Infectious Disease Reports 2018; volume 10:7654

Wound botulism caused by of wound botulism is commonly associated Clostridium subterminale after with injection drug users but has also been Correspondence: Aimee Mishler, Department described in traumatic injuries with of Pharmacy, Maricopa Medical Center, 2601 a heroin injection exposure to soil. East Roosevelt Street, Phoenix, AZ 85008, USA. Paris A. Cook,1 Aimee Mishler,1 Tel.: +1.602.344.5686 - Fax: +1.602.344.5565. E-mail: [email protected] Dan Quan,2 Ashley Parrish-Garcia2 1Department of Pharmacy; 2Department Case Report Key words: Botulism; wound botulism; anti- of Emergency Medicine, Maricopa A 33-year-old male had recently toxin; Clostridium; Clostridium subterminale. Integrated Health System, University of presented to another hospital in the area just Arizona, Phoenix, AZ, USA prior to admission at our hospital for Contributions: PC was the main author who weakness, fatigue and bilateral hip and leg completed the first draft of all sections, abscesses. At that time he elected to be excluding the abstract. AM was the author treated for cellulitis as an outpatient and who was the primary editor for the abstract, introduction, and discussion sections and was was prescribed cephalexin 250 mg by Abstract the author who completed the second draft, mouth four times daily and excluding the abstract, + coordinated all corre- Botulism is caused by toxin production sulfamethoxazole-trimethoprim 400-80 mg spondence between authors, was responsible from many species of Clostridium, most by mouth twice daily for ten days. He then for compiling each portion of the manuscript, commonly Clostridium botulinum as well presented to our hospital two days later with and was responsible for formatting and sub- as C. baratii and C. butyricum. a chief complaint of difficulty swallowing mitting the manuscript. DQ was the final edi- Development of wound botulism is and progressive weakness which he states tor for all portions. AP-G was the author who associated with injection drug users but has he had for one week. His past medical completed the abstract and was the primary also been described in traumatic injuries history included daily heroin use, editor for the case report section. with exposure to soil. A patient presented to administered by skin popping or injecting Conflicts of interest: the authors declare no the emergency department with a complaint the drug under the skin either intradermally conflictsonly of interests. of descending, progressive weakness. He or subcutaneously, and untreated hepatitis C.On presentation to our hospital, the recently reported skin popping with heroin Received for publication: 24 February 2018. injections. Heptavalent botulinum antitoxin patient was only able to open his eyelids 2- Revision received: 4 June 2018. was obtained from the [Center for Disease 3 mm wide and had difficulty keeping themuseAccepted for publication: 14 June 2018. Control and Prevention (CDC)]. On open, diplopia, difficulty swallowing and hospital day seven, the anaerobic wound pooling of secretions after 1-2 words, voice This work is licensed under a Creative cultures resulted with growth of changes, difficulty holding his head up and Commons Attribution-NonCommercial 4.0 Clostridium subterminale. proximal upper extremity weakness. International License (CC BY-NC 4.0). Strength in his upper extremities were 4/5. Initial vital signs included: blood pressure ©Copyright P. A. Cook et al., 2018 Licensee PAGEPress, Italy 136/80 mmHg; pulse rate 106 beats/min; Infectious Disease Reports 2018; 10:7654 Introduction respiratory rate 19 breaths/min; oral doi:10.4081/idr.2018.7654 temperature 36.5°C (97.7°F); and room air Botulism is an illness caused by toxin pulse oximetry 98%. Five deep cavity production from many species of the abscesses were incised and drained from the ® Clostridium genus of bacteria, most patient’s hips and thighs, and standard and antitoxin (A, B, C, D, E, F, G) –BAT commonly Clostridium botulinum, C. anaerobic wound cultures were collected. Equine was coordinated directly with the baratii, and C. butyricum. These bacteria After a few hours, the weakness became [Centers for Disease Control and are anaerobic, spore-forming, Gram- more pronounced in the patient’s neck and Prevention (CDC)]. The antitoxin arrived positive organisms found naturally in the extremities and breathing became very by freight air transport the next morning on soil. The different types of botulismNon-commercial include shallow. The decision was made to intubate hospital day two and was administered via foodborne botulism from improperly the patient in the emergency department for infusion approximately nineteen hours after canned or stored foods, infant botulism and airway protection and impending presentation to the emergency department. adult intestinal toxemia from ingestion of respiratory failure before transferring him Serum, stool and wound cultures were sent botulinum neurotoxin-producing species of to the [medical intensive care unit (ICU)]. A to the CDC for analysis. Wound cultures Clostridium in infants and adults, urine drug screen was positive for were also sent to the hospital’s lab for respectively, wound botulism, and amphetamines, opiates, and acetone. analysis. In addition, vancomycin and iatrogenic botulism as a result of cosmetic The constellation of symptoms seen in piperacillin-tazobactam, were started for or therapeutic botulinum toxin overdoses. the emergency department was suggestive broad antibiotic coverage including Wound botulism can occur when botulinum of botulism, with other differential possible [methicillin-resistant neurotoxin-producing species of diagnoses including Guillain-Barré Staphylococcus aureus (MRSA)]. Clostridium infect and germinate in wounds Syndrome and myasthenia gravis. He In the medical ICU, the patient’s and begin producing toxins. Wound reported not having eaten canned food that weakness plateaued and antibiotics were botulism presents most similarly to had been bulging and had not traveled deescalated to vancomycin and ampicillin- foodborne botulism with descending flaccid outside of the country recently. Therefore, sulbactam for continued coverage of his paralysis of facial, swallowing, and the suspicion was for possible wound complicated skin-soft tissue infection. After respiratory muscles, with the exception that botulism. The Maricopa County three days in the ICU (hospital day four), a it does not typically have accompanying Department of Public Health was contacted, tracheostomy was performed for the gastrointestinal symptoms.1-3 Development and receipt of heptavalent botulinum expected long recovery time and a PEG

[page 42] [Infectious Disease Reports 2018; 10:7654] Case Report tube was inserted. The patient was then isolated from wounds. To our knowledge, patients who were enrolled in methadone transitioned to oral antibiotics, amoxicillin- this is the first case reporting a Clostridium programs in California and had never had clavulanate 875 mg by mouth twice daily subterminale positive wound culture with wound botulism. Both groups reported and sulfamethoxazole-trimethoprim 800- type A toxin identified in the serum sample. similar rates, 96% and 97% respectively, of 160 mg, two tablets by mouth twice daily C. subterminale is a species that is similar [black tar heroin (BTH)] use. Their results for two weeks. On hospital day seven, the to Group IV Clostridia and has been shown showed that a significantly higher anaerobic wound cultures analyzed by the to be able to produce typeG toxin, which is percentage of patients with wound botulism hospital’s lab resulted with growth of not responsible for human illness and to were injecting BTH by skin popping either Clostridium subterminale . On hospital day express the gene capable of producing type subcutaneously or intramuscularly than ten, results from the CDC serum analysis B toxin, however, has not been shown to their control counterparts (92% vs 44%, reported toxin A which was identified using actually produce this toxin.4-6 One study P<0.001).17 Other studies have continued to MALDI-TOF mass spectrometry, the which focused on Clostridia infections in look at wound botulism in injection drugs wound culture analyzed by the CDC did not post-traumatic wounds identified five cases users, especially those using BTH, and have report botulinum toxin, and the stool was where the growth of C. subterminale was found similar results.18 not analyzed. found associated with soil contamination.7 Early recognition of the signs and After a twelve-day hospital stay, the C. subterminale has been previously symptoms of botulism is important. Due to patient was discharged to a skilled nursing reported in immunocompromised patients neuroparalytic effects of the toxin produced facility. He continued to have bilateral undergoing chemotherapy, with three by Clostridium bacteria, there is a cluster of ptosis, difficulty swallowing and bacteremia cases reported.8-10 A separate symptoms typical of patients presenting generalized weakness. He continued to have case of bacteremia in an immunocompetent with botulism. The most classic signs are 4/5 bilateral deltoid muscle strength but 5/5 patient was found after an esophageal cranial nerve palsies and descending flaccid strength in all other major muscle groups. rupture.11 Additionally, there were two cases paralysis. The eyes are often reported as He had a tracheostomy placed on hospital reported C. subterminale in being affected first with signs of diplopia day 5 and was being weaned off the pleuropulmonary infections, two cases of and ptosis. This is frequently followed by ventilator at time of discharge. soft tissue infection, and one case in an facialonly paralysis and paralysis of the open fracture.12-15 None of the studies muscles associated with chewing and mentioned above provide information swallowing resulting in difficulty regarding neurologic exam findings or toxin swallowing and forming words. Sometimes, Discussion and Conclusions identification. Based on these caseuse reports after that, a proximal to distal progression Wound botulism is caused by the and available literature examining the of paralysis occurs in the arms and legs. If growth of Clostridium bacteria, most ability of C. subterminale to produce paralysis continues, the toxin may commonly Clostridium botulinum, and botulinum toxin it is possible that our eventually affect the diaphragm and subsequent toxin production in a wound. patient had a co-infection with another accessory breathing muscle resulting in Many Clostridia species including: C. Clostrida species that was not identified in respiratory distress or failure. Respiratory botulinum, C. butyricum, C. argentiense, C. the sole wound culture that was obtained. failure may occur earlier in the illness due 1,2 baratii, C. subterminale, C. hastiforme, C. The CDC has compiled an annual to upper airway collapse or aspiration sporogenes, and C. perfringes, have been surveillance study since 2001 of all reported Often, this results in patients being shown to produce eight different toxins, A, cases of botulism and provide data on the intubated and a subsequent stay in the ICU. B, C-a, C-b, D, E, F, and G. However, only number of botulism cases by type, toxins Wound botulism does not frequently certain toxin types have been associated found, and states where the cases occurred. involve the gastrointestinal symptoms that 3 with human botulism which include type A, The most recent CDC Botulism Annual would be seen in foodborne botulism. B, E and F toxins with type A, B and E Survey in 2016 reported twenty-four cases Due to the type of symptoms present in accounting for the majority of cases. C. of confirmed wound botulism (12% of all botulism infections, there are a number of botulinum has been shown to produce all botulism cases that year) and an additional differential diagnoses that need to be four toxin types. C. baratii has been shown two cases of probable wound botulism. considered. Guillain-Barré syndrome is an to produce type E toxin and C.Non-commercial butyricum Twenty-three (95.8%) of the patients with autoimmune disease that demyelinates has been shown to produce type F toxin. confirmed wound botulism were injection neurons and causes an ascending paralysis. Type A toxin is most prevalent in the drug users (22 injected black tar heroin and However, the Miller Fischer variant of western United States and type B in the 1 injected methamphetamine).16 There has Guillain-Barré syndrome presents with a eastern United States and Europe. Type E is been a steady number of wound botulism descending paralysis, closer mimicking that associated with the consumption of raw cases reported since 2001 with an average of botulism. Myasthenia gravis is an marine animals around the world.2 These of 23 cases per year. The majority of wound autoimmune neuromuscular disease that toxins are taken in by presynaptic nerve botulism cases in 2016 (15 cases) occurred results in weakness of certain muscle endings where they irreversibly cleave to in California, with the next highest amount groups, sometimes including facial and soluble N-ethylmaleimide sensitive fusion in New Mexico (3 cases). Other states respiratory muscles. Bilateral or brainstem protein attachment receptor which prevents where cases were reported include Arizona, strokes can also cause similar symptoms acetylcholine-containing vesicles from Colorado, Utah, Texas, New Jersey, and such as facial drooping, limb weakness, and fusing to the cell membrane and releasing Hawaii with one case each. . breathing difficulties.1,19 Ruling out other the neurotransmitter into the synapse. This A 1998 study published in JAMA differential diagnoses is important, results in a classic flaccid paralysis in looked at twenty-six cases of wound however, until botulism can be definitively patients with botulism.2 botulism occurring in California from 1994 ruled out, treatment should be considered. In our particular case, the organism to 1996 with the intent of finding common The treatment of botulism includes the isolated was of unique interest as it is not risk factors among these cases. They administration of botulinum antitoxin. For commonly described as pathogenic nor compared these cases with 110 control wound and foodborne botulism, this refers

[Infectious Disease Reports 2018; 10:7654] [page 43] Case Report specifically to the equine-derived, for those patients who were treated early patient. IDCases 2016;5:43-5. heptavalent antitoxin that covers types A, B, (≤2 days) verses those who were treated 12. Grobach SL, Thadepalli H. Isolation of C, D, E, F, and G toxins. This antitoxin is later.23 clostridium in human infections: supplied by the CDC. Local or state health evaluation of 114 cases. J Infect Dis departments and the CDC are available 24 1975;131:S81-5. hours per day 7 days per week for urgent 13. Gubler JG, Wuest J, Hany A. clinical consultations to discuss whether References Pleuropulmonary infection due to botulism is likely and whether treatment Clostridium subterminale. J Infection 1. Sobel J. Botulism. Clin Infect Dis with botulinum antitoxin is warranted. The 1989;19:277-80. 2005;41:1167-73. antitoxin works by binding to and neutraliz- 14. Patel SB, Mahler R. Clostridial 2. Horowitz BZ. Botulinum toxin. Crit ing any free botulinum toxin and preventing pleuropulmonary infections: case report Care Clin 2005;21:825-39. them from binding to nerve endings block- and review of the literature. J Infection 20 3. Centers for Disease Control and ing the development of paralysis. 1990;21:81-5. Administration of the antitoxin does not Prevention. Botulism. Information for 15. Tappe D, Valenza G, Duwe T, et al. affect the toxin that is already bound, there- Health Professionals. Available from: Clostridium subterminale infection fore, it does not reverse any paralysis that is https://www.cdc.gov/botulism/health- secondary to an open fracture. Infect already developed but will prevent further professional.html Accessed: April 12, Med 2009;26:28-30. paralysis from forming. There have been no 2017. 16. Centers for Disease Control and randomized control trials examining equine 4.Hauschild AHW, Dodds KL. Prevention. 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The results of this study showed a recipient of allogeneic cord blood JG, et al. Wound botulism in injection that increasing the time from presentation to transplantation. Intern Med drug users: time to antitoxin correlates antitoxin administration was associated 2003;42:374-5. with intensive care unit length of stay. with an increased length of stay in the 10. Haussen DC, Macedo FY, Caperton CV, West J Emerg Med 2009;10:251-6. ICU.22 A third study reviewed 249 patients et al. Clostridium subterminale sepsis in 23. Yu AP, Lin NH, Mahon BE, et al. Safety with confirmed botulism who received the adult acute lymphoblastic leukemia. and improved clinical outcomes of equine-derived heptavalent botulinum Leuk Lymph 2011;52:1137-8. patients treated with new equine- antitoxin. This study showed a significantly 11. Daganou M, Kyriakoudi A, Moraitou derived heptavalent botulinum shorter length of hospital stay (15 vs 25 H, et al. Clostridium subterminale antitoxin. 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