Emergence of linezolid-resistant coagulase-negative Staphylococcus in a cancer centre linked to increased linezolid utilization

Objectives: The prevalence of linezolid-resistant coagulase-negative Staphylococcus (CoNS) in the MD Anderson Cancer Center rose from 0.6% in 2007 to 5.5% in 2009. The aim of our study was to analyse the relationship between linezolid use and an outbreak of linezolid-resistant CoNS. Patients and methods: We retrospectively identified 27 infection or colonization events. Eleven isolates were available for supplemental investigation; species identification, clonal relatedness and linezolid resistance mutation analysis. The medical records of the affected patients were reviewed and linezolid utilization data were obtained from the pharmacy. Results: Available isolates were confirmed as clonally related Staphylococcus epidermidis. Partial 23S rRNA gene sequencing found a G2576T mutation in all of the isolates tested. All patients received linezolid within 3 months prior to an event. Patients without a prior hospitalization had a longer time from admission to event; 29 versus 3.5 days (P=0.002). The outbreak was preceded by a 51% increase in inpatient linezolid utilization and 64% of affected patients belonged to the leukaemia service, which had a utilization rate 3.1 times that of the other services (95% confidence interval: 2.96-3.23). Conclusions: Increased linezolid utilization preceded the appearance of a linezolid-resistant CoNS clone. Patients probably acquired the clonal strain nosocomially, given the longer time from admission to event among patients with no previous admission to the MD Anderson Cancer Center. Linezolid administration then selected this strain, since all patients received linezolid prior to an event. A linezolid utilization rate of ≥13 defined daily doses/100 patient-days was similar to that reported in two other outbreaks and may be the threshold required to generate an outbreak.