Department of Laboratory Medicine, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Abstract
The oxazolidinone antibiotic linezolid has demonstrated potent antimicrobial activity against Gram-positive bacterial pathogens, including methicillin-resistant staphylococci. This article systematically reviews the published literature for reports of linezolid-resistant Staphylococcus (LRS) infections to identify epidemiological, microbiological and clinical features for these infections. Linezolid remains active against >98% of Staphylococcus, with resistance identified in 0.05% of Staphylococcus aureus and 1.4% of coagulase-negative Staphylococcus (CoNS). In all reported cases, patients were treated with linezolid prior to isolation of LRS, with mean times of 20.0 ± 47.0 months for S. aureus and 11.0 ± 8.0 days for CoNS. The most common mechanisms for linezolid resistance were mutation (G2576T) to the 23S rRNA (63.5% of LRSA and 60.2% of LRCoNS) or the presence of a transmissible cfr ribosomal methyltransferase (54.5% of LRSA and 15.9% of LRCoNS). The emergence of linezolid resistance in Staphylococcus poses significant challenges to the clinical treatment of infections caused by these organisms, and in particular CoNS.
PMID: 22949625 [PubMed - as supplied by publisher]
Three reports of LRSA (13.6% of 22 studies) and 14 reports of
LRCoNS (50% of 28 studies) documented clonal dissemination
of LRS within or across healthcare settings (Table 2). Two LRSA
outbreaks were described in Spain, each involving a single hospital,
and 15 or 12 patients, respectively.13,19 The third LRSA outbreak
was reported from Japan, and involved seven patients in
six different hospitals.20 Both outbreaks in Spain were caused
by LRSA harbouring the mobile cfr resistance gene, whereas
the Japanese study did not test for cfr. Five linezolid-resistant
S. epidermidis with identical PFGE types were recovered from
patients at two geographically disparate institutions in the USA
between 2006 and 2008.7 In Greece, two clones of LRCoNS
were identified among 26 patients in four hospitals.21 Neither
the US nor the Greek isolates harboured cfr. These publications
did not distinguish LRCoNS colonization versus infection.
Conclusions
Linezolid remains highly active against most staphylococci, and
its value in treating serious infections caused by MRSA has
been well documented. Clinicians should remain cognizant that
linezolid resistance may arise following prolonged treatment
with linezolid and of the possibility of LRS in patients that have
not been previously treated with linezolid, given the high incidence
of LRSA carrying cfr. Susceptibility testing for linezolid
resistance should be considered prior to using linezolid for
serious infections. Further, judicious use of linezolid, accurate
identification of resistance and application of strict infection
control measures are essential to the preservation of linezolid
as a therapeutic agent. To date, LRS remain susceptible to vancomycin,
daptomycin and tigecycline. Further studies are needed
to investigate the clinical outcome of LRS infections in order to
optimize treatment of these infections.