Necrotizing Fasciitis (NF)  Fourneir’S Gangrene  Diagnosis  Treatment  Outcomes © by Author

Metallidis Symeon Infectious Diseases Specialist Lecturer at Aristotle University of Thessaloniki © by author

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( ) first described by Hippocrates: “…when the exciting cause was a trivial accident or a very small wound … the erysipelas would quickly spread widely in all directions. Flesh & bones fell away in large quantities …. There were many deaths”.

• This is not dissimilar to what we see today. © by author

ESCMID Online Lecture Library Outline

 Overview of Serious skin and soft tissue infections  Clinical/ Pathological signs  Risk Factors  Type 1 vs. Type 2 Necrotizing Fasciitis (NF)  Fourneir’s Gangrene  Diagnosis  Treatment  Outcomes © by author

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Cellulitis

ESCMID Online Lecture Library Skin Normal Flora

 Mostly gram-positive bacteria  staphylococci  micrococci  corynebacteria (diphtheroids)  Propionibacterium acnes © by author

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 NSTIs are rare

 ~ 1000 cases/yr in US or 0.04 cases/1000 person yrs

 Recent literature suggested that they are increasing. © by author

ESCMID Online Lecture Library require extensive ICU resources!

United Kingdom (1995 ~ 2006)  0.24% of ICU admissions  necrotizing fasciitis

 21 days

 [survivors]: 32 days, [non-survivors] : 12 days

 Cost: $71,000 ~ $83,000 © by author

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 Decreased little over the last 30 yrs despite improvements in medical care.  In the United Kingdom (1995 ~ 2006), p’ts with NSTIs had a mortality of 41.6%.  Improvements in outcome continue to require  early diagnosis  early & aggressive surgical debridement  administration of appropriate antibiotics  & optimization of underlying© by medical author comorbidities .

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 Necrotizing infection of genital & perineal region in 1764, by Baurienne  Fournier’s gangrene in 1883 & 1884, by French dermatologist & venereologist Jean Alfred Fournier  Numerous other terms: hospital gangrene, necrotizing erysipelas, suppurative fasciitis, clostridial gangrene, & gas gangrene.  Necrotizing fasciitis © by author In 1951, by Wilson

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are classified in numerous ways & often for specific reasons.

 Uncomplicated soft tissue infections superficial infections, such as cellulitis, impetiginous lesions, furuncles, & simple abscesses, that can be treated with surgical incision alone.

 Complicated soft tissue infections, such as infected ulcers, infected burns, & major abscesses, require© by significant author surgical interventions.

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 A more useful classification ( ):  nonnecrotizing VS necrotizing infections  necrotizing infections  aggressive surgical management.

 divided into specific types based on,  anatomy  (e.g., Fournier’s, Ludwig’s angina)  depth of involvement  (e.g., necrotizing adipositis, fasciitis, or myositis)  microbial source of infection© by author  (types 1/2/3)  combination of microbial source & depth  (i.e., clostridial cellulitis, nonclostridial anaerobic cellulitis) ESCMID Online Lecture Library

Necrotizing Fasciitis (NF) Definition

 A subcutaneous infection of fascia and fat which may or may not spare the skin.

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 Type 1 infections : , the most prevalent form of NSTI, (55% ~ 75%)

• Type 2 infections: , caused by group A Streptococcus. (Some authors also consider community-associated MRSA as type 2)

• Type 3 infections : also , attributed to Clostridium species or rare virulent microbes (Vibrio vulnificus or Aeromonas© speciesby author)

ESCMID Online Lecture Library TYPE 1 NSTI

A of aerobic & anaerobic bacteria infection

Streptococcus spp., Staphylococcus spp., Enterococcus spp. & Enterobacteriaceae family (E.coli, Acinetobacter spp., Pseudomonas spp. & Klebsiella spp.).

Bacteroides© by spp. author

ESCMID Online Lecture Library Type 1 NF

 2/3 of cases have mixed aerobic and anaerobic infections  The bugs: The average case had 4.6 isolates  Staphylococcus aureus  Streptococci  Enterococci  Escherichia coli  Peptostreptococcus © by author  Preveoella and Porphyromonas  Bacteroides fragilis  Clostridium ESCMID Online Lecture Library TYPE 1 NSTI

Polymicrobial NSTIs  tend to occur on perineum & trunks of immunocompromised p’ts.  Classic example:

Predisposing factors: • Common: & • Other: , , , , ,© by author , ,

ESCMID Online Lecture Library Left upper extremity shows necrotizing fascitis in an individual who used illicit drugs. Cultures grew Streptococcus milleri and anaerobes (Prevotella species). Patient would grease, or lick, the needle before injection.

ESCMID Online Lecture Library Type 1 NF

 Primarily includes 3 categories (locations) of infection

 Diabetes Mellitus- infections of the feet  Cervical necrotizing fasciitis- infection of the neck  Fournier’s Gangrene- infection of the perineum © by author

ESCMID Online Lecture Library Diabetes Mellitus

ESCMID Online Lecture Library Prevalence of Diabetes and Diabetes- Related Lower Extremity Complications

 In 2002, the prevalence of diabetes in the United States was 18.2 million people (6% of population).1

 Approximately 15% of Americans with diabetes will develop a foot ulcer during their lifetime.2

 In a cohort of 1,666 diabetics, over a period of 24 months the incidence of foot infection was 36.5 infections per 1,000 persons© by authorwith diabetes per year.3

1. Centers for Disease Control and Prevention. Available at: http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2003.pdf. Accessed December 27, 2005. 2. Singh N et al.ESCMID JAMA. 2005;293:217–228. Online Lecture Library 3. Lavery LA et al. Diabetes Care. 2003;26:1435–1438. Bacteriology of Diabetic Foot Infections: The SIDESTEP (Ertapenem vs Piperacillin/Tazobactam) Study

 473 specimens obtained at baseline (multicenter trial)  After debridement; mostly tissue specimens  Cultured at single research laboratory  Results  1,148 aerobic and 492 anaerobic organisms isolated  50% aerobes only  42% aerobes and anaerobes  3% only anaerobes © by author  Average (range) of isolates (per positive culture)  Aerobes: 2.8 (1–8)  Anaerobes: 2.1 (1–9) ESCMID Online Lecture Library Citron DM et al. Bacteriology of diabetic foot infections (DFI): 1640 isolates from 473 specimens [abstract]. IDSA; 2005.

Cervical Necrotizing Fasciitis

ESCMID Online Lecture Library TYPE 1 NSTI

 Another example :  Bacterial penetration  fascial compartments of head & neck  rapidly progressive gangrenous cellulitis  life-threatening airway obstruction

• Most associated with (78%~90% ) • Other causes: • trauma, © by author • tongue piercing, • neoplasm, • & other parapharyngeal infections. ESCMID Online Lecture Library TYPE 1 NSTI

(submandibular space infection) &

 usually caused by mouth anaerobes, such as

Fusobacterium spp., anaerobic Streptococcus spp., Peptostreptococcus spp., Bacteroides spp., & spirochetes, which are – usually susceptible to© penicillin by author & clindamycin .

ESCMID Online Lecture Library Fournier’s Gangrene (FG)

 First described by French verenologist Jean Alfred Fournier who witnessed a rapidly progressing gangrene of the penis and scrotum of 5 previously healthy young men.

 A polymicrobial necrotizing fasciitis (NF) of the perinium, perianal© by area, author or genitals. It may involve either men or women.

ESCMID Online Lecture Library Fournier’s Gangrene

 Found in the perineal area- it is an infection caused by penetration of the gastrointestinal or urethral mucosa by bacteria.

 Characterized by an abrupt onset with severe pain which may spread rapidly to the anterior abdominal wall, gluteal© by muscles, author or the scrotum and penis in males.

ESCMID Online Lecture Library Epidemiology of FG

 Not very common. On average 97 cases were reported each year from 1989 to 1998.

 Mostly age 30-60, although all ages have been reported

 Effects men 10:1 over© by females. author This may be due to better perineal drainage in females through vaginal secretions. ESCMID Online Lecture Library

ESCMID Online Lecture Library FG following vasectomy

ESCMID Online Lecture Library TYPE 2 NSTI

 Caused by group A Streptococcus (Streptococcus pyogenes) either alone or in association with S. aureus.

 may be accompanied by toxic shock syndrome(~ 50%)

 In contrast to type 1 NSTI, type 2 NSTI can occur in any age group & without predisposing medical conditions.

Predisposing factors: , , , © by author , , ESCMID . Online Lecture Library TYPE 2 NSTI

 Over the last 10 yrs, has been increasingly seen as a monomicrobial cause of NSTI.  Community-associated MRSA associated with NSTI  clone USA300 (Panton-Valentine leukocidin cytotoxin)

• In some communities,  > 15% of NSTI

[Most]: necrotizing infection of subcutaneous tissue & skin

[Increasing]: more severe invasive diseases (necrotizing ©fasciitis by author & pyomyositis )

ESCMID Online Lecture Library MRSA: epidemiology

Witte W. Community-acquired methicillin-resistant Staphylococcus aureus: what do we need to know? Clin MicrobiolESCMID Infect 2009; 15 Suppl Online 7:17-25. Lecture Library CA-MRSA

ESCMID Online Lecture Library Chua K, et al. Clin Infect Dis 2011. CA-MRSA: high risk patients

Athletes (wrestlers, football players) Chronic illness Nursing home, jails, IVDU

Danger for epidemics (4 Cs): Contact Crowding Contaminated surfaces Cleanliness© by author

NSTIs BSIs ESCMID NecroticOnline pneumonia Lecture Library TYPE 3 NSTI

 Clostridium spp. are G (+), spore-forming anaerobic rods normally found in soil & GI tract.  Classically associated with trauma or surgery.

As surgical technique & w’d care have improved,  clostridial infections   now to be associated ©with by w’ds author from

ESCMID Online Lecture Library TYPE 3 NSTI

 70% ~ 80%  C. perfringens  Potent extracellular toxins  local & systemic manifestations  2 most potent proteins: (phospholipase C) & (perfringolysin) hemolysis, microvascular thrombosis, & myonecrosis

Spontaneous gas gangrene • a rare clostridial infection • caused by Clostridium septicum© by author from GI tract in p’ts with a perforation from colon cancer or diverticulitis.

ESCMID Online Lecture Library Description of NF

 Pathological features  Extensive tissue destruction  Thrombosis of blood vessels  Abundant bacteria spreading along fascial planes  Unimpressive infiltration of acute inflammatory cells© by author  Secondary to collagenases, hyaluronidases, and other destructive enzymes ESCMID Online Lecture Library

Diagnosis

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 greatest risk factor for NSTI in urban setting • NSTI do occur in healthy individuals: 30% Most common site: , followed by , ,

ESCMID Online Lecture Library Diagnosis Suspicion Physical exam Laboratory tests Plain films CT © by authorMRI (leads to delay)

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The most effective treatment for necrotizing soft tissue infections = EARLY© DIAGNOSIS by author Skin changes are usually much less extensive Alerts: high fever, hypotension, tachycardia, MODS ESCMID Online Lecture Library Clinical signs

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 Varies widely, ranging from & to life- threatening sepsis with & involvement.

 Initial presentation is not always obvious ◦ may involve only the deep tissues in the early phases, leaving the overlying skin appearing normal.

 Diagnosis of NSTI very difficult ! © by author  Delay in diagnosis & treatment  extensive tissue destruction, limb loss & mortality. ESCMID Online Lecture Library

: may be the© earliest by author symptom • Superficial cellulitis that , , or is

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Cellulitis, bronzing of Subcutaneous air Fournier’s gangrene skin, & hemorrhagic bullae © by author

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Laboratory tests

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The LRINEC score by Wong et al. retrospectively devised based on 6 common clinical parameters: , , , , ,

• In one study, Su et al retrospectively reviewed 209 p’ts with a confirmed diagnosis of necrotizing fasciitis & showed that only 100 (48%) of 209 had an LRINEC score of ≥ 6. A mininum score of 6 is associated • Group of p’ts with LRINECwith scores necrotizing of ≥ 6 had fasciitis, a higher with rate a of amputation & mortalityof compared 92% & with ofthe 96% group. with LRINEC scores of < 6. • This study suggests : LRINEC© by authorscore is helpful in prognosticating, but not diagnosing of NSTI.

ESCMID Online Lecture Library In a more recent cohort study (n=28 p’ts),  LRINEC score  sen: , spe: PPV: , NPV:

Mills et al recently reported that & occur simultaneously in only 22% of p’ts with NSTI  sensitivity of these parameters for detection of NSTI is low.

 Major drawback  derived© byfrom author retrospective data (selection bias)  To date, the LRINEC score has not been prospectively validated & should not be recommended for routine application. ESCMID Online Lecture Library

Imaging studies

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 Imaging studies (conventional radiographs & CT), are helpful only if there is  Presence of gas in tissue  suspicious clinical presentation  diagnostic of NSTI  Only 39% of NSTI : radiographic detection of subcutaneous emphysema

• very sensitive in detecting© byinflammatory author changes but is not necessarily specific for . • helpful in diagnosis of deep abscesses, especially intramuscular abscesses ESCMID Online Lecture Library

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 accurately differentiate between necrotizing infection & nonnecrotizing infection  not always readily accessible in many facilities  requires p’t compliance & is a very time-consuming study

 delaying diagnosis & treatment

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 based on histologic changes that include tissue necrosis, polymorphonuclear infiltration, fibrinous vascular thrombosis, & sometimes microorganisms within the destroyed tissue.  to be reliable, but experience is limited.  a pathologist is not always readily available at night for the interpretation of frozen© by sectionauthor

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 detection of organisms by Gram-stain & cultures  presence of organisms does not necessarily equate to a necrotizing infection & is not as reliable as taking deep tissue samples at time of surgical exploration.  failure to obtain fluid is nondiagnostic & does not rule out necrotizing infection.  cultures take too long to© make by author

ESCMID Online Lecture Library Diagnosis of NF- Cultures

 Blood cultures are positive  in 60% of patients with Type II NF,

 and 20% of patients with Type I NF (usually polymicrobial)  However in Type I, blood cultures may not grow all organisms involved in the tissue infection © by author  Aspiration of bullae or skin also may not give an accurate representation of the infectionESCMID Online Lecture Library

Diagnosis of NF- Surgery

 Surgical exploration with sampling of deep tissue is the most accurate means of diagnosis.

 This also allows debridement© by author of the infection

ESCMID Online Lecture Library Diagnosis of NF  DDx: include gas gangrene, pyomyositis, and myositis.

Clinical Type 1 Type 2 Gas Pyomyositis Myositis Findings Gangrene viral/ parasitic Fever ++ ++++ +++ ++ ++ Diffuse Pain + + + + ++++ Local Pain ++ ++++ ++++ ++ ++ Systemic Toxicity ++ ++++© by++++ author + + Gas in tissue ++ - ++++ - - Obvious portal of entry ++++ + ++++ - - Diabetes Mellitus ESCMID++++ +Online Lecture- - Library-

Management

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ESCMID Online Lecture Library If you want to treat successfully your patient do not start without them……………………

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 Management of NSTI requires , , , & .

 Most important : complete debridement of necrotic & infected tissues

 Major determinant of outcome : early operative debridement

 Surgical debridement should never be delayed in hope of restoration of hemodynamic© stabilityby author  Correction of septic state will not occur until all of infected & necrotic tissues have been removed. ESCMID Online Lecture Library SURGICAL MANAGEMENT

When NSTI is suspected, surgical exploration is indicated!

 Incision : the inflamed & tender area down toward the fascia.

Highly suggestive of NSTI

Change in fascia : • Tough & shiny white appearance  that can be easily separated from the fat with blunt dissection.

ESCMID Online Lecture Library SURGICAL MANAGEMENT

 All necrotic fascia & muscles  should be excised : healthy bleeding tissue  normal appearance. : left open, packed for open drainage & ease of re- exploration

completeness of surgical debridement • After adequate surgical© debridement by author  should improve significantly.

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Necrotizing fasciitis ESCMID Online Lecture Library

NecrotizingESCMID fasciitis after Online debridment Lecture Library SURGICAL MANAGEMENT

 If clinical condition , should be considered sooner

 Goal : with the  It is not at all uncommon that multiple debridements are required.  In one study, of p’ts required at least one other debridement. © by author

ESCMID Online Lecture Library Treatment

Prompt debridement of all devitalized tissue Surgical mortality 6% (<24hrs), 24% (>24hrs)

Repeat debridements © by author

ESCMID Online Lecture Library CRITICAL CARE MANAGEMENT

As soon as the diagnosis of NSTI is suspected, immediate fluid resuscitation should begin.

FLUID  Initial aggressive fluid resuscitation  restore intravascular volume  maintain adequate end-organ perfusion & tissue oxygenation  limit adverse effects of end-organ failure

Use of a to guide: • patients who are in © by or authorwho have underlying

ESCMID Online Lecture Library Antibiotics

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ESCMID Online Lecture Library Treatment of NF- Antibiotics

 Antibiotics  Virtually 100% of patients will die on antibiotics without surgical debridement

 Type 1- ampicillin or ampicillin-sulbactam and clindamycin or metronidazole. For patients with prior hospitalization substitute ticarcillin-clavulanate or piperacillin- tazobactam for ampicillin-sulbactam © by author  Type 2- clindamycin. Add vancomycin to cover for MRSA

ESCMID Online Lecture Library CRITICAL CARE MANAGEMENT

Selection of antimicrobials that inhibit toxin production:  streptococcal, clostridial, & staphylococcal infections  evidence of rapidly progressive or severe infections © by author , & : potential inhibitory agents

ESCMID Online Lecture Library CRITICAL CARE MANAGEMENT

- recruit, activate & lyse human neutrophils  eliminating a main cellular defense against staphylococcal infection. &  inhibit toxin production by suppressing translation but not transcription of S. aureus toxin genes  directly inhibiting synthesis of Gr. A Streptococcus toxins. © by author When p’ts exhibit signs & symptoms of shock, coagulopathy, organ failure, antitoxin antimicrobials should be initiated! ESCMID Online Lecture Library Clindamycin: benefit or not?

3 retrospective studies (Type II NF) Kaul 1997 77 pts No effect on mortality Zimbelman 1999 56 pts mortality Mulla 2003 © 195by pts author mortality 89%

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ESCMID Online Lecture Library Daptomycin vs Vancomycin Patients with cSSTIs

Daptomycin reduced the days of therapy

100 Daptomycin(n=53) Vancomycin(n=212) 80

of patients receiving 20

antimicrobial therapy © by author % % 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Days of therapy ESCMID Online Lecture Library Davis et al. Pharmacotherapy 2007;27:1611 Study 1002: shorter duration of i.v. therapy with linezolid vs vancomycin*

p<0.001 p<0.001 10.4 9.8 Linezolid Vancomycin

5.6 5.3

*Vancomycin dose adjusted for CrCl and trough levels PP, per protocol;ESCMID mITT, modified intent Onlineto treat Lecture Library Itani et al. Am J Surg 2010;199:804–816 Daptomycin vs Vancomycin Patients with cSSTIs

P<0,01

8000 Daptomycin(n=53) 7552 7000 Vancomycin (n=212)

6000 5027 5000 4000 3000

Διάμεσο κόστος ($) Διάμεσο κόστος 2000 P<0,01 ©P=NS by author 1000 666 678 124 256 0 i.v. antibiotic therapy. Complete cost therapy Hospitalization ESCMID Online Lecture Library Davis et al. Pharmacotherapy 2007;27:1611 CRITICAL CARE MANAGEMENT

Use of IV immunoglobulin (IVIG) for the treatment of has also been advocated by some authors.

Rationale:  antibodies can neutralize circulating streptococcal exotoxins   toxin induced tissue necrosis  may have an effect on circulating cytokines  controlling SIRS

Although some retrospective/prospective© by author studies,  a potential benefit in the use of IVIG in NSTI,  additional studies are required before it can be recommended for routine use in NSTI ESCMID Online Lecture Library CRITICAL CARE MANAGEMENT Hyperbaric oxygen (HBO) therapy has also been proposed as an adjunctive therapy for NSTI.

• Many studies  conflicting results  remains controversial • A number of small series, (role of HBO as an adjunctive therapy for severe, life- or limb threatening necrotizing infection) a potential mortality benefit© by & a authordecrease in the extent of debridement in p’ts treated with HBO.

ESCMID Online Lecture Library Hyperbaric Oxygen (HBO) Reduces local edema Increases angiogenesis and improves wound healing Kills obligate anaerobic bacteria Increases neutrophil phagocytosis

Two retrospective studies suggest improved mortality and morbidity (Jallali et al, Am J Surg 2005), several others do not © by author Animal studies of Clostridial NF show benefit (Demello et al, Surgery 1973)

ESCMID Online Lecture Library WOUND MANAGEMENT

 Wound dressing is best done with . is not necessary. & will alter the appearance of the wound, making it difficult to be examined. should not be used on an open wound, as it will cause cell damage & inhibit wound healing.  Perineal wounds are especially difficult to manage, because soilage of the wound is frequent.© by author However, stool diversion by is rarely required.

ESCMID Online Lecture Library WOUND MANAGEMENT

Majority of wound closure 

Timing:  p’t is medically stable & w’d is free from infection.  It is not necessary to wait for granulation tissue to fill the entire wound bed for STSG

ESCMID Online Lecture Library WOUND MANAGEMENT

that involve scrotum,

 Best cosmetic result: delayed primary closure (if it’s small)  If w’d is too large for primary closure, it should not be allowed to heal by secondary intention.  will lead to contracture deformity of scrotum

Scrotal reconstruction© methods: by author & from thigh & abdomen. ESCMID Online Lecture Library Extensive reconstruction post Fournier’s Gangrene

ESCMID Online Lecture Library Mortality of NF

 Type I- 21%

 Type II- 14-34%

 Cervical NF- 22%

ESCMID Online Lecture Library Prognostic Score to Predict Mortality in Patients With Necrotizing Soft Tissue Infection at the Time of First Assessment

VARIABLE (ON ADMISSION) NO. OF POINTS Heart rate >110 1 beats/min Temperature <36°C 1 Creatinine >1.5 mg/dL 1 Age >50 yr 3 White blood cell count 3 >40,000 Hematocrit >50 3 © by author GROUP NO. OF MORTALITY CATEGORIES POINTS RISK 1 0-2 6% 2 3-5 24% ESCMID3 Online≥6 Lecture88% Library CONCLUSION

 an aggressive disease  associated with significant morbidity & mortality

 Early from

 Complete  key to success.  Initial should be broad!

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Back up slides

ESCMID Online Lecture Library Pyomyositis

 Pyomyositis, which is caused mainly by S. aureus, is the presence of pus within individual muscle groups.  Occasionally, S. pneumoniae or a gram-negative enteric bacillus is responsible

 Blood culture results are positive in 5%–30% of cases

 Because of its geographical distribution, this condition is often called© by“tropical author pyomyositis ,” but cases are increasingly recognized in temperate climates, especially in patients with HIV infection or diabetesESCMID Online Lecture Library Pyomyositis

 Presenting findings are localized pain in a single muscle group, muscle spasm, and fever.

 The disease occurs most often in an extremity, but any muscle group can be involved, including the psoas or trunk muscles.

 Initially, it may not be© possible by author to palpate a discrete abscess because the infection is localized deep within the muscle, but the area has a firm, wooden feel associated with pain and tenderness ESCMID Online Lecture Library

ESCMID Online Lecture Library Pyomyositis

 In the early stages, ultrasonography or CT scan may be performed to differentiate this entity from a deep venous thrombosis.

 In more advanced cases, a bulging abscess is usually clinically apparent.

 There are bacteria on the skin that are pushed under the skin by the needle

 There are bacteria in the dope

 The dope itself can cause the same reaction under the skin that bacteria do

 When the dope is injected into a vein it goes to the lung and the lung is better at killing bacteria than the skin is

 It’s almost always “skin popping”, NOT “muscling” because the needles almost never go deep enough to reachESCMID muscle Online Lecture Library NECROTIZING CELLULITIS

 There are several different types of necrotizing cellulitis including:

 Clostridial  Nonclostridial anaerobic infections  Meleney's synergistic gangrene  Synergistic necrotizing© by cellulitisauthor

ESCMID Online Lecture Library Clostridial cellulitis

 Most often due to Clostridium perfringens.  Is usually preceded by local trauma or recent surgery.  Gas is invariably found in the skin, but the fascia and deep muscle are spared.  This entity differs from clostridial myonecrosis because of less systemic toxicity; nevertheless, thorough surgical exploration and debridement are required to distinguish between these entities.  Magnetic resonance imaging (MRI) or CT scanning and measurement of the serum creatine kinase (CK) concentration can also help to determine© byif muscle author tissue is involved. However, imaging studies should not delay critical surgical therapy when there is crepitus on examination or clinical evidence of progressive soft tissue infection ESCMID Online Lecture Library Nonclostridial anaerobic cellulitis

 This type of cellulitis is due to infection with mixed anaerobic and aerobic organisms that produce gas in tissues.

 Unlike clostridial cellulitis, this infection is usually associated with diabetes mellitus and often produces a foul odor. © by author  It must be distinguished from myonecrosis and necrotizing fasciitis by surgical exploration ESCMID Online Lecture Library Meleney's synergistic gangrene

 Meleney's synergistic gangrene is a rare infection, which occurs in postoperative patients and is characterized by a slowly expanding indolent ulceration that is confined to the superficial fascia.

 It results from a synergistic interaction between Staphylococcus aureus and microaerophilic streptococci. © by author  Antibiotic therapy and surgical debridement are the main components of treatment ESCMID Online Lecture Library Synergistic necrotizing cellulitis

 Synergistic necrotizing cellulitis is a variant of necrotizing fasciitis type I, which involves the skin, muscle, fat, and fascia.

ESCMID Online Lecture Library Classification of SSTIs

Aetiologic  Simple uncomplicated  Mostly Gram-positive organisms  Cellulitis Staphylococcus  Impetigo aureus  Erysipelas Impetigo  Simple abscesses Streptococcus  Furuncles Epidermis pyogenes  Can be treated by surgical

incision and drainage alone Folliculitis S. aureus  Complicated Hair follicle  Gram-positive/ Gram-negative Erysipelas S. pyogenes

 Decubitus ulcers Cutaneous  Cellulitis  Significant underlying Dermis S. pyogenes disease state, which S. aureus complicates response Cellulitis to treatment Haemophilus  Necrotizing fasciitis influenzae  Gangrene Subcutaneous Other  Major abscesses fat (>5 cm) © by author

Necrotizing S. pyogenes fasciitis Mixed bowel Fascia flora Muscle ESCMID Online Lecture Library FDA. Available at: http://www.fda.gov/cder/guidance/2566dft.pdf. Common pathogens in SSTIs: SENTRY United States and Canada, 2000 & 2004

20001, N=1404 20042, N=1239

32.1% 13.8% 27.2% 50% 24.4% 29.4% 10.8% 8.2% 23.2% S.8.2% aureus 9.8% 5.3% 3.4% 2.3% © by author 1.9% Methicillin-resistant Enterococcus spp. β-Haemolytic streptococci S. aureus (MRSA) Methicillin-susceptible Coagulase-negative Other S. aureus (MSSA) staphylococci Pseudomonas aeruginosa ESCMID Online Lecture Library 1. Rennie RP et al. Diagn Microbiol Infect Dis. 2003;45:287–293 2. Moet G et al. Diagn Microbiol Infect Dis. 2007;57:7–13 Methicillin-Resistant S. aureus (MRSA) and Diabetic Foot Infections

 In a large multicenter trial in patients with diabetic foot infection1:  11% of 473 specimens were MRSA  Of the MRSA specimens, only 13% were pure MRSA cultures  15% of patients grew >1 Staphylococcus species

 In another multicenter trial in patients with diabetic foot infection, MRSA was isolated from 25/361 patients (7%)2

 MRSA is isolated in both inpatient and community settings3 © by author  MRSA isolation is associated with2:  Previous antibiotic therapy  Worse clinical outcomes

1. Citron DM et al. Bacteriology of diabetic foot infections (DFI): 1640 isolates from 473 specimens [abstract]. IDSA; 2005. 2. Lipsky BA et al.ESCMID Clin Infect Dis. 2004;38:17 Online–24. Lecture Library 3. Lipsky BA et al. Clin Infect Dis. 2004;39:885–904. Pseudomonas species in Diabetic Foot Infections

 P. aeruginosa may be an “environmental” pathogen1

 P. aeuruginosa has been associated with the following foot-infection syndromes2:  Ulcer that is macerated because of soaking  Long duration nonhealing wounds with prolonged, broad-spectrum antibiotic therapy

 In 2 clinical trials in patients with diabetic foot infections:  9% of 473 specimens were P. aeruginosa and only 5% of those were pure cultures3 © by author  In the second study, Pseudomonas species were recovered from 7% (27/361) of patients4

1. Lipsky BA et al. Lancet. 2005;366:1695–1703. 2. Lipsky BA et al. Clin Infect Dis. 2004;39:885–904. 3. Citron DM etESCMID al. Bacteriology of diabetic Online foot infections (DFI): Lecture 1640 isolates from 473Library specimens [abstract]. IDSA; 2005. 4. Lipsky BA et al. Clin Infect Dis. 2004;38:17–24.