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J. Venom. Anim. Toxins vol. 3 n. 2 Botucatu 1997
INFECTIONS IN THE BITE SITE AFTER ENVENOMING BY SNAKES OF THE Bothrops GENUS
1 Department of Internal Medicine of the Center of Biomedical Sciences of the Federal University of Uberlândia, state of Minas Gerais, Brazil.
ABSTRACT. Envenomation caused by snakes of the Bothrops genus produces a lesion in the bite site and can result in extensive necrosis. The dead tissue can be secondarily infected by bacteria that come from the snake, and the bacteria can be inoculated at the moment of the bite. The bacteria that most commonly cause infection are the enterobacteria, mainly Morganella morganii, Proteus rettgeri, Enterobacter sp., and Escherichia coli. Group D streptococci including here Enterococcus sp. and the Bacteroides sp. are also involved. Based on a study of the sensibility of these bacteria, it has been suggested that this infection must be treated with chloramphenicol, as a sole antimicrobial agent, or with the combinations of benzylpenicillin or ampicillin with aminoglycoside or trimethoprim/sulfamethoxazole. Although Governmental Health Services do not recommend the prophylactic use of antimicrobial drugs, it is not yet clear that such a procedure would not be useful in cases with a high probability of infection.
KEY WORDS: snakebite, Bothrops, infection, antimicrobial agents, treatment.
GENERAL ASPECTS: Brazilian venomous snakes belong to the Viperidae and Elipidae families, and only Crotalinae (Bothrops, Lachesis and Crotalus genera) belong to the Viperidae family. Species of the Bothrops genus are distributed almost all over Brazil(6,13). Viperidae snakes are solenoglyphic, i.e, they have distinguishable inoculating fangs with ducts from which the venom is ejected through a "subterminal" orifice. When the snake is resting, the fangs lie along the upper jaw and are covered by a mucous membrane. The snake projects the front part of its body against its prey or aggressor and then the fangs move forward at the moment of the bite. They can deeply inoculate a great amount of venom, as if they were like the needle and syringe of an injection(3,8,10,38). These are the snakes best adapted for biting.
EPIDEMIOLOGY: Over 20,000 snake envenomations occur every year in Brazil and more than 80% of these accidents are caused by Bothrops(30,31). Over 2,000 cases occur annually in the state of São Paulo and about 85% of them are caused by Bothrops(36).
PHYSIOPATHOLOGY OF THE ENVENOMATION: Bothropic venom has three principal activities: a) proteolytic or necrotic activity responsible for the inflammation and necrosis in the bite site(8,38,41); b) hemorrhagic activity, produced by at least three already isolated metalloproteins which cause the outflow of blood from the capillary vessels to the interstices(1,4,26). This can cause purpura and ecchymosis in the bite site, apart from its coagulating action(19). The venom also seems to act systemically, participating in manifestations such as bleeding of the gums(7,17,24,25,40); c) coagulating activity responsible for the coagulation factor waste such as fibrinogen deficit that could cause blood incoagulability(17,38,41). Depending on the snake species, the venom activates the X factor and/or prothrombin and/or fibrinogen (thrombin-like action)(27).
CLINICAL MANIFESTATIONS: The bite caused by Bothrops snake is followed by edema of variable intensity that increases mainly on the first day(8,17,39,41). The edema shows a violet color or may be accompanied by extensive ecchymosis(38,39). Blisters can appear, mainly in cases where there is a major tissue destruction(32). Although most bites can heal without leaving sequelae(10,34,38), in some cases the damaged tissue presents necrosis which in turn can be secondarily infected. This infection generally manifests itself through abscesses that can sometimes be quite large. In these cases, functional disorders can occur or even the amputation of the affected member would be necessary. Systemically, disturbances in coagulation and bleeding commonly occur(19,33). The red blood cell counting shows leukocytosis with neutrophil preponderance with a shift to the left(38,39), which seems to be due to the acute-phase reaction(5). The presence of inflammatory signs in the bite site, and of leukocytosis with a shift to the left, both caused by the venom itself, make the diagnosis of infection difficult.
THE IMPORTANCE OF INFECTION IN BOTHROPIC ENVENOMATION: Different studies have shown that the percentage of patients who are bitten by Bothrops snakes and who develop infection in the bite site is variable and this seems to depend on the species of the snake which most frequently causes the accidents(19). The occurrence of infection is as low as 1.0% in Natal, state of Rio Grande do Norte, where envenomation caused by B. erythromelas seems to predominate(46), and as high as 15.7% in Goiânia, state of Goiás(2), where B. moojeni seems to predominate(44). In São Paulo, state of São Paulo, where envenomation caused by B. jararaca predominates, abscesses occurred in 9% among 1,984 patients(21).
Considering that over 20,000 snake envenomation cases occur every year in Brazil, that over 80% of them are caused by Bothrops(30,31) and that for calculation effects, the diverse snakes of this genus cause envenomation which frequently evolve to abscesses like those found in HVB-IB (Vital Brazil Hospital of Butantan Institute) (9%), about 1,500 cases of this complication (bothropic envenomations) may occur every year in Brazil.
BACTERIA RESPONSIBLE FOR THE INFECTION: Although the course evolution of bothropic bites is often accompanied by abscess formation, until recently very little was known about the bacteria responsible for this inflammation. In Bahia, Teixeira(45), refers to a mixed flora made up mainly of Gram-negative bacteria and also anaerobics whose participation in the process is suggested "by the physical characteristics and the odor of the purulent secretion"(45). In Rio de Janeiro, Galvão(11), found capsuled Gram-positive diplococci, Gram-positive cocci, and Trichomonas sp. in the material obtained by aspirative puncture(11). In São Paulo, Rosa et al.(37), detected Staphylococcus aureus, Streptococcus faecalis as well as also bacteria of the Clostridium genus, including C. histolyticum, in the abscesses of 14 patients (37). In São Paulo, in a first study, Jorge et al.(15) found Morganella morganii (3 cases), Proteus sp. (2 cases) and Bacterioides sp. (2 cases) in five abscesses, and in a second study(22), M. morganii (10 cases), Escherichia coli (4 cases), Proteus rettgeri (3 cases), group D estreptococci (3 cases) and Streptococcus viridans (1 case) in 15 abscesses. In Goiás, Andrade et al.(2), found mainly, M. morganii (44 cases), E. coli (20 cases), Providencia sp. (13 cases), Klebsiela sp. (10 cases), Alcaligenes sp. (9 cases), Enterobacter sp. (8 cases), S. aureus (8 cases), and S. epidermidis (7 cases) in 99 abscesses(2). In Minas Gerais, Nishioka and Silveira (28), found E. coli (5 cases), M. morganii (2 cases) and Citrobacter diversus (2 cases) in 18 abscesses.
These studies are retrospective and/or are obtained from cultures of materials from previously opened lesions, and/or are based on the results of cultures which were examined only for aerobic bacteria.
More recently, in São Paulo, in a prospective study, Jorge et al.(23) aseptically punctured the closed abscesses of 40 patients bitten by bothropic snakes, mainly B. jararaca. They performed bacterioscopy and culture for aerobic and anaerobic organisms and isolated M. morganii (23 cases), P. rettgeri (7 cases), Enterobacter sp. (4 cases), E. coli (3 cases), Citrobacter freundi (1 case), group D estreptococci (11 cases), S. aureus (2 cases), S. viridans (1 case) and Bacteroides sp. (6 cases)(23).
ORIGINS OF THE BACTERIA: Various origins for the bacteria in the site of the venomous snakebite have been considered. The victim's clothes and skin which were pierced through by the fangs of the snake, the substances applied to the region of the bite, the cutting or puncturing instruments used in the attempt to facilitate the sucking out of some of the venom and the saliva of the person who did the sucking are all possible sources of the infection. In hospitalized patients, bacteria from the hospital itself could contaminate the lesion and cause the infection.
Prospective studies have shown that the inoculating fangs of the snake pierce the victim's clothes in percentages as low as 4.3% in São Paulo and as high as 26.7% in Uberlândia (29,35,43). Although the fangs have to pass through the victim's skin before penetrating into the deep tissues, bacteria such as Streptococcus pyogenes and S. aureus, commonly found in the human skin(9), are rarely reported to be present in the abscesses(2,15,22,28). The substances applied to the bite site, the frequency that they are applied as well as the frequency that the patients lesion the bite site and try to suck out the venom are not well known in the various parts of the country. An incision or perforation at the bite site was performed in 7.7%, 8.3% and 9.6% of the cases and sucking was performed in 7.7%, 10% and 19.3% of the cases according to studies carried out in São Paulo (SP), Uberlândia (MG), and Goiânia (GO)(29,35,43), respectively.
The hypothesis that germs from the snake itself participate in the genesis of the abscesses has been enhanced by the studies of various authors who isolated potentially pathogenic bacteria from the mouth and/or from the venom of venomous snakes from various parts of the world. Group D streptococci and enterobacteria including M. morganii were found in the inoculating fangs and in the venom of large B. jararaca snakes recently captured in the state of São Paulo(16). Pathogenic bacteria such as the enterobacteria were also isolated from the venom of Crotalus durissus terrificus(12). However, envenomations by this species (Crotalus durissus terrificus) do not usually cause infection or macroscopic necrosis in the bite site(20,39). The infection can be the result of the development of the bacteria in the tissue previously injured by the venom, the bacteria itself originally coming from the snake and inoculated at the moment of the bite(10,14,19).
TREATMENT OF THE INFECTION: In Brazil, at the present time, antimicrobial agents are recommended only after the infection has been diagnosed(7,42). The choice of the drug used, however, has been made on empirical basis. The State Health Service in 1982 and the Ministry of Health, in 1987 recommended, respectively, penicillin benzatine(41) and penicillin G associated with oxacillin(7). Such antimicrobial agents do not possess the necessary amplitude against for the bacteria found in the abscesses. Based on recent studies, the use of chloramphenicol as a sole antimicrobical agent, or a combination of benzylpenicillin or ampicillin with aminoglycoside or trimethoprim/ sulfamethoxazole(18) has been recommended. This procedure has also been adopted by the State Health Service(42). Some antimicrobial agents such as cephalosporins of the second and third generations could turn out to be useful in some cases(23).
PROPHYLAXIS OF THE INFECTION: The use of an antimicrobial agent before an infection has been diagnosed has not been recommended and it would not seem sensible to apply to administer one for the prophylaxis of an infection which occurs in only about 10% of the patients, and which in most cases is restricted to the bite site(19). Prognostic factors are known, however, for the occurrence of the abscess(32). Thus, the use of antimicrobial agents should be restricted to the cases in which there is a great probability of infection. A randomized and double-blind study which is now underway evaluates whether or not this procedure reduces the occurrence of abscess after a bothropic snakebite.
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Received 16 October 1996.
Accepted 16 November 1996.
M. T. JORGE - Departamento de Clínica Médica, Centro de Ciências Biomédicas, Universidade Federal de Uberlândia, Avenida Pará, 1720, CEP 38.400-902, Uberlândia, Minas Gerais, Brasil.