Necrotizing soft tissue infections (NSTIs) and Clostridium difficile

1. Necrotizing soft tissue infections (NSTIs) and Clostridium difficile Dr. enikő Tóth Semmelweis university 2nd department of surgery

2. NSTIs • Group of rare, fulminant type of complicated soft tissue infections • Characterized by advancing tissue necrosis • “flesh-eating bacteria” • Life threatening medical emergencies which requires early, aggressive treatment • Includes: gas gangrene, streptococcal gangrene, gangrenous cellulitis, necrotizing cellulitis/fasciitis, Clostridial myonecrosis, Fournier’s gangrene

3. Epidemiology • 500-1500 cases annually in the USA • Surgeons/primary care physicians will encounter at least one NSTIs in their lifetime • Mortality rate is more than 35%

4. Classification TYPE II TYPE III TYPE I 55-75% Polymicrobial – Staphylococcus aureus, E.coli, Clostridium, Bacteriodes Compromised immune system, DM, peripherial vascular disease, surgical procedures, obesity, alcohol abuse, chr. kidney disease Fournier’s gangrene, Ludwig‘s angina! 10-15% Group A beta hemolytic Streptococci with/without Staphylococcus aureus Young, healthy individuals Mostly on the extremities Originates from minor injuries Least common Clostridium and Vibrio

5. Other classificationDepth of the invasion Erysipelas, Impetigo, Folliculitis, Furunculosis, Carbunculosis Epidermis Dermis Superficial fascia Subcutaneous fat, arteries, veins Deep fascia Muscle Cellulitis Necrotizing fasciitis Myonecrosis (Clostridial or non-clostridial)

6. Histopathological findings (degree of neutrophilic infiltration, presence of necrosis and microabscesses) Anatomic location (perineum –fournier’s gangrene, submandibular region –ludwig’s angina) Other classifications

7. Risk factors • Often develop in healthy, young individuals • Diabetes mellitus • Peripheral vascular disease • Obesity • Chronic renal failure • Cirrhosis • Heart failure • AIDS • Immunosuppression • Injection drug use, alcoholism • Insect bites, abscesses, recent trauma/surgery

8. Pathophysiology • Production of endotoxins and exotoxins: • Tissue destruction • Ischemia and necrosis • Endothelial damage • Increased tissue edema and impaired capillary blood flow • Increased escape from host defense (e.g. phagocytosis) • Neutrophil infiltration • Activation of coagulation cascade thrombosis and worsened ischemia • STREPTOCOCCI • M protein facilitates attachment to the host cells, prevents bacterial endocytosis • Enzymes  facilitate the spread of the infection and prevent the migration of neutrophils to the site of the infection • Superantigens  stimulate pro-inflammatory response

9. Clinical presentation • Nonspecific findings: tenderness on palpation, swelling, erythema, warmth, pain • “hard signs” – bullae, crepitation, skin anaesthesia, skin necrosis and dusky discoloration • Haemodinamic instability, organ failure (predictive of mortality)

10. Fournier’s gangrene

11. Ludwig’s angina

14. Diagnosis • Physical examination • Laboratory risk indicators – LRINEC score: CRP, WBC, hemoglobin, sodium, creatinine, glucose • Radiographic imaging – X ray, ultrasound ( >4mm fluid), CT, MRI • Fluid and tissue sampling • Surgical exploration  loss of tissue resistance to blunt dissection, thrombosis of subcutaneous vessels, smelling, grayish appearance of the fascia with/without obvious tissue necrosis • Frosen-section biopsy!

16. Management 1. BROAD SPECTRUM ANTIBIOTICS • Early, empiric, broad spectrum antibiotics are strongly recommended • Aerobic and anaerobic gram-positive and negative agents • Carbapenems (imipenem/cilastatin, meropenem) • Beta lactams (piperacillin/tazobactam) • Vancomycin

17. Management 2. SURGICAL DEBRIDEMENT • Prompt and aggressive • Complete resection of necrotic tissues and drainage of fluid collections • 10-25% amputation (sometimes several times) • Frequent reevaluation

18. Adjunctive therapies • ICU • Hyperbaric oxygen therapy • IVIG, plasmaphersis?

19. Clostridium difficile

20. Clostridium difficile colitis • Disturbance of the normal bacterial flora in the colon due to antibiotics • C.difficile colonization and releasing of toxins which cause mucosal inflammation and damage • Primarily in hospitalized patients • Most common nosocomial infection • Occurs 15-30% in hospitalized patients • Metronidazol and vancomycin helps in 95% and improves in 3-4days • 20-27% of successfully treated relapses (3days-3weeks after)

21. Pathophysiology • Clostridium difficile is a gram-positive, anaerobic, heat resistant spore forming bacillus • Fecal-oral route • Toxin A (enterotoxin) and Toxin B (cytotoxin)  bind to intestinal mucosal cells

22. Etiology • Primary risk factor is previous antibiotic exposure  most common cephalosporins (II, III. Gen.), fluoroquinolone and amoxicillin/ampicillin • Prolonged use or the use of 2 or more antibiotics • antibiotic use in the last 3months • Recently hospitalized • Diarrhea >48hours after hospitalization

23. Symptoms • History of antibiotic use • Mild to moderate WATERY diarrhea • Cramping abdominal pain • Anorexia • Malaise • Fever in more severe cases • Lower abdominal tenderness • Dehydration

24. Differential diagnosis • IBDs • Other infectious diseases (salmonellosis, shigellosis, viral gastroenteritis) • Diverticulitis

25. Diagnosis • Clinical picture • Stool sampling  both toxins and antigens • Endoscopy  pseudomembranous colitis with yellow plaques overlying an erythematous, edematous mucosa • CT – thickened bowel wall

26. Treatment • Vancomycin and metronidazol • Fecal microbiota transplantation • Surgical intervention only in complications e.g. toxic megacolon!

27. Thank you for your attention!