Aminoglycoside resistance mechanisms in Enterobacteriaceae: an experimental study based on human clinical isolates from western Norway

Abstract

Escherichia coli(E.coli) belongs to the Enterobacteriaceae family of gram negative rods. It is the most common cause for bacterial sepsis. According to NORM (Norwegian system for surveillance of antibiotic resistance in microbes); E.coli is the main pathogen found in blood samples from humans submitted to Norwegian microbial laboratories (page 49 NORM report 2008)(1). E.coli is also the most common cause of human urinary tract infections (The Journal of the Norwegian Medical Association) (2). Empiric treatment for sepsis and urosepsis in Norway is betalactam antibiotics in combination with aminoglycosides(3). In case of allergy, patients with urosepsis are treated with quinolones and aminoglycosides(4). There is concern related to recent years development of resistance against gentamicin (aminoglycoside) and ciprofloxacin (quinolone) among E.coli strains (page 52 NORM report 2008) (1). This work was initiated as a first step to identify the most common mechanisms for aminoglycoside resistance in Enterobacteriaceae collected in western Norway. The focus for this work was to characterize antibiotic resistance and detect the presence of the genes encoding two aminoglycoside modifying enzymes. The genes chosen encodes two enzymes from the group aminoglycoside acetyltransferases (AAC`s); aac(6`)-Ib and aac(3)-IIc (aacC2). The use of ciprofloxacin has increased markedly during the past few years. Recent studies have reported a variant of AAC(6`)-Ib characterized by two amino acid changes, Trp102Arg and Asp179Tyr. This variant called AAC(6`)-Ib-cr inflicts ciprofloxacin resistance in addition to aminoglycoside resistance. We suspected that increased use of ciprofloxacin could cause selection of isolates resistant to aminoglycosides by selecting the isolates that possess AAC(6`)-Ib-cr. We decided to examine the prevalence of aac(6`)-Ib-cr in isolates of Enterobaceriaceae resistant aminoglycosides, in order to provide either indirect support or rejection of this hypothesis.