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

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

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

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

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)

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

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

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

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

Fournier’s gangrene

Ludwig’s angina

   

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

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

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

Adjunctive therapies ICU Hyperbaric oxygen therapy IVIG, plasmaphersis?

Clostridium difficile

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)

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

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

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

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

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

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

Thank you for your attention!