Salmonella isolates with decreased susceptibility to extended-spectrum cephalosporins in the United States.
OBJECTIVE
We describe the antimicrobial susceptibility to extended-spectrum cephalosporins in non-Typhi Salmonella (NTS) isolated from humans in the United States and explore resistance mechanisms for isolates displaying decreased susceptibility to ceftriaxone or ceftiofur. We further explore the concordance between the newly revised Clinical and Laboratory Standards Institute (CLSI) breakpoints for ceftriaxone and the presence of a β-lactamase.


METHODS
In 2005 and 2006, public health laboratories in all U.S. state health departments forwarded every 20th NTS isolate from humans to Centers for Disease Control and Prevention as part of the National Antimicrobial Resistance Monitoring System (NARMS) for enteric bacteria. Minimum inhibitory concentrations (MICs) were determined by broth microdilution. Isolates displaying decreased susceptibility (MIC ≥ 2 mg/L) to ceftriaxone or ceftiofur were included in the study. The presence of β-lactamase genes was investigated by polymerase chain reaction amplification and sequencing, targeting six different genes (bla(TEM), bla(OXA), bla(SHV), bla(CTX-M), bla(PSE), and bla(CMY)). Plasmid location of bla(CMY) was confirmed by transforming plasmids into Escherichia coli.


RESULTS
Among the 4236 isolates of NTS submitted to NARMS in 2005 and 2006, 175 (4.1%) displayed decreased susceptibility to either ceftriaxone or ceftiofur. By polymerase chain reaction screening, one or more β-lactamase genes could be detected in 139 (80.8%) isolates. The most prevalent resistance mechanism detected was the AmpC β-lactamase gene bla(CMY.) Other β-lactamase genes detected included 11 bla(TEM-1), 3 bla(PSE-1), 2 bla(OXA-1), and 1 bla(CTX-M-15). The ceftriaxone MIC values for the bla(CMY)-containing isolates ranged from 4 to 64 mg/L; all bla(CMY)-bearing isolates were classified as ceftriaxone resistant according to current CLSI guidelines.


CONCLUSIONS
Among NTS isolates submitted to NARMS in 2005 and 2006, cephamycinase β-lactamases are the predominant cause of decreased susceptibility to ceftriaxone. The fact that all bla(CMY)-containing isolates were classified as resistant to ceftriaxone (MIC ≥ 4 mg/L) supports the newly revised CLSI breakpoints for cephalosporins and Enterobacteriaceae.
Sjölund-Karlsson
Maria
M
National Antimicrobial Resistance Monitoring System, Centers for Disease Control and Prevention, Atlanta, Georgia 30329, USA. fwt4@cdc.gov
Rickert
Regan
R
Matar
Caline
C
Pecic
Gary
G
Howie
Rebecca L
RL
Joyce
Kevin
K
Medalla
Felicita
F
Barzilay
Ezra J
EJ
Whichard
Jean M
JM
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000302:isolation & purification; D002443:Ceftriaxone / Q000494:pharmacology*; D018550:Cephalosporin Resistance; D002511:Cephalosporins / Q000494:pharmacology*; D016521:Electrophoresis, Gel, Pulsed-Field; D005798:Genes, Bacterial; D006801:Humans; D008826:Microbial Sensitivity Tests; D012475:Salmonella / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000302:isolation & purification; D014481:United States; D001618:beta-Lactamases / Q000235:genetics / Q000302:isolation & purification
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002511:Cephalosporins; D002443:Ceftriaxone; C053503:ceftiofur; C048795:AmpC beta-lactamases; D001618:beta-Lactamases