Tetanus, Botulism, & Anaerobic Infections (RCSI) 2024 Lecture Notes PDF

Leading the world to better health Tetanus, botulism and other anaerobic bowel infections Dr James Donnelly Clinical Lecturer Dept. of Cinical Microbiology RCSI  RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in...

Leading the world to better health Tetanus, botulism and other anaerobic bowel infections Dr James Donnelly Clinical Lecturer Dept. of Cinical Microbiology RCSI  RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn SESSION ID: GIHEPMicroL2 Tetanus, botulism and other anaerobic bowel infections Class: Year 2 24/25 Course: Undergraduate Medicine Lecturer: Dr. James Donnelly Date: 18th September 2024  LEARNING OUTCOMES By the end of the lecture, you will be able to: Outline the basic laboratory features of clinically important anaerobic bacteria and explain the biological role of each in the pathogenesis of infection Discuss the epidemiology of clinically important anaerobic bacteria Describe the pathogenesis of infections caused by clinically important anaerobic bacteria Recognise and describe the clinical features and complications of infections caused by clinically important anaerobic bacteria  LEARNING OUTCOMES By the end of the lecture, you will be able to: Outline the laboratory diagnosis of infections caused by clinically important anaerobic bacteria and describe their laboratory features e.g. Gram stain appearance etc. Choose the appropriate antimicrobial agents to treat infections caused by clinically important anaerobic bacteria Use the appropriate measures to prevent the acquisition and spread of infections caused by clinically important anaerobic bacteria  BACTERIAL CLASSIFICATION: ENERGY GENERATION, METABOLISM & GROWTH Classification is a continuum Bacteria can be classified on how they handle O2 Aerobes require O2 as a terminal electron acceptor Anaerobes depend on other substances Facultative organisms preferentially use O2 as a terminal electron acceptor, but can metabolise without it by reducing other compounds MAJOR CLINICALLY IMPORTANT ANAEROBES GRAM POSITIVE GRAM NEGATIVE Cocci Bacilli* Peptostreptococcus Bacteroides spp. Bacilli Prevotella spp. Clostridium spp.* Fusobacterium spp. Lactobacillus spp. Cutibacterium spp. * Key pathogens Also classified into spore- & non-spore forming anaerobes. Clostridia spp. are spore-forming.  EXAMPLES OF NON-SPORE- FORMING ANAEROBES Gram +ve Gram +ve Gram –ve Gram –ve bacilli cocci bacilli* cocci Cutibacterium Peptostreptoco Bacteroides, Veillonella spp. spp. ccus & Strep Prevotella, spp. Fusobacterium spp. & others Found in the Skin flora but Mouth & GIT mouth, low increasingly infections such Head & neck grade found in as gingivitis infections pathogen & orthopaedic & (Fusobacterium usually causing other )& infections with complicated surgical/abdom other bacteria surgical inal infections infections e.g. peritonitis (Bacteroides & *Probably the most important group vis a vis intra-abdominal Prevotella) infection (peritonitis) & post-operative surgical site infections  EPIDEMIOLOGY: ANAEROBES Endogenous Exogenous Oral cavity / URT Clostridium spp. – Fusobacterium – Decaying vegetable – Peptostreptococcus spp. matter / soil, etc. Skin – Cutibacterium acnes Animal flora Colon – Capnocytophaga – Bacteroides canimorsus – Clostridium – Peptostreptococcus – Prevotella Female genital tract – Lactobacillus spp. EXAMPLES OF ANAEROBIC INFECTIONS Endogenous Oral cavity / URT Endogenous (cont’d) – Dental abscesses/ Infections assoc with Periodontitis ischaemia / trauma – Vincent’s angina – Diabetic foot infections – Aspiration pneumonia – Gas gangrene (C. – Pulmonary abscess perfringens) Skin – review SSTI lecture BMF Colon Exogenous – Abscesses Abdominal / biliary – Peritonitis secondary to – Diarrhoea & colitis perforation – Food poisoning Female genital tract – Post-partum or post-abortal infections DIAGNOSING ANAEROBIC INFECTIONS Clues to anaerobic infection include: Infection adjacent to a mucosal surface Free gas in infected tissues (palpation – crepitus, or X-ray) Foul smelling pus/infected tissues/lesion Necrotic infected tissues, abscess formation, gas gangrene Predisposing factors, e.g., ischaemia, perforation of bowel Infection not responding to antimicrobials active against aerobes only e.g., cefotaxime, aminoglycosides “Sterile pus” Diarrhoeal illness/colitis in a patient who has recently received antibiotics PATHOGENESIS - MICROBIAL FACTORS Many anaerobic infections arise from Get in – the host’s normal flora; Portal of spores Entry Get out and Attach to spread cells further Polysaccharide capsule (e.g., B. fragilis): impairs phagocytosis Production of Cause Defeat/evade short chain fatty damage to the immune acids - inhibit host cells system phagocytosis Toxin production PREDISPOSING FACTORS Host External Impaired gag / cough GI surgery reflex – Often co-pathogens in – GA, stroke, drug OD post-op polymicrobial – Aspiration pneumonia infections Trauma & tissue LL amputation + PVD – Skin contaminated with C. ischaemia – Reduced blood supply perfringens spores (or other) lowers oxidation / reduction potential Antibiotics – Can predispose to – Altered normal colonic anaerobic infection flora (C. difficile) CLOSTRIDIA: COMMON FEATURES Gram positive bacilli All: – Form spores – Produce powerful exotoxins Mostly STRICT anaerobes Ubiquitous organisms, present in soil, water, sewage Focus on the main pathogenic spp: – Clostridium tetani – Clostridium botulinum – Clostridioides difficile – Clostridoides perfringens CLOSTRIDIUM TETANI Tetanus is a life-threatening illness Manifested by muscle rigidity & spasms Image: medical-labs.net Caused by the spore forming organism Cl. tetani Symptoms & signs are caused by a neurotoxin (tetanospasmin) Produced by the vegetative form of Cl. tetani Tetanus is a vaccine preventable disease Image: Merck Manuals Professional edition TETANUS: EPIDEMIOLOGY Incidence varies worldwide Wealthier countries = decreasing due to immunisation Cl. tetani spores survive in environment – Inoculated via skin trauma 2000-2015, 12 cases in Ireland with 2 deaths In 2015 34,000 newborn infants died from neonatal tetanus Most cases within 14 days of introduction of the organism Person-to-person transmission does not occur MATERNAL & NEONATAL TETANUS C Louise Thwaites, Nicholas J Beeching, Charles R Newton Maternal and Neonatal Tetanus Lancet 2015:385;362-70 TETANUS: PATHOGENESIS Spores in wound germinate when there is a localized anaerobic environment (e.g., necrotic tissue) Tetanus neurotoxin (TeNT) produced and absorbed by the peripheral neuron with retroaxonal transport to the spinal cord TeNT blocks neurotransmitter release from the spinal inhibitory interneurons -> prevents ‘relaxation’ of muscles resulting in sustained muscle contraction/spasms (inhibition of inhibitory interneurons) TETANUS: CLINICAL PRESENTATION Muscle Spasms – May be frequent, last for minutes, & persist for 3-4 weeks – Muscles of the thorax, abdomen and extremities = flexion of arms, extension of legs, arching of back – Trismus or “lockjaw” – “risus sardonicus” / rictus grin Produced by increased tone of orbicularis oris Complications – Laryngospasm – Autonomic nervous system dysfunction (labile BP, arrhythmias, sweating) – The mortality rate is ≥ 60% in severe cases A Colour Atlas. Zatouroff, Wolfe TREATMENT OF CLINICAL TETANUS Time is key! Diagnosis & Management 1. Tetanus is a clinical diagnosis - early recognition 2. ABC – some patients require intubation 3. Treat infected source tissue Wound debridement Antimicrobials such as benzylpenicillin/metronidazole 4. Neutralize the toxin by administration of human tetanus immunoglobulin (TIG) 5. Manage spasms 6. Avoid touch, light, & other stimuli TETANUS PREVENTION & IMMUNISATION Prevented by immunisation with toxoid vaccines Recovery from tetanus does confer natural immunity The majority of cases are birth-associated among newborn babies & mothers not vaccinated In 2016, 86% of infants worldwide were vaccinated with 3 doses of diphtheria-tetanus-pertussis (DTP) Toxoid vaccine is part of childhood vaccination programme in many countries: DTP (diphtheria-tetanus-pertussis) vaccine – Clinical efficacy almost 100% but immunity wanes & after 10 years may not provide protection – i.e., if you stand on a dirty nail & it is more than 10 years since your last tetanus shot you may need a booster! POST EXPOSURE PROPHYLAXIS Tetanus prone wounds include: – Puncture type injuries acquired in a contaminated environment – Wounds containing foreign bodies – Compound fractures – Wounds or burns with systemic sepsis – Some animal bites/scratches (note most domestic pets are unlikely to have saliva containing spores unless animal rooting in soil or lives in an agricultural setting) High risk wounds: – Heavy contamination with material likely to contain spores e.g. soil, manure – Wounds or burns with extensive devitalised tissue (anaerobic environment) POST EXPOSURE PROPHYLAXIS Management will depend on vaccination history Discuss with Clinical Microbiology if TIG indicated https://rcpi.access.preservica.com/ uncategorized/IO_8a0eda3f-c7cb-456c- ae1a-1e3583567fa2/ CLOSTRIDIUM BOTULINUM Image: cdc.org Botulism is a paralytic illness caused by Cl. botulinum neurotoxin Botulinum toxin is used medically as “Botox” Toxin inhibits the release of acetylcholine at neuromuscular junction results in weakness/acute flaccid paralysis Cl botulinum can survive in soil & untreated water for protracted periods There are several types of botulism: foodborne botulism wound botulism infant botulism CATEGORIES OF BOTULISM 1. Foodborne (ingestion of toxin) Most common form following ingestion of contaminated food (e.g., home canned foods) – Food contaminated by spores – If not cooked thoroughly & then put in an anaerobic environment (e.g., sealed jar)  spores germinate  toxin produced – If the contaminated food is then eaten = Fast onset of symptoms 12 –36 hours after ingestion – Typically the food will look & taste normal 2. Wound botulism (spores deposited in open wounds) Then germinate & produce toxin 3. Infant botulism (ingestion of spores e.g., via food) Germinate in the GIT Toxin then released in the GIT & absorbed BOTULISM PRESENTATION Symmetrical descending flaccid paralysis – Bilateral cranial nerves palsies = double vision, difficulty swallowing – General muscle weakness – Respiratory failure without impairment of consciousness Fever is classically absent Infant botulism – Constipation & then muscle weakness / lethargy / poor feeding / ‘floppy’ baby BOTULISM OUTBREAKS Outbreak of botulism in Bordeaux, France in 2023 during the rugby world cup 15 cases, at least 8 hospitalised and required management in the intensive care unit One person died Linked to contaminated canned sardines produced at a local restaurant  DIAGNOSIS & MANAGEMENT Clinical picture Prevention History of possible exposure – Care with home Laboratory tests help confirm the preserving diagnosis – Infants: No raw honey – Foodborne: detect toxin in stool / less than 12 months vomitus – Hand hygiene & care with – Infant botulism: organism or toxin in stool preparation of food – Wound: culture from wound site Management – ABC – Antitoxin: Botulism IG There is an infant formulation BabyBIG – Wound: Debridement & metronidazole CLOSTRIDIOIDES DIFFICILE C. difficile can cause symptoms ranging from diarrhoea to life-threatening inflammation of the colon C. difficile in soil, air, water, human & animal faeces Spores survive outside of the body Up to 1 in 10 healthy adults carry C. difficile in the colon (colonisation) 70% of infants but infection is RARE Infection occurs typically in people in contact with healthcare/been on antibiotics Infection with C. difficile occurs in ~half a million people/yr in the US ANTIBIOTICS & C. DIFFICILE Use predisposes to colonisation & infection Antibiotics are the principal risk factor for infection – Disruption of normal colonic flora Virtually all antibiotics have been implicated The most frequently associated are: – Fluoroquinolones – β lactam antibiotics, particularly co-amoxiclav, & third generation cephalosporins (cefotaxime & ceftriaxone) – Clindamycin The symptoms & signs are caused by toxins – There are at least 2 types of toxin: A & B  C. DIFFICILE & THE CHAIN OF INFECTION Infectious agent C.difficile Advanced age Bowel Antibiotic use Contaminated Hospitalisation Susceptible host environment ‘At-risk’ patients Reservoir or residents en tr y Means of CONTACT lo f Po r t a Transmission Transmission 1. Hands Faecal/Oral 2. Equipment 3. Environment  TWO CATEGORIES OF C. DIFFICILE INFECTION (CDI) New Recurrent – Occurs within 8 weeks after onset of a previous episode – Risk of recurrence increases with each recurrence Symptoms of CDI – Asymptomatic to potentially fatal Diarrhoea Fever Acute abdomen / pseudomembranous colitis  Suspect it S where there is no clear alternative cause for diarrhoea (e.g., diarrhoea during or after antibiotics) Isolate the patient What do you do if I you suspect CDI? Gloves & aprons G Contact precautions Hand washing (not alcohol gel) H after each contact with the patient & their environment Test the stool for toxin- T producing C. difficile - PCR for the toxin gene  DIAGNOSIS Clinical suspicion, e.g. diarrhoea during or after antibiotics **Test faeces for C. difficile toxin** Diarrhoeal specimen – same day test result PCR for presence of toxin gene tcdB - sensitive EIA for presence of toxin – confirmatory, specific TREATMENT: GENERAL PRINCIPLES 1. Isolation + contact precautions 2. Review & stop antibiotic(s) if possible a) If not, switch to agents with a lower propensity to induce C. difficile infection 3. Supportive therapy (fluids etc) 4. Antibiotic treatment of CDI a) (oral) Vancomycin OR b) Fidaxomicin c) Metronidazole no longer first line agent (reduced efficacy v. vancomycin/fidaxomicin) CLOSTRIDIOIDES DIFFICILE INFECTION: PREVENTION & CONTROL 1. Antibiotic stewardship 2. Infection prevention & control guidelines, e.g. hand hygiene CLOSTRIDIOIDES PERFRINGENS Cl. perfringens causes tissue necrosis Well known for its association with gas gangrene (clostridial myonecrosis) & emphysematous cholecystitis Common cause of food poisoning Ingestion of food contaminated with toxin producing organisms/spores Cl. perfringens ubiquitous in nature Decaying vegetation, soil, marine sediment, GIT of humans & animals  CLINICAL PRESENTATION Produce many virulent toxins – Toxin involved in gas gangrene is α toxin, a lecithinase Inserts into the cell membrane causing holes & disrupting cellular function – Cl. perfringens food poisoning is caused by an enterotoxin Food poisoning after ingestion of contaminated food – Contaminated meat products (beef, poultry, gravy, dried or precooked foods) served without adequate reheating – Abdominal cramps/diarrhoea Cellulitis/wound infection: usually in devitalised tissue Gas gangrene – Contaminated wounds with poor blood supply & tissue necrosis – Progressive invasion & destruction of healthy muscle tissue GAS GANGRENE Rapidly progressive infection Destruction of muscle Severe systemic toxicity Investigations: Wound swab/ blister fluid for culture Blood cultures Prompt debridement of all nonviable tissue is essential Antimicrobials: – Combination therapy § High dose penicillin / clindamycin § Antitoxin activity Mortality 40-100% PREVENTION OF CLOSTRIDIUM PERFRINGENS DISEASE Food Poisoning Cook & keep food at correct temperature; serve meat dishes hot, within 2 hours after cooking Refrigerate leftovers & reheat them properly When in doubt, throw it out! Cellulitis/Wound Infection, Gas Gangrene Clean wounds thoroughly Remove foreign objects & dead tissue from wounds IV antibiotic prophylaxis with abdominal surgery Skin preparation & administer IV antibiotics if lower limb amputation in patients with peripheral vascular disease PREVENTION OF ANAEROBIC INFECTION Non-specific = wound debridement, safe food preparation Specific = toxoid vaccine Clostridial infections already covered under individual clinical conditions Surgery on bowel – Prophylactic antibiotics using an agent with anaerobic cover – Care with surgery to avoid/minimise the risk of spillage of bowel content into peritoneal cavity – If peritoneal contamination occurs – treatment using appropriate antimicrobial SUMMARY Anaerobic bacteria are ubiquitous in nature & as part of normal flora Predisposing conditions include trauma, necrosis & ischaemia Spore-forming include clostridia that produce toxins with characteristic presentations, e.g. C. tetani Clostridioides difficile is a major cause of healthcare- associated diarrhoea Anaerobic Gram negative bacilli such as Prevotella spp. common in surgical infections such as peritonitis Not all antibacterial agents have anaerobic culture 40YO FEMALE WITH WEAKNESS & FLACCID PARALYSIS AFTER EATING HOME MADE PÂTÉ A.Clostridioides difficile B.Clostridium botulinum C.Clostridium perfringens D.Clostridium tetani 32YO CARPENTER WITH A SMALL WOOD SPLINTER IN HAND FOR 7 DAYS WITH SEVERE SPASMS EVERY FEW MINUTES, WORSE WITH NOISE A. Clostridioides difficile B. Clostridium botulinum C. Clostridium perfringens D. Clostridium tetani 75 YO MALE WITH FEVER & DIARRHOEA AFTER HOSPITAL DISCHARGE FOLLOWING TREATMENT FOR URINARY TRACT INFECTION A. Clostridioides difficile B. Clostridium botulinum C. Clostridium perfringens D. Clostridium tetani 18YO MALE ADMITTED 6 DAYS AGO WITH MULTIPLE TRAUMA: GAS ON X-RAYS OF LEFT LEG A. Clostridioides difficile B. Clostridium botulinum C. Clostridium perfringens D. Clostridium tetani 23YO FEMALE INTRAVENOUS DRUG USER WITH INFECTED LEG WOUND; NOW DOUBLE VISION & DIFFICULTY SWALLOWING A. Clostridioides difficile B. Clostridium botulinum C. Clostridium perfringens D. Clostridium tetani  1 2 4 5 6 7 8 3 SAMPLE PSA MCQ: Case presentation: A 75 year old male presents to the Emergency Department A.Ciprofloxacin with a 48 hours history of diarrhoea, 7 500mg BD PO episodes of type 6 stool over the last 24 B.Metronidazole hours. He recently completed a course of 400mg IV TDS cephalexin for a urinary tract infection. C.Metronidazole Investigations: Faeces is sent to the 500mg TDS PO microbiology laboratory where D.Vancomycin 1g BD Clostridioides difficile toxin is detected by IV PCR and EIA E.Vancomycin 125 Question: What is the most appropriate mg QDS PO treatment for Clostridioides difficile infection in this patient? Thank you