AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Background

In 1883, the French venereologist Jean Alfred Fournier described a series in which 5 previously healthy young men suffered from a rapidly progressive gangrene of the penis and scrotum without apparent cause. This condition, now known as Fournier gangrene, is defined as a polymicrobial necrotizing fasciitis of the perineal, perianal, or genital areas. In contrast to Dr Fournier's initial description, doctors today know that the disease is not limited to young or male patients, and a causative etiology usually is identified.

Pathophysiology

Localized infection adjacent to a portal of entry is the inciting event in the development of Fournier gangrene.

Wound cultures from patients with Fournier gangrene reveal that it is a polymicrobial infection with an average of 4 isolates per case. The bacteria involved act synergistically, via collagenases, hyaluronidases, and other enzymes to invade and destroy fascial planes. See Causes section for specific microbes involved and specific inciting factors.

Ultimately, an obliterative endarteritis develops, and the ensuing cutaneous and subcutaneous vascular necrosis leads to localized ischemia and further bacterial proliferation. Rates of fascial destruction as high as 2-3 cm/h have been described. Infection of superficial perineal fascia (Colles fascia) may spread to the penis and scrotum via Buck and dartos fascia, or to the anterior abdominal wall via Scarpa fascia, or vice versa. Colles fascia is attached to the perineal body and urogenital diaphragm posteriorly and to the pubic rami laterally, thus limiting progression in these directions. Testicular involvement is rare, as the testicular arteries originate directly from the aorta and thus have a blood supply separate from the affected region.

Frequency

United States

Fournier gangrene is relatively uncommon. The true incidence of the disease is unknown. A retrospective case review revealed 1726 cases documented in the literature from 1950-1999.¹ An average of 97 cases per year were reported from 1989-1998.

Mortality/Morbidity

• The reported mortality rate for Fournier gangrene varies widely from 4-75%.
• Factors associated with high mortality include an anorectal source, advanced age, extensive disease (involving abdominal wall or thighs), shock or sepsis at presentation, renal failure, and hepatic dysfunction.
• Death usually results from systemic illness, such as sepsis, coagulopathy, acute renal failure, diabetic ketoacidosis, or multiple organ failure.

Sex

Male-to-female ratio is approximately 10:1. Lower incidence in females may be caused by better drainage of the perineal region through vaginal secretions. Men who have sex with men may be at higher risk, especially for infections caused by community-associated methicillin-resistant Staphylococcus aureus (MRSA).

Age

Most reported cases occur in patients aged 30-60 years. A 1997 literature review found only 56 pediatric cases, with 66% of those in infants younger than 3 months.

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

History

Obtain a thorough review of systems, including history of diabetes, alcohol abuse, cancer, colorectal or urogenital disease or surgery, steroid use, sexual history, and HIV status.

• Fournier gangrene usually begins with an insidious onset of pruritus and discomfort of the external genitalia.
• Patients wait an average of 5 days before seeking medical attention.
• Early in the course of the disease, pain may be out of proportion to physical findings.
• Swelling and erythema of the region follow pain, and patients may complain of systemic symptoms such as fever or chills.
• As gangrene develops, pain actually may subside as nerve tissue becomes necrotic.

Physical

• Skin overlying the affected region may be normal, erythematous, edematous, cyanotic, bronzed, indurated, blistered, and/or frankly gangrenous. Skin appearance often underestimates the degree of underlying disease.
• A feculent odor may be present secondary to infection with anaerobic bacteria.
• Crepitus may be present, but its absence does not exclude the presence of Clostridium species or other gas-producing organisms.
• Systemic symptoms, eg, fever, tachycardia, hypotension, may be present.
• A thorough genital and perianal examination is required to detect potential portal of entry.

Causes

Idiopathic cases still are reported, but causative factors are found in more than 75% of patients.

• Inciting events: Localized infection adjacent to a portal of entry is often the inciting event in the development of Fournier gangrene. Colorectal, genitourinary, and dermatologic sources are implicated in the pathogenesis of the disease. Trauma, recent surgery, and the presence of foreign bodies may also lead to the disease. Examples include the following:  
• • Perianal, perirectal, and ischiorectal abscesses; anal fissures; colonic perforations; urethral strictures with urinary extravasation; chronic urinary tract infections; epididymitis; orchitis; or hidradenitis may lead to the disease.
  • Urethral instrumentation, prosthetic penile implants, superficial soft-tissue injuries, intramuscular injections, genital piercings, steroid enemas (used for the treatment of radiation proctitis), blunt thoracic trauma, and penile self-injection with cocaine have been reported in the literature as causative factors.
  • In women, septic abortions, vulvar or Bartholin gland abscesses, hysterectomy, and episiotomy are documented sources.
  • In men, anal intercourse may increase risk of perineal infection, either from blunt trauma to the area or by spread of rectally carried microbes. 
  • In children, circumcision, strangulated inguinal hernia, omphalitis, insect bites, trauma, urethral instrumentation, perirectal abscesses, systemic infections, and burns have led to the disease.
  • Inability to practice adequate perineal hygiene or the presence of chronically indwelling catheters, such as in paraplegic patients, poses an increased risk.
• Causative microbes isolated in wound cultures: Wound cultures from patients with Fournier gangrene reveal that it is a polymicrobial infection with an average of 4 isolates per case.
• • Escherichia coli is the predominant aerobe, and Bacteroides is the predominant anaerobe.
  • Other common microflora include Proteus, Staphylococcus, Enterococcus, aerobic and anaerobic Streptococcus, Pseudomonas, Klebsiella, and Clostridium.
  • Incidence of methicillin-resistant Staphylococcus aureus may be increasing.
• Predisposition to disease: Any condition with depressed cellular immunity may predispose a patient to the development of Fournier gangrene. Examples include the following:
• • Diabetes mellitus (present in up to 60% of cases)
  • Alcoholism
  • Extremes of age
  • Malignancy
  • Chronic steroid use
  • Malnutrition
  • HIV infection

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Other Problems to be Considered

Testicular fracture
Testicular hematoma
Testicular abscess
Scrotal abscess
Vasculitis
Warfarin gangrenosum
Polyarteritis nodosum
Wegener granulomatosis

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Lab Studies

• Complete blood count (CBC)
• Electrolytes, blood urea nitrogen (BUN), creatinine, blood glucose levels
• • Acidosis with hyperglycemia or hypoglycemia may be present.
  • Dehydration occurs as the disease progresses.
• Arterial blood gas (ABG) sampling may provide a more accurate assessment of acid/base disturbance.
• Blood and urine cultures
• DIC panel (coagulation studies, fibrinogen/fibrin degradation product levels) may provide evidence of severe sepsis.
• Cultures of any open wound or abscess

Imaging Studies

• Diagnosis of Fournier gangrene primarily is based on clinical findings. Sensitivities and specificities of different radiologic modalities are not established.
• Conventional radiography
• • Conventional radiography may demonstrate soft-tissue gas collections (manifest as areas of hyperlucency), even before they are clinically apparent.
  • Scrotal tissue edema may be observed on radiographs.
  • Absence of air on plain films does not exclude the diagnosis.
• Ultrasonography
• • Ultrasonography may reveal other causes of acute scrotal pain, including intratesticular injury, scrotal cellulitis, epididymoorchitis, testicular torsion, and inguinal hernia.
  • Gas in the scrotal wall is the "sonographic hallmark" of Fournier gangrene.
  • Air may be appreciated in perineal and/or perirectal areas.
  • Scrotal wall edema may be seen.
  • Testes and epididymides usually are normal.
• Computed tomography
• • Findings include soft-tissue and fascial thickening, fat stranding, and soft-tissue gas collections.
  • CT scan defines the extent of the disease more specifically than plain films or ultrasound.
  • CT scan often identifies the underlying cause of the infection (eg, perirectal abscess).
  • This modality may assist in surgical planning.
• Magnetic resonance imaging
• • MRI use is not well described in the literature.
  • MRI may define soft-tissue pathology more distinctly than CT scan but should not delay operative intervention if the diagnosis is highly suspected.

TREATMENT

Section 6 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Emergency Department Care

• Aggressive resuscitation in anticipation of surgery  
• • Airway management if indicated
  • Crystalloid replacement if dehydrated or displaying signs of shock
• Supplemental oxygen, IV access, and continuous cardiac monitoring
• Early, broad-spectrum antibiotics; examples include the following:
• •  Ampicillin/sulbactam
  • Ticarcillin/clavulanate
  • Piperacillin/tazobactam
  • Penicillinase-resistant penicillin, aminoglycoside, and metronidazole or clindamycin
  • Coverage for methicillin-resistant Staphylococcus aureus, such as vancomycin
• Tetanus prophylaxis is indicated if soft-tissue injury is present.
• Irrigation with superoxidized water and packing with gauze soaked with zinc peroxide and hydrogen peroxide may be helpful.

Consultations

• Fournier gangrene is a surgical emergency. Surgical consultation is imperative.
• Immediate urologic consultation is mandatory.

MEDICATION

Section 7 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

The goals of pharmacotherapy are to reduce morbidity and to control the infection.

Drug Category: Antibiotics

Initiate early broad-spectrum antibiotics as soon as possible. Providing coverage for gram-positive, gram-negative, aerobic, and anaerobic bacteria is essential. Penicillins and beta-lactamase inhibitors or triple antibiotics are potential choices.

Drug Name	Ampicillin-sulbactam sodium (Unasyn)
Description	Drug combination that uses a beta-lactamase inhibitor with ampicillin; covers skin, enteric flora, and anaerobes; not ideal for nosocomial pathogens.
Adult Dose	1.5 (1 g ampicillin + 0.5 g sulbactam) to 3 g (2 g ampicillin + 1 g sulbactam) IV/IM q6-8h; not to exceed 4 g/d sulbactam or 8 g/d ampicillin
Pediatric Dose	<3 months: Not established 3 months to 12 years: 100-200 mg ampicillin/kg/d (150-300 mg Unasyn) IV divided q6h >12 years: Administer as in adults; not to exceed 4 g/d sulbactam or 8 g/d ampicillin
Contraindications	Documented hypersensitivity
Interactions	Probenecid and disulfiram elevate ampicillin levels; allopurinol decreases ampicillin effects and has additive effects on ampicillin rash; may decrease effects of oral contraceptives
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Adjust dose in renal failure; if rash occurs, evaluate and differentiate from hypersensitivity reaction

Drug Name	Ticarcillin and clavulanate potassium (Timentin)
Description	Inhibits biosynthesis of cell wall mucopeptide and is effective during active growth stage; antipseudomonal penicillin plus beta-lactamase inhibitor that provides coverage against most gram-positive and gram-negative organisms and most anaerobes; contains 4.7-5 mEq of sodium per gram.
Adult Dose	200-300 mg/kg/d IV divided into equal doses q6h; usual dose is 3-4 g q4-6h
Pediatric Dose	Preterm to 1 week: 75 mg/kg IV q8h 2 weeks to 1 month: 75 mg/kg IV q6h >1 month: (3 dosing schedules exist) (A) 3.1 g IV q6h (B) 75 mg/kg IV q6h (C) 100 mg/kg IV q12h
Contraindications	Documented hypersensitivity; do not treat severe pneumonia, bacteremia, pericarditis, emphysema, meningitis, and purulent or septic arthritis with oral penicillin during acute stage
Interactions	Tetracyclines may decrease effects of ticarcillin; high ticarcillin concentrations may physically inactivate aminoglycosides if administered in same IV line; effects when administered concurrently with aminoglycosides are synergistic; probenecid may increase penicillin levels
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Perform CBCs prior to initiation of therapy and at least weekly during therapy; monitor for liver function abnormalities by measuring AST and ALT during therapy; caution in patients with hepatic insufficiencies; perform urinalysis, BUN, and creatinine determinations during therapy, and adjust dose if values become elevated; monitor blood levels to avoid possible neurotoxic reactions

Drug Name	Piperacillin/tazobactam (Zosyn)
Description	Antipseudomonal penicillin plus beta-lactamase inhibitor; inhibits biosynthesis of cell wall mucopeptide and is effective during the stage of active multiplication.
Adult Dose	12 g piperacillin/1.5 g tazobactam IV for 7-10 d in divided doses of 3.375 g q6h
Pediatric Dose	<12 years: Not established >12 years: Administer as in adults
Contraindications	Documented hypersensitivity; do not treat severe pneumonia, bacteremia, pericarditis, emphysema, meningitis, and purulent or septic arthritis with an oral penicillin during the acute stage
Interactions	Tetracyclines may decrease effects of ticarcillin; high ticarcillin concentrations may physically inactivate aminoglycosides if administered in same IV line; effects when administered concurrently with aminoglycosides are synergistic; probenecid may increase penicillin levels
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Perform CBC prior to initiation of therapy and at least weekly during therapy; monitor for liver function abnormalities by measuring AST and ALT during therapy; exercise caution in patients diagnosed with hepatic insufficiencies; perform urinalysis, BUN, and creatinine determinations during therapy, and adjust dose if values become elevated; monitor blood levels to avoid possible neurotoxic reactions

Drug Name	Gentamicin (Gentacidin, Garamycin)
Description	Aminoglycoside antibiotic used for gram-negative bacterial coverage; commonly used in combination with both an agent against gram-positive organisms and one that covers anaerobes; consider using when penicillins or other less toxic drugs are contraindicated, when bacterial susceptibility tests and clinical judgment indicate use, and in mixed infections caused by susceptible strains of staphylococci and gram-negative organisms; dosing regimens are numerous and are adjusted based on CrCl and changes in the volume of distribution; may be administered IV/IM.
Adult Dose	Serious infections and normal renal function: 3 mg/kg/d IV/IM divided q8h Life-threatening infections: 5 mg/kg/d IV/IM q6-8h Loading dose: 1-2.5 mg/kg IV q8h Maintenance dose: 1-1.5 mg/kg IV q8h Each regimen must be followed by at least a trough level drawn on the third or fourth dose, 0.5 h before dosing, and may draw a peak level 0.5 h after the 30-min infusion; extended dosing regimen for pulmonary infections is 7 mg/kg/d divided q8h
Pediatric Dose	<5 years with normal renal function: 2.5 mg/kg/dose IV/IM q8h >5 years: 1.5-2.5 mg/kg/dose q8h or 6-7.5 mg/kg/d IV/IM divided q8h; not to exceed 300 mg/d with adjustments for renal function prn; monitor levels as in adults
Contraindications	Documented hypersensitivity; non–dialysis-dependent renal insufficiency
Interactions	Coadministration with other aminoglycosides, cephalosporins, penicillins, and amphotericin B may increase nephrotoxicity; aminoglycosides enhance effects of neuromuscular blocking agents, thus prolonged respiratory depression may occur Coadministration with loop diuretics may increase auditory toxicity of aminoglycosides; possible irreversible hearing loss of varying degrees may occur (monitor regularly)
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions	Narrow therapeutic index (not intended for long-term therapy); caution in renal failure (not on dialysis), myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission; adjust dose in renal impairment

Drug Name	Metronidazole (Flagyl)
Description	Imidazole ring-based antibiotic active against anaerobes; usually used in combination with other antimicrobial agents, except when used for Clostridium difficile enterocolitis in which monotherapy is appropriate; active against various anaerobic bacteria and protozoa. Agent appears to be absorbed into cells of microorganisms that contain nitroreductase; then, unstable intermediate compounds are formed that bind DNA and inhibit synthesis, causing cell death.
Adult Dose	Loading dose: Infuse 15 mg/kg IV over 1 h or 1 g for a 70-kg adult Maintenance dose: 6 h following the loading dose, infuse 7.5 mg/kg IV over 1 h q6-8h or 500 mg for a 70-kg adult; not to exceed 4 g/d
Pediatric Dose	15-30 mg/kg/d IV divided bid/tid; not to exceed 2 g/d
Contraindications	Documented hypersensitivity
Interactions	May increase toxicity of anticoagulants, lithium, and phenytoin; cimetidine may increase toxicity of metronidazole; disulfiram reaction may occur with orally ingested ethanol
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Adjust dose in hepatic disease; monitor for seizures and development of peripheral neuropathy

Drug Name	Clindamycin (Cleocin)
Description	Lincosamide useful in treatment against serious skin and soft-tissue infections caused by most staphylococci strains; also effective against aerobic and anaerobic streptococci, except enterococci; inhibits bacterial protein synthesis by inhibiting peptide chain initiation at the bacterial ribosome, where it preferentially binds to the 50S ribosomal subunit, causing bacterial growth inhibition.
Adult Dose	600-1200 mg/d IV/IM divided q6-8h depending on degree of infection
Pediatric Dose	8-16 mg/kg/d IV/IM divided tid/qid Severe infections: May increase dose to 16-20 mg/kg/d divided tid/qid
Contraindications	Documented hypersensitivity; regional enteritis; ulcerative colitis; hepatic impairment; antibiotic-associated colitis
Interactions	Increases duration of neuromuscular blockade, induced by tubocurarine and pancuronium; erythromycin may antagonize effects of clindamycin; antidiarrheals may delay absorption of clindamycin
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Adjust dose in severe hepatic dysfunction; no adjustment necessary in renal insufficiency; associated with severe and possibly fatal colitis

Drug Category: Immunizations

Patients with fatal tetanus associated with Fournier gangrene have been documented in the literature. Patients with noncurrent tetanus status require immunization in the emergency department.

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Further Inpatient Care

• The consulting urologist or surgeon may order further diagnostic tests, including cystourethroscopy, retrograde urethrography, sigmoidoscopy, barium enema, tissue biopsy, and examination under anesthesia.
• Urinary and/or fecal diversion (eg, suprapubic catheterization, colostomy) may be required depending on the source of infection.
• Multiple debridements in the operating room may be required to effectively remove all necrotic tissue. Patients with Fournier gangrene undergo an average of 2-4 operative procedures during their initial hospitalization.
• Orchidectomy and/or penectomy rarely are required.
• Hyperbaric oxygen therapy (HBO) has been used as an adjuvant to surgical and antimicrobial therapy, especially in patients for whom conventional treatment has failed, in those with documented clostridial involvement, or in those with myonecrosis or deep tissue involvement. HBO is postulated to reduce systemic toxicity, prevent extension of necrotizing infection, and inhibit growth of anaerobic bacteria. However, in one series, there was actually a trend toward increased mortality in patients undergoing HBO therapy.² (This trend may have been related to selection bias). Decisions regarding hyperbaric therapy must be made on an individual basis and should be an adjuvant to debridement and antimicrobial therapy.
• A Fournier gangrene severity index score has been developed, which has been shown to aid in prognosis. A score from 0 to 4 is assigned to each of the following parameters³: temperature; heart rate; respiratory rate; serum sodium, potassium, bicarbonate, and creatinine levels; hematocrit; and white blood cell count. Mortality is associated with a total score >9.
• 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. This treatment is controversial, and no current studies support this practice.
• 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.

Transfer

• Fournier gangrene is a true surgical emergency. If the initial facility does not have the capability to provide operative therapy in a timely fashion, arrange for transfer once the patient has been stabilized and resuscitative efforts have begun.
• Patients often require a multidisciplinary team, including a urologist, general surgeon, and intensivist. Transfer to a tertiary facility may be required if these resources are not available at the initial facility.

Complications

• Progression to single-organ or multiorgan failure may occur, usually as a result of gram-negative sepsis and typically is the cause of death. Examples include acute renal failure and adult respiratory distress syndrome.
• Large scrotal, perineal, penile, and abdominal wall skin defects may require reconstructive procedures.
• Fatal tetanus associated with Fournier gangrene has been reported in the literature.

Prognosis

• Factors associated with an improved prognosis include age younger than 60 years, localized clinical disease, absence of systemic toxicity, and sterile blood cultures.
• Surprisingly, diabetes and HIV infection are not associated with higher mortality.
• The scrotum has a remarkable ability to heal and regenerate once the infection and necrosis have subsided.

Patient Education

Encourage diligent hygiene of the perineum, especially in immunocompromised patients or those with other risk factors for the disease. 

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Medical/Legal Pitfalls

• Failure to realize that cutaneous findings often underestimate the extent of underlying disease
• Failure to initiate early broad-spectrum antibiotics
• Failure to obtain immediate urologic consultation or to transfer the patient to an appropriate facility if such resources are not available at the current facility

ACKNOWLEDGMENTS

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors, Todd Thomsen, MD, and Eric Legome, MD, to the development and writing of this article.

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

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Article Last Updated: Mar 4, 2008