Clostridium Sordellii as an Uncommon Cause of Fatal Toxic Shock Syndrome in a Postpartum 33-Year-Old Asian Woman, and the Need for Antepartum Screening for This Clostridia Species in the General Female Population

Abstract

Clostridium sordellii (C. sordellii) is an anaerobic gram-positive rod most commonly found in the soil and sewage but also as part of the normal flora of the gastrointestinal tract and vagina of a small percentage of healthy individuals. C. sordellii infection is considered to result from childbirth, abortion, and/or gynecological procedures. Although many strains of C. sordellii are nonpathogenic, virulent toxin-producing strains exist. Infection with this organism typically manifests as a patient experiencing septic shock rapidly followed by end-organ failure. Identification of C. sordelli has been successful by traditional culture, mass spectrometry methods, and via molecular methods. Herein, we present a fatal case of C. sordellii infection of a postpartum 33-year-old Asian woman. The organism was isolated by culture and identified using matrix-assisted laser desorption/ionization–time-of-flight (MALDI-TOF) technology. With the advent of rapid detection methods, antepartum screening for the fatal Clostridium species should be implemented in the general female population.

Clostridium sordellii (C. sordellii) is an anaerobic gram-positive rod with subterminal spores and peritrichous flagella. Commonly found in the soil and sewage, the organism is also part of the normal intestinal and vaginal flora; as many as 10% of healthy women harbor C. sordellii in their vagina. C. sordellii infection can complicate childbirth, abortion, and gynecological procedures. Although most strains of C. sordellii are nonpathogenic, some virulent, toxin-producing strains cause fatal infections. The virulence of such C. sordellii strains is related to their production of exotoxins that cause toxic shock syndrome, even when there are minimal signs of tissue infection. Identification of C. sordellii has been successful from clinical specimens via traditional culture, mass spectrometry methods, and molecular methods.^1,2

Case Presentation

A 33-year-old Asian woman arrived at the Emergency Department (ED) of our institution reporting increased perineal pain, nausea, vomiting, and 1 syncopal episode during the past 2 days. After spontaneous vaginal delivery of a healthy neonate 4 days previously, which entailed a midline episiotomy during delivery, the overall health status of the patient was normal. In the ED, computed tomography (CT) imaging showed heterogeneous intrauterine material and inflammation of pelvic tissue; the results of laboratory work on patient specimens were notable for leukocytosis, with 87% neutrophils. The patient was admitted to the hospital for evaluation of a postpartum infection. On readmission, her health rapidly deteriorated, becoming hemodynamically unstable to the point that she required pressors; clinically, we interpreted these symptoms as indicating septic shock. The source of infection was suspected retained products of conception. At this time blood cultures were drawn and ertapenem antibiotic treatment was started.

Early the next day, the patient was taken to the operating room (OR), where the surgeon performed dilation and curettage (D&C), as well as exploration of the perineum. At this time, tissue cultures were obtained from the episiotomy site and perineum. Although her health was initially stable, the patient began to experience decompensation and was therefore taken back to the OR, where a total abdominal hysterectomy, bilateral salpingectomy, and bowel exploration were performed. After the procedure, she had multiple episodes of hemodynamic instability and cardiac arrest that required multiple rounds of cardiopulmonary resuscitation. At this time, vancomycin and clindamycin were added to her treatment regimen.

On day 2 of her admission to the hospital, the wound culture taken from the episiotomy site grew aerobic and anaerobic organisms, including Escherichia coli, Bacteroides fragilis, C. sordellii, and Enterococcus faecalis. The culture of the endometrial tissue grew no pathogens. The 2 sets of blood cultures drawn in the ED yielded negative results; the results remained negative thereafter. Presumptive identification of C. sordellii was provided to the medical team based on the Gram stain and matrix-assisted laser desorption/ionization–time-of-flight (MALDI-TOF) results (see the microbiology section later in this article).

At this time, the patient developed coagulopathic manifestations, for which she was treated with multiple blood products and intravenous immunoglobulin therapy for presumed Clostridial sepsis. She was taken back to the OR for additional exploration of the perineum, pelvis, and abdomen because the surgeons were concerned about an abscess or possibly another source of infection. However, the patient became hemodynamically unstable, again requiring resuscitation multiple times. Intravenous immunoglobulin (IVIG) and methylene blue treatment were initiated to treat septic/toxic shock. However, the health of the patient continued to decline; eventually, the patient died.

Microbiology

Clostridial growth was visible on the anaerobic blood agar plate after overnight incubation. The colonies were transparent and flat, with irregular borders. A Gram stain showed large Gram-variable bacilli. The colony was taken directly from the primary plate and tested on the VITEK-MS (bioMérieux SA) automated MALDI-TOF mass spectrometry system. The organism was identified as C. sordellii, with a 99.9% confidence value. The presumptive result was provided to the medical team on the first day of work-up of the culture. This testing was repeated on subcultures the following day, and the identification was verified. Also, the isolate was confirmed as being “not aero-tolerant” and was identified as C. sordellii, at 99.9% confidence value, via the RapID ANA (Thermo Fisher Scientific, Inc) manual biochemical identification panel. C. sordellii biochemical reactions are similar to Clostridium bifermentans in that they are indole positive; however, unlike C. bifermentans, C. sordellii are distinctively urease positive.

Autopsy Findings

At autopsy, examiners observed extensive swelling of the soft tissues, fluid accumulations in the body cavities, and terminal ischemic changes in the bowel mucosa and liver, all of which were consistent with cardiovascular collapse secondary to profound third spacing of fluid. Examination of the perineum revealed disruption, hemorrhage, and necrosis of the tissues associated with the episiotomy site. However, there was no evidence of disease in adjacent anatomic regions or elsewhere in the body.

Histologic examination of the vulva and pelvic organs showed urethral, bladder, vaginal, anorectal, and perineal soft tissues with variable degrees of disruption, necrosis, predominantly acute inflammation, vascular congestion, and hemorrhage. These changes were most pronounced in sections of the labia minora and vagina that were taken from the episiotomy site (Image 1). Focal microscopic abscesses were present, mainly within the perineal soft tissue, but the results of a Gram stain for organisms were negative.

Image 1.

Tissue specimens from sections of the labia minora and vagina taken from the episiotomy site of the patient, a postpartum 33-year-old Asian woman. A, Episiotomy site showing necrosis, predominantly acute inflammation, vascular congestion and hemorrhage (original magnification x40). B, Episiotomy site showing necrosis, predominantly acute inflammation, vascular congestion and hemorrhage (original magnification x40). C, Myonecrosis and hemorrhage (original magnification x400). D, Magnification of myonecrosis (original magnification x400).

Discussion

C. sordellii is an anaerobic, motile, spore-forming Gram-positive bacillus. Similar to other clostridia, it can be found primarily in soil, water, and animal gastrointestinal (GI) tracts. C. sordellii also colonizes the human GI tract and female genital tract. The rate of human carriage is not well known; studies have reported 0.5% to 10%.^1,3 Although this organism is not commonly observed clinically, C. sordellii has been identified in cases of infections after trauma; surgical procedures; injection of drugs of abuse; and gynecological events, such childbirth, miscarriage, and medical abortion. Gynecological patients usually seek treatment with nonspecific symptoms, such as malaise, low or absent fever, nausea, and pain at the infection site. These symptoms are followed by the rapid decline (within 1 to 2 days) of the health of the patient, with refractory hypotension, leukemoid reaction, and edema. Death occurs with 2 to 6 days of symptom onset, despite antibiotic treatment. The results of blood cultures frequently have been negative.^2‐6

C. sordellii infection gains entry into the bodies of patients through trauma, operations, or procedures such as episiotomy and proliferates in low-oxygen environments, such as foci of devascularized tissue. C. sordellii, like many other clostridia, secretes several toxins, including hemorrhagic toxin and lethal toxin, which are believed to be responsible for vascular permeability, refractory hypotension, and edema. Researchers have speculated that reduced pH may trigger toxin gene expression in C. sordellii or increase the activity of C. sordellii toxins. High levels of circulating toxins explain the systemic symptoms and continuing decline of patients despite antibiotic treatment.^1‐6

In our case, the organism was isolated by antemortem culture of the episiotomy site and identified using MALDI-TOF technology within 24 hours and verified within 48 hours. Although C. sordellii infections are relatively rare in humans, the high mortality rate associated with these infections makes it important for these pathogens to be identified. Thus, deploying rapid microbiologic detection methods of the vaginal and rectal flora, antepartum and preprocedural, for the fatal Clostridium species should be considered by health care professionals. As with group B streptococcal screening during the prenatal period, it may be feasible to do the same for Clostridial species. This screening could be performed by traditional culture methods or molecular methods, depending on which type is available at the institution. In our case, we used traditional culture with MALDI-TOF confirmation. In our routine practice, group B streptococcal screening is performed by traditional culture methods if in-house or by molecular methods using BioFire FilmArray polymerase chain reaction (PCR) if performed in our core laboratory.

We believe that screening for this organism in patients who are pregnant or undergoing a gynecological procedure can build a knowledge base that is lacking in the medical community. Because C. sordellii has not been thoroughly investigated, it is impossible to know its true incidence or its biological characteristics in humans; little is known about the organism other than the few case reports that have been published so far. Hence, there is a need for further study. Further, to our knowledge, there is no commercially available antitoxin for C. sordellii; we hope that drug companies will develop such a treatment in the future.

Glossary

Abbreviations

ED

emergency department

CT

computed tomography

OR

operating room

D&C

dilation and curettage

MALDI-TOF

matrix-assisted laser desorption/ionization–time-of-flight

IVIG

intravenous immunoglobulin

GI

gastrointestinal

PCR

polymerase chain reaction