A penicillin and metronidazole resistant Clostridium botulinum strain responsible for an infant botulism case

Christelle Mazuet (1) , Eun-Jeong Yoon (2) , Sophie Boyer (3) , Stéphanie Pignier (4) , Thierry Blanc (5) , Isabelle Doehring (6) , Djalal Meziane-Cherif (2) , Clémentine Dumant-Forest (4) , Jean Sautereau (1) , Christine Legeay (1) , Philippe Bouvet (1) , Christiane Bouchier (7) , Suzana Quijano-Roy (8, 9, 6) , Martine Pestel-Caron (3) , Patrice Courvalin (2) , Michel R Popoff (1)

1 Bactéries anaérobies et Toxines
2 Agents antibactériens
3 GRAM 1.0 - Groupe de Recherche sur les Antimicrobiens et les Micro-Organismes
4 Service de pédiatrie médicale et médecine de l'adolescent [Rouen]
5 Service de pédiatrie néonatale et réanimation - neuropédiatrie [CHU Rouen]
6 Hôpital Raymond Poincaré [AP-HP]
7 Génomique (Plate-Forme) - Genomics Platform
8 END-ICAP - Handicap neuromusculaire : Physiopathologie, Biothérapie et Pharmacologies appliquées
9 FILNEMUS - Filière Neuromusculaire

An infant botulism clinical course was characterized by several relapses despite therapy with amoxicillin and metronidazole. Botulism was confirmed by identification of botulinum toxin and C. botulinum in stools. A C. botulinum A2 strain resistant to penicillins and with heterogeneous resistance to metronidazole was isolated from stool samples up to 110 days after onset. Antibiotic susceptibility was tested by disk agar diffusion and minimum inhibitory concentrations were determined by Etest. Whole genome sequencing allowed detection of a gene cluster composed of blaCBP for a novel penicillinase, blaI for a regulator, and blaR1 for a membrane bound penicillin receptor in the chromosome of the C. botulinum isolate. The purified recombinant penicillinase was assayed. Resistance to β-lactams was in agreement with the kinetic parameters of the enzyme. In addition, the β-lactamase gene cluster was found in three C. botulinum genomes in databanks and in two out of 62 genomes of our collection, all the strains belonging to group I C. botulinum. This is the first report of a C. botulinum isolate resistant to penicillins. This stresses the importance of antibiotic susceptibility testing for adequate therapy of botulism.

Keywords: infant botulism; botulism; Clostridium botulinum; antibiotic-resistance; penicillin; metronidazole

Domains: Bacteriology

Christelle Mazuet, Eun-Jeong Yoon, Sophie Boyer, Stéphanie Pignier, Thierry Blanc, et al.. A penicillin and metronidazole resistant Clostridium botulinum strain responsible for an infant botulism case. Clinical Microbiology and Infection, 2016, ⟨10.1016/j.cmi.2016.04.011⟩. ⟨pasteur-01325747⟩