Use of Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G)-(Equine) (BAT®) in Clinical Study Subjects and Patients: A 15-Year Systematic Safety Review.

Botulism is a rare, sometimes fatal paralytic illness caused by botulinum neurotoxins. BAT® (Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G)-(Equine)) is an equine-derived heptavalent botulinum antitoxin indicated for the treatment of symptomatic botulism in adult and pediatric patients. This review assesses the cumulative safety profile for BAT product from 2006 to 2020, using data received from clinical studies, an expanded-access program, a post-licensure registry, spontaneous and literature reports. The adverse event (AE) incidence rate for BAT product was calculated conservatively using only BAT product exposures for individuals with a record (512) and was alternatively estimated using all BAT product exposure data, including post-licensure deployment information (1128). The most frequently reported BAT product-related AEs occurring in greater than 1% of the 512-1128 BAT product-exposed individuals were hypersensitivity, pyrexia, tachycardia, bradycardia, anaphylaxis, and blood pressure increase reported in 2.3-5.1%, 1.8-3.9%, 1.0-2.2%, 0.89-2.0%, 0.62-1.4%, and 0.62-1.4%, respectively. For patients properly managed in an intensive care setting, the advantages of BAT product appear to outweigh potential risks in patients due to morbidity and mortality of botulism. AEs of special interest, including bradycardia, hemodynamic instability, hypersensitivity, serum sickness, and febrile reactions in the registry, were specifically solicited.

Safety and Improved Clinical Outcomes in Patients Treated With New Equine-Derived Heptavalent Botulinum Antitoxin.

Background: Botulism is a rare, life-threatening paralytic illness. Equine-derived heptavalent botulinum antitoxin (HBAT), the only currently available treatment for noninfant botulism in the United States, was licensed in 2013. No reports have systematically examined safety and clinical benefit of HBAT among botulism patients. Methods: From March 2010 through March 2013, we collected data prospectively and through medical record reviews of patients with confirmed or suspected botulism who were treated with HBAT under an expanded-access Investigational New Drug program. Results: Among 249 HBAT-treated patients, 1 (<1%) child experienced an HBAT-related serious adverse event (hemodynamic instability characterized by bradycardia, tachycardia, and asystole); 22 (9%) patients experienced 38 nonserious adverse events reported by physicians to be HBAT related. Twelve (5%) deaths occurred; all were determined to be likely unrelated to HBAT. Among 104 (42%) patients with confirmed botulism, those treated early (≤2 days) spent fewer days in the hospital (median, 15 vs 25 days; P < .01) and intensive care (10 vs 17 days; P = .04) than those treated later. Improvements in any botulism sign/symptom were detected a median of 2.4 days and in muscle strength a median of 4.8 days after HBAT. Conclusions: HBAT was safe and provided clinical benefit in treated patients. HBAT administration within 2 days of symptom onset was associated with shorter hospital and intensive care stays. These results highlight the importance of maintaining clinical suspicion for botulism among patients presenting with paralytic illness to facilitate early HBAT treatment before laboratory confirmation might be available. Clinical consultation and, if indicated, HBAT release, are available to clinicians 24/7 through their state health department in conjunction with CDC.

Workgroup Report by the Joint Task Force Involving American Academy of Allergy, Asthma & Immunology (AAAAI); Food Allergy, Anaphylaxis, Dermatology and Drug Allergy (FADDA) (Adverse Reactions to Foods Committee and Adverse Reactions to Drugs, Biologicals, and Latex Committee); and the Centers for Disease Control and Prevention Botulism Clinical Treatment Guidelines Workgroup-Allergic Reactions to Botulinum Antitoxin: A Systematic Review.

Background: Naturally occurring botulism is rare, but a large number of cases could result from unintentional or intentional contamination of a commercial food. Despeciated, equine-derived, heptavalent botulinum antitoxin (HBAT) is licensed in the United States. Timely treatment reduces morbidity and mortality, but concerns that botulinum antitoxin can induce anaphylaxis exist. We sought to quantify the allergy risk of botulinum antitoxin treatment and the usefulness of skin testing to assess this risk. Methods: We conducted a systematic review of (1) allergic reactions to botulinum antitoxin and (2) the predictive value of skin testing (ST) before botulinum antitoxin administration. We searched 5 scientific literature databases, reviewed articles' references, and obtained data from the HBAT manufacturer and from the Centers for Disease Control and Prevention. Anaphylaxis incidence was determined for HBAT and previously employed botulinum antitoxins. We calculated the positive predictive value (PPV) and negative predictive value (NPV) of ST for anaphylaxis related to HBAT and other botulinum antitoxins. Results: Seven articles were included. Anaphylaxis incidence was 1.64% (5/305 patients) for HBAT and 1.16% (8/687 patients) for all other botulinum antitoxins (relative risk, 1.41 [95% confidence interval, .47-4.27]; P = .5). Observed values for both PPV and NPV for HBAT-ST (33 patients) were 100%. Observed PPVs and NPVs of ST for other botulinum antitoxins (302 patients) were 0-56% and 50%-100%, respectively. There were no reports of fatal anaphylaxis. Conclusions: Considering the <2 % rate of anaphylaxis, fatal outcomes, modest predictive value of ST, resource requirements for ST, and the benefits of early treatment, data do not support delaying HBAT administration to perform ST in a mass botulinum toxin exposure. Anaphylactic reactions may occur among 1%-2% of botulinum antitoxin recipients and will require epinephrine and antihistamine treatment and, possibly, intensive care.

Retrospective survey to evaluate the safety and efficacy of Japanese botulinum antitoxin therapy in Japan.

Japanese botulinum antitoxins have been used for more than 50 years; however, their safety and therapeutic efficacy are not clear. In order to analyze the available data on botulinum antitoxin therapy in Japan, we surveyed published reports about botulism cases in which botulinum antitoxins were used, and retrospectively analyzed the safety and efficacy of the therapy. A total of 134 patients administered botulinum antitoxins were identified from published reports. Two cases of side effects (1.5%) were detected after antitoxin administration, both not fatal. The fatality rate was 9.4%, and more than 70% of the patients showed improvement in their symptoms and better clinical conditions than those not treated with antitoxins. These data suggest that the therapy with Japanese antitoxins is safe and highly effective.

Foodborne botulism treated with heptavalent botulism antitoxin.

OBJECTIVE: To report a case of foodborne botulism and subsequent use of the investigational heptavalent botulism antitoxin (H-BAT). CASE SUMMARY: A 60-year-old man was hospitalized with blurred vision, diplopia, and dysarthria. On hospital day 2, the patient was transferred to the intensive care unit for progressive fatigable weakness with ptosis, dysphagia, dysarthria, and nausea. Secondary to worsening respiratory distress, the patient was intubated and placed on a ventilator. The patient could open his eyes only with assistance but still had normal strength in all extremities. H-BAT was administered 48 hours after presentation for possible botulism. The patient then revealed that he consumed home-canned corn several days prior to admission. On hospital day 8, botulinum neurotoxin was confirmed in the patient's serum and the home-canned corn. The patient slowly regained muscle strength and was discharged to a long-term acute care facility on hospital day 22. DISCUSSION: Foodborne botulism is caused by a neurotoxin from Clostridium botulinum and usually occurs after the consumption of improperly prepared home-canned food. Botulism is characterized by symmetrical descending paralysis that may progress to respiratory arrest. The standard confirmatory test for botulism is a mouse bioassay to prove the presence of botulinum neurotoxin. Outside of supportive care, the treatment options for botulism are limited. Individuals with botulism often require intensive care unit monitoring and potentially ventilatory support. H-BAT, the only treatment available for botulism in patients older than 1 year, is a purified and despeciated equine-derived immunoglobulin active against all known botulinum neurotoxins. H-BAT's despeciation significantly reduces the risk of hypersensitivity reactions, anaphylaxis, and serum sickness. CONCLUSIONS: In a confirmed case of foodborne botulism treated with H-BAT, the patient tolerated H-BAT and did not develop any hypersensitivity reactions or serum sickness.

Equine botulinum antitoxin for the treatment of infant botulism.

Infant botulism is the most common form of human botulism in Argentina and the United States. BabyBIG (botulism immune globulin intravenous [human]) is the antitoxin of choice for specific treatment of infant botulism in the United States. However, its high cost limits its use in many countries. We report here the effectiveness and safety of equine botulinum antitoxin (EqBA) as an alternative treatment. We conducted an analytical, observational, retrospective, and longitudinal study on cases of infant botulism registered in Mendoza, Argentina, from 1993 to 2007. We analyzed 92 medical records of laboratory-confirmed cases and evaluated the safety and efficacy of treatment with EqBA. Forty-nine laboratory-confirmed cases of infant botulism demanding admission in intensive care units and mechanical ventilation included 31 treated with EqBA within the 5 days after the onset of signs and 18 untreated with EqBA. EqBA-treated patients had a reduction in the mean length of hospital stay of 23.9 days (P = 0.0007). For infants treated with EqBA, the intensive care unit stay was shortened by 11.2 days (P = 0.0036), mechanical ventilation was reduced by 11.1 days (P = 0.0155), and tube feeding was reduced by 24.4 days (P = 0.0001). The incidence of sepsis in EqBA-treated patients was 47.3% lower (P = 0.0017) than in the untreated ones. Neither sequelae nor adverse effects attributable to EqBA were noticed, except for one infant who developed a transient erythematous rash. These results suggest that prompt treatment of infant botulism with EqBA is safe and effective and that EqBA could be considered an alternative specific treatment for infant botulism when BabyBIG is not available.

Botulismo del lactante: formas clínicas graves, experiencia en Neuquén / Infant botulism: serious clinical forms experience in Neuquén

Se presentan nueve casos de botulismo del lactante (BL) internados en el Servicio de Pediatría del Hospital Provincial Neuquén durante el período abril 1985 marzo 1991: dos de ellos con severo compromiso del sistema nervioso autónomo, manifestado por midriasis paralítica bilateral, y otros tres sin la constipación previa habitual de observar en el ingreso. Los nueve niños tenían de dos a nueve meses de vida (X: 4,4 m), detectándose en seis de ellos toxina en sangre y heces y desarrollando en el coprocultivo de ocho pacientes Clostridum botulinum tipo A. Uno de los niños falleció y los restantes requirieron asistencia respiratoria mecánica por tiempo prolongado (X: 24,5 días). La mayoría de los casos se registró en primavera y verano (época de vientos moderados a intensos en ésta zona). El electromiograma fue útil para el diagnóstico en los ocho pacientes en que se realizó con "potenciales en escalera" en el 75 por ciento de los casos. Es probable que se registren más casos en ésta región de la Patagonia, y que algunos se presenten como síndromes de muerte súbita del lactante. Se analizan algunos aspectos epidemiológicos, cuadro clínico y tratamiento de ésta enfermedad, que debe ser bien conocida por todos los pediatras. Se rescata también la importancia del EMG en el diagnóstico

Botulismo del lactante: formas clínicas graves, experiencia en Neuquén / Infant botulism: serious clinical forms experience in Neuquén

Se presentan nueve casos de botulismo del lactante (BL) internados en el Servicio de Pediatría del Hospital Provincial Neuquén durante el período abril 1985 marzo 1991: dos de ellos con severo compromiso del sistema nervioso autónomo, manifestado por midriasis paralítica bilateral, y otros tres sin la constipación previa habitual de observar en el ingreso. Los nueve niños tenían de dos a nueve meses de vida (X: 4,4 m), detectándose en seis de ellos toxina en sangre y heces y desarrollando en el coprocultivo de ocho pacientes Clostridum botulinum tipo A. Uno de los niños falleció y los restantes requirieron asistencia respiratoria mecánica por tiempo prolongado (X: 24,5 días). La mayoría de los casos se registró en primavera y verano (época de vientos moderados a intensos en ésta zona). El electromiograma fue útil para el diagnóstico en los ocho pacientes en que se realizó con "potenciales en escalera" en el 75 por ciento de los casos. Es probable que se registren más casos en ésta región de la Patagonia, y que algunos se presenten como síndromes de muerte súbita del lactante. Se analizan algunos aspectos epidemiológicos, cuadro clínico y tratamiento de ésta enfermedad, que debe ser bien conocida por todos los pediatras. Se rescata también la importancia del EMG en el diagnóstico (AU)

Hypersensitivity reactions associated with botulinal antitoxin.

During an 11-year period (1967 through 1977) CDC monitored reactions of hypersensitivity to botulinal antitoxin of equine origin. Of 268 persons given botulinal antitoxin, 24 (9.0 percent) had nonfatal acute (5.3 percent) or delayed (3.7 percent) hypersensitivity reactions to a skin test or therapeutic dose. The over-all rate of reaction did not differ with the age or sex of the recipient or with the type (AB or ABE) of antitoxin administered. Serum sickness occurred significantly more frequently in persons who received more than 40 ml of serum antitoxin (p < 0.02). The over-all reaction, rate was higher than that associated with other equine serum products and probably cannot be substantially reduced. This risk, however, would be substantially reduced if not eliminated by using botulinal immune globulin obtained from hyperimmunized human donors.