Background

Fournier’s gangrene is a life-threatening infection that primarily affects the perineum and external genitalia [1]. It is a form of necrotizing fasciitis characterized by rapid spread of infection along the fascial plane and necrosis of the skin, subcutaneous tissue, and fascia, with a high risk of multiple organ failure and septic shock, leading to death [2]. It was first documented by Baurienne in 1764 as scrotal gangrene and was later named after the French dermatologist Jean Alfred Fournier who reported a series of five young men experiencing spontaneous fulminant gangrene of the penis and scrotum in 1883 [3]. Fournier’s gangrene can occur in both sexes and across various age groups. However, global epidemiological data are limited. It is generally considered a rare disease, affecting individuals between 50 and 70 years, with a higher incidence in males than that in females, estimated at approximately 1.6 cases per 100,000 males annually [4].

Several factors, including diabetes mellitus, chronic alcoholism, poor personal hygiene, immunosuppression, obesity, liver cirrhosis, malignancy, chemotherapy, steroid use, and trauma, predispose individuals to Fournier’s gangrene. However, there are no identifiable risk factors in approximately 10% of the cases [5]. The primary causes of Fournier’s gangrene are commonly reported in the following order: gastrointestinal tract-related infections (perianal abscess, perirectal abscess), genitourinary tract infections, and cutaneous injuries in the perineal area due to local trauma [1]. However, accurately determining the origin of severe Fournier’s gangrene clinically is often challenging.

The treatments for Fournier’s gangrene focus on early recognition, use of broad-spectrum antibiotics, resuscitation, and aggressive debridement [6]. However, in rare cases, early diagnosis before the exacerbation of necrosis and gangrene is difficult. Late detection and inappropriate treatment ultimately lead to high mortality rates [2, 5]. Factors influencing such outcomes include the extent and severity of the infection, presence of comorbidities, timely diagnosis and treatment, and the effectiveness of surgical debridement and antibiotic therapy, which is further exacerbated by the complicated features of polymicrobial infections [7,8,9]. Despite advances in medical and surgical interventions, this condition remains challenging to manage, with reported mortality rates ranging from 20 to 88%, averaging approximately 40% [4, 10].

Considering the complexity and severity of Fournier’s gangrene, it is important to identify prognostic factors that can predict clinical outcomes and guide treatment strategies. This study aimed to analyze the characteristics of patients with Fournier’s gangrene and to elucidate the prognostic factors influencing clinical outcomes.

Methods

Ethical considerations

This study was approved by the Institutional Review Board (IRB) of Keimyung University Dongsan Hospital (approval number: DSMC 2023-05-033). Considering the noninterventional and observational nature of this study, the requirement for obtaining informed consent was waived by the IRB of Keimyung University Dongsan Hospital (approval number: DSMC 2023-05-033). Data were collected and analyzed in accordance with ethical guidelines, protecting the privacy rights of the participants.

Study description and definitions

This retrospective cohort study involved analyzing the medical records of patients admitted to our institution between January 1, 2005, and December 31, 2022. Our study focused on 50 patients aged > 18 years who were admitted for Fournier’s gangrene. Fifteen patients who provided do not resuscitate orders and received palliative care, were initially treated at another hospital, or had incomplete medical records were excluded from the study. This study ultimately included 35 patients admitted for Fournier’s gangrene (Figs. 1 and 2). All patients underwent aggressive debridement and were administered broad-spectrum antibiotics. Although the treatment physicians changed over an 18-year period, we mostly used a consistent treatment strategy, since we enrolled physicians receiving training from the same institution.

Fig. 1
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Flow chart of patients’ enrollment. DNR, do not resuscitate

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Fig. 2
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A case of Fournier’s gangrene. A 55-year-old male with paraplegia due to a history of falling down. Necrotizing fasciitis spread to the perianal area, scrotum, and both hip and thigh area. ⓐ: Status before debridement and at the time of admission. ⓑ, ⓒ: After debridement, testicles were exposed. ⓓ: A photograph obtained two weeks postoperatively. ⓔ: Reconstruction with split thickness skin graft. ⓕ: A photograph after vacuum assisted dressing two weeks after reconstruction

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Fournier’s gangrene was classified using the International Statistical Classification of Diseases and Related Health Problems codes and diagnosed based on the patients’ medical record review and computer tomography (CT) scan records. Fournier’s gangrene is defined as a polymicrobial necrotizing fasciitis affecting the genital, perineal, perianal, and adjacent areas. The diagnosis is primarily clinical, and is based on the identification of signs such as severe pain, erythema, edema, and crepitus in the affected regions. Key findings on CT scans include subcutaneous emphysema, fascial thickening, and fluid collection [11, 12]. Information and scores were based on data obtained in the first 24 h after admission to the emergency room (ER).

As defined by the Clinical Criteria of the Third International Consensus Definition (Sepsis-3), sepsis is a life-threatening organ dysfunction resulting from an uncontrolled host response to infection [13]. Organ dysfunction was included in the definition of sepsis and the presence or absence of organ dysfunction was determined using Sequential Organ Failure Assessment (SOFA) scores. The Fournier’s Gangrene Severity Index (FGSI) is a numerical score calculated using a combination of clinical and laboratory assessments, including temperature, heart rate, respiratory rate, blood electrolytes, creatinine level, and hematocrit. The study established a score > 9 as a sensitive and specific mortality predictor in patients with perineal gangrene [14]. The Charlson comorbidity index (CCI) and Acute Physiology and Chronic Health Evaluation (APACHE) II scores were calculated to evaluate the severity of underlying medical conditions in the patients. Source control was defined as surgical debridement at the bedside or operating theatre. Multidrug resistant (MDR) bacterial infection is defined as the resistance of microorganisms to three or more distinct categories of antibiotics [15]. The pathogens under consideration were those identified in the preliminary culture conducted during source control.

Data collection

The data collected retrospectively were as follows: [1] patient characteristics, including age, sex, body mass index (BMI), CCI, American Society of Anesthesiologists (ASA) score, APACHE II score, SOFA score, FGSI, and medical history; [2] clinical data, including laboratory data at the admitted ER, presence of sepsis and septic shock, extent of disease, length of hospital stay, length of intensive care unit (ICU) stay, the duration from admitted time to antibiotic administration, and duration from admitted time to source control implementation; [3] infection and microbiological data, including the type of isolated bacteria and fungi, and occurrence of bacteremia and MDR bacterial infection; and [4] organ dysfunction data, including the type, number, and occurrence ratio of organ dysfunction results.

Statistical analyses

Continuous data are expressed as the mean ± standard deviation. Categorical data are expressed as frequencies and percentages. Data normality was assessed using the Kolmogorov–Smirnov test and confirmed by visual inspection of the histograms. Continuous variables were analyzed using Student’s t-test or Mann–Whitney U test, whereas categorical variables were analyzed using the chi-square or Fisher’s exact test. Multivariate logistic regression analysis was used to estimate the association between organ dysfunction and in-hospital mortality with unadjusted and adjusted (for age, BMI, and CCI and FGSI scores) for evaluations. Odds ratios (ORs) were used to determine the effects of organ dysfunction on in-hospital mortality. Univariable and multivariable logistic regression analyses were performed to identify the risk factors associated with in-hospital mortality, with the degree of association presented as ORs and their corresponding 95% confidence intervals. Logistic regression performance was evaluated using C-statistics and Hosmer–Lemeshow tests. Statistical significance was set at a p-value < 0.05. The IBM Corporation’s SPSS (version 28.0; Armonk, NY, USA) was used for all the analyses.

Results

Patient characteristics, clinical data, and operative outcomes

The in-hospital mortality rate of the enrolled patients with Fournier’s gangrene was 17.1% (n = 6/35). The patient characteristics and clinical data at the time of Fournier’s gangrene diagnosis are summarized in Tables 1 and 2.

The mean age of the patients was 57.9 ± 13.1 years, with a higher mean age observed in the non-survivor group. The CCI and APACHE II scores were non-significantly higher in the non-survivor group than those in the survivor group. Even the FGSI score, which is used globally as a prognostic factor, showed no significant difference between the two groups (7.5 ± 3.6 vs. 6.8 ± 4.6, p = 0.724). Notably, the initial SOFA scores at arrival to the ER were significantly higher in the non-survivor group than those in the survivor group (5.0 ± 2.3 vs. 2.0 ± 2.8; p = 0.018).

Incidences of hypertension and immune deficiency were significantly higher in the non-survivor group than those in the survivor group. Other comorbidities, including diabetes mellitus, chronic kidney disease, chronic liver disease, and malignancy, were higher in the non-survivor group; however, the difference was not significant. The proportion of patients who underwent anorectal surgery was 20% (n = 7/35), and the types of surgeries performed included incision and debridement for perianal abscess, hemorrhoidectomy, and low anterior resection for rectal cancer. However, there was no significant difference between the non-survivor and survivor groups (16.7% vs. 20.7%; p = 0.823).

The ratio of patients in a bedridden state and sanatorium stay were similar between the two groups (Table 1).

In the patient clinical data, the evaluation of sepsis and septic shock was based solely on the initial assessment that occurred at the time of ER admission. Sepsis (83.3% vs. 44.8%; p = 0.086) and septic shock (66.7% vs. 27.6%; p = 0.066) were more frequent in the non-survivor group compared to the survivor group, although this difference was not statistically significant. In the initial laboratory test, platelet levels were non-significantly lower in the non-survivor group than those in the survivor group. There was no difference in the extent of disease between the two groups, including in the Y area, which is a known prognostic factor [16]. The time from admission to the administration of antibiotics, time to source control measures, length of ICU stay, length of hospital stay, number of organ dysfunctions, operation type, and number of operations were not significantly different between the two groups (Table 2).

Table 1 Patient characteristics
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Table 2 Patient clinical data
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Data are shown as mean ± standard deviation or number (percentage).

SD, standard deviation; WBC, white blood cell; Hb, hemoglobin; BUN, blood urea nitrogen; AST, aspartate aminotransferase; ALT, alanine aminotransferase; INR, International Normalized Ratio; CRP, C-reactive protein; BNP, brain natriuretic peptide; ICU, intensive care unit.

Microbiological spectrum and characteristics

Among the 35 patients, 34 were identified to be infected with causative pathogens. Bacteremia occurred in 14.3% of all patients and did not differ significantly between the non-survivor and survivor groups. Gram-positive bacteria, gram-negative bacteria, and fungi were isolated from the patients and were not significantly different between the two groups. Mixed growth was defined as the detection of more than one type of gram-positive, gram-negative, or fungal pathogen. Samples from 20.0% of the patients infected with causative pathogens showed mixed growth in the culture. The overall rate of infection with MDR pathogens was significantly higher in the non-survivor group than that in the survivor group. The most common MDR pathogens were Escherichia coli, followed by Klebsiella pneumoniae, Acinetobacter spp., Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecalis. (Table 3).

Table 4 shows the distribution of the isolated microbiological pathogens, expressed as the percentage of bacteria and fungi per species, in patients with Fournier’s gangrene. Among the isolated causative pathogens, the most common were Escherichia coli (48.6%), Klebsiella pneumoniae (20.0%), and Streptococcus anginosus (11.4%). Candida tropicalis was the only causative fungus identified (2.9%).

Table 3 Microbiological profile of survivors and non-survivors
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Table 4 Distribution of microbiological pathogens isolated from cultures in patients with Fournier’s gangrene
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Organ dysfunction

The most common type of organ dysfunction in patients with Fournier’s gangrene was renal dysfunction, followed by liver, respiratory, cardiovascular, coagulation, and central nervous system dysfunctions. The incidence of coagulation dysfunction was significantly higher in the non-survivor group than that in the survivor group. The incidence of renal dysfunction was higher in the non-survivor group than that in the survivor group, but this difference was not statistically significant (Table 5). Multivariate logistic regression analysis was performed to determine the association between organ dysfunction and in-hospital mortality. Results showed that the in-hospital mortality rate was significantly affected only by coagulation dysfunction. Furthermore, we adjusted for previously known risk factors for Fournier’s gangrene, including age, BMI, CCI, and FGSI. Among all the organ dysfunctions, only coagulation dysfunction had the most significant impact on in-hospital mortality (Table 6).

Table 5 Organ dysfunction analysis data in sepsis due to Fournier’s gangrene
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Table 6 Multivariable logistic regression analysis of organ dysfunction and in-hospital mortality in patients with Fournier’s gangrene
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Values were adjusted for age, body mass index, Charlson Comorbidity Index, Fournier’s gangrene severity index.

Predictive factors for in-hospital mortality

Table 7 shows the results of multivariate logistic regression analysis for in-hospital mortality in patients with Fournier’s gangrene. After accounting for individual risk and confounding factors, only MDR bacterial infection was independently associated with significantly high in-hospital mortality.

Table 7 Multivariable logistic regression analysis for in-hospital mortality in patients with Fournier’s gangrene
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Discussion

Notably, our results underscore the critical impact of coagulation dysfunction on in-hospital mortality, and independently identify MDR bacterial infections as a significant predictive factor, shedding light on crucial considerations for managing Fournier’s gangrene.

Fournier’s gangrene is associated with a high mortality rate, necessitating prompt diagnosis and robust treatment [9]. Therefore, understanding the factors related to adverse prognoses and mortality is crucial, as it can enhance survival rates, making the research of prognostic indicators significantly important. Overall, various underlying disease factors, including age, ASA score, and the CCI, have been established as significant determinants of clinical outcomes and prognosis in critically ill patients [17,18,19]. Additionally, the SOFA scoring system is particularly useful for predicting clinical outcomes, particularly mortality, in critically ill patients [13, 14, 20,21,22]. Parameters such as the FGSI, a multi-factor prognostic indicator specifically designed for patients with Fournier’s gangrene, proved to be a significant prognostic tool, as corroborated by recent literature [22,23,24,25]. Specifically, the FGSI showed a consistent correlation with increased mortality and complications across multiple studies, with scores above 9 being associated with a marked rise in mortality rates [26,27,28]. However, contrary to previous studies, our analysis revealed no significant differences in age (p = 0.161), CCI (p = 0.139), ASA score (p = 0.193), or FGSI (p = 0.724) between the survivor and non-survivor groups. This will be elaborated upon in the limitations section; however, we posit that the discrepancies in our results compared to those of other studies may stem from the relatively small sample size in our research. Conversely, the initial SOFA score emerged as a notably significant differentiator between these groups. This finding suggests that the degree of organ dysfunction may play a more crucial role than existing comorbidities at the time of presentation in determining the clinical trajectory and prognosis of Fournier’s gangrene. The markedly higher initial SOFA score in the non-survivor group (5.0 ± 2.3 vs. 2.0 ± 2.8; p = 0.018) underscores its potential utility as an early predictor of poor outcomes in patients with Fournier’s gangrene. This highlights the critical need for promptly assessing organ dysfunction upon patient presentation and implementing swift interventions to address any identified organ dysfunction. Additionally, early identification and aggressive surgical debridement, alongside appropriate antibiotic therapy, are paramount for improving survival rates [9, 29]. Strategies focused on the early management of organ dysfunction, supported by a thorough understanding of the patient’s overall clinical condition through SOFA and FGSI scoring, can significantly improve clinical decision-making. As such, the integration of these scoring systems into routine practice may provide valuable insight into patient prognosis, ultimately guiding therapeutic strategies, and enhancing survival outcomes.

The contribution of coagulation dysfunction to the negative impact on mortality in necrotizing soft tissue infections is well established, with declining platelet counts indicating severity in critically ill patients, and coagulopathy correlating with high mortality rates [30, 31]. Bleeding or disseminated intravascular coagulation events from coagulopathy complicate the treatment of critically ill patients and adversely affect their clinical outcomes [32, 33]. Our study suggests that coagulation dysfunction with reduced platelet count, as a prognostic factor for Fournier’s gangrene, is an independent negative prognostic factor for survival. The significantly higher prevalence of coagulation dysfunction in the non-survivor group compared to that in the survivor group demonstrates its association with adverse clinical outcomes. The OR value indicated a significant impact of coagulation dysfunction on in-hospital mortality, and this robust association persisted even after adjusting for demographic and clinical factors. These findings suggest the importance of monitoring coagulation abnormalities in patients with Fournier’s gangrene. Proactive strategies for addressing coagulopathy may be crucial for improving survival rates.

The detection of MDR bacterial infections in critically ill patients is a notable predictor of poor prognosis [34]. MDR bacterial infections in ICUs correlate with poor clinical outcomes, extended hospitalization, and high mortality, presenting challenges owing to high antimicrobial therapy failure rates [35, 36]. Clinicians and institutions are actively researching antibiotics and exploring various strategies for treating MDR bacterial infections [37, 38]. In one notable study of 40 patients with Fournier’s gangrene, MDR bacterial infections were reported in 25% of the patients, with a significantly higher rate of MDR bacterial infection in the non-survivor group (62.5% vs. 15.6%; p < 0.05) [25]. Similarly, our study detected MDR bacterial infections in 22.9% of the patients, revealing a significant association between MDR bacterial infections and in-hospital mortality. This finding highlights the issue of antibiotic resistance in the community, although the underlying disease or nursing home residence status were similar among patients with MDR bacterial infections detected in the initial culture in this study. Although the exact reason for this remains unclear, strategies such as developing an antimicrobial stewardship program to reduce the occurrence of MDR bacterial infection and active and judicious use of antibiotics in the early stages may precede efforts to improve the clinical outcomes of patients.

This study has several limitations. First, it includes selection and confirmation biases, similar to other retrospective studies. Second, this study was conducted at a single institution and had a relatively small sample size. Therefore, unlike other studies, the non-significant results observed in the non-survivor group for sepsis, septic shock, and some scoring systems such as FGSI can be attributed to the limitations stemming from the relatively small sample size of the study [22,23,24,25]. Furthermore, with a limited number of cases, treatment modalities and techniques varied slightly among patients, although similar strategies and methods had been employed in patient treatment. To overcome these limitations, it is essential to validate these findings through meticulous interpretations of data from subsequent multicenter cohort studies.

Conclusion

Our study highlights the intricate nature of Fournier’s gangrene and emphasizes the pivotal role of the initial SOFA score in predicting clinical outcomes. Notably, coagulation dysfunction and MDR bacterial infections are independent negative prognostic factors, highlighting the importance of prompt monitoring and proactive strategies. These findings provide crucial insights into the challenging landscape of Fournier’s gangrene, calling for ongoing research and multicenter studies to validate and enhance our understanding, and ultimately improve patient care and survival rates.