Antibiotic therapy for snakebite envenoming

Resiere, Dabor; Gutiérrez, José Marı́a; Nevière, Rémi; Cabie, André; Mehdaoui, Hossein; Kallel, Hatem

doi:10.1590/1678-9199-jvatitd-2019-0098

Cited by 18 publications

(12 citation statements)

References 14 publications

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“…On the other hand, resistance to antibiotics in bacteria found in infections of snakebite patients ( López et al, 2008 ; Sachett et al, 2017 ) opens the debate on whether antibiotic treatment should be supplemented prophylactically, or whether instead, the infection should be confirmed first and antibiotic resistance testing requested in all cases before trying antibiotics ( Tagwireyi et al, 2001 ; Wagener et al, 2017 ). The prophylactic use of antibiotics has been recommended in cases when (a) there is objective evidence of infection, or (b) there is marked local tissue damage, which greatly favors infection ( Resiere et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

New insights into snakebite epidemiology in Costa Rica: A retrospective evaluation of medical records

Sasa

Cano

2020

Toxicon: X

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Continuous monitoring of the snakebite envenoming allows elucidating factors that affect its incidence at spatial and temporal scales, and is a great tool to evaluate the proper management of snakebite in health centers. To determine if there have been changes over time in snakebite epidemiology in Costa Rica, we conducted a retrospective study using medical records from six hospitals for the years 2012–2013. A total of 475 snakebite patients were treated at the selected hospital during this period. Most bites occurred during the rainy season and primarily affected young men, mainly farm workers and schoolchildren. About 55% of bites occur in peri-domiciliary environments, although its prevalence varies geographically. Bothrops asper generates the vast majority of envenoming in the country, which is why the main local symptoms registered are edema, pain, and bleeding disorders. The time elapsed until treatment did not explain the degree of severity at admission. However, complications were observed more frequently in patients who took longer to receive treatment. The primary complications were bacterial infections, whereas kidney failure and compartment syndrome documented at very low frequencies. Only one death was recorded, reflecting the low fatality rate exhibited in the country. Hospital treatment included the rapid administration of antivenom and complementary treatment of antibiotics, analgesics, and antihistamines. The application of the latter as prophylactic does not seem to prevent the appearance of mild early adverse reactions, registered in 22.5% of the cases. Morbidity and mortality rates from snakebite have continued to decrease in the country, as a result of the efforts that Costa Rica has made to improve its public health system. Among those efforts, the creation of primary care centers (EBAIS) has reduced the time to treatment in many regions of the country. The Costa Rican experience of using antivenom in primary health care centers and maintaining good medical records could be considered for application in other countries where snakebite is a major health problem.

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Section: Discussionmentioning

confidence: 99%

New insights into snakebite epidemiology in Costa Rica: A retrospective evaluation of medical records

Sasa

Cano

2020

Toxicon: X

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“…Consisting of immunoglobulins purified from hyperimmunized ovine or equine plasma/serum, these products save thousands of lives each year, but are associated with a number of therapeutic challenges, including limited cross-snake species efficacies, poor safety profiles and, for many snakebite victims residing in remote rural areas in developing countries, unacceptable issues with affordability and accessibility [17]. Small molecule toxin inhibitors are regarded as promising candidates for the development of affordable broad-spectrum snakebite treatments, as these can block the enzymatic activities of venoms [18][19][20]. Varespladib, an indole-based nonspecific pan-secretory PLA 2 inhibitor has been studied extensively for repurposing for snakebite.…”

Section: Introductionmentioning

confidence: 99%

Neutralizing Effects of Small Molecule Inhibitors and Metal Chelators on Coagulopathic Viperinae Snake Venom Toxins

et al. 2020

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Animal-derived antivenoms are the only specific therapies currently available for the treatment of snake envenoming, but these products have a number of limitations associated with their efficacy, safety and affordability for use in tropical snakebite victims. Small molecule drugs and drug candidates are regarded as promising alternatives for filling the critical therapeutic gap between snake envenoming and effective treatment. In this study, by using an advanced analytical technique that combines chromatography, mass spectrometry and bioassaying, we investigated the effect of several small molecule inhibitors that target phospholipase A2 (varespladib) and snake venom metalloproteinase (marimastat, dimercaprol and DMPS) toxin families on inhibiting the activities of coagulopathic toxins found in Viperinae snake venoms. The venoms of Echis carinatus, Echis ocellatus, Daboia russelii and Bitis arietans, which are known for their potent haemotoxicities, were fractionated in high resolution onto 384-well plates using liquid chromatography followed by coagulopathic bioassaying of the obtained fractions. Bioassay activities were correlated to parallel recorded mass spectrometric and proteomics data to assign the venom toxins responsible for coagulopathic activity and assess which of these toxins could be neutralized by the inhibitors under investigation. Our results showed that the phospholipase A2-inhibitor varespladib neutralized the vast majority of anticoagulation activities found across all of the tested snake venoms. Of the snake venom metalloproteinase inhibitors, marimastat demonstrated impressive neutralization of the procoagulation activities detected in all of the tested venoms, whereas dimercaprol and DMPS could only partially neutralize these activities at the doses tested. Our results provide additional support for the concept that combinations of small molecules, particularly the combination of varespladib with marimastat, serve as a drug-repurposing opportunity to develop new broad-spectrum inhibitor-based therapies for snakebite envenoming.

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“…Although current snakebite treatments, known as antivenoms (equine/ovine polyclonal antibodies), can be effective therapies capable of reducing morbidity and mortality, they have many limitations associated with them, leaving a critical therapeutic gap between snakebite and effective treatment [6,12]. Small molecule toxin inhibitor-based approaches are gaining much traction as promising alternatives and/or complementary treatments for snakebite [12][13][14][15][16], as they show a number of characteristics desirable for use as either early prehospital or adjunct therapies [13].…”

Section: Introductionmentioning

confidence: 99%

Varespladib Inhibits the Phospholipase A2 and Coagulopathic Activities of Venom Components from Hemotoxic Snakes

et al. 2020

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Phospholipase A2 (PLA2) enzymes are important toxins found in many snake venoms, and they can exhibit a variety of toxic activities including causing hemolysis and/or anticoagulation. In this study, the inhibiting effects of the small molecule PLA2 inhibitor varespladib on snake venom PLA2s was investigated by nanofractionation analytics, which combined chromatography, mass spectrometry (MS), and bioassays. The venoms of the medically important snake species Bothrops asper, Calloselasma rhodostoma, Deinagkistrodon acutus, Daboia russelii, Echis carinatus, Echis ocellatus, and Oxyuranus scutellatus were separated by liquid chromatography (LC) followed by nanofractionation and interrogation of the fractions by a coagulation assay and a PLA2 assay. Next, we assessed the ability of varespladib to inhibit the activity of enzymatic PLA2s and the coagulopathic toxicities induced by fractionated snake venom toxins, and identified these bioactive venom toxins and those inhibited by varespladib by using parallel recorded LC-MS data and proteomics analysis. We demonstrated here that varespladib was not only capable of inhibiting the PLA2 activities of hemotoxic snake venoms, but can also effectively neutralize the coagulopathic toxicities (most profoundly anticoagulation) induced by venom toxins. While varespladib effectively inhibited PLA2 toxins responsible for anticoagulant effects, we also found some evidence that this inhibitory molecule can partially abrogate procoagulant venom effects caused by different toxin families. These findings further emphasize the potential clinical utility of varespladib in mitigating the toxic effects of certain snakebites.

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Antibiotic therapy for snakebite envenoming

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.

Cited by 18 publications

References 14 publications

New insights into snakebite epidemiology in Costa Rica: A retrospective evaluation of medical records

New insights into snakebite epidemiology in Costa Rica: A retrospective evaluation of medical records

Neutralizing Effects of Small Molecule Inhibitors and Metal Chelators on Coagulopathic Viperinae Snake Venom Toxins

Varespladib Inhibits the Phospholipase A2 and Coagulopathic Activities of Venom Components from Hemotoxic Snakes

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