A novel aminoglycoside-modifying enzyme gene aac(6′)-Ib in a pandrug-resistant Acinetobacter baumannii strain

Abstract

Acinetobacter spp., especially Acinetobacter baumannii, are important opportunistic pathogens responsible for a variety of nosocomial infections, including ventilator-associated pneumonia, bacteraemia, surgical site infections, secondary meningitis, and urinary tract infections. Aminoglycosides are widely used for the treatment of infections in hospitalised patients and remain an important alternative for therapy of infections caused by multidrug-resistant organisms, including A. baumannii. 1 Bergogne-Bérézin E. Towner K.J. Acinetobacter spp. as nosocomial pathogens: microbiological, clinical, and epidemiological features. Clin Microbiol Rev. 1996; 9: 148-165 PubMed Google Scholar However, resistance rates to standard aminoglycosides such as amikacin and gentamicin are high among A. baumannii in many regions. Antimicrobial activity of aminoglycosides depends on binding to a highly conserved motif of 16S rRNA. The mechanism of resistance to these compounds is frequently due to the acquisition of aminoglycoside-modifying enzymes (AMEs) that vary in their substrate ranges, such as acetyltransferases, phosphorylases, and adenylyltransferases. 2 Kotra L.P. Haddad J. Mobashery S. Aminoglycosides: perspectives on mechanisms of action and resistance and strategies to counter resistance. Antimicrob Agents Chemother. 2000; 44: 3249-3256 Crossref PubMed Scopus (361) Google Scholar , 3 Yamane K. Wachino J. Doi Y. Kurokawa H. Arakawa Y. Global spread of multiple aminoglycoside resistance genes. Emerg Infect Dis. 2005; 11: 951-953 Crossref PubMed Scopus (114) Google Scholar Recently, production of 16S rRNA methylases has been described as a mechanism of high-level resistance to most clinically important aminoglycosides, including arbekacin, amikacin, tobramycin, and gentamicin. Since the first 16S rRNA methylase, ArmA, was found in 2003, six plasmid-mediated 16S rRNA methylases (ArmA, RmtA, RmtB, RmtC, RmtD, and NpmA) have been found in clinical isolates of Gram-negative bacilli. 4 Galimand M. Courvalin P. Lambert T. Plasmid-mediated high-level resistance to aminoglycosides in Enterobacteriaceae due to 16S rRNA methylation. Antimicrob Agents Chemother. 2003; 47: 2565-2571 Crossref PubMed Scopus (274) Google Scholar , 5 Doi Y. Arakawa Y. 16S Ribosomal RNA methylation: emerging resistance mechanism against aminoglycosides. Clin Infect Dis. 2007; 45: 88-94 Crossref PubMed Scopus (385) Google Scholar , 6 Wachino J. Shibayama K. Kurokawa H. et al. Novel plasmid-mediated 16S rRNA m1A1408 methyltransferase, NpmA, found in a clinically isolated Escherichia coli strain resistant to structurally diverse aminoglycosides. Antimicrob Agents Chemother. 2007; 51: 4401-4409 Crossref PubMed Scopus (138) Google Scholar We now report on a pandrug-resistant A. baumannii strain from China co-carrying four AME genes, including a novel AME gene aac(6′)-Ib.