NECROTIZING SKIN AND SOFT-TISSUE INFECTIONS

NECROTIZING SKIN AND SOFT-TISSUE INFECTIONS

Current diagnosis

•   Physical examination of the affected area may detect:

•   Exquisite pain and tenderness out of proportion to local signs of infection.

•   Cutaneous anesthesia, firm woody subcutaneous tissue, edema, and tenderness extending outside involved skin margins, hemorrhage or bullae of the overlying skin, and soft tissue crepitus.

•   Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score useful in diagnosing necrotizing fasciitis. Imaging (computed tomography [CT] or magnetic resonance imaging [MRI] in adults; ultrasonography [US] in children) is confirmatory. Imaging should not delay surgery if indicated based on suspicion.

Current treatment

• Empiric high-dose intravenous polymicrobial antibiotics and surgical debridement remain the cornerstones of initial management of necrotizing skin and soft-tissue infections. Organism-specific antibiotics continued until resolution of infection and debridement complete (usually 7–14 days).

Epidemiology

Necrotizing skin and soft tissue infections are rare with an estimated annual incidence of 1000 cases in the United States. These infections may be polymicrobial or monomicrobial. Polymicrobial infections are most common (70%–80%), generally caused by synergistic activity of aerobes and anaerobes originating from the bowel or genitourinary tracts. They are more prevalent among older immunocompromised patients, individuals with significant comorbidities, and those with underlying abdominal pathology. These infections typically involve the trunk and perineal regions, and follow penetrating abdominal injuries or surgery, genital or perianal sepsis, or decubitus ulcers.

They have a more indolent course and thus are easier to diagnose. Monomicrobial infections (20%–30%) frequently follow minor trauma and are usually caused by group A streptococcus (GAS), occasionally with methicillin-resistant Staphylococcus aureus (MRSA) or by clostridia. They are more aggressive, involve the extremities and occur more often in younger healthy individuals. Type 3 infections follow exposure to contaminated fresh or warm seawater or ingestion of raw seafood; organisms responsible include Aeromonas hydrophila, Vibriavulnificus, Mycobacterium marinum, Pasteurellamultocida, Haemophilus and Klebsiella species. Type 4 (fungal) infections generally follow burns or major trauma. Both types 3 and 4 infections are rare, progress rapidly, and have a high mortality, especially in immune- suppressed patients.

Risk Factors

Cardiopulmonary disease, debility, diabetes mellitus, hepatorenal disease, immunocompromised states, obesity, arteriovenous/lymphatic insufficiency, and senescence all increase risk by reducing tissue vascularity and oxygenation, increasing fluid stasis and risk of trauma, and decreasing ability to counter infections.

Diabetes mellitus and hepatic cirrhosis favor polymicrobial infections due to staphylococcus and streptococcus species, anerobes and gram- negative bacilli. Neutropenia, intravenous drug use and hot tub exposure support pseudomonas infection. Human and animal bite wounds cause infections with oral flora, staphylococci, Pasteurella multocida and anerobes. Poor sanitation and soil contamination propagate clostridial infections. Postoperative infections typically follow wound contamination with microorganisms from the patient during surgery.

Pathophysiology

Necrotizing skin and soft tissue infections advance rapidly, breaking down and traversing anatomic barriers, initiating extensive destruction of the subcutaneous tissue, fascia, and muscle and damaging the neurovascular bundle, thrombosing the subcutaneous vessels, and causing necrosis of the overlying skin. Most infections follow a rift in the protective cutaneous barrier due to trauma or increased tissue tension. Necrotizing fasciitis may also result from blunt injuries (bruise, muscle strain) and, occasionally vascular or lymphatic spread from a distant focus of infection. Various toxins expressed by the organisms (GAS and clostridia) exhibit local and systemic effects (platelet aggregation and thrombosis, decreasing phagocytosis, neutrophil function and vascular tone, myocardial inhibition) triggering the systemic inflammatory response syndrome (SIRS) and multiple organ failure.

Prevention

Preserving cutaneous integrity prevents infection. Abrasions and lacerations should be cleaned with antibacterial soap, and foreign bodies should be removed, and dead/devitalized tissue excised to minimize infection risk. Preoperative skin cleansing with chlorhexidine/alcohol (Hibiclens) or povidone iodine diminishes rates of superficial and deep incisional infections. Intranasal 2% mupirocin ointment (Bactroban) twice daily with chlorhexidine total body wash daily for 5 days in nasal carriers of staphylococcus reduces hospital- acquired deep surgical–site infections, as does administering antibiotics (aminopenicillins, a second- or third-generation cephalosporin) 60 minutes before incision, sterile surgical technique, minimal tissue handling, and minimally invasive surgery.

Clinical Manifestations

Features of inflammation (redness, warmth, swelling, pain) and loss of function characterize necrotizing skin and soft tissue infections.

Altered mental status, anorexia, diaphoresis, fatigue, fever, hypotension, nausea, and tachycardia may suggest systemic spread. The extremities, trunk, or anogenital regions are usually involved.

Induration denotes cutaneous involvement. Patients with necrotizing fasciitis have severe pain disproportionate to the physical findings and rapid progression of infection. Examination reveals cutaneous anesthesia, firm and woody subcutaneous tissue, edema and tenderness extending beyond involved skin, hemorrhage or bullae of the overlying skin, and crepitus (indicates soft tissue gas; seen especially with gas-forming organisms such as clostridia). Tense edema and bullae have high specificity and positive predictive value for necrotizing fasciitis. Fournier gangrene is a form of polymicrobial necrotizing soft-tissue infection involving the loose groin and genital skin, where subcutaneous vessel thrombosis causes extensive tissue loss.

Diagnosis

Diagnosis is based on a strong clinical suspicion followed by confirmatory laboratory and imaging studies (if time permits), and surgery. Leukocytosis with a marked left shift, elevated C-reactive protein, elevated serum creatinine and creatine phosphokinase (denotes muscle injury), and low serum bicarbonate (suggests acidosis) signify severe infection. The LRINEC score uses six different laboratory parameters (hemoglobin, white count, C-reactive protein, glucose, creatinine, sodium) to predict risk of necrotizing fasciitis (score ≥ 6 suggestive, ≥ 8 strongly predictive). White count (< 15,000 mm3) and serum sodium (> 135 mmol/L) levels alone are useful in ruling out necrotizing fasciitis (99% negative predictive value). Gram stains and wound cultures of aspirates or tissue biopsies and blood cultures have high specificity, and are valuable options in detecting infecting organisms and systemic spread; contamination may yield false positive results. Biopsy or debridement typically demonstrates swollen gray soft tissue with undermining of the overlying skin, a brownish and odorous exudate and noncontractile muscle. Imaging (plain x-rays, ultrasonography [US], computed tomography [CT], magnetic resonance imaging [MRI]) may show edema or thickening, fluid collections or free air in the soft tissues. US, CT, and MRI are highly sensitive (MRI highest) in detecting deep soft tissue involvement distinguishing necrotizing fasciitis; specificity is lower. US is sufficient in children, whose tissues are thin enough to allow adequate evaluation on imaging. Imaging should not delay debridement, if considered necessary.

Therapy

Patients with necrotizing skin and soft-tissue infections typically require in-hospital management, as many have underlying unstable comorbid illnesses, systemic sepsis, severe dehydration and acidosis, muscle breakdown, and organ dysfunction. Initial resuscitation may require airway and oxygen support, large volume rehydration, and invasive monitoring. High-dose intravenous (IV) broad-spectrum antibiotics effective against the usually infecting polymicrobial spectrum of pathogens are commenced followed by early and aggressive debridement of all necrotic tissue. IV antibiotics are maintained until the patient is afebrile for 48 to 72 hours and tolerates oral intake, debridement is completed and culture results are available. For polymicrobial necrotizing fasciitis acceptable antimicrobial choices include vancomycin plus piperacillin/tazobactam (Zosyn), a carbapenem (meropenem [Merrem], ertapenem [Invanz] or imipenem-cilastatin [Primaxin]), or cefotaxime (Claforan) with metronidazole (Flagyl) or clindamycin (Cleocin). Streptococcal and clostridial infections are treated with penicillin G with clindamycin. Antibiotic options in methicillin- susceptible S. aureus infections include nafcillin or oxacillin or cefazolin. Options for methicillin-resistant S. aureus (MRSA) infections and in penicillin-allergic patients include vancomycin, daptomycin (Cubicin), or linezolid (Zyvox). Antibiotic doses are adjusted in children. Recommended duration is 7 to 14 days; longer as needed.

Doxycycline combined with ciprofloxacin (Cipro) treats Vibria vulnificus infection. Ceftriaxone (Rocephin) or cefotaxime combined with doxycycline is useful in aeromonos infections. Doxycycline is contraindicated in children (< 8 years), as is ciprofloxacin (< 17 years), unless the infection is considered life-threatening. Fungal infections respond well to fluconazole (Diflucan), voriconazole (Vfend) or amphotericin B; the antifungals are usually continued for 2 weeks after resolution of symptoms. Debridement/drainage may need to be repeated until all diseased tissue or collections are eradicated and healing begins. Wound vacuum dressings help remove drainage and encourage formation of healing granulation tissue. The tissue defect heals by secondary intention or may require skin grafting or flap closure. Hyperbaric oxygen (3–4 daily treatments at 2–3 atmosphere pressure for 30–90 minutes each) is useful, especially in clostridium- related synergistic infections. Adding intravenous immunoglobulin1 0.5–2 g/kg daily for 3 days has shown some success, and is an option in critically ill hemodynamically unstable patients not responding to conventional measures, especially in those with streptococcal toxic shock syndrome. Fournier gangrene is managed along the same principles as above.

Monitoring

Patients in shock or with acute respiratory distress syndrome, SIRS, or multiorgan failure are best managed in an intensive care unit and often require invasive monitoring, cardiorespiratory and renal support, and occasionally, endotracheal intubation.

Complications

Significant disfigurement, limb loss, respiratory and renal failure, and mortality (14%–50%) may eventuate despite timely and appropriate treatment; mortality is influenced by age, extent of infection, degree of biochemical/acid-base imbalance, presence of comorbidities, and treatment delay.

References

1.     Kaafarani H.M.A., King D.R. Necrotizing skin and soft tissue infections. Surg Clin North Am. 2014;94:155–163.

2.    Hakkarainen T.W., Kopari N.M., Pham T.N., Evans H.L. Necrotizing soft tissue infections: review and current concepts in treatment, systems of care and outcomes. Curr Probl Surg. 2014;51:344–362.

3.     Morgan M.S. Diagnosis and management of necrotizing fasciitis: a multiparametric approach. J Hosp Infect. 2010;75:249–257.

4.    Stevens D.L., Bisno A.L., Chambers H.F., et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014;59:e10–52.

5.     Ramakrishnan K., Salinas R.C., Agudelo Higuita N.I. Skin and soft tissue infections. Am Fam Physician. 2015;92:474–483.

1  Not FDA approved for this  indication.

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