Necrotizing Soft Tissue Infections of the Perineum

Abstract

Necrotizing soft tissue infections of the perineum are rapidly progressing infections associated with significant morbidity and mortality. Prompt diagnosis and management with early surgical debridement is necessary to improve survival from this deadly disease. Repeat debridements are not uncommon. Important adjuncts to surgery include broad-spectrum antibiotics and management in an intensive care unit, as patients frequently develop multisystem organ failure. Once the acute phase is managed, fecal diversion with either an ostomy or fecal management catheter can be considered to decrease soiling of the wound and facilitate healing. Long-term management requires meticulous wound care, often with the assistance of negative pressure wound therapy. Patients may ultimately require skin grafts or tissue flaps for soft tissue coverage following extensive surgical debridements.

Necrotizing soft tissue infections (NSTIs) of the perineum are highly lethal infections that require early surgical management with extensive debridement of necrotic tissue. ^{1 2 3} NSTIs have been described in the literature as early as 1871, referred to as “hospital gangrene” based on experiences in the American Civil War. ⁴ In 1883, Jean-Alfred Fournier described “overwhelming gangrene” of the genitals and perineum of male patients, leading to the eponymous name of Fournier's gangrene. ⁵ Although Fournier's gangrene classically refers to involvement of the penis, scrotum, and/or perineum, the infection can occur in both males and females. Approximately 500 to 1,500 NSTI cases are diagnosed in the United States every year, ⁶ with a mortality of approximately 25%. ^{3 7} Morbidity is high as well, with many patients suffering from physiologic derangements such as multisystem organ failure during their hospitalization. ⁷

Etiology and Pathophysiology

The rapid development and spread of necrosis that characterizes an NSTI is caused by an aggressive immune response to microbial organisms ( Fig. 1 ). Inoculation of tissue occurs via the skin from external trauma or via spread from perforated viscus. Toxins, enzymes, and surface proteins from bacteria stimulate CD4 T-cells and macrophages to produce large quantities of cytokines, including tumor necrosis factor-α, interleukin-1, and interleukin-6. This causes ischemia due to thrombosis of perforating vessels, leading to tissue necrosis. Concurrently, the systemic release of these cytokines presents as septic shock with multisystem organ failure and possibly death. ^{1 2} Infections by Streptococcus and Clostridium species are particularly destructive, as they produce toxins that induce platelet/neutrophil aggregates resulting in occlusion of the microvasculature. ^{8 9}

Fig. 1.

Diagram representing the steps of NSTI development. NSTI, necrotizing soft tissue infection.

According to the original classification system, NSTIs were categorized into Type I (polymicrobial) or Type II (monomicrobial) infections. Type I infections are composed of a combination of gram-positive cocci, gram-negative rods, and anaerobes. These account for up to 75% of all NSTIs and over 50% of perineal NSTIs. ^{10 11} Polymicrobial infections are most common in patients who are immunosuppressed, obese, and/or diabetic. ² Type II infections occur classically in the extremities, although they can occur rarely in the perineum as well. ² Streptococcus pyogenes is the most common organism to cause a type II infection but Staphylococcus aureus , especially methicillin-resistant Staphylococcus aureus , can also be causative. ^{12 13}

There are several other less common pathogenic microorganisms that are now included in various classifications of NSTIs. Although Clostridium perfringens was previously a major cause of NSTIs, the incidence of this organism has decreased with improving sanitation. ² Clostridium septicum is found in the colonic flora and, therefore, isolation in a wound culture should raise suspicion of perforated colorectal carcinoma. ¹ Specific environmental exposures include Aeromonas hydrophila in fresh water and Vibrio vulnificans in salt water. A history of liver failure increases the risk of infection with Vibrio species and leads to a particularly aggressive infection, often classified as a type III NSTI. ² Finally, certain fungal species have been found to contribute to NSTIs. Fungal NSTIs have been classified as type IV and are associated with trauma. A description of type I through IV NSTIs can be found in Table 1 .

Table 1. Comparison of NSTI types.

	Type I	Type II	Type III	Type IV
Percent NSTIs	70–80%	20–30%	Rare	Rare
Organisms	Polymicrobial, Mixed GPCs, GNRs, and/or anaerobes	Monomicrobial, Streptococcus, or Staphylococcus	Vibrio species, often Vibrio vulnificans	Fungal organisms
Location	Perineum/trunk, less commonly extremities	Extremities, rarely perineum/trunk	Any location	Any location
Source	Bowel or skin flora	Usually skin flora	Seawater, seafood	Soil
Comorbidities	Immunosuppression, obesity, diabetes, peripheral vascular disease	IV drug abuse, recent trauma	Open wounds	Recent trauma, immunosuppression

Abbreviations: GNR, gram-negative rod; GPC, gram-positive cocci; NSTI, necrotizing soft tissue infection.

Physical Examination and Diagnostic Evaluation

NSTI of the perineum can be inconspicuous as it may initially present in similar fashion to a simple cellulitis or abscess (i.e., pain, erythema, swelling, or warmth). As the disease progresses, the signs on physical exam include blisters, bullae, and/or tense, ecchymotic skin over the infected area ( Fig. 2A ). ³ Subcutaneous emphysema can develop, leading to crepitus on examination and soft tissue air on radiographic imaging. Although this is pathognomonic for NSTI, it is neither always present nor readily apparent on exam. Findings of crepitus and skin necrosis are found in less than one-third of patients with NSTIs. ^{14 15} In these cases, necrosis is often much more extensive than the overlying skin changes would suggest ( Fig. 2B ).

Fig. 2.

Tissue involvement in perineal NSTIs may be more extensive than what can be appreciated on external examination. ( A ) Perineal cellulitis with an area of necrotic skin. ( B ) Emphysema tracking into pelvis on computed tomography imaging. Photograph provided courtesy of Dr. Walter Koltun. NSTI, necrotizing soft tissue infection.

Computed tomography (CT) or magnetic resonance imaging (MRI) can show the extent of NSTI to aid in operative planning but should not delay surgical debridement. CT has been shown to have a sensitivity of 80 to 90%. Findings include asymmetric fascial thickening, fluid collections, and soft tissue gas. ^{16 17} On MRI, hyperintense signal of the fascia can be seen on T2-weighted images. However, it is difficult to distinguish between infectious and noninfectious causes of inflammation on MRI and, therefore, the specificity is low despite its high sensitivity. ¹⁶ Additionally, the increased time and cost of MRI makes it less commonly used in clinical practice.

Laboratory factors can be useful in the diagnosis of NSTI. In 2004, the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score was developed to help diagnose NSTIs ( Table 2 ). ¹⁸ A total score of 6 or greater is associated with a positive predictive value of 92% and negative predictive value of 96% in the original study. ¹⁸ However, a recent prospective validation study found a positive predictive value of only 25% while the negative predictive value was maintained at 92%. ¹⁹ A comprehensive meta-analysis of 14 studies found a sensitivity of 68.2% and specificity of 84.8% when using a LRINEC score of 6 or greater to diagnose NSTIs. ¹⁷ Based on these updated studies, the LRINEC is not a definitive test for NSTI, but it remains commonly used in clinical practice.

Table 2. Laboratory risk indicator for necrotizing fasciitis (LRINEC) score ¹⁸ .

Variable	Score
C-reactive protein (mg/L)
< 150	0
≥ 150	4
Leucocytes (x10 3 /mm 3 )
< 15	0
15–25	1
> 25	2
Hemoglobin (g/dL)
> 13.5	0
11–13.5	1
< 11	2
Sodium (mmol/L)
≥ 135	0
< 135	2
Creatinine (mg/dL)
≤ 1.6	0
> 1.6	2
Glucose (mg/dL)
≤ 180	0
> 180	1

Note: The total score is calculated as a sum of all six variables (range 0–13). ¹⁸

The Fournier's gangrene severity index (FGSI) was developed to predict mortality in perineal NSTIs ( Table 3 ). ²⁰ In the initial study, scores of more than 9 were associated with 75% risk of mortality. A more recent validation study showed a score of more than 10.5 was associated with an even more significant risk of mortality of 96%. ²¹ In actuality, this score is similar to the Acute Physiology and Chronic Health Evaluation (APACHE) score used to predict mortality in any severely ill patient and, thus, has not sustained much clinical utility.

Table 3. Fournier's gangrene severity index (FGSI) ²⁰ .

Physiologic variable	+4	+3	+2	+1	Score	+1	+2	+3	+4
					0
Temperature (C)	>41	39–40.9		38.5–38.9	36–38.4	34–35.9	32–33.9	<31.9	<29.9
Heart rate	>180	140–179	110–139		70–109		55–69	40–54	<39
Respiratory rate	>50	35–49		25–34	12–24	10–11	6–9		<5
Sodium (mmol/L)	>180	160–179	155–159	150–154	130–49		120–129	111–119	<110
Potassium (mmol/L)	>7	6–6.9		5.5–5.9	3.5–5.4	3–3.4	2.5–2.9		<2.5
Bicarbonate (mmol/L)	>52	41–51.9		32–40.9	22–1.9		18–21.9	15–17.9	<15
Creatinine (mg/dL)	>3.5	2–3.4	1.5–1.9		0.6–1.4		<0.6
Hematocrit (%)	>60		50–59.9	46–49.9	30–5.9		20–29.9		<20
Leucocytes (x10 3 /mm 3 )	>40		20–39.9	15–19.9	3–14.9		1–2.9		<1

Bedside surgical procedures, such as fascial biopsies, can be effective in the diagnosis of NSTIs but usually result in delayed time to therapy. ²² Common findings on histopathology include inflammation, thrombosis, or necrosis of small blood vessels, as well as, polymorphonuclear infiltration of the fascia and deep dermis. ²³ In another bedside procedure named the “finger test,” under local anesthesia, a 2-cm incision is made and a finger is gently passed down to the level of the fascia. The test is positive if the tissues dissect with minimal resistance. Other associated findings can include “murky dishwater fluid” and lack of bleeding. ²⁴

Operative Timing and Approach

Multiple studies in the literature have identified the importance of early surgical debridement in decreasing the morbidity and mortality of NSTIs. ^{22 25 26} Once an NSTI is recognized, excision of all devitalized tissue is mandatory to achieve appropriate source control. ²² Unfortunately, due to the rapid spread of infection, debridements can often be extensive ( Fig. 3 ). At the first debridement, deep tissue cultures should be sent so that antibiotic therapy can be specifically tailored. After debridement and dressing application, repeat inspection of the wound should be performed within 24 hours. There should be a low threshold to return to the operating room for examination under anesthesia and additional surgical debridement within 24 to 48 hours, especially in patients with extensive initial debridement. ²² Although rare, any fistula-in-ano should be treated with a loose seton to facilitate wound drainage rather than fistulotomized during the acute phase. The extent and location of debridement may lead to challenges in positioning and intraoperative re-positioning may be required to ensure adequate evaluation and debridement. Early and aggressive debridement has been shown to decrease the number of subsequent surgeries and, most importantly, decreases mortality. ²⁶

Fig. 3.

NSTIs can require extensive debridement. ( A ) Patient with a perineal NSTI that extended into the left lower extremity. ( B ) Lateral view of the same patient, showing the extent and depth of the debridement required. Photographs provided courtesy of Dr. Michael Deutsch. NSTI, necrotizing soft tissue infection.

Adjuvant Treatments to Surgical Debridement

In addition to adequate surgical debridement, antimicrobial therapy is a vital treatment for perineal NSTIs. This therapy should be initiated immediately with empiric, broad-spectrum coverage of gram-positive, gram-negative, and anaerobic bacteria regardless of suspected pathogen. The Infectious Diseases Society of America guidelines recommend empiric therapy with vancomycin or linezolid plus piperacillin-tazobactam or a carbapenem. ²⁷ Protein synthesis inhibitors, such as clindamycin, should also be initiated with other antimicrobial coverage as it inhibits the toxin production from streptococcal or clostridial infections. ²⁸ Recommendations for antibiotic regimen and dosing are summarized in Table 4 . There have been few studies comparing antibiotic duration in perineal NSTIs but one recent study showed no difference in outcomes in patients receiving less than 7 days of therapy compared with longer durations. ²⁹ Expert opinion suggests antibiotics can be discontinued after source control is achieved and no further debridement is required. ²²

Table 4. Antibiotic recommendations for perineal NSTIs.

Antibiotic	Dose
One of the following:
Piperacillin-tazobactam  or	3.375 g every 6 to 8 h
Imipenem-cilastatin  or	1 g every 6 to 8 h
Meropenem  or	1 g every 8 h
Ertapenem	1 g daily
Plus one of the following:
Vancomycin  or	15 mg/kg/d every 12 h
Daptomycin  or	4 to 6 mg/kg daily
Linezolid	600 mg every 12 h
Plus:
Clindamycin	600 to 900 mg every 8 h

Patients with NSTIs often require admission to an intensive care unit setting to manage the multisystem organ failure that results from the systemic response to infection. Aggressive fluid resuscitation is often required as suggested by severe sepsis guidelines. ³⁰ Enteral nutritional support should be initiated early if possible and, if not possible, parenteral nutrition should be considered. ²²

Intravenous immune globulin (IVIG) has been proposed as an adjunct to the management of NSTIs caused by streptococci, but its efficacy remains controversial. IVIG is believed to reduce tumor necrosis factor-α and interleukin-6 produced in response to bacterial exotoxins. ⁸ A recent study of 67 patients with toxic shock syndrome (19 of which had NSTIs) showed a survival benefit in the 23 patients who were administered IVIG. ³¹ However, controlled trials are limited, so recommendations on IVIG are largely based on expert opinions. ²² Additionally, these studies have not addressed the efficacy of IVIG specifically in perineal NSTIs.

After adequate debridement, negative pressure and hyperbaric oxygen (HBO) therapy have been used to improve wound healing. Negative pressure wound therapy reduces the wound healing time and decreases the frequency of dressing changes, improving patient comfort. ³² Dressing adherence can be difficult to achieve in the perineum and often requires adjuncts such as adhesive pastes or tape to create a vacuum seal. ³³ HBO therapy is predicated on facilitating enhanced oxygenation of the wound to improve healing. HBO treatment is not universally available due to the specialized equipment and can require several weeks of treatments, up to three times per day. Initial studies on HBO therapy showed a decrease in the number of debridements as well as overall mortality. ³⁴ A single center retrospective study found a 12% mortality in patients treated with HBO therapy compared with 24% mortality in those who did not undergo HBO therapy. ³⁵ However, two Cochrane reviews found a lack of high quality evidence evaluating HBO therapy, and therefore could not support its efficacy. ^{36 37} The World Society of Emergency Surgery guidelines for the management of skin and soft tissue infections only recommend HBO therapy if available ²² and the Infectious Diseases Society of America does not recommend HBO therapy due to lack of evidence. ²⁷ Until higher quality studies validate the benefit of HBO therapy, the utility can be debated but certainly should not result in a delay of timely debridement for purposes of hospital transfer.

Role of Fecal Diversion

Fecal diversion can be considered in perineal NSTIs to prevent soiling of the wound either immediately after initial debridement or in a delayed fashion in conjunction with repeat debridement. ³⁸ The timing of fecal diversion is variable but should not be performed in the setting of ongoing sepsis or hemodynamic instability. Unfortunately, fecal diversion has not been shown to decrease the number of debridements required and some studies have found an increased mortality in patients with perineal NSTIs who undergo diverting colostomy creation. ^{39 40} Fecal diversion in perineal NSTIs is best achieved with a colostomy as opposed to an ileostomy when feasible. Although no studies have been performed comparing types of ostomies in perineal NSTIs specifically, ileostomies are associated with higher fluid loss and resultant renal injury. ⁴¹ Therefore a colostomy is likely of less physiologic insult in a critically ill patient. While an ileostomy could be considered in a stable patient who appears to be a good candidate for re-establishing continuity after recovery, a colostomy is likely a better option if a permanent stoma is anticipated. Strong emphasis must be placed on preoperative marking by an enterostomal therapist, if available, as a well-accepted method to reduce postoperative complications, as well as increase patient satisfaction and quality of life. ^{42 43} A carefully selected position for a stoma will be of tremendous benefit particularly if the debridement has to extend onto the anterior abdominal wall, as such conditions would likely favor use of an upper abdominal stoma. Lastly, our preference is for a laparoscopic-assisted technique to allow for any necessary intestinal mobilization to minimize tension on the stoma. A trephine stoma is certainly acceptable, but all surgical techniques should be used to avoid a laparotomy in an already debilitated patient. ⁴⁴

Recent studies have evaluated fecal management catheters as a less invasive way to decrease contamination of the perineal wound. Fecal management catheters have been shown to be effective in studies of patients with perineal burns, as well as perineal NSTIs. ⁴⁵ While these catheters may be useful for stool diversion while the wound heals, they are unlikely to be helpful for chronic fecal incontinence caused by sphincter dysfunction. Additionally, the concept of a distal rectal washout initially popularized by traumatic extraperitoneal rectal injuries has fallen out of favor as it can be associated with up to a threefold increase in infectious complications. ^{46 47}

Long-Term Outcomes

Literature on long-term outcomes after recovery from perineal NSTIs mainly focuses on reconstruction of the defect. Due to the complexity of the wound coverage, consultation with reconstructive plastic surgeons is recommended. For well-vascularized tissue beds, split-thickness skin grafting is most commonly utilized. ⁴⁸ For more extensive surgical defects resulting from wide debridements, myocutaneous flaps have been utilized successfully. These flaps have the added benefit of providing improved cosmesis. Gracilis flaps are often used, as they have a reliable vascular supply and the donor site is easy to close. Fasciocutaneous flaps such as the pudendal thigh flap can also be used as they provide the good cosmesis but they require more protection of small vessels for adequate blood supply. ⁴⁹ The timing of closure of a diverting ostomy is not well studied in the literature, but should be delayed until the patient has clinically recovered, any reconstruction has been completed, and the wound is healed. Studies focusing on ostomy closure after perineal NSTIs would be beneficial to determine the rates of stoma closure as well as the functional outcomes in these patients.

Long-term management of patients having undergone debridement of the anal sphincter complex has not been evaluated. However, recommendations can be extrapolated from management of traumatic perineal injuries. Depending on the extent of sphincter injury, various reconstruction options can be considered. For an isolated defect of the sphincter, sphincteroplasty can be performed. Although over 50% of patients will experience reduced continence over the long term after this procedure, as many as 75% continue to report good quality of life and satisfaction. ⁵⁰ For more extensive injuries, reconstruction options that have been studied include graciloplasty, gluteoplasty, circular smooth muscle cuff, and artificial sphincters. Unfortunately, these procedures have associated morbidity and generally poor functional outcomes. ⁵¹

Conclusion

NSTIs of the perineum are rapidly progressive infections that can be deadly if not managed expeditiously and appropriately. Source control with surgical debridement of all necrotic tissue is the most critical factor associated with survival. Due to the aggressive nature of this disease, early surgical consultation should be considered if the diagnosis of NSTI is suspected, as scoring systems are not always reliable. Even with early and extensive debridement, repeat debridements are often required, and there should be a low threshold to return to the operating room, especially in the first 24 to 48 hours. Fecal diversion via ostomy creation or bowel management catheters can be used to allow for decreased wound soilage. Once source control is achieved and the patient is recovering, management moves into a second phase that is focused on wound care. There are few long-term studies on perineal NSTIs, and those focus on tissue replacement and coverage. The proportion of patients who have ostomies reversed after recovery is unknown, as is their function.

Funding Statement

Funding This work was supported by the Marshia and Peter Carlino Early Career Professorship at Penn State Hershey Medical Center.