Antibiotic therapy for snakebite envenoming

Dabor Resiere José María Gutiérrez Rémi Névière André Cabié Mehdaoui Hossein Hatem Kallel About the authors

Abstract

There are numerous conflicting recommendations available on the use of antibiotics following snakebite. The present letter to the editor presents some recommendations based on recent studies, and aims to stimulate debate on this topic.

Dear Editor,

According to international guidelines amoxicillin-clavulanate is recommended to prevent secondary infections from animal bites [11. Stevens DL, Bisno AL, Chambers HF, Dellinger EP, Goldstein EJC, Gorbach SL, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the infectious diseases society of America. Clin Infect Dis. 2014;59:147-59. ]. However, the systematic antibiotic administration after snakebite is questionable. Most authors recommend antibiotics for severely bitten patients or when inflammatory signs are suggestive of infection. Interestingly, empiric amoxicillin-clavulanate use was shown to be ineffective in preventing secondary infections after snakebites, because of the resistance to β-lactam antibiotics in the bacterial species commonly found infecting snakebite site [22. Sachett JAG, da Silva IM, Alves EC, Oliveira SS, Sampaio VS, do Vale FF, et al. Poor efficacy of preemptive amoxicillin clavulanate for preventing secondary infection from Bothrops snakebites in the Brazilian Amazon: A randomized controlled clinical trial. PLoS Negl Trop Dis. 2017;11(7):e0005745. ]. Recently, analysis of the antibiotic susceptibility of bacteria isolated from Bothrops lanceolatus mouth showed 67% of strains resistant to amoxicillin-clavulanate, whereas the majority of isolated bacteria were susceptible to third-generation cephalosporins [3].

Wound infection following snakebite usually accounts for 9 to 77% of the bitten patients, as described in several studies [22. Sachett JAG, da Silva IM, Alves EC, Oliveira SS, Sampaio VS, do Vale FF, et al. Poor efficacy of preemptive amoxicillin clavulanate for preventing secondary infection from Bothrops snakebites in the Brazilian Amazon: A randomized controlled clinical trial. PLoS Negl Trop Dis. 2017;11(7):e0005745. , 44. Garg A, Sujatha S, Garg J, Acharya NS, Chandra Parija S. Wound infections secondary to snakebite. J Infect Dev Ctries. 2009;3:221-3.

5. Wagener M, Naidoo M, Aldous C. Wound infection secondary to snakebite. S Afr Med J. 2017;107(4):315-9.

6. Mao Y-C, Liu P-Y, Hung D-Z, Lai W-C, Huang S-T, Hung Y-M, et al. Bacteriology of Naja atra snakebite wound and its implications for antibiotic therapy. Am J Trop Med Hyg. 2016;94:1129-35.

7. Chen C-M, Wu K-G, Chen C-J, Wang C-M. Bacterial infection in association with snakebite: a 10-year experience in a northern Taiwan medical center. J Microbiol Immunol Infect. 2011;44(6):456-60.
-88. Hsieh Y-H, Hsueh J-H, Liu W-C, Yang K-C, Hsu K-C, Lin C-T, et al. Contributing factors for complications and outcomes in patients with snakebite: experience in a medical center in southern Taiwan. Ann Plast Surg. 2017;78(3 Suppl 2):S32-S36.]. The large differences in the reported prevalence of secondary infections in snakebites can be related to variations in the criteria used to establish the presence of infection. Indeed, there is no precise set of clinical criteria to define infection in snakebite envenomings. In addition, a high proportion of microbiological cultures are negative because of systematic preemptive use of antibiotics in snake bitten patients. The main involved bacteria are Enterococcus faecalis, Aeromonas hydrophila and Morganella morganii [22. Sachett JAG, da Silva IM, Alves EC, Oliveira SS, Sampaio VS, do Vale FF, et al. Poor efficacy of preemptive amoxicillin clavulanate for preventing secondary infection from Bothrops snakebites in the Brazilian Amazon: A randomized controlled clinical trial. PLoS Negl Trop Dis. 2017;11(7):e0005745. , 44. Garg A, Sujatha S, Garg J, Acharya NS, Chandra Parija S. Wound infections secondary to snakebite. J Infect Dev Ctries. 2009;3:221-3.

5. Wagener M, Naidoo M, Aldous C. Wound infection secondary to snakebite. S Afr Med J. 2017;107(4):315-9.

6. Mao Y-C, Liu P-Y, Hung D-Z, Lai W-C, Huang S-T, Hung Y-M, et al. Bacteriology of Naja atra snakebite wound and its implications for antibiotic therapy. Am J Trop Med Hyg. 2016;94:1129-35.

7. Chen C-M, Wu K-G, Chen C-J, Wang C-M. Bacterial infection in association with snakebite: a 10-year experience in a northern Taiwan medical center. J Microbiol Immunol Infect. 2011;44(6):456-60.

8. Hsieh Y-H, Hsueh J-H, Liu W-C, Yang K-C, Hsu K-C, Lin C-T, et al. Contributing factors for complications and outcomes in patients with snakebite: experience in a medical center in southern Taiwan. Ann Plast Surg. 2017;78(3 Suppl 2):S32-S36.
-99. Resiere D, Mehdaoui H, Névière R, Olive C, Severyns M, Beaudoin A, et al. Infectious complications following snakebite by Bothrops lanceolatus in Martinique: a case series. Am J Trop Med Hyg. Forthcoming 2019. doi: 10.4269/ajtmh.
https://doi.org/10.4269/ajtmh...
].

The snake mouth is colonized by bacteria that can be transmitted to the bitten patient through the skin injury associated with the bite [33. Résière D, Olive C, Kallel H, Cabié A, Névière R, Mégarbane B, et al. Oral microbiota of the snake Bothrops lanceolatus in Martinique. Int J Environ Res Public Health. 2018;15(10):2122., 1010. Barbosa LN, Ferreira Jr RS, Luiza Mello P, Garcia Garces H, Luana Chechi J, Frachin T, et al. Molecular identification and phylogenetic analysis of Bothrops insularis bacterial and fungal microbiota. J Toxicol Environ Health A. 2018;81(6):142-53.

11. Campagner MV, Bosco SMG, Bagagli E, Cunha MLRS, Jeronimo BC, Saad E, et al. Microbiological evaluation of different strategies for management of snakes in captivity. J Toxicol Environ Health A. 2012;75(16-17):1070-80.
-1212. Krishnankutty SP, Muraleedharan M, Perumal RC, Michael S, Benny J, Balan B, et al. Next-generation sequencing analysis reveals high bacterial diversity in wild venomous and non-venomous snakes from India. J Venom Anim Toxins incl Trop Dis. 2018;24:41. doi: 10.1186/s40409-018-0181-8.
https://doi.org/10.1186/s40409-018-0181-...
]. Inoculation of bacteria from the mouth, fangs, or venom following snakebite can cause local infection with abscess and necrotizing fasciitis in most severe cases [1313. Lam KK, Crow P, Ng KHL, Shek KC, Fung HT, Ades G, et al. A cross-sectional survey of snake oral bacterial flora from Hong Kong, SAR, China. Emerg Med J. 2011;28(2):107-14.]. In one recent study, isolated Enterobacteriaceae following snake bite infection showed 69% resistance to ampicillin, 60% resistance to amoxicillin/clavulanate, and 66% resistance to second-generation cephalosporins [1313. Lam KK, Crow P, Ng KHL, Shek KC, Fung HT, Ades G, et al. A cross-sectional survey of snake oral bacterial flora from Hong Kong, SAR, China. Emerg Med J. 2011;28(2):107-14.]. Conformingly, our experimental study examining the bacteria sampled from the oral cavity of 26 B. lanceolatus specimens collected from various areas in Martinique supported that 67% of the isolated bacteria were resistant to amoxicillin/clavulanate. In addition, the majority of isolated bacteria were susceptible to third-generation cephalosporins (i.e., 73% to cefotaxime and 80% to ceftazidime) [33. Résière D, Olive C, Kallel H, Cabié A, Névière R, Mégarbane B, et al. Oral microbiota of the snake Bothrops lanceolatus in Martinique. Int J Environ Res Public Health. 2018;15(10):2122.]. Based on the most frequently isolated bacteria and susceptibility profiles documented in cases of infection after snakebite, active antibiotics include third generation cephalosporins, piperacillin-tazobactam and ciprofloxacin.

In conclusion, preemptive antibiotic administration in snake-bitten patients should be considered only in those with severe local signs of envenomation, and empiric one in those having local or general signs of infection, regardless of the degree of envenoming. The most appropriate empirical antibiotics are third generation cephalosporins. Empirical amoxicillin-clavulanate should no longer be used in this context.

References

  • 1. Stevens DL, Bisno AL, Chambers HF, Dellinger EP, Goldstein EJC, Gorbach SL, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the infectious diseases society of America. Clin Infect Dis. 2014;59:147-59.
  • 2. Sachett JAG, da Silva IM, Alves EC, Oliveira SS, Sampaio VS, do Vale FF, et al. Poor efficacy of preemptive amoxicillin clavulanate for preventing secondary infection from Bothrops snakebites in the Brazilian Amazon: A randomized controlled clinical trial. PLoS Negl Trop Dis. 2017;11(7):e0005745.
  • 3. Résière D, Olive C, Kallel H, Cabié A, Névière R, Mégarbane B, et al. Oral microbiota of the snake Bothrops lanceolatus in Martinique. Int J Environ Res Public Health. 2018;15(10):2122.
  • 4. Garg A, Sujatha S, Garg J, Acharya NS, Chandra Parija S. Wound infections secondary to snakebite. J Infect Dev Ctries. 2009;3:221-3.
  • 5. Wagener M, Naidoo M, Aldous C. Wound infection secondary to snakebite. S Afr Med J. 2017;107(4):315-9.
  • 6. Mao Y-C, Liu P-Y, Hung D-Z, Lai W-C, Huang S-T, Hung Y-M, et al. Bacteriology of Naja atra snakebite wound and its implications for antibiotic therapy. Am J Trop Med Hyg. 2016;94:1129-35.
  • 7. Chen C-M, Wu K-G, Chen C-J, Wang C-M. Bacterial infection in association with snakebite: a 10-year experience in a northern Taiwan medical center. J Microbiol Immunol Infect. 2011;44(6):456-60.
  • 8. Hsieh Y-H, Hsueh J-H, Liu W-C, Yang K-C, Hsu K-C, Lin C-T, et al. Contributing factors for complications and outcomes in patients with snakebite: experience in a medical center in southern Taiwan. Ann Plast Surg. 2017;78(3 Suppl 2):S32-S36.
  • 9. Resiere D, Mehdaoui H, Névière R, Olive C, Severyns M, Beaudoin A, et al. Infectious complications following snakebite by Bothrops lanceolatus in Martinique: a case series. Am J Trop Med Hyg. Forthcoming 2019. doi: 10.4269/ajtmh.
    » https://doi.org/10.4269/ajtmh
  • 10. Barbosa LN, Ferreira Jr RS, Luiza Mello P, Garcia Garces H, Luana Chechi J, Frachin T, et al. Molecular identification and phylogenetic analysis of Bothrops insularis bacterial and fungal microbiota. J Toxicol Environ Health A. 2018;81(6):142-53.
  • 11. Campagner MV, Bosco SMG, Bagagli E, Cunha MLRS, Jeronimo BC, Saad E, et al. Microbiological evaluation of different strategies for management of snakes in captivity. J Toxicol Environ Health A. 2012;75(16-17):1070-80.
  • 12. Krishnankutty SP, Muraleedharan M, Perumal RC, Michael S, Benny J, Balan B, et al. Next-generation sequencing analysis reveals high bacterial diversity in wild venomous and non-venomous snakes from India. J Venom Anim Toxins incl Trop Dis. 2018;24:41. doi: 10.1186/s40409-018-0181-8.
    » https://doi.org/10.1186/s40409-018-0181-8
  • 13. Lam KK, Crow P, Ng KHL, Shek KC, Fung HT, Ades G, et al. A cross-sectional survey of snake oral bacterial flora from Hong Kong, SAR, China. Emerg Med J. 2011;28(2):107-14.

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Publication Dates

  • Publication in this collection
    03 Feb 2020
  • Date of issue
    2020

History

  • Received
    06 Dec 2019
  • Accepted
    12 Dec 2019
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