Hidden dissemination of carbapenem-susceptible OXA-48-producing Proteus mirabilis
Investigation published in The Journal of Antimicrobial Chemotherapy
October 28th, 2022
Objectives: To detect a potential hidden dissemination of the blaOXA-48 gene among Proteus mirabilis isolates obtained from a single centre.
Methods: P. mirabilis from diverse clinical samples presenting an ESBL phenotype or obtained from blood cultured from 2017 to 2019 were evaluated. Bacterial identification was performed using MALDI-TOF MS. MICs were determined using International Organization for Standardization (ISO) standard microdilution and interpreted following EUCAST guidelines. WGS was performed using both short- and long-read technologies and assemblies were done using Unicycler. Resistomes were assessed using the ResFinder database. SNPs were detected using the PATRIC bioinformatics platform. Cloning experiments were performed using the pCRII-TOPO cloning kit.
Results: Thirty-one out of 108 (28.7%) isolates were positive for blaOXA-48 and blaCTX-M-15. Twenty-nine out of 31 of the isolates were susceptible to temocillin, piperacillin/tazobactam, ertapenem and meropenem, whereas only 2/31 showed a resistance phenotype against these antibiotics. Both blaOXA-48 and blaCTX-M-15 genes were detected within the same chromosomally integrated new transposon in all isolates. The resistant isolates displayed a single mutation located in the putative promoter upstream of blaOXA-48. Cloning experiments confirmed that the mutation was responsible for the resistance phenotype.
Conclusions: The presence of a chromosomal copy of blaOXA-48 did not confer resistance to carbapenems, but a single mutation in the promoter could lead to an increase in resistance. This study shows a hidden circulation of OXA-48-positive, but carbapenem- and piperacillin/tazobactam-susceptible, P. mirabilis isolates that can become resistant to β-lactams after a single mutation
Pedraza R., Kieffer N., Guzman-Puche J., Artacho MJ., Pitart C., Hernandez-Garcia M., Vila J., Canton R. and Martinez-Martinez L.
| Hospital Universitario Reina Sofía de Córdoba. Universidad de Córdoba (UCO). | |
| Instituto Maimonides de Investigación Biomédica de Cordoba. | |
 | Centro de Vigilancia Sanitaria Veterinaria (VISAVET). Universidad Complutense (UCM). |
| Departamento de Sanidad Animal. Facultad de Veterinaria. Universidad Complutense (UCM). |
 | Red Española de Investigación en Patología Infecciosa (REIPI). Instituto de Salud Carlos III (ISCIII). |
| Centro de Investigación de Enfermedades Infecciosas (CIBERINFEC). Instituto de Salud Carlos III (ISCIII). |
 | Hospital Clínic. Universitat de Barcelona (UB). |
 | Hospital Universitario Ramón y Cajal. Salud Madrid. Comunidad de Madrid. |
