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Antimicrobial Agents and Chemotherapy, June 2007, p. 2117-2122, Vol. 51, No. 6
0066-4804/07/$08.00+0     doi:10.1128/AAC.01604-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Neisseria gonorrhoeae Isolates with Reduced Susceptibility to Cefixime and Ceftriaxone: Association with Genetic Polymorphisms in penA, mtrR, porB1b, and ponA{triangledown}

Robert Lindberg,1 Hans Fredlund,1 Robert Nicholas,2 and Magnus Unemo1*

National Reference Laboratory for Pathogenic Neisseria, Department of Clinical Microbiology, Örebro University Hospital, Örebro, Sweden,1 Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina2

Received 22 December 2006/ Returned for modification 15 January 2007/ Accepted 23 March 2007

The recent emergence and transmission of Neisseria gonorrhoeae isolates with reduced susceptibility to expanded-spectrum cephalosporins such as cefixime and ceftriaxone have been reported. The aim of this study was to determine the correlation of different polymorphisms in the penA, mtrR, porB1b (penB), and ponA genes of N. gonorrhoeae with reduced susceptibility to cefixime and ceftriaxone. Eighteen gonococcal isolates with reduced cefixime and ceftriaxone susceptibility (Cefi) and two susceptible isolates were characterized using serovar determination, antibiograms, N. gonorrhoeae multiantigen sequence typing (NG-MAST), and sequencing of penA, mtrR, porB1b, and ponA alleles. For the Cefi isolates (n = 18), the MICs of cefixime and ceftriaxone ranged between 0.032 to 0.38 µg/ml and 0.064 to 0.125 µg/ml, respectively. These isolates were assigned five different serovars and six divergent NG-MAST sequence types. Eleven isolates (61%) with higher MICs of cefixime and ceftriaxone contained a nearly identical penA mosaic allele and previously described polymorphisms in mtrR (a single nucleotide [A] deletion in the promoter), penB (mutations in porB1b encoding loop 3 of PorB1b), and ponA (ponA1 polymorphism). The remaining seven Cefi isolates (39%), which had somewhat lower MICs of cefixime and ceftriaxone, contained an aspartic acid insertion (Asp-345a) in PBP 2 in conjunction with alterations of 4 to 10 amino acid residues in the C-terminal region of the transpeptidase domain of penA. In conclusion, an unambiguous association between penA mosaic alleles, in conjunction with genetic polymorphisms in mtrR, porB1b, and ponA, and greater reduced susceptibility to cefixime and ceftriaxone was identified.

* Corresponding author. Mailing address: Department of Clinical Microbiology, Örebro University Hospital, SE-701 85 Örebro, Sweden. Phone: 46 19 6021520. Fax: 46 19 127416. E-mail: magnus.unemo{at}orebroll.se

{triangledown} Published ahead of print on 9 April 2007.

Antimicrobial Agents and Chemotherapy, June 2007, p. 2117-2122, Vol. 51, No. 6
0066-4804/07/$08.00+0     doi:10.1128/AAC.01604-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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