Clinical characteristics of bloodstream infections due to ampicillin-sulbactam-resistant, non-extended-spectrum-β-lactamase-producing Escherichia coli and the role of TEM-1 hyperproduction

Rebecca I. Waltner-Toews, David L. Paterson, Zubair A. Qureshi, Hanna E. Sidjabat, Jennifer M. Adams-Haduch, Kathleen A. Shutt, Mark Jones, Guo Bao Tian, Anthony W. Pasculle, Yohei Doi

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29 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)495-501
Number of pages7
JournalAntimicrobial agents and chemotherapy
Volume55
Issue number2
DOIs
Publication statusPublished - 02-2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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