A penicillin- and metronidazole-resistant Clostridium botulinum strain responsible for an infant botulism case.
The clinical course of a case of infant botulism was characterized by several relapses despite therapy with amoxicillin and metronidazole. Botulism was confirmed by identification of botulinum toxin and Clostridium 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 disc agar diffusion and MICs 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 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.
Unité des Bactéries anaérobies et Toxines, Institut Pasteur, Paris, France.
C
C
Mazuet
Unité des Agents Antibactériens, Institut Pasteur, Paris, France.
E-J
EJ
Yoon
Département de Microbiologie, Hôpital Charles Nicolle, Rouen, France.
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S
Boyer
Pédiatrie médicale, Hôpital Charles Nicolle, Rouen, France.
S
S
Pignier
Pédiatrie néonatale et réanimation, Hôpital Charles Nicolle, Rouen, France.
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T
Blanc
AP-HP, Service de Pédiatrie-Réanimation, Pôle Pédiatrique, Hôpital R. Poincaré, Garches, Hôpitaux Universitaires Paris-Ile-de-France Ouest, France.
I
I
Doehring
Unité des Agents Antibactériens, Institut Pasteur, Paris, France.
D
D
Meziane-Cherif
Pédiatrie médicale, Hôpital Charles Nicolle, Rouen, France.
C
C
Dumant-Forest
Unité des Bactéries anaérobies et Toxines, Institut Pasteur, Paris, France.
J
J
Sautereau
Unité des Bactéries anaérobies et Toxines, Institut Pasteur, Paris, France.
C
C
Legeay
Unité des Bactéries anaérobies et Toxines, Institut Pasteur, Paris, France.
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P
Bouvet
Plateforme Genomique-Pôle Biomics, Institut Pasteur, Paris, France.
C
C
Bouchier
AP-HP, Service de Pédiatrie-Réanimation, Pôle Pédiatrique, Hôpital R. Poincaré, Garches, Hôpitaux Universitaires Paris-Ile-de-France Ouest, France; Centre de Référence des Maladies Neuromusculaires GNMH (FILNEMUS), France.
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S
Quijano-Roy
Département de Microbiologie, Hôpital Charles Nicolle, Rouen, France.
M
M
Pestel-Caron
Unité des Agents Antibactériens, Institut Pasteur, Paris, France.
P
P
Courvalin
Unité des Bactéries anaérobies et Toxines, Institut Pasteur, Paris, France. Electronic address: michel-robert.popoff@pasteur.fr.
M R
MR
Popoff
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001905:Botulinum Toxins / Q000032:analysis; D001906:Botulism / Q000175:diagnosis* / Q000188:drug therapy / Q000382:microbiology* / Q000473:pathology; D003014:Clostridium botulinum / Q000187:drug effects* / Q000302:isolation & purification*; D024881:Drug Resistance, Bacterial; D005243:Feces / Q000737:chemistry / Q000382:microbiology; D005260:Female; D005809:Genes, Regulator; D016680:Genome, Bacterial; D006801:Humans; D007223:Infant; D026901:Membrane Transport Proteins / Q000235:genetics; D008795:Metronidazole / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D005810:Multigene Family; D010405:Penicillinase / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D010406:Penicillins / Q000494:pharmacology*; D017422:Sequence Analysis, DNA
D000900:Anti-Bacterial Agents; D026901:Membrane Transport Proteins; D010406:Penicillins; D008795:Metronidazole; D001905:Botulinum Toxins; D010405:Penicillinase
Antibiotic-resistance; Botulism; Clostridium botulinum; Infant botulism; Metronidazole; Penicillin