Natural and experimental salinomycin poisoning associated with the use of florfenicol in pigs

ABSTRACT: This study describes the spontaneous and experimental salinomycin poisoning associated with the use of florfenicol and warns about the effects of the administration of antibiotics to animals that receive ionophores in the feed as growth promoters. A batch with 1,200 finishing pigs fed a diet containing 30ppm of salinomycin received florfenicol (60ppm via feed) to control respiratory diseases. Twenty-seven pigs had difficulty walking, tip-toe walking, muscle tremors, and anorexia seven days after the start of treatment. Twenty-two animals died, 10 recovered, and two were sent to the Laboratory of Animal Pathology of CAV-UDESC to be necropsied. The experimental reproduction of the disease was carried out to clarify the possible influence of florfenicol on salinomycin poisoning using 12 pigs divided into four groups with three animals each, treated for 16 days with diets containing no additives (Group 1), 50ppm of salinomycin (Group 2), 40ppm of florfenicol (Group 3), and 50ppm of salinomycin and 40ppm of florfenicol (Group 4). Only animals in Group 4 became ill. The clinical disease was reproduced from the ingestion of 24.67mg/kg/LW of salinomycin and 19.74mg/kg/LW of florfenicol. Both natural and experimental salinomycin poisoning associated with the use of florfenicol caused a condition of myopathy characterized in histology by hyaline degeneration and floccular necrosis of skeletal fibers, with macrophage infiltrate, associated with the figures of regeneration in skeletal muscles and multifocal areas of the proliferation of fibroblasts, being more intense in the longissimus dorsi and semimembranosus muscles. Therefore, florfenicol can cause the accumulation of ionophore salinomycin in the animal organism, resulting in a condition of toxic myopathy.

Drug-induced Myopathies

Differential diagnosis of muscle pain and weakness is extensive, including neurological, vertebral, arthrogenic, vascular, traumatic, immunological, endocrine, genetic and infectious aetiologies, as well as medication or toxin-related causes. Muscles are highly sensitive to a large number of drugs, especially with high doses. Although many drug classes can cause toxic myopathy, a significant number of cases are caused by lipid-lowering drugs, long-term use of corticosteroids, and, most often, alcohol misuse. Some drug interactions, e.g. those that are metabolised via the enzyme CYP3A4, can increase the serum levels of the drugs and drug-induced toxicity. A careful history of patientʼs drug and alcohol consumption is therefore vital. Clinical symptoms depend on the drug, dosage and patientʼs sensitivity. They can vary from asymptomatic increase in serum levels of creatine kinase, mild myalgia and cramps to muscle weakness, rhabdomyolysis, kidney failure and even death. The pathogenesis is often only partially known and multifactorial. Toxic myopathy is often reversible once the drug is discontinued, alternative drug therapy is started or a different dosage regimen is chosen. Complications such as acute kidney failure must be avoided, and analgesic therapy may be indicated.

Salinomycin intoxication in pigs associated with the use of tiamulin in the State of Santa Catarina, Brazil

This paper describes a spontaneous outbreak of toxic myopathy in finishing pigs due to the ingestion of feed with salinomycin associated with tiamulin and addresses the control methods performed during the outbreak to minimize economic losses resulting from the intoxication. A lot of 940 pigs fed feed containing 30 ppm salinomycin received 100 ppm tiamulin (via water) to control recurrent respiratory diseases on the farm. After ingesting tiamulin, some animals manifested clinical signs of motor incoordination, stiff gait, reluctance to move, muscle weakness and tremors, dyspnea, depression, and decubitus, remaining in “sitting-dog position” or with the abduction of the pelvic limbs, and rested on tip-toes when in a standing position. Two animals were euthanized for macro-and microscopic evaluation. The other sick animals received supportive anti-inflammatory treatment. The most relevant macroscopic finding observed during necropsy was the slight pallor of the pelvic limb muscles. The main histopathological findings consisted of multifocal areas of hyaline degeneration and marked necrosis of skeletal myofibers, with macrophage infiltrate associated with cell regeneration and skeletal fiber phagocytosis. These lesions were more intense in the longissimus dorsi, diaphragm, and masseter muscles. The definitive diagnosis was based on epidemiological aspects and clinical lesional conditions compatible with toxic myopathy secondary to ionophore intoxication.

Myopathy following statin use

Introduction: Myopathies can be caused by various drugs, including statins and corticosteroids, and can be toxic or inflammatory, one example being necrotizing myositis triggered by statins. Objectives: Describe the case of a patient with weakness after statin use. Design and setting: Case report Methods: Analysis of medical record, photographic record of the diagnostic methods and literature review. Case description: 69-year-old female, obese, hypertensive, diabetic, dyslipidemic and hypothyroid, taking atorvastatin since 2017, referred by endocrinology for generalized myalgia in 2019, with increased creatine phosphokinase (CPK). Discontinued statin use since then, maintaining symptoms. Neurological examination showed tetraparesis, with proximal predominance. Electroneuromyography (ENMG) showed signs of myopathy. Corticotherapy with deflazacort was initiated, with improvement of symptoms and reduction of CPK levels. Investigation for paraneoplastic syndrome was performed, with negative results. He started using pioglitazone, prescribed by endocrinology, with reduced corticotherapy, for better glycemic control, presenting worsening weakness, frequent falls, and dyspnea on effort. The patient repeated ENMG in one month, without changes. Performed an anti-HMG-CoA reductase autoantibody test, with a positive result, concluding the diagnosis of immune-mediated necrotizing myositis triggered by statins, with a probable toxic myopathy after use of pioglitazone. Azathioprine was introduced, with gradual weaning from corticosteroids, and physical therapy was started. Conclusion: Several medications can cause myopathy, directly (toxic) or indirectly (immune-mediated), and this patient used 3 potentially myopathy-causing drugs (atorvastatin, deflazacort, and pioglitazone). The nonimprovement upon medication withdrawal suggested an immune-mediated inflammatory cause, confirmed in this case by the determination of a specific autoantibody for statin-induced necrotizing myositis.

Hydroxychloroquine-Induced Toxic Myopathy Causing Diaphragmatic Weakness and Lung Collapse Requiring Prolonged Mechanical Ventilation

A 42-year-old woman with juvenile idiopathic arthritis was treated with anakinra, corticosteroids, and hydroxychloroquine when she developed chronic hypoxic respiratory myopathy. She was admitted to the intensive care unit for acute hypercapnic respiratory failure and required prolonged intubation, subsequent tracheostomy, and long-term ventilatory support due to multiple failed spontaneous breathing trials after discontinuation of anakinra and steroids. Muscle biopsy revealed type II fiber atrophy with the accumulation of autophagosomes and vacuoles presenting as curvilinear bodies, elevated MHC class I antigen expression, and infiltration by CD68+ macrophages and CD8+ T cells. Type II fiber atrophy was attributed to corticosteroid use and curvilinear bodies due to blockade of autophagy by hydroxychloroquine. After hydroxychloroquine was discontinued, the patient recovered to her prehospitalization baseline.

Favorable Outcome of Severe Poisoning by Snake Green Mamba (Dendroaspis viridis) Clinical Case

This clinical case of acute poisoning due to bite of snake Dendroaspis viridis seems interesting to share because of its rare incidence inRussiaand management peculiarities: the critical care was conducted without specific antidote therapy due to absence of the antidote.The prevailing clinical presentation included signs of toxic myopathy combined with paresis of skeletal and breathing muscles that led to development of acute respiratory failure and metabolic disorders. The processes described were induced by the action of snake poison dendrotoxins featuring the activities of potassium channel blockers and acetyl cholinesterase inhibitors.The proper critical care included conduct of syndrome therapy aimed at maintaining life support systems adequately to condition (replacement of the breathing and circulation functions), antibiotic therapy and desensitizing treatment and metabolic care by administration of drugs characterized by antihypoxant/antioxidant mechanism of action.The comprehensive therapy applied has resulted in a favorable outcome of acute poisoning by snake green mamba without development of possible complications even when the specific antidote drug has not been included into the treatment protocol.