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FOUR Rules for FOURnier’s Gangrene

CASE

A 41-year-old man present to the ED with one week of suprapubic pain.

  • PMH of uncontrolled HIV

  • Complains of penile lesion, progressive erythema, swelling, and pain in genitals for past 1 week

  • Endorses fever, chills, fatigue, dysuria

  • On exam, suprapubic area is erythematous and warm to touch, has multiple open wounds draining purulent material

  • Vitals: T 39.3°C, HR 88, BP 99/74 (82), RR 19, SpO2 99%


Images: CT Abdomen + Pelvis with IV Contrast, Sagittal (L) and Axial (R) views showing soft tissue infection and penile hypodensity concerning for abscess formation.


Clinical Question: Does the management of Fournier’s Gangrene differ from other skin and soft tissue infections?


Summary of Evidence:

Fournier’s Gangrene (FG) is a rare polymicrobial necrotizing soft tissue infection (NSTI) of the perineum and genitals, occurring ten times more often in men than women (1). Mortality rates between 20-40% in case series make it one of the deadliest adult necrotizing skin infection (2,3). It is most commonly seen in those with diabetes, HIV, or other immune compromise (4).

  • The two largest epidemiological studies related to FG in the US were conducted in 2000 and 2009, and report an overall incidence of 1.6 per 100,000 men per year, with men 50-79 years old and those living in the southern United States most affected, and reporting an overall mortality in the US of 7.5% to 16% (3,5).

  • A “Fournier’s Gangrene Severity Index” (FGSI) has been developed based on vitals, CBC and CMP values (6). Patients whose FGSI scores are 9 or above have a 75% probability of death while those with a score under 9 have a 22% probability of death (6). While studies have not used the FSGI prospectively, several retrospective studies have found it to predict mortality but not length of hospital stay (7–9).

  • A meta-analysis of 1,990 patients found that sepsis causes 76% of deaths in FG. However, while treatment for sepsis with hemodynamic resuscitation and broad spectrum antibiotics is highly recommended, aggressive wide-field surgical debridement remains the definitive treatment. (10)

  • A retrospective study (n=379) comparing early vs late surgical debridement showed that surgical intervention within the first 48 hours of hospital presentation reduced case fatality rate in patients with FG by 62% (p = 0.031) (11).

  • The Johns Hopkins Antibiotic Guide does not recommend a specific treatment for FG[i], but for mixed Necrotizing Fasciitis with anaerobes such as FG, recommends: 1.Vancomycin + 2.Cefotaxime or Ceftriaxone + 3.Clindamycin or Metronidazole (13) for anti-staphylococcal action, as well as broad gram-positive and gram-negative coverage.

  • Broad coverage is needed as FG infections are polymicrobial in 76-83% of infections: the most common pathogens isolated differ by study but include Bacteriodes, E. coli, Prevotella, Enterococcus sp., and A. baumannii (14,15).

  • While not studied in FG specifically, Clindamycin may be superior to Metronidazole in treatment of toxin-producing bacteria such as E. coli and S. aureus as its inhibition of the 50S ribosomal subunit reduces bacterial protein synthesis and can decrease Endotoxin release in gram-negatives (16,17).

[i] Adjunctive treatments of sterile honey, maggot therapy, hyperbaric oxygen, and negative pressure wound therapy have all shown promise in individual cases but do not yet have sufficient evidence to recommend them broadly (12)


RECOMMENDATIONS/"FOUR RULES":

1. Begin with fluid resuscitation

a. Our patient was given 3 L of Lactated Ringer’s Solution to meet the sepsis fluid goal of 30 CCs/Kg. Afterwards, BP improved to 138/66.

2. Draw blood cultures and begin antibiotic administration immediately

a. Vancomycin, Metronidazole, and Cefepime were given. Antibiotic therapy was narrowed to Ceftriaxone and Metronidazole after cultures returned.

3. Consult surgery immediately, suspicion for FG should be communicated

a. The patient emergently to the OR for same-day wide surgical debridement by Urology. Six days later, he returned with Plastic Surgery for reconstruction.

4. Calculate FSGI to prognosticate

a. FSGI was 7 for our patient, indicating a low risk of mortality.

Patient Outcome:

Blood cultures did not grow any bacteria. Surgical site cultures grew Peptostreptococcus anaerobius and Cutibacterium avidum, bacteria seen in polymicrobial anaerobic infections. Surgical debridement was successful and after a second reconstructive procedure, the patient was discharged 11 days after ED presentation. HIV ART to be restarted outpatient.


CLINICAL QUESTION ANSWER

While FG may present like cellulitis or superficial soft tissue infection, any soft tissue infection of the perineum should raise suspicion and be treated aggressively given FG’s high mortality rate and tendency to develop into sepsis. Early fluid resuscitation, antibiotics, and prompt surgical treatment (<48 hours) are highly recommended.


REFERENCES:

1. Chernyadyev SA, Ufimtseva MA, Vishnevskaya IF, Bochkarev YM, Ushakov AA, Beresneva TA, et al. Fournier’s Gangrene: Literature Review and Clinical Cases. UIN. 2018;101:91–7.

2. Laucks SS. Fournier’s gangrene. Surg Clin North Am. 1994 Dec;74(6):1339–52.

3. Sorensen MD, Krieger JN, Rivara FP, Broghammer JA, Klein MB, Mack CD, et al. Fournier’s Gangrene: population based epidemiology and outcomes. J Urol. 2009 May;181(5):2120–6.

4. Singh A, Ahmed K, Aydin A, Khan MS, Dasgupta P. Fournier’s gangrene. A clinical review. Arch Ital Urol Androl. 2016 Oct 5;88(3):157–64.

5. Eke N. Fournier’s gangrene: a review of 1726 cases. Br J Surg. 2000 Jun;87(6):718–28.

6. Laor E, Palmer LS, Tolia BM, Reid RE, Winter HI. Outcome prediction in patients with Fournier’s gangrene. J Urol. 1995 Jul;154(1):89–92.

7. Chawla SN, Gallop C, Mydlo JH. Fournier’s gangrene: an analysis of repeated surgical debridement. Eur Urol. 2003 May;43(5):572–5.

8. Wang L, Han X, Liu M, Ma Y, Li B, Pan F, et al. Experience in management of Fournier’s gangrene: a report of 24 cases. J Huazhong Univ Sci Technolog Med Sci. 2012 Oct;32(5):719–23.

9. Kabay S, Yucel M, Yaylak F, Algin MC, Hacioglu A, Kabay B, et al. The clinical features of Fournier’s gangrene and the predictivity of the Fournier’s Gangrene Severity Index on the outcomes. Int Urol Nephrol. 2008;40(4):997–1004.

10. El-Qushayri AE, Khalaf KM, Dahy A, Mahmoud AR, Benmelouka AY, Ghozy S, et al. Fournier’s gangrene mortality: A 17-year systematic review and meta-analysis. Int J Infect Dis. 2020 Mar;92:218–25.

11. Sugihara T, Yasunaga H, Horiguchi H, Fujimura T, Ohe K, Matsuda S, et al. Impact of surgical intervention timing on the case fatality rate for Fournier’s gangrene: an analysis of 379 cases. BJU Int. 2012 Dec;110(11 Pt C):E1096-1100.

12. Lewis GD, Majeed M, Olang CA, Patel A, Gorantla VR, Davis N, et al. Fournier’s Gangrene Diagnosis and Treatment: A Systematic Review. Cureus. 2021 Oct;13(10):e18948.

13. Necrotizing Fasciitis | Johns Hopkins ABX Guide [Internet]. [cited 2022 Jun 16]. Available from: https://www.hopkinsguides.com/hopkins/view/Johns_Hopkins_ABX_Guide/540378/all/Necrotizing_Fasciitis?refer=true

14. Bjurlin MA, O’Grady T, Kim DY, Divakaruni N, Drago A, Blumetti J, et al. Causative Pathogens, Antibiotic Sensitivity, Resistance Patterns, and Severity in a Contemporary Series of Fournier’s Gangrene. Urology. 2013 Apr 1;81(4):752–9.

15. Yilmazlar T, Gulcu B, Isik O, Ozturk E. Microbiological aspects of Fournier’s gangrene. International Journal of Surgery. 2017 Apr 1;40:135–8.

16. Campbell AJ, Dotel R, Blyth CC, Davis JS, Tong SYC, Bowen AC. Adjunctive protein synthesis inhibitor antibiotics for toxin suppression in Staphylococcus aureus infections: a systematic appraisal. Journal of Antimicrobial Chemotherapy. 2019 Jan 1;74(1):1–5.

17. Kishi K, Hirai K, Hiramatsu K, Yamasaki T, Nasu M. Clindamycin Suppresses Endotoxin Released by Ceftazidime-Treated Escherichia coli O55:B5 and Subsequent Production of Tumor Necrosis Factor Alpha and Interleukin-1β. Antimicrob Agents Chemother. 1999 Mar;43(3)

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