From a poison to an infection
Helena Rabie1, Marlize Kunneke2, Penny Rose1
A 3 year old girl presented with a short history of rapidly progressive decreasing level of consciousness at a day care center. She was taken to the local level one hospital where she was intubated and transferred to the local level 2 and subsequently level 3 hospital.
She was a previously well, HIV uninfected child that was well that morning prior to attending daycare. She lives in an informal settlement in a small town in the Boland. All her vaccinations were up to date. She had no history of recent travel or relevant animal exposure, her food was purchased from the local supermarket and her house has piped water. There were no children with a similar illness in the community.
On examination she was well nourished. She was febrile with a temperature of 38.5°C. Her pulse rate was 190 per minute with normal blood pressure. Neurological assessment revealed a deeply comatose child with no spontaneous breathing or and no motor response to painful stimulation.
Question 1: What is your differential diagnosis? Outline the initial management of this case?
Answer to Q1: Discussion
The neurology initially suggested brain stem involvement with either an infectious or post infectious state. Meningitis, viral encephalitis and acute disseminated encephalomyelitis (ADEM) are possible causes of the condition. Empiric therapy included ceftriaxone, ampicillin (to provide empiric listeria cover) and acyclovir, as well with supportive care.
Though the clinical features where consistent with a brain stem lesion, the rapidity of symptom onset, myosis, autonomic instability and increased respiratory secretions required consideration of other causes including poisoning and drug ingestion.
There was no history of herbicide or insecticide spraying close to the school, poison ingestion, chewing of tobacco products, nicotine containing gum or ingestion of vaping liquid and there was no known exposure to opioid containing drugs or antipsychotic medications.
She was washed and gastric contents were cleared, a test dose of atropine was given with no improvement, pseudo-cholinesterase level was normal. Brain CT excluded mass lesions and no significant brain swelling was detected.
Question 2: What envenomation(s) would you consider in this child?
Answer to Q2: Discussion
Snake and scorpion envenomation are frequently encountered and should be considered in children with unexplained neurological features. In this case, the treating clinicians actively pursued this as a possible cause of the clinical presentation. The history was reviewed with her teacher who mentioned that shortly before the child collapsed she was shaking her leg and the teacher thought that something may have bitten her, she noted a small spot of blood below her knee. She did not observe a snake, scorpion or spider.
Snake bite is a public health problem. A 2008 review of the global burden of disease estimated that 1.2 to 5.5 million snake bites occur annually. These bites result in approximately 421,000 envenomations with 20 000 deaths (up to 1,841,000 envenomations and 94,000 deaths). A review of snake bites in sub-Saharan Africa estimates the number of envenomations at 251,513–377,462 per year, of which 95% occur in rural areas. The annual mortality was estimated at 7,331 with envenomations resulting in 5,908 to 14,614 amputations. (1,2)
Children are at highest risk. In a study from Kwa-Zulu Natal, 57.9% of 164 patients with snake bites were under 10 years of age. (3)
Most South African scorpion stings are relatively benign with most severe morbidity and mortality related to Parabuthus granulatus stings. As with snake bites children carry the bulk of scorpion sting morbidity and mortality. Mortality of up to 20% is reported in some series.(4)
With this history it was considered that one or two of the small skin lessons could be the site of envenomation. Both snake and scorpion anti-venoms were administered because the event was not observed and the type of envenomation could not be clinically distinguished. Flaccid paralysis is reported with cobra bite but less commonly in scorpion envenomation. Excessive secretions are more common with scorpion stings. The low sodium, raised CRP and increased creatine kinase also support snake bite envenomation.(5) Anivenom test doses where not provided as these are no longer recommended.
Knowing which scorpions, snakes and spiders are endemic is essential. Cobras (with neurotoxic venom), Parabuthus granulatus scorpions as well as button spiders are found in this area.
Over the course of the next 48 hours the child started moving and spontaneous respiration returned with gradual recovery of neuromuscular control. After normal lumbar puncture results acyclovir and ceftriaxone were stopped. However, fever persisted and a significant area of cellulitis developed over the left knee with severe swelling and erythema. Ultrasound of the knee excluded fluid in the joint but confirmed soft tissue swelling. A complex wound with a deep area of necrosis resulted. (Picture 1)
Question 3: Which infections are associated with snake envenomation and which empiric antibiotic(s) would you provide?
Answer to Q3: Discussion
Bacterial pathogens are common in the oral cavities of venomous and non-venomous snakes. Cases of severe envenomation with snake bite are commonly complicated by serious wound infection, particularly in cases of cytotoxic envenomation. Even when there is no cytotoxic venom the proteolytic enzymes present in venom may result in extensive tissue destruction and devitalisation which predisposes to infection. Some cobra species have neurotoxic and cytotoxic venom.
Earlier recommendations included prophylactic antibiotics, however, current guidelines suggest they do not prevent wound infections, however, where wounds were interfered with or incised, broad spectrum antibiotics should be started at presentation. Tetanus vaccine status also needs to be assessed for each case.(6)
We summarize information of 2 local studies in the table below: in the first, swabs were taken from the oral cavity of venomous and non- venomous snakes from Kwa-Zulu Natal and Gauteng and cultured, the second is a study of wound infections following snake bite from Kwa-Zulu Natal.
Wound infections were mostly due to gram negative bacteria particularly Morganella morganii, the most common gram positive organism was Enterococcus faecalis. In this series a substantial number of wounds had more than one pathogen identified.(3)
Similar to local data a case series of wound infections secondary to the Chinese cobra (Naja atra) bite in southeast-Asia also identified gram negative aerobic bacteria particularly Morganella morganii and Proteus species as well as Enterococcus as common. Rare organisms including Shewanella spp are also reported. (8,9) This suggests that ciprofloxacin or amoxicillin-clavulanic acid plus ciprofloxacin, ceftriaxone with gentamicin or piperacillin-tazobactam will be good empiric choices and these are also suggested by WHO.(6)
Scorpion sting wounds usually heal without complication, but infections particularly with staphylococci and streptococci are reported and can result in severe complications including endocarditis.(10) These infections are not common and in a study from Iran only 2.8% of 1381 cases of scorpion sting required antibiotics. (11)
We chose amoxicillin-clavulanic acid for empiric therapy. This provided coverage of Enterococcus faecalis, Morganella morganii, Proteus species as well as Staphylococcus, after the wound infection progressed ciprofloxacin was added ciprofloxacin, to provide activity against Salmonella Pseudomonal species.
Deep and superficial tissue cultures grew Staphylococcus aureus sensitive to cloxacillin, Proteus vulgaris sensitive to amoxicillin- clavulanic acid, cotrimoxazole and 3rd generation cephalosporins and Enterococcus faecalis sensitive to amoxicillin-clavulanic acid, cotrimoxazole and 3rd generation cephalosporins.
Amoxicillin- clavulanic acid was continues and the wound was surgically debrided twice. In addition, tibial osteitis developed that also required debridement
The child made a good recovery and is currently being followed up as an outpatient.
We believe this was a case of snake bite associated envenomation complicated by a severe polymicrobial wound infection.
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