Linezolid-resistant ST36 methicillin-resistant Staphylococcus aureus associated with prolonged linezolid treatment in two paediatric cystic fibrosis patients

• Published in: Journal of antimicrobial chemotherapy Vol. 65; no. 3; pp. 442 - 445
• Main Authors: Hill, Robert L. R., Kearns, Angela M., Nash, James, North, Sarah E., Pike, Rachel, Newson, Timothy, Woodford, Neil, Calver, Richard, Livermore, David M.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.03.2010; Oxford Publishing Limited (England)
• Subjects: Acetamides - therapeutic use; Adolescent; Anti-Bacterial Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Bacterial diseases; Bacterial Typing Techniques; Bacteriophage Typing; Biological and medical sciences; Child; colonization; Cystic fibrosis; Cystic Fibrosis - complications; Deoxyribonucleic acid; DNA; DNA Fingerprinting; Drug resistance; Drug Resistance, Bacterial; Drug therapy; Errors of metabolism; follow-up; Genes, rRNA; Human bacterial diseases; Humans; Infectious diseases; Linezolid; Lungs; Male; Medical sciences; Metabolic diseases; Methicillin-Resistant Staphylococcus aureus - classification; Methicillin-Resistant Staphylococcus aureus - drug effects; Methicillin-Resistant Staphylococcus aureus - genetics; Methicillin-Resistant Staphylococcus aureus - isolation & purification; Microbial Sensitivity Tests; Miscellaneous hereditary metabolic disorders; Mutation; Oxazolidinones - therapeutic use; Pediatrics; Pharmacology. Drug treatments; Polymorphism, Restriction Fragment Length; Pseudomonas aeruginosa; Pseudomonas aeruginosa - isolation & purification; RNA, Bacterial - genetics; RNA, Ribosomal, 23S - genetics; Sputum - microbiology; Staphylococcal Infections - drug therapy; Staphylococcal Infections - microbiology; Staphylococcal infections, streptococcal infections, pneumococcal infections; Staphylococcus aureus; Staphylococcus infections; subtherapeutic; United Kingdom; follow-up; colonization; subtherapeutic; Linezolid; Bacteria; Micrococcales; Micrococcaceae; Protein synthesis inhibitor; Oxazole derivatives; Child; Staphylococcus aureus; Pancreatic disease; Human; Respiratory disease; Metabolic diseases; Cystic fibrosis; Genetic disease; Infection; Resistance; Antibiotic; Treatment; Follow up study; Oxazolidinone derivative; Bacteriosis; Digestive diseases; Antibacterial agent; Staphylococcal infection; Colonization; Prolonged
• DOI: 10.1093/jac/dkp494
• ISSN: 0305-7453; 1460-2091

Objectives To describe the emergence of linezolid-resistant methicillin-resistant Staphylococcus aureus (MRSA) of sequence type (ST)36 lineage in two paediatric patients with cystic fibrosis, after long-term low-dose linezolid treatment. Methods Two paediatric males with cystic fibrosis had sputum samples quantitatively cultured during hospitalization. After the isolation of MRSA from both patients, oral treatment with 300 mg linezolid twice daily was initiated for periods of 1–2 months separated by up to 6 months. Isolates cultured 9 months after the start of treatment were tested for resistance to linezolid by agar dilution (BSAC). Resistant isolates were examined for 23S rDNA mutations, and typed by phage and macrorestriction with SmaI. Isolates from follow-up sputum samples were obtained until 44–51 months after treatment with linezolid. Results Colonization with MRSA was at a density of ∼106 cfu/mL sputum for both subjects. Initial isolates were susceptible to linezolid, but, 9 months later, isolates from both patients were resistant (MICs > 16 mg/L). Both isolates were epidemic MRSA-16 variant A1 (ST36-MRSA-II), which is widespread in UK hospitals. Both isolates were heterozygous for a G2576T mutation in their 23S rDNA genes, but one was resistant to fusidic acid and tetracycline. In follow-up sampling, the younger patient yielded linezolid-resistant EMRSA-16 for a further 42 months, whilst the other lost the linezolid-resistant MRSA and had alternately Pseudomonas aeruginosa or linezolid-susceptible EMRSA-16 variant A1 isolated over 35 further months. Conclusions Linezolid resistance emerged in two isolates of ST36 MRSA colonizing the lungs of two paediatric cystic fibrosis patients. Subtherapeutic levels of linezolid may have facilitated the selection of resistance.