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JAC Advance Access originally published online on October 7, 2004
Journal of Antimicrobial Chemotherapy 2004 54(5):889-896; doi:10.1093/jac/dkh453
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JAC vol.54 no.5 © The British Society for Antimicrobial Chemotherapy 2004; all rights reserved

Phenotypic and genotypic aminoglycoside resistance in blood culture isolates of coagulase-negative staphylococci from a single neonatal intensive care unit, 1989–2000

Claus Klingenberg1,2,*, Arnfinn Sundsfjord3,4, Arild Rønnestad5, Jarle Mikalsen3, Peter Gaustad6 and Trond Flægstad1,2

1 Department of Paediatrics, University Hospital of North-Norway, N-9038 Tromsø; 2 Department of Paediatrics, Institute of Clinical Medicine, University of Tromsø, Tromsø; 3 Department of Microbiology and Virology, Institute of Medical Biology, University of Tromsø, Tromsø; 4 Division of Infectious Disease Control, Norwegian Institute of Public Health, Oslo; 5 Department of Paediatrics, National Hospital, Oslo; 6 Department of Microbiology, National Hospital, Oslo, Norway

* Corresponding author. Tel: +47-77-62-60-00; Fax: +47-77-62-63-69; Email: claus.klingenberg{at}unn.no

Objectives: To investigate the prevalence of aminoglycoside resistance and genes encoding aminoglycoside-modifying enzymes (AME) in blood culture isolates of coagulase-negative staphylococci (CoNS) from neonates.

Materials and methods: A total of 180 isolates from 148 patients collected in a single neonatal unit over a 12 year period were examined for susceptibility to gentamicin, tobramycin, netilmicin, amikacin and arbekacin by Etest and/or disc diffusion. AME genes were detected by PCR.

Results: The overall non-susceptibility rates to gentamicin, tobramycin, netilmicin, amikacin and arbekacin were 66%, 68%, 52%, 38% and 1%, respectively. Gentamicin non-susceptibility rates were 4% and 91% in methicillin-susceptible and -resistant isolates, respectively. aac(6')-Ie-aph(2'')-Ia, aph(3')-IIIa and/or ant(4')-Ia were encountered in 125 (69%), 1 (0.5%) and 30 (16.6%) isolates, respectively. Forty-six (26%) isolates negative for AME genes were susceptible to all aminoglycosides. In contrast, 115 (92%), 91 (73%) and 66 (53%) of aac(6')-Ie-aph(2'')-Ia positive isolates were non-susceptible to gentamicin, netilmicin and amikacin, respectively. Only one isolate showed arbekacin resistance. However, aac(6')-Ie-aph(2'')-Ia positive isolates and isolates with gentamicin MIC ≥128 mg/L displayed a significant reduction in arbekacin inhibition zones.

Conclusions: A high prevalence of aminoglycoside resistance was detected and associated with methicillin resistance. Discrepancies between phenotypic and genetic detection of aminoglycoside resistance were discerned. Gentamicin was the preferred substrate for phenotypic detection of aac(6')-Ie-aph(2'')-Ia. Arbekacin showed favourable antibacterial activity even in aac(6')-Ie-aph(2'')-Ia-positive isolates. We suggest including arbekacin in future clinical trials of empirical treatment of late onset neonatal sepsis.

Keywords: arbekacin , aminoglycoside-modifying enzymes , methicillin resistance


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