Clostridium sordelli Toxic Shock After Endometrial Ablation: Review of Gynecologic Cases

Introduction

Clostridium sordelli is anaerobic, gram-positive, spore-forming rod that is commonly found in soil and the intestines of animals, including 0.5% of humans. ¹ C. sordelli is highly virulent due to exotoxin-mediated toxic shock, with nearly 100% mortality in the obstetric population. Gynecologic cases in women have been reported related to postpartum endometritis, spontaneous abortion, medically induced abortion, and childbirth. ² This illness is most commonly associated with medically induced abortions, although this still remains extremely rare in these patients.^3–5 Common features in the majority of C. Sordelli toxic-shock cases include presentation within 1 week of the antecedent event, lack of fever, exceptional leukocytosis, hemoconcentration, hypotension, isolation of other organisms in culture, and onset of symptoms to death being ∼2–6 days. ¹ This report describes the only case of C. sordelli–associated septic shock after an endometrial ablation. This is also one of the only gynecologic cases with patient survival.

Case

Six weeks following a NovaSure® (Hologic, Inc., Marlborough, MA) endometrial ablation for abnormal heavy uterine bleeding, a 45-year-old, gravida 2, para 2, woman presented to an emergency department for evaluation of acute pelvic pain and malaise. Initially after the ablation, she had experienced some spotting that resolved rapidly, followed by no abnormal bleeding or discharge. Seven days prior to presentation, she had experienced vague lower abdominal discomfort, that was similar to menstrual cramping, and diarrhea. Findings included a normal blood-cell count, vitals within normal limits, and mild abdominal tenderness noted on examination. She was discharged to home with opioid pain management.

Her pain persisted and she presented again on the following day to her local emergency room. Her white blood-cell count had increased significantly to 33,000 over the course of 30 hours. Computed tomography (CT) scan showed air in the vaginal tissues, which raised a concern regarding the potential for necrotizing fasciitis. She received intravenous piperacillin/tazobactam and metronidazole and was transferred to the current authors' tertiary care center.

Upon arrival, she remained afebrile with normal vital signs and a gynecologic ultrasound (US) revealed a thickened endometrium, an enlarged fibroid uterus, thickened endometrium, and complex free fluid extending to the diaphragm bilaterally. A reevaluation of the local CT images revealed mucosal thickening of the cervix and vagina, and an enhanced endometrial cavity. This raised a concern regarding the potential for pyometra due to cervical stenosis with air locules in the vagina. A pelvic examination did not reveal any abnormality of the vaginal mucosa but did reveal a tender, grossly enlarged, and edematous cervix with cervical motion tenderness. Intravenous cefoxitin and metronidazole, and oral doxycycline were started due to presumed pelvic inflammatory disease.

Over the next few days, her vital signs remained within normal limits aside from an intermittent low-grade fever. Clinically, her symptoms of pain continued to worsen and she continued to feel generally more unwell. On hospital day 3, she underwent cervical dilation and curettage (D&C) under US guidance. The tissue that was obtained was grossly purulent and necrotic, and was sent for tissue culturing. While she was in the operating room, her laboratory results were returned showing an exceptional increase in leukocytosis from 36.4 K/mm³ on admission to 65.6 K/mm³ and hemoconcentration with a hemoglobin increase from 14.8 to 20.8 g/dL. She began to require pressor support. She was transferred to the intensive care unit (ICU) following the D&C. She was transitioned to broad-spectrum antibiotic coverage with piperacillin/tazobactam and vancomycin. Clindamycin was also added due to concern regarding a potential ongoing toxin-mediated infectious process.

The following day, her clinical condition continued to deteriorate with increasing intra-abdominal pressure, significant respiratory support requirement with ventilator settings of Servo/20/320/12/0.45, and multiple pressors to maintain adequate mean arterial pressures. She thus underwent an emergent exploratory laparotomy. At that time, 1 L of ascites was drained. Her uterus, fallopian tubes, and ovaries appeared to be grossly infected and necrotic, which necessitated a total abdominal hysterectomy and bilateral salpingo-oophorectomy.

The patient remained intubated and on pressor support in the ICU postoperatively. Overnight, she had an increasingly tense abdomen with a rise in intra-abdominal pressure to 27 mm Hg. She also had worsening end organ function that was shown by rising lactic acid and worsening kidney function. A decision was made to perform an exploratory laparotomy with an abdominal washout. The incision was left open at that time with an Abthera^tm device in place. On post-operative day one, she developed worsening respiratory decompensation and acute respiratory distress syndrome (ARDS) which required venous-to-venous extracorporeal membranous oxygenation (ECMO). Broad-spectrum and toxin-preventing antibiotic coverage was administered, including meropenem, caspofungin, vancomycin, and clindamycin. An aerobic culture of the infected uterine tissue grew out Enterococcus faecalis and an anaerobic culture grew out C. sordelli.

The patient became coagulopathic, with disseminated intravascular coagulopathy on postoperative day 3 and required multiple blood products. She had a tracheostomy placed on postoperative day 10. Her ARDS significantly improved and ECMO was discontinued on postoperative day 11. She was weaned off her ventilator settings. After multiple washouts of her abdomen, her incision was closed on postoperative day 12.

Results

She improved steadily, her tracheostomy was removed, the antibiotics were discontinued, she transitioned to an oral diet, she ambulated with physical therapy, she voided, and she was discharged to go home on postoperative day 22 (26 days after admission).

Four months following her hospitalization she had returned to work, and now enjoys her normal activities and reports having normal bowel function. Her incision is well-healed without any evidence of herniation.

Discussion and Review of the Literature

Aldape et al. summarized 45 human cases of C. sordelli infection, with 17 cases related to hysterectomy, endometritis, spontaneous abortion, medically induced abortion, and childbirth. Other human-related C. sordelli infections were noted to be associated with injection drug use and trauma. ¹ All obstetric and gynecologic causes in this review resulted in death and were most commonly associated with childbirth and medically induced abortion. ¹ Several other case reports have described C. sordelli induced toxic shock syndrome, all with maternal death aside from 1 case.^4–8 This maternal survival was noted after a second-trimester abortion. In this case, the patient presented with a fever and was started immediately on penicillin, gentamicin, and clindamycin, with recovery after 7 days. ⁸ Maternal mortality was seen in 11 cases associated with medically induced abortion,^5,7,8 2 cases associated with second-trimester spontaneous abortions, ⁴ 7 cases associated with postpartum endometritis,^9,10 and 1 case after an episiotomy. ¹¹ It is important to note that medically induced abortion has been associated with C. sordelli–related death, but it has an overall low prevalence and was reported to occur in 1 in 120,000 patients who underwent medically induced abortion.^1,3

As noted before, C. sordelli is an anaerobic organism that forms spores and is characterized as a gram-positive rod found in 0.5% of humans. ¹ C. sordelli is a toxin-mediated organism and is associated with 7 endotoxins. The 2 most virulent endotoxins include lethal toxin and hemorrhagic toxin. ⁹ These toxins are thought to be the cause of the increased capillary permeability, tissue necrosis, and profound shock associated with a C. sordelli infection.^1,12 Clinical manifestations include treatment-refractory hypotension, absence of fever, gastrointestinal symptoms, hemoconcentration, and a severe leukemoid reaction. All of these characteristics were commonly seen in published cases and also in the current case.

The characteristic absence of fever in C. sordelli infections might be associated with the phenomenon that the C. sordelli toxin-mediated mechanism of shock does not involve large production of cytokines; instead, the toxin mediates endothelium leakage. ¹³ This leads to the profound septic shock seen with this infection, its high mortality rate, and characteristic absence of fever.

C. sordelli has been found to colonize vaginal tissue, and this is thought to be the source of infection after uterine manipulation. Researchers have found C. sordelli in the vaginal flora in 4%–18% of healthy women. ¹⁴ One study showed that vaginal colonization with Clostridium species (sordelli and perfringens) in the postpartum period has been reported to be as high as 29%, ¹⁵ but in the overall female population ∼3.4% are colonized with C. sordelli. The higher rate of vaginal colonization in the postpartum period could partially explain why this infection is most commonly associated with medical abortions. It is interesting to note that no C. sordelli–related deaths have been reported following instrumented abortion or routine D&C, ¹ although it is thought that cervical dilation induced opening of the vaginal canal enables these organisms to move into the uterine cavity. C. sordelli as an anaerobic organism is more preferential to growth in necrotic tissue. The combination of these two factors make it reasonable to conclude that an endometrial ablation may create an environment where Clostridium can flourish.

Common features in the majority of C. sordelli toxic-shock cases include presentation within 1 week of the incident, lack of fever, severe leukocytosis, hemoconcentration, hypotension, isolation of other organisms in cultures, and onset from symptoms to death being ∼2–6 days (Table 1).^1,16–18 In the current case, the patient had a lack of fever on initial presentation, profound leukocytosis, hemoconcentration, hypotension, and 2 organisms isolated on culture. These similarities were recognized relatively early in this case, which indicated an addition of clindamycin to the patient's antimicrobial regimen and quick surgical intervention. It is unclear if early recognition was a differentiating factor for this patient, although survival was achieved.

Some researchers have speculated that the lack of fever could delay initiation of broad-spectrum antibiotics and could contribute to the high mortality rate of the infection. Antibiotics that suppress toxin synthesis—such as clindamycin, penicillin, tetracyclines, rifampin, and metronidazole—have been considered as potentially helpful for combatting these infections. Clindamycin may be additionally beneficial, as it interferes with bacterial protein synthesis. ¹⁹ In the current case, clindamycin was added to the broad-spectrum antibiotic regimen because there was an initial suspicion that C. sordelli could have been a contributing organism.

This case differed from other cases of C. sordelli infection in that the course of the current patient's infection was more indolent. She presented 6 weeks after her gynecologic procedure and did not become profoundly septic until 4 days after presentation. It is also interesting to note that her course of illness did not severely worsen until the D&C was performed. One other major difference in this current case is that the infection occurred after an endometrial ablation. To date, there have been no other reports of C. sordelli infection after an endometrial ablation.

Conclusions

C. sordelli is an almost universally fatal toxin-mediated infection that can occur after endometrial ablation and should be considered as part of an early differential diagnosis in gynecologic patients who present with profound septic shock, as early treatment could prevent patient mortality.