Clinical characteristics of bloodstream infections due to ampicillin-sulbactam-resistant, non-extended- spectrum-beta-lactamase-producing Escherichia coli and the role of TEM-1 hyperproduction.
Ampicillin-sulbactam is commonly used as an empirical therapy for invasive infections where Escherichia coli is a potential pathogen. We evaluated the clinical and microbiologic characteristics of bloodstream infection due to E. coli, with focus on cases that were nonsusceptible to ampicillin-sulbactam and not producing extended-spectrum β-lactamase (ESBL). Of a total of 357 unique bacteremic cases identified between 2005 and 2008, 111 (31.1%) were intermediate or resistant to ampicillin-sulbactam by disk testing. In multivariate analysis, a history of liver disease, organ transplant, peptic ulcer disease, and prior use of ampicillin-sulbactam were independent risk factors for bloodstream infection with ampicillin-sulbactam-nonsusceptible E. coli. Among cases that received ampicillin-sulbactam as an empirical therapy, an early clinical response was observed in 65% (22/34) of susceptible cases but in only 20% (1/5) of nonsusceptible cases. Among 50 ampicillin-sulbactam-resistant isolates examined, there was no clonal relatedness and no evidence of production of inhibitor-resistant TEM (IRT). Instead, the resistance was attributed to hyperproduction of TEM-1 β-lactamase in the majority of isolates. However, promoter sequences of bla(TEM-1) did not predict resistance to ampicillin-sulbactam. While the plasmid copy number did not differ between representative resistant and susceptible isolates, the relative expression of bla(TEM-1) was significantly higher in two of three resistant isolates than in three susceptible isolates. These results suggest high-level bla(TEM-1) expression as the predominant cause of ampicillin-sulbactam resistance and also the presence of yet-unidentified factors promoting overexpression of bla(TEM-1) in these isolates.
Division of Infectious Diseases, University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USA.
Rebecca I
RI
Waltner-Toews
David L
DL
Paterson
Zubair A
ZA
Qureshi
Hanna E
HE
Sidjabat
Jennifer M
JM
Adams-Haduch
Kathleen A
KA
Shutt
Mark
M
Jones
Guo-Bao
GB
Tian
Anthony W
AW
Pasculle
Yohei
Y
Doi
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000667:Ampicillin / Q000494:pharmacology*; D000668:Ampicillin Resistance; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D016470:Bacteremia / Q000382:microbiology / Q000503:physiopathology*; D016521:Electrophoresis, Gel, Pulsed-Field; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000382:microbiology / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D010957:Plasmids; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D013407:Sulbactam / Q000494:pharmacology*; D055815:Young Adult; D018440:beta-Lactam Resistance / Q000235:genetics*; D001618:beta-Lactamases / Q000096:biosynthesis* / Q000235:genetics
D000900:Anti-Bacterial Agents; D000667:Ampicillin; D001618:beta-Lactamases; C034413:beta-lactamase TEM-1; D013407:Sulbactam