Clostridium innocuum is a gram-positive spore forming bacillus that normally exists in the oral cavity and gastrointestinal tract. Although it is a rare pathogen for humans, C. innocuum can cause sepsis, especially in patients with immunodeficiency, such as those presenting with acquired immunodeficiency syndrome, leukemia, tumors or organ transplants. Since C. innocuum is resistant to several common antibiotics (including vancomycin), it can lead to serious infection.1–5 We report a case of puerperal sepsis caused by C. innocuum in a patient with placenta accreta. The clinical characteristics of C. innocuum infection, as well as its antibiotic susceptibility, were reviewed. A treatment strategy for this rare infection was proposed. This is the first report of Puerperal sepsis caused by C. innocuum in English literature.
A 25-year-old Chinese female, pregnant 39+5 weeks, was admitted to the hospital for regular abdominal pain for 3 hours in October 23, 2017. She delivered a female baby at 12:54 on the same day. The placenta did not evacuate due to placenta accreta. The uterine curettage, guided by B-ultrasound had failed. The placenta was left intrauterine. Bilateral uterine arterial embolization was performed at 16:10 on the same day. The patient received oral mifepristone 25 mg, twice a day (bid) for 3 days. The anti-infective therapy was cefuroxime 2 g, intravenous drip, bid. On October 26, the patient experienced a fever of 39°C, abdominal tenderness and an increased blood procalcitonin (PCT) (0.37 ng/mL). She was diagnosed with uterine infection. At 19:00 on October 27, uterine curettage was performed with lumbar anesthesia. A beef-like placenta, approximately 80 × 80 × 50 mm3 with 50 mL blood was evacuated. Some residual placenta was left at the bottom of the uterus. The patient was transferred to the intensive care unit due to her fever of 40.9°C accompanied by chills. She was treated with meropenem 1 g every 8 hours and supportive therapies, including albumin infusion. Gram-positive rods were reported positive in her anaerobic blood culture on October 29. The bacteria were identified as C. innocuum based on matrix-assisted laser desorption ionization time-of-flight mass spectrometry on the same day (Fig. S1, http://links.lww.com/MFM/A1). On the next day, another blood culture positive bacteria isolate was cultured and identified as Escherichia coli. In the next 3 days, the blood bacteria culture was negative. E. coli, which was susceptible to cephalosporin, meropenem, penicillin and quinolones, and Enterococcus faecalis, which was susceptible to quinolones, vancomycin, tigecycline, penicillin, and resistant to tetracycline, were also cultured and identified from her vaginal and placenta tissue. The patient was transferred back to the obstetrics ward due to her stable life signs. She was treated with meropenem 1 g every 8 hours and with moxifloxacin 0.4 g daily. Her temperature was at 37.7–38.1°C on the following days. On November 6, the anti-infective therapy was changed to meropenem 1 g every 8 hours, vancomycin 1 g, every 12 hours, and ornidazole 0.5 g, every 12 hours for her high white blood cell (WBC) count (17.0 × 109/L) and high PCT concentration (0.13 ng/mL). On November 7, an uterine B-ultrasound showed a significant amount of gas (approximately range 106 × 63 mm2) in her uterine cavity and myometrium (Fig. 1). Magnetic resonance imaging (MRI) also demonstrated congregated gas in the uterine cavity and myometrium on the next day (Fig. 2). The C. innocuum and E. coli were cultured and identified from her curettage tissue. On the next day, the anti-infective therapy was changed to tigecycline 50 mg every 12 hours, piperacillin sulbactam 4.5 g every 8 hours, and ornidazole 0.5 g every 12 hours. On November 13, a second uterine B-ultrasound showed a decreased amount of gas (54 × 57 × 47 mm3) with a vague boundary in the uterine cavity and myometrium (Fig. 1). MRI showed a similar finding (Fig. 2). On November 14, a 10 × 10 × 12 cm3 section of placenta tissue was evacuated. Then, her temperature recovered to normal. Her uterine discharge was E. faecalis and E. coli positive. On November 18, her uterine discharge ended, and her blood WBC returned to normal. On November 23, the anti-infective therapy was changed to ceftazidime 2 g every 12 hours, teicoplanin 0.4 g daily, fluconazole 0.4 g daily, and recombinant human granulocyte-macrophage colony-stimulating factor was used for her low blood WBC count, high alanine aminotransferase and positive Candida parapsilosis from her stool. On November 21 and November 28, her uterine B-ultrasound scan result was normal. On November 26, her uterine discharge bacteria culture was negative, while a positive culture of Candida tropicalis and her antibiotics therapy ceased. The patient was discharged from the hospital on December 1 following 5 days of oral caspofungin.
Her menstruation did not recover until four months after her delivery despite not breastfeeding. The uterine B-ultrasound showed an inhomogeneous echo in the uterus, with a blurred endometrial line. Hysteroscopy was performed on March 3, 2018. Severe intrauterine adhesions were diagnosed (Fig. S2, http://links.lww.com/MFM/A2). No endometrium was found at the pathology examination of tissue from uterine curettage. The patient received oestrogen and progestogen cyclical treatment (Estradiol Valerate tablets) for 3 months. She had her first postpartum menstruation on August 25, 2018 and then had regular periods. The clinical symptoms, examinations, and treatment of the patient are summarized in Table 1.
Smith and King first reported and named C. innocuum.1 The first eight strains were isolated from an empyema pocket in the chest, an infected infarct of the brain, an appendiceal abscess, a subdiaphragmatic abscess, abdominal fluid after an acute intestinal obstruction, a wound drainage, a sinus of the abdominal wall, and a compound fracture that had been contaminated with soil. C. innocuum included gram-positive rods with terminal oval spores. The spores were readily formed when these strains were grown in chopped-meat medium for 2 days. They were also evident in preparations made from 3- to 5-day-old colonies on liver infusion agar. Motility was not observed in cells from young broth cultures under coverslips, nor could it be demonstrated in semisolid medium. The colonies were 1.5–2.5 mm in diameter, glossy, white, raised, with entire margins. No zones of hemolysis were observed around colonies on blood agar. Milk was slowly and softly clotted by two strains and was unchanged by the others (except for the formation of a few small bubbles of gas). Growth was obtained only under anaerobic conditions. The optimal temperature for growth appeared to be near 35°C. These strains were not pathogenic for laboratory animals.1 After the first report, C. innocuum infection cases were reported worldwide6–21 (Fig. S3, http://links.lww.com/MFM/A3). We summarized the main characteristics of C. innocuum blood infection reported in English language literature. The median age of cases was 38 years, and 62% were men. Most cases had a primary disease, such as acute leukemia, acquired immunodeficiency syndrome, chronic hepatitis, urogenital malignancy, gastrointestinal malignancy or organ transplantation.4,11–14,18 The most common presenting symptom was fever of unknown etiology, with gastrointestinal symptoms and/or respiratory diseases being the second most common clinical manifestation. The prognosis was poor, with a mortality rate of 33.3% (Table 2).
Clinical features and diagnosis
Currently, the early diagnosis of C. innocuum infection is clinically challenging. The culture of anaerobic bacteria and accurate identification of bacteria are the most important challenges, and mass spectrometric analysis of C. innocuum is one important identification methods reported.22–29 Almost all patients who were infected with C. innocuum developed bacteraemia due to bacterial resistance to most antibiotics. The common clinical features were fever, increased WBC, elevated C-reactive protein, and PCT. Immunodeficiency, such as tumor, immunodeficiency, or immunotherapy and delivery, may contribute to the progression of infection.9
Local tissue necrosis and abscess formation were common features of the infection. Of the eight patients reported by Smith and King, six cases had abscess.1 In the case reported by Cutrona, the patient developed pyothorax.14 In the case reported by Mutoh et al., fever gradually resolved over the next 3 weeks, but lumbar pain persisted. Computed tomography (CT) imaging identified a small abscess in the iliacus muscle.5 CT-guided drainage was performed. No pathogens were detected in cultures of the abscess fluid or blood. In this report, pyometra persisted after dilation and curettage, E. coli and E. fecal were cultured from the abscess fluid.
Local gas formation was another feature of the infection. On in vitro culture, bubbles are formed around the C. innocuum.1 In the case reported by Castiglioni, CT showed C. innocuum bacteraemia secondary to infected hematoma with gas formation in a kidney transplant recipient.10 In this report, B-ultrasound and MRI showed gas in the uterine cavity and myometrium. Like other anaerobic infections, the foul odor of pus was a feature of C. innocuum infection.
Mixed infection was more common in C. innocuum infections. Mixed bacterial infection with C. innocuum bacteremia was reported in eight of twelve cases by Bodey et al.13 In our current report, the blood culture was positive for C. innocuum and E. coli. In this case, the gas in the uterine cavity and myometrium suggest the C. innocuum other than E. coli infection play a more important role in her illness.
Antibiotic susceptibility and treatment strategy
The Goldstein research team published a number of studies to monitor the susceptibility of C. innocuum.30–45C. innocuum is susceptible to antibiotics, including tigecycline, amoxicillin sulbactam, and amoxicillin clavulanic acid. The resistant antibiotics include vancomycin (general resistant), clindamycin (resistant rate 20%), moxifloxacin (resistant rate 26.7%), and imipenem (resistant rate 6.7%).3,4 (Table 3). The treatment strategy for bacteraemia caused by C. innocuum should employ combination therapy for the high ratio of mixed infection.52
C. innocuum is an anaerobe, which frequently developed blood stream infection with bacterial resistance to many commonly used antibiotics. The early diagnosis of C. innocuum infection is clinically challenging. The treatment strategy for blood stream infection caused by C. innocuum should be combination therapy for its high ratio of mixed infection.52
Funding was provided by the Shenzhen Science and Technology Innovation Commission (JCYJ20160428175005906).
Conflicts of Interest
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