Clinical resistance to the currently recommended extended-spectrum
cephalosporins (ESCs), the last remaining treatment options for
gonorrhea, is being reported.
Gonorrhea may become untreatable, and new treatment options are crucial. We investigated the in vitro activity of
ertapenem, relative to
ceftriaxone, against N. gonorrhoeae isolates and the effects of ESC resistance determinants on
ertapenem. MICs were determined using
agar dilution technique or Etest for international reference strains (n = 17) and clinical N. gonorrhoeae isolates (n = 257), which included the two extensively
drug-resistant (XDR) strains H041 and F89 and additional isolates with high ESC MICs, clinical ESC resistance, and other types of clinical high-level and multidrug resistance (MDR). Genetic resistance determinants for ESCs (penA, mtrR, and penB) were sequenced. In general, the MICs of
ertapenem (MIC(50) = 0.032 μg/ml; MIC(90) = 0.064 μg/ml) paralleled those of
ceftriaxone (MIC(50) = 0.032 μg/ml; MIC(90) = 0.125 μg/ml). The ESC resistance determinants mainly increased the
ertapenem MIC and
ceftriaxone MIC at similar levels. However, the MIC ranges for
ertapenem (0.002 to 0.125 μg/ml) and
ceftriaxone (<0.002 to 4 μg/ml) differed, and the four (1.5%)
ceftriaxone-resistant isolates (MIC = 0.5 to 4 μg/ml) had
ertapenem MICs of 0.016 to 0.064 μg/ml. Accordingly,
ertapenem had in vitro advantages over
ceftriaxone for isolates with
ceftriaxone resistance. These in vitro results suggest that
ertapenem might be an effective treatment option for
gonorrhea, particularly for the currently identified ESC-resistant cases and possibly in a dual antimicrobial
therapy regimen. However, further knowledge regarding the genetic determinants (and their evolution) conferring resistance to both antimicrobials, and clear correlates between genetic and phenotypic laboratory parameters and clinical treatment outcomes, is essential.