Sonia K. Morgan-Linnell

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In defined, isogenic strains, at least three mutations, two of which must be in gyrA, were required to exceed the CLSI breakpoint for fluoroquinolone resistance. Strains with double mutations in both gyrA and parC had even higher MICs of fluoroquinolones than strains with totals of three mutations.
Fluoroquinolone MICs are increased through the acquisition of chromosomal mutations in the genes encoding gyrase (gyrA and gyrB) and topoisomerase IV (parC and parE), increased levels of the multidrug efflux pump AcrAB, and the plasmid-borne genes aac(6')-Ib-cr and the qnr variants in Escherichia coli. In the accompanying report, we found that(More)
Fluoroquinolones are some of the most prescribed antibiotics in the United States. Previously, we and others showed that the fluoroquinolones exhibit a class effect with regard to the CLSI-established breakpoints for resistance, such that decreased susceptibility (i.e., an increased MIC) to one fluoroquinolone means a simultaneously decreased susceptibility(More)
In a single quantitative study, we measured acrA, acrB, tolC, mdfA, and norE expression in Escherichia coli clinical isolates by using real-time PCR. acrA and acrB overexpression strongly correlated with fluoroquinolone and multidrug resistance; tolC, mdfA, and norE expression did not. The order of abundance of efflux pump transcripts in all(More)
BACKGROUND EZN-2208 is a water-soluble, polyethylene glycol drug conjugate of SN38, which is the active moiety of irinotecan. In this study, the authors evaluated the tolerability, pharmacokinetics (PK), and activity of EZN-2208 in adult patients with advanced solid tumors. METHODS Patients in sequential cohorts (3 + 3 design) received intravenous(More)
BACKGROUND Preclinical data indicate EGFR signals through both kinase-dependent and independent pathways and that combining a small-molecule EGFR inhibitor, EGFR antibody, and/or anti-angiogenic agent is synergistic in animal models. METHODS We conducted a dose-escalation, phase I study combining erlotinib, cetuximab, and bevacizumab. The subset of(More)
Both prokaryotes and eukaryotes have two major classes of topoisomerases that make transient single- or double-strand cuts in DNA. While these enzymes play critical roles in cellular processes, they are also important targets of therapeutic agents. This unit describes assays to use in characterizing topoisomerase II-targeting agents in vitro and in(More)
The U.S. Food and Drug Administration (FDA) Center for Drug Evaluation and Research is responsible for evaluating drug safety and efficacy, including oversight of clinical trials and principal investigators. The FDA Clinical Investigator Inspection List (CIIL) contains online, detailed, relevant information of all FDA inspections. We reviewed FDA(More)
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