Fournier’s gangrene is a very rare and severe infection affecting the soft tissues of the genital and pelvic areas. In a population-based study, the overall incidence was estimated to be 1.6 in 100,000 men, and it is expected to be much lower in women, as the study identified only 39 female patients as opposed to 1461 male patients [11]. However, the female ratio may be higher, as a recent study reported 20.2% female among 124 Founier’s gangrene patients [12]. Also, in a recent report, 9249 Fournier’s gangrene patients were identified for a weighted estimate of 43,146 cases using the National Inpatient Sample, and this study reported a mortality rate of 4.7%, which is lower than those of most previous reports [13].
Scoring systems have been proposed to establish a timely diagnosis and predict outcome of Fournier’s gangrene. One such system, Uludag Founier’s Gangrene Severity Index (UFGSI), evaluates the physiological status, age, and extent of the gangrene, and is reported to be more powerful than FGSI, another scoring system for Fournier’s gangrene that can predict mortality with a 78% probability and survival with a probability of 78% [14]. UFGSI score greater than 9 resulted in a 94% probability of death in contrast to a score of 9 or less that showed a high survival probability of 81% [15]. Our patient had FGSI score of 8 and UFGSI score of 14 upon admission, which increased to 12 and 18, respectively, at the time of debridement because electrolytes fluctuated due to central diabetes insipidus, and the prognosis was poor at that point.
In the present case, many possible underlying factors were identified: susceptibility to infection due to diabetes mellitus and undernutrition, the history of splenectomy, and compromised skin and mucosal barriers due to edema, incontinence, and urinary catheter placement for central diabetes insipidus. In addition, hypernatremia due to central diabetes insipidus complicated the postoperative management.
Moreover, the subacute onset of Fournier’s gangrene in this patient may have delayed the definite diagnosis. The presence of pain for 2 weeks suggested a less fulminant progression, but the condition was more severe internally than it seemed externally at presentation.
In the present case, the C. ramosum was isolated from the blood of a patient with Fournier’s gangrene for the first time in literature. C. ramosum cultures were also found in children with ear infections and in older adults with co-morbidities, sometimes forming abscesses [16]. The identification of C. ramosum in culture may be difficult: C. ramosum has a variability in Gram stain positivity, weak spore formation, and atypical clostridial colony morphology [17]. Molecular identification should be considered to identify suspected species of C. ramosum.
As for the pathogenic potential of C. ramosum, IgA protease of C. ramosum is able to degrade both IgA1 and IgA2, which helps the evasion of the microbe from the host immune defense to penetrate in to the deep tissue [2]. This IgA protease, cloned in 2002 [18], is not found in other Clostridium species. Because C. ramosum is among the normal intestinal flora, C. ramosum in this case may have entered the deep tissue of the genitalia via the intestinal mucosa. It is difficult to assess the pathogenic role of C. ramusum, but the blood cultures also yielded S. constellatus, a part of the S. anginosus group (formerly “S. milleri”) that causes various abscesses in humans and is often involved in polymicrobial infections with obligate anaerobes [19]. Anaerobes can enhance the growth of S. constellatus and inhibit the bactericidal activity of the host [20, 21]. In this case, the severity of the clinical course might be due to the synergistic infection of the C. ramosum and S. constellatus. Although antibiotic resistance is uncommon in C. ramosum, a 74% resistance to clindamycin was reported in one study [3]. In our case, this C. ramosum strain showed resistance to moxifloxacin and cefoxitin, but was susceptible to meropenem and clindamycin and showed low MIC of the initial antibiotic used, ceftriaxone. S. constellatus was also susceptible to ceftriaxone, meropenem, vancomycin, and clindamycin. The reason for the lethal course despite the use of multiple susceptible antibiotics combinations may be due to the uncontrollable progression of invasion with poor host-defense mechanism.
In conclusion, to our knowledge, we report the first case of Fournier’s gangrene with C. ramosum in a female patient with multiple comorbidities. The condition was more severe than it seemed at presentation, and the disease progressed rapidly despite multimodal treatment. The accumulation of more information on C. ramosum infections and gangrene may lead to the identification of the disease patterns and methods for timely diagnosis and treatment.