595. Prevalence of Arbekacin Resistance Genes Among Gram Negative Bacteria Isolated from Infected Patients in a Large Military Hospital 
Session: Poster Abstract Session: Novel Antimicrobial Agents
Friday, October 21, 2011
Room: Poster Hall B1
Background: Interest in the aminoglycoside arbekacin has increased over the last number of years due to its broad spectrum of activity and the fact that it is impervious to many aminoglycoside-modifying enzymes (AMEs).  However, this drug is only licensed in Japan, where it is used for the treatment of patients with septicemia and pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA).  Arbekacin resistance is mediated in part through the actions of 16S rRNA methylase genes, notably the armA gene and members of the rmt gene family.  We wished to screen arbekacin resistant gram negative organisms isolated from our patients for the genes conferring resistance.

Methods: 100 gram negative bacteria from four genera with arbekacin MICs ≥8 μg/mL by microbroth dilution were used in this study. Specimen sources included blood, sputum, urine, and wound samples collected at a large military hospital between 2004 and 2010.  Real-time PCR using gene-specific primers was used to screen all isolates for the armA, rmtB and rmtD/rmtD2 genes.  Gene presence was confirmed by sequencing, using gene-specific conventional primers.

Results: 44 Pseudomonas aeruginosa, 28 Acinetobacter baumannii, 19 Klebsiella pneumoniae, and 9 Escherichia coli were screened for armA, rmtB and rmtD.  Two isolates (one A. baumannii and one K. pneumoniae) carried the armA gene.  Fourteen P. aeruginosa isolates showed amplification with the rmtD/rmtD2 primer set, and melting curve analysis confirmed that these isolates carried the rmtD allele, rmtD2. RmtB was not detected in any isolate.  

Conclusion: The prevalence of the 16S rRNA methylase gene armA was very low among the clinical isolates tested.  Interestingly, both strains carrying the armA gene had very high arbekacin MICs (>64), in contrast to all other A. baumannii and K. pneumoniae isolates, where arbekacin MICs were ≤32 μg/mL.  In contrast, the presence of rmtD2 in the P. aeruginosa isolates was not associated (p>0.5) with increased MICs to arbekacin, suggesting other mechanisms contribute to arbekacin resistance in this species. 


Subject Category: A. Antimicrobial agents and Resistance

Patrick Mc Gann, PhD1, Melissa Barber, AS, MLT (AMT)2, Glenn Wortmann, MD3, Paige Waterman, MD1,3 and Michael Zapor, MD, PhD3,4, (1)Walter Reed Army Institute of Research, Silver Spring, MD, (2)Infectious Diseases Clinical Research Program, Washington, DC, (3)Uniformed Services University, Bethesda, MD, (4)Infectious Diseases, Walter Reed Army Medical Center, Washington, DC

Disclosures:

P. Mc Gann, None

M. Barber, None

G. Wortmann, None

P. Waterman, None

M. Zapor, None

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