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%
The total number greatly exceeds this estimate, because of the difficulty of definition and classification
Our clinic already had 2 of this urgent cases in this year

4. Classification TYPE I TYPE II TYPE III Least common
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
No standard classification
one method for descrribing nstis is based on microbiology
Most common type, aerob and anaerob species
Predisposing factores

5. Other classification Depth of the invasion
Erysipelas, Impetigo, Folliculitis, Furunculosis, Carbunculosis
Epidermis
Dermis
Superficial fascia
Subcutaneous fat, arteries, veins
Deep fascia
Muscle
Cellulitis
necrotizing fasciitis at the level of subcutaneous fat with thrombosed vessels and necrosis in the deep fascia)necrotizing fasciitis at the level of subcutaneous fat with thrombosed vessels and necrosis in the deep fascia)
Necrotizing fasciitis
Myonecrosis (Clostridial or non-clostridial)

6. Other classifications
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)
Hard to distinguish from non necrotizing inflammations
The associated morbidity and mortality rates are increased because of the late diagnosis – when hard signs are present it is already late
Number of failing organs are predictive

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!
ct, mri delays the diagnosis

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!