Affiliation:
1. JMI Laboratories, North Liberty, Iowa, USA
2. Pfizer Inc., New York, New York, USA
3. Tufts University School of Medicine, Boston, Massachusetts, USA
Abstract
ABSTRACT
The
l
inezolid
e
xperience and
a
ccurate
d
etermination of
r
esistance (LEADER) surveillance program has monitored linezolid activity, spectrum, and resistance since 2004. In 2014, a total of 6,865 Gram-positive pathogens from 60 medical centers from 36 states were submitted. The organism groups evaluated were
Staphylococcus aureus
(3,106), coagulase-negative staphylococci (CoNS; 797), enterococci (855),
Streptococcus pneumoniae
(874), viridans group streptococci (359), and beta-hemolytic streptococci (874). Susceptibility testing was performed by reference broth microdilution at the monitoring laboratory. Linezolid-resistant isolates were confirmed by repeat testing. PCR and sequencing were performed to detect mutations in 23S rRNA, L3, L4, and L22 proteins and acquired genes (
cfr
and
optrA
). The MIC
50/90
for
Staphylococcus aureus
was 1/1 μg/ml, with 47.2% of isolates being methicillin-resistant
Staphylococcus aureus
. Linezolid was active against all
Streptococcus pneumoniae
strains and beta-hemolytic streptococci with a MIC
50/90
of 1/1 μg/ml and against viridans group streptococci with a MIC
50/90
of 0.5/1 μg/ml. Among the linezolid-nonsusceptible MRSA strains, one strain harbored
cfr
only (MIC, 4 μg/ml), one harbored G2576T (MIC, 8 μg/ml), and one contained
cfr
and G2576T with L3 changes (MIC, ≥8 μg/ml). Among CoNS, 0.75% (six isolates) of all strains demonstrated linezolid MIC results of ≥4 μg/ml. Five of these were identified as
Staphylococcus epidermidis
, four of which contained
cfr
in addition to the presence of mutations in the ribosomal proteins L3 and L4, alone or in combination with 23S rRNA (G2576T) mutations. Six enterococci (0.7%) were linezolid nonsusceptible (≥4 μg/ml; five with G2576T mutations, including one with an additional
cfr
gene, and one strain with
optrA
only). Linezolid demonstrated excellent activity and a sustained susceptibility rate of 99.78% overall.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology