Evolution of Ceftaroline-Resistant Mrsa in a Child with Cystic Fibrosis Following Repeated Antibiotic Exposure.
Ceftaroline is the first β-lactam antibiotic with activity against methicillin-resistant Staphylococcus aureus (MRSA). We describe a ceftaroline-resistant MRSA strain, isolated from a girl with cystic fibrosis after 22 ceftaroline treatment courses. MRSA genome sequencing documented a Tyr446Asn alteration in penicillin binding protein 2 that appeared responsible for resistance. Noncompartmental ceftaroline pharmacokinetic evaluation in our patient documented increased clearance and volume of distribution compared with adults.
From the *Division of Infectious Diseases, Department of Pediatrics, University of California at San Diego and Rady Children's Hospital San Diego, San Diego, California; †JMI Laboratories, North Liberty, Iowa; ‡Cerexa, Inc., Oakland, California; and §Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, La Jolla, California.
Christopher R
CR
Cannavino
Rodrigo E
RE
Mendes
Helio S
HS
Sader
David J
DJ
Farrell
Ian A
IA
Critchley
Donald
D
Biek
Jennifer
J
Le
Shannon M
SM
Skochko
Ronald N
RN
Jones
John S
JS
Bradley
D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001483:Base Sequence; D002511:Cephalosporins / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000378:metabolism / Q000382:microbiology*; D004269:DNA, Bacterial / Q000235:genetics; D024881:Drug Resistance, Bacterial; D005260:Female; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000235:genetics / Q000302:isolation & purification*; D008826:Microbial Sensitivity Tests; D009154:Mutation; D046915:Penicillin-Binding Proteins / Q000235:genetics; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology*
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D004269:DNA, Bacterial; D046915:Penicillin-Binding Proteins