In vitro carbapenem activity in Neisseria gonorrhoeae

Neisseria gonorrhoeae is a common bacterium responsible for sexually transmitted infections. The WHO recommends the use of 1 g ceftriaxone to treat gonococcal infections. However, ceftriaxone-resistant strains are emerging, and carbapenems may be the last remaining treatment option.

We compared MICs for ceftriaxone, ertapenem, imipenem and meropenem in a collection of 81 clinical isolates and nine WHO reference isolates with various penA alleles. This previously characterized collection included nine ceftriaxone-resistant isolates. It was selected to include 42 different penA alleles (27 non-mosaic and 15 mosaic), 26 TEM penicillinase-producing isolates, five MDR and four XDR isolates.

The MICs of ceftriaxone, ertapenem, imipenem and meropenem ranged from <0.002 to 2 mg/L, <0.002 to 0.064 mg/L, 0.008 to 1 mg/L and 0.002 to 0.125 mg/L, respectively. In ceftriaxone-resistant isolates, the MIC₅₀ of ertapenem, imipenem and meropenem were 0.012 mg/L (0.004-0.032 mg/L), 0.75 mg/L (0.125-1 mg/L) and 0.032 mg/L (0.016-0.064 mg/L), respectively. For all antibiotics, MICs were significantly higher in isolates with a mosaic penA allele (P-value <0.001). No significant difference in carbapenem MICs was found between isolates with and without a TEM beta-lactamase.

Carbapenem MICs remain low in N. gonorrhoeae isolates but are higher in those with mosaic penA alleles than in those with non-mosaic penA alleles. MICs for ertapenem are lower than those for other carbapenems, supporting its use for the treatment of infections with ceftriaxone-resistant N. gonorrhoeae. However, the establishment of breakpoints for carbapenem resistance in N. gonorrhoeae is required.