Correlation between the mutation rates for ampC derepression and species or ampC genotypes in Enterobacter cloacae complex.

Background: In this study, we investigated the correlation between the mutation rates for ampC derepression and species or ampC genotypes in Enterobacter cloacae complex (ECC) susceptible to ceftriaxone. Non-duplicate ceftriaxone-sensitive ECC isolates (90) were obtained from September 2021 to January 2023 at Ruijin Hospital, Shanghai. hsp60 genotyping and PCR were used for species and ampC identification, respectively. Thirteen strains with the negative ampC amplification results were sequenced, and the mutation rates for ampC derepression were determined by performing Luria-Delbrück fluctuation analyses.

Results: Among these isolates, E. hormaechei was the most prevalent (54.44%), followed by E. roggenkampii (12.22%), E. cloacae (11.11%), E. bugandensis (10.00%), E. asburiae (4.44%), and E. kobei (4.44%). For E. ludwigii, E. mori, and E. sichuanensis, only a single strain was identified. There were 72 strains with bla_ACT, 13 with bla_MIR, and five with bla_CMH. The ampC-derepressed mutation rate was (2.25 ± 1.81) × 10^-8 for E. asburiae, (3.21 ± 2.96) × 10^-8 for E. bugandensis, (6.06 ± 11.95) × 10^-8 for E. cloacae, (1.12 ± 3.44) × 10^-7 for E. hormaechei, (7.76 ± 11.41) × 10^-8 for E. kobei, (3.99 ± 9.65) × 10^-8 for E. roggenkampii, 5.87 × 10^-8 for E. ludwigii, 1.12 × 10^-7 for E. mori, and 2.17 × 10^-7 for E. sichuanensis. The mutation rate was (8.94 ± 28.61) × 10^-8 for bla_ACT, (2.62 ± 2.16) × 10^-8 for bla_CMH, and (8.10 ± 13.84) × 10^-8 for bla_MIR.

Conclusions: ECC was found to have high mutation rate-inducible AmpC production with no species or ampC genotype differences. This highlights an important clinical concern, i.e., the high risk of treatment failure with third-generation cephalosporins in individuals with inducible AmpC-containing ECC.