The (bug) juice ain’t worth the squeeze

Starting antibiotics or antihistamines are two common ways snakebites are mismanaged.

Spencer Greene, MD, MS, FACEP, FACMT, FAACT, FAAEM •

As I have documented many times previously, snakebites often go mismanaged by healthcare professionals who are unfamiliar with envenomations. While the most frequent mistakes of omission are failure to monitor patients long enough and failure to treat with antivenom when it is indicated, common mistakes of commission are attempting to treat the envenomation with antihistamines and administering unnecessary antibiotics.

I often hear people say, “Anything with a mouth can bite, and any bite can cause an infection” but to me this is as preposterous as the famous line from the movie Meet the Parents, in which Ben Stiller’s character proclaims, “You can milk anything with nipples.” Yes, a snakebite CAN become infected. But this occurs rarely. How rarely? In a study of 53 rattlesnake envenomations out of Phoenix, there were zero documented infections. None. Nada. Three (6%) patients did receive prophylactic antibiotics from their primary care providers.

A huge study of 2748 rattlesnake bite patients conducted at the University of Arizona identified 27 (0.98%) post-bite infections, often after the victims themselves manipulated the wound. Furthermore, of the microorganisms isolated from nine patients, only one (Salmonella sp.) was of reptilian origin.

My colleagues and I looked at infections and antibiotic usage using data from the North American Snakebite Registry. We found that 32 (11%) of 280 snakebite patients received at least one dose of antibiotics, but only two had documented infection, one of which was pre-existing. Another patient who was not treated with antibiotics but whose wound was incised and who did receive prednisolone subsequently developed an infection.

Finally, a prospective controlled trial of 114 crotalid envenomations in Ecuador found no significant difference in outcomes between patients who received prophylactic antibiotics and those who did not.

There are additional studies that make the same point, but I am restrained by a word limit.

It is clear that infection following snakebite is really uncommon, and there is no need to start antibiotics prophylactically. Some people may ask what the harm is in prescribing them, “just in case.” There are actually several potential dangers. First, people can have allergic reactions, some of which can be severe. Other side effects, including, but not limited to, diarrhea, QT prolongation, and tendinopathy, are reported. Some antibiotics have significant drug interactions with other medications. Unnecessary antibiotics also lead to unnecessary costs.

Furthermore, it is well-established that indiscriminate use of antibiotics can contribute to antibiotic resistance, which can have serious long-term implications in our efforts to treat bacterial illnesses.

Finally, it has been demonstrated that some antibiotics can potentiate certain venom components! Imagine that! You start antibiotics for a snakebite, and you end up directly exacerbating the envenomation.

So, are antibiotics EVER necessary? Yes. But only if there is a documented soft tissue infection. Otherwise, the risks (low, but not zero) clearly outweigh the benefits (essentially zero.)


Now let’s talk about antihistamines.

It seems like some of the most viral posts on social media over the past few snakebite seasons were “testimonials” of how diphenhydramine is helpful in treating snake envenomation in humans and pets. However, post shares and retweets are not substitutes for evidence.

We know that snake venom is complex. Histamine, however, is not a particularly clinically significant factor in snake envenomation, and antagonizing its effects provides no particular benefit. Some people may argue that there is no harm in treating patients with antihistamines. But that is not exactly true. First, diphenhydramine can cause sedation, and I am aware of at least one case where a snakebite victim was too drowsy to provide important medical information to the team treating him. My bigger concern is that some people may mistakenly believe that antihistamines are a safe, cheap alternative to antivenom following snakebite and, as a result, fail to seek timely medical attention for themselves or a loved one. Hopefully the Reuters story has educated people.

Are antihistamines ever helpful in snakebite? Yes, if there is an allergic reaction to antivenom – which is rare – or to the venom itself, which is even more uncommon. But remember: severe allergic reactions require epinephrine. Antihistamines won’t suffice.

The definitive treatment for a snake envenomation is antivenom. You can read about emergency department snakebite management here.

Dr. Greene is a paid consultant for BTG International Inc.

Spencer Greene, MD, MS, FACEP, FACMT, FAACT, FAAEM is a board-certified medical toxicologist and emergency physician. He currently serves as the Director of Toxicology and an attending emergency physician at HCA Houston Healthcare-Kingwood. He is a Clinical Professor at the University of Houston College of Medicine. Dr. Greene is a recognized expert in the management of snake envenomation in the US. He has treated more than 1000 snakebites at the bedside and has authored more than 50 scholarly articles and book chapters. He has also served as the course director for the Houston Venom Conference since 2013.


CroFab® Crotalidae Polyvalent Immune Fab (Ovine) is a sheep-derived antivenin indicated for the management of adult and pediatric patients with North American crotalid envenomation. The term crotalid is used to describe the Crotalinae subfamily (formerly known as Crotalidae) of venomous snakes which includes rattlesnakes, copperheads and cottonmouths/water moccasins.



Do not administer CroFab® to patients with a known history of hypersensitivity to any of its components, or to papaya or papain unless the benefits outweigh the risks and appropriate management for anaphylactic reactions is readily available.


Coagulopathy: In clinical trials, recurrent coagulopathy (the return of a coagulation abnormality after it has been successfully treated with antivenin), characterized by decreased fibrinogen, decreased platelets, and elevated prothrombin time, occurred in approximately half of the patients studied; one patient required re-hospitalization and additional antivenin administration. Recurrent coagulopathy may persist for 1 to 2 weeks or more. Patients who experience coagulopathy due to snakebite should be monitored for recurrent coagulopathy for up to 1 week or longer. During this period, the physician should carefully assess the need for re-treatment with CroFab® and use of any type of anticoagulant or anti-platelet drug.

Hypersensitivity Reactions: Severe hypersensitivity reactions may occur with CroFab®. In case of acute hypersensitivity reactions, including anaphylaxis and anaphylactoid reactions, discontinue infusion and institute appropriate emergency treatment. Patients allergic to papain, chymopapain, other papaya extracts, or the pineapple enzyme bromelain may also have an allergic reaction to CroFab®. Follow-up all patients for signs and symptoms of delayed allergic reactions or serum sickness (e.g., rash, fever, myalgia, arthralgia).


The most common adverse reactions (incidence ≥ 5% of subjects) reported in the clinical studies were urticaria, rash, nausea, pruritus and back pain. Adverse reactions involving the skin and appendages (primarily rash, urticaria, and pruritus) were reported in 12 of the 42 patients. Two patients had a severe allergic reaction (severe hives and a severe rash and pruritus) following treatment and one patient discontinued CroFab® due to an allergic reaction. Recurrent coagulopathy due to envenomation and requiring additional treatment may occur.

Please see full Prescribing Information.

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