4 Omar Sami M.Madadha 1 P a g e
Studying microbiology might not seem so appealing to many of us; yet no one denies how important it is. However, microbiology is one of the, if not the most medical sharpening subject in medical school, despite the way it is taught; just push it an extra hour & you will never need to study it again; it is never too late :) To decrease the pages number, No pictures will be included in this sheet; please refer to the slides. Throughout today s lecture, we will be introduced to several dermatological manifestations caused by different pathogens, mainly Necrotizing Fasciitis, Cellulitis & Folliculitis. Few General points to draw a frame to the bigger picture: Necrotizing fasciitis has two types: Classical spread: caused by group A streptococci, Flesh Eating Bacteria. Necrotizing fasciitis with bolus production: caused by group A streptococci + anaerobic bacteria. If the individual was infected by Anaerobic bacteria only, this will not cause acute spreading, and causes what so called Gas Gangrene Gas Production. Necrotizing fasciitis {NF} RAPIDLY progressing infection in the area between the fascia and deep subcutaneous tissue. Fibrous bands in this area prevents spread of infection these fibrous bands are responsible to isolate the dermis from the muscles; thus limiting the pathogen s ability to spread to muscles. These bands are present in the head but not in the extremities (thus extremities are more susceptible to infection) 2 P a g e
So, head is least susceptible than extremities for NF. Necrotizing fasciitis or gas gangrene (anaerobic clostridia infection) Both can induce bulla formation; according to which microbial organism is present. In the USA, the estimated incidence of invasive GAS Group A Streptococci infection is 3.5 cases per 100000 persons necrotizing infections account for 6% of these. Risk factors that may aid in developing NF: All of the following factors lie under either reduced immunity or reduced nutrition and blood supply to the skin; thus the skin is not adequately supplied. Malnutrition Patient conditions Immunocompromised Poor blood supply Skin trauma in last 3 months Breaks in mucosa of GI or GU tracts (anaerobes) -Hypoalbuminemia -Alcoholism -Cirrhosis - >50 Year olds -Obesity -Cancer -Steroid therapy -Heart disease -PVD -DM -Burns -penetrating trauma -IV drugs -surgery -colon cancer -diverticulae -hemorrhoids or fissues -urethral tears -cirrhosis Read them loud, all of them & Let us discuss some of these risk factors: Liver Cirrhosis: disrupted liver will not be able to synthesize globulins, the immunity proteins. Patient above 50: reduced immunity and decreased blood supply. Obesity: due to increased surface area, parts of the skin & skin folds won t be able to survive; thus, developing gangrene. Cancer & steroid therapy: directly & indirectly affecting the patient, upon administering the chemotherapy, which is through IV route, underlying fever of unknown origin might be a hook for a sneaky peaky Strep A 3 P a g e
bacterium from the patient s normal flora through the catheter to the blood. Heart disease: the heart is not pumping enough blood, less oxygen to certain extremities & a higher chance for the growth of anaerobes. PVD (Peripheral Vascular Disease): peripheral vascular disease (PVD) is a blood circulation disorder that causes the blood vessels outside of your heart and brain to narrow, block or spasm & you know the rest of the story. Signs and Symptoms; which BTW occur in order Pain & tenderness Unexplained fever; Early diagnosis may be difficult when pain or unexplained fever are the only presenting manifestations, remember infection is deep, might not present with pain yet & the dermatological manifestation is just a reddened skin. Early diagnosis is so hard in such a case. From such a mild sign, no one but House can suspect in NF. Swelling. Dark red induration BULLAE, filled with blueish or purple fluid Note that such a huge bullea; are formed by anaerobic bacteria; as G+VE cant cause such a damage alone. Thrombosis of dermal blood vessels (The affected area becomes anesthetic as a result of small vessel thrombosis and destruction of superficial nerves) Stasis, slowness of the blood, is a normal process through the inflammatory response in which inflammatory cells have the opportunity to leave the blood circulation to the inflamed area. If the inflammation is severe, stasis can turn to thrombosis. Extension to deep fascia with rapid spread. 4 P a g e
Most progressed symptoms: toxicity, shock and multi organ failures. Microbial Causes Types 5 P a g e Type I necrotizing fasciitis: a- polymicrobial more than one bacterial strain ; involves at least one anaerobic species; Bacteroides or Peptostreptococcus (anaerobic cousin of streptococci), PLUS non-group A Streptococci {non GAS} b- usually a mix of aerobes and anaerobic bacteria (clostridium perfringens) 1 - Break in Gastrointestinal or Genitourinary mucosa, typically on trunk and extremities 2- Fournier's Gangrene (in genitalia/perineal area) 3- mixed infection usually have comorbid states (DM, PVD, immunocompromised). Type II necrotizing fasciitis Usually caused by GAS alone or in combination with other species, S. aureus S. pyogenes +- S. aureus. The ability of certain bacterial strains to survive throughout harsh times enables it to acquire advanced virulence factors & behave more aggressive than before. Let us take MRSA as an example, because of its potential ability to resist chemotherapy; Strains of MRSA developed Panton Valentine leukocidin (PVL) toxin that have been reported to cause necrotizing fasciitis. skin popping: which Is often seen in drug abusers, due to the usage of the syringe many times in the same area until it is deformed, then the addict uses another area and so on. In the newborn, necrotizing fasciitis may complicate omphalitis and spread to involve the abdominal wall, flanks, and chest wall.
What is Omphalitis? Omphalitis of newborn is the medical term for inflammation of the umbilical cord stump in the neonatal newborn period, most commonly attributed to a bacterial infection Fournier s gangrene is a form of necrotizing fasciitis that affects the male genitals and is usually polymicrobial. Craniofacial necrotizing fasciitis is usually associated with trauma and caused by GAS. Cervical necrotizing fasciitis is usually associated with dental or pharyngeal infections and is polymicrobial. How to Diagnose NF? Clinical findings are either suggestive or through surgical exploration using a sample: Altered mental status; which may appear as a late symptom. Soft tissue infection signs: (redness/swelling/pain) 70-80% of cases & the remaining 20% are asymptomatic. Fever in less than 50% of the cases: which indicates that the patient is not having a proper inflammatory reaction against the offending agent. Low BP in 21%: which means that not all individuals will progress to shock. Crepitation: feeling of air pockets under skin upon examination, seen in 20% of the patients. Treatment 3 or 2 drug combinations, or only 1 drug (each +MRSA coverage) The reason behind this diversity in combos; is just due to the probability of a shortage of one of the drugs, or some might not be available in the hospital. 3 drug combo: 1- anaerobic coverage (and inhibits ribosomal production of toxins) = Clindamycin. 2- G +ve coverage (Ampicillin-sulbactam) or (Piperacillin-tazobactam). 3- G-ve coverage (Ciprofloxacin). 6 P a g e 2 drug combo:
2 drug combo (Cefotaxime covers G+ and G- bacteria) + (anaerobic coverage by metronidazole or clindamycin). 1 drug combo: 1 drug combo (Carbapenem, Imipenem, meropenem & ertapenem); which are last drug option, used mainly in very nasty bugs. MRSA Coverage The MRSA coverage to be added to any chosen empiric regimen includes = Vancomycin or Linezolid. A Point which the professor didn t mention: Hemorrhagic bullae may indicate presence of vibrio vulnificus, in which case doxycycline is used. Surgeons job: Surgical debridement, and treatment in hospital Emergency surgical exploration and debridement confirm the diagnosis and are the mainstay of therapy. Reducing compartment pressure in extremities; as each muscle compartment is surrounded by a tight trouser. Prophylaxis for exposed house hold members (penicillin, rifampin, clindamycin or azithromycin) Necrotizing Fasciitis; if early misdiagnosed can lead to preventable amputation & can be life threatening, feel free to check our article on Bel- Arabi Nec-Fash, the flesh eater. Gas gangrene (Clostridium infection) Remember that gas gangrene is gram positive, spore forming bacteria. The story here is breakage of subcutaneous tissue towards the deep tissue and causes what so called gas gangrene. Typically due to contaminated DEEP wounds, no oxygen, following a surgery, car crash to introduce spores of G+ve clostridia into the wound. C. perfringens is the predominant cause (80 95%), and its pathological effects are mediated by α and λ toxins. However, it might be caused by clostridium Septicum as well. 7 P a g e
Spontaneous or non-traumatic gas gangrene may occur in the absence of an obvious wound. What are the clinical features for such a condition? The incubation period is usually 2 3 days but may be shorter. Patients usually present with acute onset of excruciating pain and signs of shock (fever, tachycardia, hypotension, jaundice & renal failure). Local edema and tenderness may be the only early signs, or there may be an open wound, herniation of muscle, a serosanguinous and foul (bad) smelling discharge, crepitus, skin discoloration, and necrosis. Progression is rapid, the real problem in the rapid progression is that the patient is heading towards a really bad shock. How to diagnose? The diagnosis is usually clinical, but may be confirmed by Gram stain of the wound or aspirate; notice that we are looking for an anaerobic bacteria which must be collected by a specific way to avoid its death. Liquid anaerobic cultures may be positive within 6h. Plain radiographs may show gas in the affected tissues Management Emergency surgical exploration and debridement of the affected area should be performed. Empirical antibiotic therapy with piperacillin tazobactam plus vancomycin (if risk of MRSA) is appropriate. Definitive treatment for clostridial myonecrosis is with penicillin and clindamycin. Hyperbaric oxygen therapy is not recommended, as its benefit is unproven and it may delay resuscitation/surgery. 8 P a g e
Cellulitis Less severe; yet it is more common. Remember that; as you move upwards dermatological disorders are less severe, but more common & vise versa. Cellulitis is an acute inflammatory condition of the skin that is characterized by: localized pain Erythema, swelling, and heat (inflammation signs). Usually caused: by indigenous flora colonizing the skin (S. aureus and S. pyogenes) or by a variety of non colonizing exogenous bacteria. Supporting data which gives clues to other causes include: Physical activities, trauma, water contact, animal, insect or human bites immunosuppressant patients. ** Examples of exogenous bacteria : Enterobacteriaceae, L. pneumophila, A. hydrophila, V. vulnificus, and C. neoformans. Clinical features Spreading, erythematous, hot, tender lesion Usually accompanied by systemic symptoms. Can do culture if there is drainage or a site of entry is seen. The Diagnosis is usually clinical, as cultures are rarely positive (only 20%) WHY?; Cellulitis is more likely an inflammatory response rather than a bacterial infection; this suggests bacterial numbers are low but the inflammatory effect is exaggerated due to toxins. Thus, when a sample is taken it will be full of neutrophils & inflammatory mediators, as a result the offending agent will be undistinguishable. Treatment empiric treatment: IV flucloxacillin or clindamycin. Vancomycin, teicoplanin, linezolid, or daptomycin are for MRSA cellulitis. Gram-negative and anaerobic cover may be required for Cellulitis in the context of diabetic ulcers (ulcer+cellulitis is the common case). 9 P a g e
Pathogenesis Cellulitis caused by S. aureus spreads from a central localized infection (abscess, folliculitis, or an infected foreign body such as a splinter, a prosthetic device, or an IV catheter). MRSA is rapidly replacing methicillin-sensitive S. aureus (MSSA) as a cause of cellulitis in both inpatient and outpatient settings. Recurrence is seen in patients with eosinophilia Cellulitis due to S. pyogenes is more rapidly spreading, diffuse process that is frequently associated with lymphangitis and fever. Recurrent streptococcal cellulitis of the lower extremities may be caused by organisms of group A, C, or G, in association with chronic venous stasis or with saphenous venectomy for coronary artery bypass surgery; as the area from which the vein has been removed will be more prone to recurrent infection. Also recurrent streptococcal cellulitis is seen among patients with chronic lymphedema resulting from elephantiasis, lymph node dissection, or Milroy s disease. This is all due to the fact that streptococci use the lymphatic system in their spread. Cellulitis caused by (group B Streptococcus) occurs mostly in elderly patients (usually patients with diabetes mellitus or peripheral vascular disease. H. influenzae typically causes periorbital cellulitis in children in association with sinusitis, otitis media, or epiglottitis. It is unclear if this form of cellulitis will become less common as a result of the efficacy of the H. influenzae type b vaccine. Cats bites, dog bites Pasteurella multocida and Staphylococcus intermedius and Capnocytophaga canimorsus (more in dog bites). Cellulitis and abscesses are associated with dog bites and human bites also contain a variety of anaerobic organisms, including Fusobacterium, Bacteroides, aerobic and anaerobic streptococci, and Eikenella corrodens. 10 P a g e
Pasteurella is known to be resistant to dicloxacillin and nafcillin however, it is sensitive to all other β-lactams as well as to quinolones, tetracycline, and erythromycin. Thus for animal or human bites the treatment is usually Ampicillin, clavulanate, ampicillin/sulbactam, and cefoxitin. Aeromonas hydrophila: - Usually aggressive Cellulitis occurs in injuries sustained in freshwater (lakes, rivers, and streams). - Very severe if occurred in in the external ear; but may happen anywhere. - Treatment according to known sensitivity of this organism, fluoroquinolones, chloramphenicol, trimethoprimsulfamethoxazole, and third-generation cephalosporins (ampicillin doesn t work) Pseudomonas Aeruginosa: Causes 3 types of infections in MSS: 1 ecthyma gangrenosum in neutropenic patients 2 hot-tub folliculitis 3 Cellulitis following penetrating injury (usually stepping on a nail). Commonly seen in hospital setting/immune compromised patients. Diagnosis: surgical inspection and drainage/debridement (recall biofilm of pseudomonas) Empirical Treatment : Aminoglycoside, third-generation cephalosporin (ceftazidime, cefoperazone, or cefotaxime), semisynthetic penicillin piperacillin, or a fluoroquinolone, not in pediatric patient) Now, We will start with the last skin disorder 11 P a g e
Folliculitis Definition: A superficial infection of the hair follicles and apocrine structures. Clinically: lesions consist of small, erythematous, pruritic papules, often with a central pustule. Causative organisms: S. aureus (commonest), P. aeruginosa ( hot tub Folliculitis, in case of unclean water), Enterobacteriaceae (complication of acne), Candida spp., and M. furfur (in patients taking corticosteroids). Treatment: empiric treatment is with oral flucloxacillin. If the clinical response is slow consider other pathogens This table is extremely important, read it carefully. Love is wise, Hatred is Foolish 12 P a g e