Approach Considerations
Early recognition and high clinical suspicion are important in making a timely diagnosis, as early manifestations are often subtle. The most significant modifiable risk factor associated with NSTI mortality is delay to surgical intervention.
Treatment of Fournier gangrene involves several modalities. Surgery is necessary for definitive diagnosis and excision of necrotic tissue. High clinical suspicion is required for early diagnosis as the initial manifestations are often subtle. The most significant modifiable risk factor associated with mortality is delay to surgical intervention. [66] Earlier surgical intervention has been associated with reduced mortality. [67, 68]
In patients who present with systemic toxicity manifesting as hypoperfusion or organ failure, aggressive resuscitation to restore normal organ perfusion and function must take precedence over diagnostic maneuvers, especially if these diagnostic studies could compromise the resuscitative interventions.
Thus, the emergency department (ED) treatment of patients with Fournier gangrene includes aggressive resuscitation in anticipation of surgery. Provide airway management if indicated, give supplemental oxygen, and establish intravenous (IV) access and continuous cardiac monitoring. Crystalloid replacement is indicated for patients who are dehydrated or displaying signs of shock. A balanced crystalloid such as lactated Ringer’s solution is preferable. [66]
Early, broad-spectrum antibiotics are indicated. Tetanus prophylaxis is indicated if soft-tissue injury is present.
In addition, any underlying comorbid conditions (eg, diabetes, alcoholism) must ultimately be addressed. Such conditions are common in these patients, and potentially predispose to Fournier gangrene. Failure to adequately manage the comorbid conditions may threaten the success of even the most appropriate interventions to resolve the infectious disease.
Antibiotic and Antifungal Therapy
Treatment of Fournier gangrene involves the institution of broad-spectrum antibiotic therapy. The antibiotic spectrum should cover staphylococci, streptococci, the Enterobacteriaceae family of organisms, coliforms and anaerobes. [66]
A reasonable empiric regimen might consist of ciprofloxacin and clindamycin. Clindamycin is particularly useful in the treatment of necrotizing soft-tissue infections because of its gram-positive and anaerobic spectrum of activity. In animal models of streptococcal infection, clindamycin has been shown to yield response rates superior to those of penicillin or erythromycin, even in the context of delayed treatment. [69]
Other possible choices include ampicillin/sulbactam, ticarcillin/clavulanate, or piperacillin/tazobactam in combination with an aminoglycoside and metronidazole or clindamycin. Vancomycin can be used to provide coverage for methicillin-resistant Staphylococcus aureus (MRSA). [66]
In cases associated with sepsis syndrome, therapy with intravenous immunoglobulin (IVIG), which is thought to neutralize superantigens (eg, streptotoxins A and B) believed to mitigate the exaggerated cytokine response, has been shown to be a good adjuvant to appropriate antibiotic coverage and complete surgical debridement. [70]
If initial tissue stains (ie, potassium hydroxide [KOH] stain) show fungi, add an empiric antifungal agent such as amphotericin B or caspofungin.
Surgical Diagnosis and Debridement
In the event of a presumptive diagnosis based on a clinical examination or diagnostic study, the definitive diagnosis of Fournier gangrene is provided by examination with the patient under anesthesia followed by incision into the area of greatest clinical concern. If frankly gangrenous tissue is found or purulence is drained, the diagnosis of Fournier gangrene is established. See image below.
In a man with alcoholism and known cirrhosis who presented with exquisite pain limited to the scrotum, opening of the scrotum along the median raphe liberated foul-smelling brown purulence and exposed necrotic tissue throughout the mid scrotum. The testicles were not involved. Courtesy of Thomas A. Santora, MD.
Occasionally, early-stage Fournier disease manifests as severe cellulitis. If an incision is made, the fascia may appear edematous rather than exhibiting the gray-black appearance of well-established Fournier gangrene. In this instance, obtain an incisional biopsy sample of the deep fascia for frozen-section evaluation to exclude early necrotizing disease.
Excising necrotic tissue
Once a diagnosis of Fournier gangrene is established, all necrotic tissue must be excised. In a large retrospective review of 379 patients, Sugihara et al confirmed the opinion that early surgical intervention reduces mortality. Those who underwent earlier intervention had a lower fatality rate (odds ratio, 0.38) than those whose intervention was delayed to 3 days or later. [67]
The skin should be opened widely to expose the full extent of the underlying fascial and subcutaneous tissue necrosis. All fascial planes that separate easily with blunt dissection should be considered involved and therefore excised. The dissection should be carried out to include bleeding tissues (ie, tissue that is well vascularized).
Send samples of excised tissue for aerobic and anaerobic cultures and a histologic assessment.
Given the characteristic thrombosis of the nutrient vessels, the overlying skin has impaired blood supply and should be excised if significantly undermined. The authors strongly recommend radical excisional debridement (see below image) with electrocautery in order to reduce the considerable operative blood loss if the area of involvement is extensive.
Patient with Fournier gangrene following radical debridement. A dorsal slit was made in the prepuce to expose the glans penis. Urethral catheterization was performed. Incision into the point of maximal tenderness on the right side of the perineum revealed gangrenous necrosis that involved the anterior and posterior aspects of the perineum, the entirety of the right hemiscrotum, and the posterior medial aspect of the right thigh. The skin and involved fascia were excised from these areas. Reconstruction of this defect was performed in a staged approach. A gracilis rotational muscle flap taken from the right thigh was used to fill the cavity in the posterior right perineum as the first step. The remainder of the defect was covered with split-thickness skin grafts. This patient made a full recovery.
The testicles are often spared in the necrotizing process. If they are uninvolved, place the exposed testicles in a subcutaneous pocket to prevent desiccation. If a testicle is involved in the necrotic process or its viability is questioned, perform orchiectomy.
Reconstruction
Once the infection is eradicated, healthy granulation tissue develops; this signifies the time to proceed to reconstruction.
Options for reconstruction include the following:
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Primary closure of the skin, if possible
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Local skin flap coverage
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Split-thickness skin grafts
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Muscular flaps, which are used to fill a cavity (eg, ischiorectal space)
On the basis of a systematic review of 16 studies, Karian et al concluded that, "most reconstructive techniques provide reliable coverage and protection of testicular function with an acceptable cosmetic result. There is no conclusive evidence to support flap coverage of exposed testes rather than skin graft." However, these authors recommended skin grafting or flap reconstruction for defects larger than 50% of the scrotum or extending beyond the scrotum; for defects confined involving less than 50% of the scrotum that cannot be closed primarily without tension, they recommended reconstruction with a scrotal advancement flap or healing by secondary intention. [71]
Konofaos and Hickerson have reported a two-step technique for treating scrotal defects with total skin loss involving exposed testes. The first step consists of primary closure with a wrap-around skin grafting. The second step comprises reapproximating the testes and shaping the neoscrotum to optimize cosmesis. [72]
Hyperbaric Oxygen Therapy
Hyperbaric oxygen therapy (HBO) has been used as an adjuvant to surgical and antimicrobial therapy. Indications include failure of conventional treatment, documented clostridial involvement, or myonecrosis or deep tissue involvement. HBO is postulated to reduce systemic toxicity, prevent extension of necrotizing infection, and inhibit growth of anaerobic bacteria.
HBO has shown some promising results. [73, 74, 75] A retrospective single-center study by Mladenov et al found that the survival rate for 192 patients with necrotizing fasciitis or Fournier gangrene who underwent HBO was higher than that for individuals who were ineligible for HBO treatment owing to contraindications (73.5% vs 36.4%, respectively). The survival rate of the patients who received HBO was comparable to that of patients who did not require HBO (75.5%). [76]
However, in one series, there was actually a trend toward increased mortality in patients undergoing HBO, although this trend may have been related to selection bias (ie, HBO may have been used in patients who were more ill). [77] The role of HBO in the treatment of Fournier disease needs to be clarified with a prospective controlled trial. [77]
Decisions regarding HBO must be made on an individual basis, taking into consideration the stability of the patient. Use of HBO must not delay surgical debridement.
Investigational Treatments
The role of topical agents in wound care requires further investigation. Unprocessed honey, applied directly to the surface of the wounds, has been reported by some authors to enzymatically debride, sterilize, and dehydrate wounds and to improve local tissue oxygenation and re-epithelialization. However, the salutatory effect of honey is likely related to its physical property of hyperosmolarity. [78] Therefore, honey holds little advantage over other hygroscopic agents. [79]
The application of growth hormones and other trophic agents holds the potential to promote faster wound healing.
One published case report advocates irrigation of the perineum with superoxidized water as well as application of gauze soaked in zinc peroxide and hydrogen peroxide.
In patients who require cutaneous reconstruction for tissue loss secondary to necrotizing soft tissue infections, including Fournier gangrene, Hersant et al reported significantly improved clinical outcomes and shortened wound healing time when split-thickness skin grafting (STSG) is followed by spraying autologous platelet-rich plasma (A-PRP) and thrombin gel on the wound bed and on the graft after stable fixation. In their prospective, controlled, open-label randomized study, the mean complete healing time was almost 50% shorter in patients (n=14) who received STSG plus A-PRP/thrombin gel than in those (n=13) receiving STSG alone (37.9 vs. 73.7 days, respectively; P=0.01). [80]
Use of intravenous immunoglobulins (IVIG) and therapeutic plasma exchange (TPE) have been reported, although evidence is limited. [66]
Transfer
Fournier gangrene is a true surgical emergency. At minimum, immediate urologic or general surgical consultation is mandatory, and management often requires a multidisciplinary team, including a urologist, a general surgeon, and an intensive care specialist.
Transfer to a tertiary facility may be required if these resources are not available at the initial facility. Initial debridement may be performed if required in anticipation of transfer. Arrange for transfer once the patient has been stabilized and resuscitative efforts have begun.
Results of a retrospective review of 1801 cases of necrotizing soft tissue infections in the 2010-2015 American College of Surgeons National Surgical Quality Improvement Program Participant Use Data Files suggest that interhospital transfer status is not an independent risk factor for mortality or morbidity after surgical management. Of the 1801 patients with necrotizing soft tissue infections, gas gangrene, or Fournier gangrene, 1243 (69.0%) were in the non-transfer group and 558 (31.0%) were in the transfer group. Although the transfer group experienced higher rates of 30-day mortality (14.5% versus 13.0%) and major morbidity (64.5% versus 60.1%) than the non-transfer group, the differences were not significant after risk adjustment. [81]
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Necrotizing infection results when the pathogen is extremely virulent or, most commonly, when a combination of microorganisms act synergistically in a susceptible immunocompromised host.
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Photomicrograph of Fournier gangrene (necrotizing fasciitis), oil immersion at 1000X magnification. Note the acute inflammatory cells in the necrotic tissue. Bacteria are located in the haziness of their cytoplasm. Courtesy of Billie Fife, MD, and Thomas A. Santora, MD.
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Photograph of a morbidly obese male with long-standing phimosis. This condition led to urinary incontinence, perineal diaper rash–like dermatitis, and urinary tract infection. Ultimately, he presented with exquisite perineal pain. An examination with the patient under anesthesia was necessary to discover the necrotizing infection that appeared to originate in the right bulbourethral gland. Courtesy of Thomas A. Santora, MD.
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Patient with Fournier gangrene following radical debridement. A dorsal slit was made in the prepuce to expose the glans penis. Urethral catheterization was performed. Incision into the point of maximal tenderness on the right side of the perineum revealed gangrenous necrosis that involved the anterior and posterior aspects of the perineum, the entirety of the right hemiscrotum, and the posterior medial aspect of the right thigh. The skin and involved fascia were excised from these areas. Reconstruction of this defect was performed in a staged approach. A gracilis rotational muscle flap taken from the right thigh was used to fill the cavity in the posterior right perineum as the first step. The remainder of the defect was covered with split-thickness skin grafts. This patient made a full recovery.
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Fascial envelopment of the perineum (male). Note how Colles fascia completely envelops the scrotum and penis. Colles fascia is in continuity cephalad to the level of the clavicles. In the inguinal region, this fascial layer is known as Scarpa fascia. Familiarity with this fascial anatomy, along with recognition that necrotizing fasciitis tends to spread along fascial planes, makes it easy to understand how a process that starts in the perineum can spread to the abdominal wall, the flank, and even the chest wall.
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Examination of an anesthetized man with alcoholism and known cirrhosis who presented with exquisite pain limited to the scrotum. Note the erythema of the scrotum and the look of skepticism on the face of one of the surgeons. Courtesy of Thomas A. Santora, MD.
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In a man with alcoholism and known cirrhosis who presented with exquisite pain limited to the scrotum, opening of the scrotum along the median raphe liberated foul-smelling brown purulence and exposed necrotic tissue throughout the mid scrotum. The testicles were not involved. Courtesy of Thomas A. Santora, MD.
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The same patient depicted in Images 6 and 7. Following resolution of the infection, the wound was covered with a split-thickness skin graft. The option of delayed primary closure of this wound was not chosen in this patient because of concern for tension on the closure. Courtesy of Thomas A. Santora, MD.
