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APMIS ; 119(6): 356-63, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21569093

ABSTRACT

Antimicrobial resistance (AMR) in Neisseria gonorrhoeae remains a global public health problem. Susceptibility to first-line treatment extended-spectrum cephalosporins (ESCs) is decreasing worldwide resulting in therapeutic failures with oral ESCs. This study describes a cefpodoxime 10 µg disc test for screening for gonococci containing a penA mosaic allele encoding a mosaic penicillin-binding protein 2 (PBP2) and decreased ESC susceptibility. Selected clinical gonococcal isolates (n = 315), containing a high proportion of gonococci with decreased ESC susceptibility and high geographical, temporal and genetic diversity, were examined using agar dilution (n = 149; cefpodoxime and ceftriaxone) and Etest (n = 315; cefixime), and disc diffusion using a commercially available cefpodoxime 10 µg disc (n = 315). penA sequencing was performed on all isolates. The 2008 WHO gonococcal reference strains (n = 8) were included as quality controls. Using a ≤11 mm annular radius of growth inhibition as the breakpoint for the cefpodoxime 10 µg disc, all 78, with exception of one isolate (13 mm), mosaic PBP2-containing isolates, which also displayed decreased susceptibility to oral ESCs, were identified. In addition, 85 non-mosaic PBP2-containing isolates (44% of which contained a PBP2 A501 alteration) had annular radii ≤11 mm and raised minimal inhibitory concentrations to the ESCs. Screening for detection of mosaic PBP2-containing gonococci and decreased ESC susceptibility, most pronounced to oral ESCs, using a commercially available cefpodoxime 10 µg disc was rapid, inexpensive and sensitive. This test can be used in AMR surveillance programmes for public health purposes especially in less-resourced settings. Further studies to refine this disc testing-based approach are in progress.


Subject(s)
Anti-Bacterial Agents/pharmacology , Ceftizoxime/analogs & derivatives , Cephalosporins/pharmacology , Drug Resistance, Bacterial , Neisseria gonorrhoeae/drug effects , Neisseria gonorrhoeae/genetics , Alleles , Cefixime/pharmacology , Ceftizoxime/pharmacology , Ceftriaxone/pharmacology , Dose-Response Relationship, Drug , Gonorrhea/microbiology , Microbial Sensitivity Tests/methods , Penicillin-Binding Proteins/genetics , Penicillin-Binding Proteins/metabolism , Sequence Analysis, DNA , Cefpodoxime
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