Susceptibility of C botulinum and C baratii to Antimicrobials

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The researchers were unable to identify an antimicrobial to which <i>C botulinum</i> and neurotoxigenic <i>C baratii</i> were consistently resistant.
The researchers were unable to identify an antimicrobial to which C botulinum and neurotoxigenic C baratii were consistently resistant.

Nearly all isolates from infants with botulism in California are susceptible both to commonly used antibiotics and to newer antibiotics not yet tested against large numbers of Clostridium botulinum isolates, according to data published in Antimicrobial Agents and Chemotherapy.

Botulism, usually caused by C botulinum, is often misdiagnosed as a condition such as sepsis that requires immediate antimicrobial therapy. However, this can lead to lysing of the C botulinum vegetative cells in the large bowel and increases in the amount of botulinum neurotoxin absorbed by patients. Therefore, an antibiotic susceptibility test was used to find an antimicrobial with little to no activity against C botulinum that could be used to treat infants with botulism initially diagnosed with sepsis or meningitis, or who had acquired secondary infections.

A total of 260 botulinum-neurotoxin-producing strains of Clostridium isolated from patients in California were included in the study. The most common strain was type A (n=156), followed by proteolytic C botulinum type B (n=89). Other strains included were type Ba bivalent (n=12), type Bf bivalent (n=2), neurotoxigenic C baratii type F (n=1), as well as C baratii type F strains isolated from 2 non-Californian patients and 1 adult Californian patient. The minimum inhibitory concentrations of 12 antimicrobials were assessed.

Almost all the Californian strains showed susceptibility to the 12 antimicrobials tested: amoxicillin-clavulanic acid (2/1), ampicillin, cefepime, cefotaxime, ceftriaxone, cefuroxime, gentamicin, moxifloxacin, nalidixic acid, penicillin, trimethoprim-sulfamethoxazole (1/19), and vancomycin.

A single strain of type A demonstrated substantial resistance to ampicillin and penicillin. Ceftriaxone had the greatest activity of all the cephalosporins tested, meaning patients treated with cephalosporins, and especially ceftriaxone, are at risk for paralysis from increased botulinum neurotoxin. No differences in susceptibility between type A and B or between strains from different geographical regions were found. The susceptibilities of bivalent strains Ba and Bf were comparable.

Overall, the researchers were unable to identify an antimicrobial to which C botulinum and neurotoxigenic C baratii were consistently resistant. According to investigators, these results demonstrated the importance of treating infants with botulism with human botulism immune globulin because of its large toxin-neutralizing capacity and long half-life. If patients are treated with botulism immune globulin before the use of antibiotics or shortly thereafter, physicians may then choose the optimal antibiotic treatment without concern for the susceptibility of C botulinum.

Reference

Barash JR, Castles JB 3rd, Arnon SS.  Antimicrobial susceptibility of 260 Clostridium botulinum types A, B, Ba and Bf strains and a neurotoxigenic Clostridium baratii type F strain isolated from California infant botulism patients [published online October 1, 2018]. Antimicrob Agents Chemother. doi: 10.1128/AAC.01594-18

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