Poor efficacy of preemptive amoxicillin clavulanate for preventing secondary infection from Bothrops snakebites in the Brazilian Amazon: A randomized controlled clinical trial

Abstract

BackgroundSecondary bacterial infections from snakebites contribute to the high complication rates that can lead to permanent function loss and disabilities. Although common in endemic areas, routine empirical prophylactic use of antibiotics aiming to prevent secondary infection lacks a clearly defined policy. The aim of this work was to estimate the efficacy of amoxicillin clavulanate for reducing the secondary infection incidence in patients bitten by Bothrops snakes, and, secondarily, identify risk factors for secondary infections from snakebites in the Western Brazilian Amazon.Methods and findingsThis was an open-label, two-arm individually randomized superiority trial to prevent secondary infection from Bothrops snakebites. The antibiotic chosen for this clinical trial was oral amoxicillin clavulanate per seven days compared to no intervention. A total of 345 patients were assessed for eligibility in the study period. From this total, 187 accomplished the inclusion criteria and were randomized, 93 in the interventional group and 94 in the untreated control group. All randomized participants completed the 7 days follow-up period. Enzyme immunoassay confirmed Bothrops envenoming diagnosis in all participants. Primary outcome was defined as secondary infection (abscess and/or cellulitis) until day 7 after admission. Secondary infection incidence until 7 days after admission was 35.5% in the intervention group and 44.1% in the control group [RR = 0.80 (95%CI = 0.56 to 1.15; p = 0.235)]. Survival analysis demonstrated that the time from patient admission to the onset of secondary infection was not different between amoxicillin clavulanate treated and control group (Log-rank = 2.23; p = 0.789).Secondary infections incidence in 7 days of follow-up was independently associated to fibrinogen >400 mg/dL [AOR = 4.78 (95%CI = 2.17 to 10.55; p<0.001)], alanine transaminase >44 IU/L [AOR = 2.52 (95%CI = 1.06 to 5.98; p = 0.037)], C-reactive protein >6.5 mg/L [AOR = 2.98 (95%CI = 1.40 to 6.35; p = 0.005)], moderate pain [AOR = 24.30 (95%CI = 4.69 to 125.84; p<0.001)] and moderate snakebites [AOR = 2.43 (95%CI = 1.07 to 5.50; p = 0.034)].Conclusions/SignificancePreemptive amoxicillin clavulanate was not effective for preventing secondary infections from Bothrops snakebites. Laboratorial markers, such as high fibrinogen, alanine transaminase and C-reactive protein levels, and severity clinical grading of snakebites, may help to accurately diagnose secondary infections.Trial registrationBrazilian Clinical Trials Registry (ReBec): RBR-3h33wy; UTN Number: U1111-1169-1005.

Serum Procalcitonin Concentration and Its Relationship with Local Manifestations after Snakebites

“…Prophylactic antibiotics are routinely used in patients with local manifestations after snakebites, despite no clear benefits from such therapy reported in previous clinical studies. 6,[10][11][12][13] It is important to know whether local manifestations after snakebites are due to venom or bacteria to avoid inappropriate antibiotic usage.…”

Infectious Complications Following Snakebite by Bothrops lanceolatus in Martinique: A Case Series

“…Wound infection following snakebite usually accounts for 9-77% of the bitten patients, as described in several studies (Table 4). 5,6,8,[12][13][14][15] The large differences in the reported prevalence of secondary infections in snakebites between different studies can be related to variations in the criteria used to establish the presence of infection. A strict criterion is the laboratory isolation and identification of bacteria from the affected tissues or blood in envenomed patients.…”

Stepping into a dangerous quagmire: environmental determinants of human-lancehead pit vipers (Bothropsgenus) contact resulting in injuries, Brazilian Amazon

“…A PI metalloproteinase, called batroxase, isolated from B. atrox venom, has fibrinolytic, thrombolytic activities and induces weak bleeding through the digestion of the extracellular matrix components such as laminin, type IV collagen and fibronectin (31). Bothrops envenoming shows pain, swelling, regional lymphadenopathy, ecchymosis, blistering and necrosis as the most common local clinical manifestations (32)(33)(34). Secondary bacterial infections were observed in around 40% of the Bothrops snakebites (34) .…”

“…Bothrops envenoming shows pain, swelling, regional lymphadenopathy, ecchymosis, blistering and necrosis as the most common local clinical manifestations (32)(33)(34). Secondary bacterial infections were observed in around 40% of the Bothrops snakebites (34) . Spontaneous systemic bleeding and acute renal failure are common systemic complications after Bothrops envenomings (32)(33)(34).…”

“…Secondary bacterial infections were observed in around 40% of the Bothrops snakebites (34) . Spontaneous systemic bleeding and acute renal failure are common systemic complications after Bothrops envenomings (32)(33)(34).…”