Botulism: a rare complication of injecting drug use

Botulism is a rare, naturally occurring disease that may also be caused by deliberate or accidental exposure to the toxins of Clostridium botulinum. The three types of naturally occurring disease are food-borne, wound and intestinal colonisation botulism, dependent on the route of ingress of the toxins. Food related botulism remains rare in the UK, but wound botulism is increasing, particularly associated with intravenous drug use. It presents with an afebrile, descending, symmetrical, flaccid paralysis of motor and autonomic but not sensory nerves. Respiratory failure can occur rapidly with little prior ventilatory deterioration. Management includes respiratory support, specific antitoxin and surgical debridement and antibiotics for cases of wound botulism. We report a case of wound botulism and discuss the presenting features that should alert the emergency physician to the diagnosis of wound botulism.     

Descending polyneuropathy in an intravenous drug user.

A 27-year-old male intravenous drug user presented to the Emergency Department of St James's Hospital with a 1-week history of progressive dysphasia, dysphagia and difficulty 'holding his head up' and 'keeping his eyes open'. He also complained of increasing weakness in his upper limbs, as a result of which he kept dropping things. He was on a methadone program but was using both intravenous heroin and cocaine at the time of presentation. Examination of his motor function revealed generalized hypotonia, hyporeflexia and reduced power in both upper limbs. No sensory loss was observed. Co-ordination was intact. The clinical picture of a proximal symmetrical descending weakness and an absence of sensory loss was suggestive of botulism. Clostridium botulinum is a spore-forming, obligate anaerobe. The three forms of human botulism are food-borne, wound and intestinal. A fourth man-made form is produced from aerosolized botulinum toxin and results in inhalational botulism. A little as 1 g of aerosolized botulinum toxin has the potential to kill 1.5 million people. Toxin is detected in serum or stool specimens in only approximately 46% of clinically diagnosed cases. Treatment involves supportive care and early passive immunization with equine antitoxin. Patients should be regularly assessed for loss of gag and cough reflex, control of oropharyngeal secretions, oxygen saturation, vital capacity and inspiratory force. When respiratory function begins to deteriorate, anticipatory intubation is indicated. Early symptom recognition and early treatment with antitoxin are essential in order to prevent mortality, and to prevent additional cases, it is important to ascertain the presence of similar symptoms in contacts of the patient and local public health officials must be notified as one case may herald an outbreak. Given the continued threat of bioterrorism, the Centre for Disease Control Surveillance System in the United States must also be notified of any cases of botulism.     

Type E botulism

There are seven known serotypes of botulism, designated A through G; almost all human cases of botulism are caused by types A, B, and E. Botulism type E is the predominant serotype causing disease associated with native Arctic foods. In the circumpolar regions of the world, the coastal soils are rich in botulism type E, and consumption of fish and marine animals in these areas are the sources of clusters of botulism. Unlike spores of type A and B, botulism type E can withstand freezing down to 3.5°C. Alaskan native fermentation of fish heads, fish eggs, and beaver tail allow proper anaerobic conditions for botulinum toxin to be elaborated from Clostridium botulinum. The consumption of whale meat, "muktuk" has also been associated with outbreaks of botulism in Alaska and the Canadian Arctic. Elsewhere in the Arctic regions, type E botulism has been associated with Norwegian "rakfisk" prepared by a process similar to fermented Alaskan foods. Outbreaks in Egypt with the salted gray mullet "faseikh", in Israel and New York linked to salted uneviscerated whitefish "kapchunka", in Iran from eating "ashbal" an uncooked salmon, and in Japan with "izushi" a traditional fermented fish preserved in rice have occurred. Importation of vacuum-packed whitefish from Alaska and Canada has also been associated with sporadic cases of botulism type E in Europe. In March 2010, the Center for Disease Control and Prevention released the heptavalent antitoxin (H-BAT) for use in the USA, under an Investigational New Drug program, as the preferred treatment for food-borne botulism, including type E, which had not been covered by the bivalent antitoxin, the prior approved antitoxin product in the USA.     

Type E botulism

There are seven known serotypes of botulism, designated A through G; almost all human cases of botulism are caused by types A, B, and E. Botulism type E is the predominant serotype causing disease associated with native Arctic foods. In the circumpolar regions of the world, the coastal soils are rich in botulism type E, and consumption of fish and marine animals in these areas are the sources of clusters of botulism. Unlike spores of type A and B, botulism type E can withstand freezing down to 3.5°C. Alaskan native fermentation of fish heads, fish eggs, and beaver tail allow proper anaerobic conditions for botulinum toxin to be elaborated from Clostridium botulinum. The consumption of whale meat, “muktuk” has also been associated with outbreaks of botulism in Alaska and the Canadian Arctic. Elsewhere in the Arctic regions, type E botulism has been associated with Norwegian “rakfisk” prepared by a process similar to fermented Alaskan foods. Outbreaks in Egypt with the salted gray mullet “faseikh”, in Israel and New York linked to salted uneviscerated whitefish “kapchunka”, in Iran from eating “ashbal” an uncooked salmon, and in Japan with “izushi” a traditional fermented fish preserved in rice have occurred. Importation of vacuum-packed whitefish from Alaska and Canada has also been associated with sporadic cases of botulism type E in Europe. In March 2010, the Center for Disease Control and Prevention released the heptavalent antitoxin (H-BAT) for use in the USA, under an Investigational New Drug program, as the preferred treatment for food-borne botulism, including type E, which had not been covered by the bivalent antitoxin, the prior approved antitoxin product in the USA.     

肉毒抗毒素现状和发展趋势概述

肉毒毒素是已知毒性最强的生物毒素,其引起的肉毒中毒时有发生,甚至会致死.肉毒抗毒素是目前唯一的肉毒中毒特异性治疗手段,尽早使用肉毒抗毒素对提高肉毒中毒的治疗效果具有重要意义.目前国内外批准上市的肉毒抗毒素基本都是马源性制剂,存在引起过敏反应等不良反应的风险.本文对肉毒抗毒素的国内外现状、生产工艺、质量控制和临床应用等现...     

Wound Botulism Associated with Black Tar Heroin

The incidence of wound botulism is increasing and the epidemiology of the disease is changing. The majority of new cases are associated with injection drug use, in particular, the use of Mexican black tar heroin. This case report and discussion of wound botulism illustrate the following important points: Dysphagia, dysphonia, diplopia, and descending paralysis, in association with injection drug use, should alert the treating physician to the possibility of wound botulism. In such patients, the onset of respiratory failure may be sudden and without clinically obvious signs of respiratory weakness. For the reported patient, maximum inspiratory force measurements were the only reliable indicator of respiratory muscle weakness. This is a measurement not routinely performed in the ED, but may prove essential for patients with suspected wound botulism. To minimize the effect of the botulinum toxin and to decrease length of hospital stay, antitoxin administration and surgical wound debridement should be performed early.     

Botulinum toxin

Botulinum toxin is regarded as the most lethal substance known. It is estimated that the human LD50 for inhalation botulism is 1 to 3 nanograms of toxin/kilogram body mass. Although only three cases of inhalational botulism have been described, an understanding of the pathophysiology of food-borne outbreaks, wound botulism, and infant botulism, and their therapies, enables the medical community to plan treatment in the event of an aerosol release of botulinum toxin. Antitoxin, vaccine, and F(ab')2 immune fragment therapies are discussed as adjuncts to supportive therapy.     

Formes graves de botulisme du nouveau-né et du nourrisson : trois observations récentes et algorithme de prise en charge

Botulism rarely involves young children. Food borne botulism is a direct toxin contamination that can affect infants following the ingestion of a food product contaminated by botulinum toxin. Infant botulism occurs after intestinal colonisation by Clostridium botulinium and secondary toxin production in children less than 12 months of age. Both forms lead to a presynaptic blockage of the neuromuscular junction. In its natural course, the disease ultimately resolves completely, but some patients will require ventilatory and nutritional support, thus experiencing intensive care complications. Early administration of intravenous antitoxin has been proved to accelerate recovery, which requires physicians to be aware of this rare disease. Here we report three recent cases of botulism in young children that are especially relevant, and propose guidelines to optimise diagnosis and treatment.     

Susceptibility of Clostridium botulinum to thirteen antimicrobial agents.

A total of 224 strains of Clostridium botulinum (including isolates from 14 patients with infant botulism and 4 with wound botulism) and 15 strains of C. sporogenes were tested by agar dilution for susceptibility to tetracycline, metronidazole, erythromycin, penicillin, rifampin, chloramphenicol, clindamycin, cephalothin, cefoxitin, vancomycin, sulfamethoxazole-trimethoprim, nalidixic acid, and gentamicin. At least 90% of the C. botulinum strains tested (except for nonproteolytic strains of toxin type F with penicillin) were susceptible to all drugs except sulfamethoxazole-trimethoprim, nalidixic acid, and gentamicin. Minimal inhibitory concentrations for strains from patients with infant and wound botulism were similar to those for other C. botulinum strains.     

Opioid antagonists in the treatment of opioid-induced constipation and pruritus

OBJECTIVE: To describe the role of opioid antagonists in the treatment of opioid-induced constipation and pruritus. DATA SOURCES: A MEDLINE search was performed (1966-February 2000) for narcotics and opioid antagonists. Results were limited to English-language and clinical trials. Background information was obtained from pharmacology and pharmacotherapy references and review articles. Hand searching of selected bibliographies yielded several references. STUDY SELECTION AND DATA EXTRACTION: Studies were reviewed that examined the use of naloxone, naltrexone, and methylnaltrexone for opioid-related constipation and pruritus. Selected citations included various clinical trials and case series. DATA SYNTHESIS: Opioid agents are used for cancer and nonmalignant pain. Peripheral opioid receptor stimulation due to endogenous (i.e., endorphins) or exogenous (i.e., morphine) stimulants may result in negative adverse effects, including constipation and pruritus. Adjuvant agents, such as laxatives and antihistamines, are often used to treat these adverse effects, but are themselves associated with adverse effects and are sometimes ineffective. Opioid antagonists have demonstrated reversal of peripheral opioid receptor stimulation. Clinical trials show adequate maintenance of pain control, as well as decreases in opioid-induced constipation and pruritus. CONCLUSIONS: Opioid antagonists offer a therapeutic alternative to conventional adjuvant agents, with the risk of loss of analgesia at higher doses. Methylnaltrexone offers the advantage of peripheral action only, therefore not reversing analgesia. Results are promising; however, larger clinical trials are necessary before opioid antagonists become the standard of care for opioid-induced constipation and pruritus.     

新疆维吾尔自治区乌鲁木齐市一起肉毒中毒事件调查分析

  目的  通过对新疆维吾尔自治区乌鲁木齐市一起肉毒中毒事件进行调查分析和实验室检测,并采取有效措施预防。  方法  通过查阅就诊记录、访谈相关医生并通过入户调查方式进行现场流行病学调查,采集病例粪便、剩余食物等进行肉毒毒素实验室检测及分型鉴定。  结果  确诊病例2例,均被收治入院。 使用A、B型肉毒抗毒素治疗后, 症状明显缓解。 实验室分离到肉毒梭菌,经荧光定量PCR方法检测携带A型毒素基因,确定为A型肉毒梭菌,小鼠实验检测到A型肉毒毒素。  结论  本次事件是一起由家庭自制豆豉引起的肉毒梭菌中毒,由A型肉毒梭菌污染导致,建议加强居民教育,防止食品制作和储存环节污染。     

Botulin toxin: a weapon in terrorism.

Clostridium botulinum, the causative agent of botulism is an anaerobic, spore forming gram-positive bacillus. C. botulinum causes three types of botulism; foodborne botulism, wound botulism, and infant botulism. Most strains of the bacterium produce a potent, muscle-paralyzing neurotoxin. Respiratory failure secondary to paralysis of the respiratory muscles can lead to death unless appropriate therapy is promptly initiated. Due to the severity and potency of this neurotoxin, its importance as a biological weapon is of major concern to public health officials.     

Food-borne botulism

Botulism is a neuroparalytic disease caused by neurotoxins produced by Clostridium botulinum, and classically presents as palsies of cranial nerves and acute descending flaccid paralysis. Food-borne botulism is the most common form of botulism, and caused by preformed neurotoxins produced by Clostridium botulinum. Electrophysiological studies play an important role in the early diagnosis. Confirmation of the diagnosis is based on the detection of botulinum toxins in the patient's serum or stool. In Japan, decades ago, botulism type E occurred, though only sporadically, almost every year, but in recent years, has dramatically decreased in frequency. Botulism is a curable disease when treated early and adequately. Differential diagnosis of cranial nerves and limb muscle palsies with rapid exacerbation should include food-borne botulism.     

Wound botulism associated with black tar heroin and lower extremity cellulitis

Wound botulism is a rare and potentially fatal disease. The use of black tar heroin has spawned an increase in the incidence of the disease, with the majority of cases occurring in California. The use of botulism antitoxin and surgical debridement are recommended to decrease hospital stay. For this to be effective, the diagnosis of wound botulism first must be considered, followed by an aggressive search for any area of infection that may be debrided. This case report demonstrates several factors to consider in patients presenting with symptoms of botulism poisoning: occurrence away from the Mexico border, no obvious abscess, and the need for prolonged ventilatory support. This case report documents a prolonged hospital stay, possibly caused by delay in administration of antitoxin in a patient with cellulitis that was not considered appropriate for debridement.     

Strategies to prevent antimicrobial resistance in the intensive care unit

OBJECTIVE: To assemble the available clinical data for the prevention of antimicrobial resistance into practical recommendations for clinicians. DATA SOURCE: A Medline database and references from identified articles were employed to perform a literature search relating to the prevention of antimicrobial resistance. CONCLUSIONS: Antimicrobial resistance has emerged as an important determinant of mortality for patients in the intensive care unit. This is largely due to the increasing presence of pathogenic microorganisms with resistance to existing antimicrobial agents, resulting in the administration of inappropriate treatment. Effective strategies for the prevention of antimicrobial resistance within intensive care units are available and should be aggressively implemented. These strategies can be divided into nonpharmacologic infection control strategies (e.g., routine hand hygiene, implementation of infection-specific prevention protocols) and antibiotic management strategies (e.g., shorter courses of appropriate antibiotic treatment, narrowing of antimicrobial spectrum based on culture results). Increasing current efforts aimed at the prevention of antimicrobial resistance is especially important given the limited availability of new antimicrobial drug classes for the foreseeable future.     

Clostridium botulinum: an increasing complication of heroin misuse.

Wound botulism is a rare infectious disease due to neurotoxin release from the anaerobic, spore-forming bacterium Clostridium botulinum that is becoming an ever more frequent complication of parenteral drug abuse in the Western world. Before the year 2000, no such cases had been reported in the UK and Ireland, but since then the number of proven and suspected cases of wound botulism occurring in parenteral drug users has increased markedly. The diagnosis is often difficult, based on a high degree of clinical suspicion and if not considered in the initial differential diagnosis, then considerable delays in treatment may result. This is the case report of a male heroin user who presented three times to an Emergency Department in the UK before a diagnosis of wound botulism was made and treatment commenced. It is important that emergency clinicians are aware of the possibility of wound botulism in parenteral drug users that present with unusual neurological or respiratory symptomatology.     

Infant botulism: case report and clinical update

Infant botulism occurs in infants between 1 week and 11 months of age and results from the in vivo production of neurotoxin by Clostridium botulinum. The clinical spectrum ranges from asymptomatic carriers, through various degrees of paralysis, to sudden death. The classic clinical presentation is an afebrile child with constipation and generalized weakness manifested by poor head control, poor suck, and weak cry. Symptoms can progress to include cranial nerve palsies, respiratory arrest, and adynamic ileus. Treatment is supportive in an intensive care setting. Antibiotics and antitoxin are not indicated. The morbidity and mortality is less than 3% in hospitalized patients and complete recovery can be expected. The environmental and dietary factors associated with infection are discussed.     

Pathogenesis and treatment of rhabdomyolysis

PURPOSE: To provide clinicians in primary and acute care settings with information on the evaluation, diagnosis, and treatment of rhabdomyolysis. DATA SOURCES: Selected review articles from print and electronic sources, and a case study. CONCLUSIONS: Rhabdomyolysis is a common disorder, which may result from a large variety of diseases, trauma, or toxic insults to skeletal muscle. It is caused by skeletal muscle injury and results in the release of muscle contents (i.e., myoglobin) into the plasma. Muscular, urinary, and general internal disturbances are the three areas where signs and symptoms occur. IMPLICATIONS FOR PRACTICE: Clinical signs and symptoms vary widely. Associated life-threatening complications include acute renal failure, cardiac arrhythmias and arrest, disseminated intravascular coagulation, and compartment syndrome. Early recognition and treatment in the acute phase of rhabdomyolysis are keys to successful outcomes and an excellent recovery.     

Shot by a Gun … Missed by a Provider

Background

Botulism is a paralytic disease caused by the neurotoxin produced by Clostridium botulinum. The majority of cases are due to ingestion or injection drug use. Wound botulism from traumatic injury is exceedingly rare, with only one to two cases reported each year in the United States.

Olmesartan medoxomil: the seventh angiotensin receptor antagonist

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and adverse effects of olmesartan medoxomil, an angiotensin II receptor antagonist for the treatment of hypertension. DATA SOURCES: Information was obtained from MEDLINE searches (1996-April 2002) of English-language medical literature. Search terms included CS-866, olmesartan, olmesartan medoxomil, RNH-6270 (active metabolite of olmesartan), Benicar, angiotensin receptors, and antihypertensive agents. In addition, references from relevant articles were reviewed for additional citations. The authors independently reviewed literature identified in the searches. Studies evaluating olmesartan (i.e., abstracts, clinical trials, data on file with manufacturer) were considered for inclusion. STUDY SELECTION: All articles identified from data sources with pertinent information regarding olmesartan medoxomil were evaluated, and all information deemed relevant was included in this review. DATA SYNTHESIS: Olmesartan medoxomil is a competitively priced addition to the class of angiotensin II receptor antagonists. Monotherapy with olmesartan medoxomil in once-daily doses of 20-40 mg has produced significant reductions in systolic and diastolic blood pressure in hypertensive patients. Adverse effects have been minimal with olmesartan medoxomil, with dizziness being the only adverse effect occurring more often than with placebo in clinical trials. Additionally, animal studies indicate that olmesartan medoxomil may prove to be useful treatment for diabetic nephropathy, as well as atherosclerosis. CONCLUSIONS: Olmesartan medoxomil has a favorable safety and efficacy profile, with blood pressure-lowering effects comparable to those of other angiotensin receptor blockers (i.e., losartan, valsartan, irbesartan). At this time, formulary decisions will be driven primarily by economic issues. Theoretical benefits of olmesartan medoxomil in reducing atherogenesis and lowering angiotensin II concentrations better than the alternative agents will be determined only with more extensive research.