomycin; D008712:Methicillin