Clostridium ramosum Bacteremia: Case Report and Literature Review

Abstract

Background:

Clostridium ramosum is a common enteric anaerobe but infrequently also a cause of pathologic infection.

Methods:

Case report and literature review.

Results:

We reviewed 12 case reports describing infection with C. ramosum. When pathogenic, C. ramosum is cultured most commonly from the inner ear, anaerobic blood samples, or abscesses. Patients with such infections fall into two demographic groups, consisting of young children with ear infections or immunocompromised adults with bacteremia. Resistance of C. ramosum to antibiotics is uncommon.

Conclusion:

Clostridium ramosum is a common but generally commensal bacterial species. Rarely, it becomes pathogenic in young children or immunosuppressed adults.

C lostridium ramosum is a common enteric bacterium but is pathogenic rarely. It was described originally by Veillon and Zuber in 1898 after being isolated from a patient with appendicitis and pulmonary gangrene [1]. Originally named Bacillus ramosum, it was renamed C. ramosum in 1971 after being found to be a spore-forming anaerobe [1 –3]. It is a member of the genus Clostridium, a group of gram-positive, obligate anaerobic spore-forming bacilli. Within the clostridia is a subgroup of organisms known as the RIC group, for the initial letters of its species' names, and consisting of C. ramosum, C. innocuum, and C. clostridioforme [4]. This group has gram-stain variability, spores that are absent or difficult to see, and atypical clostridial colony morphology [4]. Despite C. ramosum being a common gut bacteria, it is isolated rarely as a pathogen and is generally considered non-pathogenic [5 –8]. We present a case of C. ramosum bacteremia associated with sigmoid perforation and septic shock in a patient with metastatic pancreatic adenocarcinoma.

Case Report

An 80-year-old female presented to the emergency department with 5 d of abdominal pain, nausea, and bilious emesis. These symptoms had been getting worse progressively. The patient reported that the pain was diffuse throughout her abdomen, non-radiating, and severe. Several days after the onset of her pain she developed a temperature of 38.6°C.

Her history was notable for endometrial cancer, for which she had undergone a hysterectomy and chemoradiation, as well as a partial pancreatectomy with splenectomy for a T₂N₀M₀ pancreatic adenocarcinoma.

When the patient presented to the emergency department she had a systolic blood pressure of 80 mm Hg with SaO₂ saturation of 80%. Her laboratory results were notable for a blood glucose of 380, a white blood cell count (WBC) of 5,900/mm³ with 41% immature band forms, an elevated serum creatinine concentration of 3.5 mg/dL, and an arterial blood lactate concentration of 7 mg/dL. There were notable air fluid levels on a plain film of the abdomen. Placement of a nasogastric tube resulted in the return of 500 mL of bilious and feculent material. Blood cultures were drawn and a regimen of piperacillin-tazobactam 3.375 g q8h was begun. Because of the patient's elevated creatinine concentration, a non-contrast-enhanced computed tomographic (CT) scan was done of her abdomen/pelvis and demonstrated a small bowel obstruction as well as free air. The patient was taken urgently to the operating room. Intra-operatively, the patient's bowel was edematous and the sigmoid colon was perforated, with multiple diverticula. There was feculent contamination of the patient's abdominal cavity. There were also multiple dusky areas of the small bowel, and re-operation was planned. Fifteen centimeters of the patient's sigmoid colon were resected for presumed perforated diverticulitis, her abdomen was left open, and she was transferred to the intensive care unit (ICU) for resuscitation. At this time her antibiotic regimen was changed from piperacillin-tazobactam to ertapenem 1 g QD.

The blood cultures drawn on admission yielded C. ramosum and Bacteroides fragilis. The MIC values for the C. ramosum in the cultures, obtained with a MicroScan analyzer (Siemens, Munich, Germany), were as follows: Ampicillin-sulbactam 0.12 (susceptible), clindamycin 16 (resistant), meropenem 1 (susceptible), metronidazole 0.5 (susceptible), and penicillin 0.06 (susceptible). There was no growth in any of the aerobic culture bottles. A day later the patient was taken back to the operating room for a repeat laparotomy, washout, small bowel resection, and sigmoid colostomy. The cecum and right colon were dusky, but because of the morbidity associated with resection, a third operation was planned to reassess viability. Again the patient became unstable in the operating room with septic shock, which necessitated return to the ICU. Two days later she was taken to the operating room a third time for an abdominal washout, ileocecectomy with end-ileostomy, and closure. Her sepsis resolved gradually and treatment with vasopressors was stopped gradually by the third post-operative day. She ultimately received 6 d of antimicrobial treatment with ertapenem. Blood cultures obtained on hospital day 8 demonstrated no persistent bacteremia.

On hospital day 13 the patient was extubated. The pathology report from her initial operation demonstrated perforated diverticulitis with extensive involvement by metastatic pancreatic adenocarcinoma. Do not resuscitate/do not intubate (DNR/DNI) orders were written according to her wishes. On hospital day 18 an intra-abdominal drain was placed in a suspected abscess cavity identified by CT. Organisms found on culture of the drainage fluid from the cavity included Candida krusei, B. fragilis, two species of Enterococcus, and Pseudomonas aeruginosa. Despite drain placement the patient continued to deteriorate and died on hospital day 21.

Discussion

Clostridium ramosum is a common yet infrequently pathogenic enteric bacterium. The species is typically weakly gram positive initially, becoming more strongly gram positive later in its culture [9,10]. The organisms have a terminal spore, are non-motile, produce acetic acid, and ferment D-glucose, lactose, maltose, D-mannitol, D-mannose, D-melibiose, and sucrose. Clostridium ramosum is unique in having an IgA protease that can cleave both IgA1 and IgA2 [9], the latter of which is the predominant immunoglobulin in respiratory, intestinal, and mammary secretions [9]. Resistance of C. ramosum to antimicrobial agents has not been widespread, although its resistance to rifampin was noted in 1971, with resistance to tetracycline also noted [7,11,12]. Clostridium ramosum has been sensitive consistently to chloramphenicol, vancomycin, and metronidazole, and resistant to rifampin and aminoglycosides [1].

Clostridium ramosum is a common fecal pathogen. In a study of 160 patients it was found in the feces of 83% of adults, and has been cited as one of the more common commensal clostridial species in human beings [9,13]. In a survey of 1,543 pediatric clinical culture specimens, C. ramosum represented only 4% of all clostridial isolates [14]. Of the C. ramosum specimens in that survey, three of 13 were from abscesses and five of 13 were from peritoneal aspirates [14]. In a large survey of patients with clostridial bacteremia, only 9% of all blood cultures positive for clostridia were found to contain C. ramosum [7], representing fewer than 0.2 infections per 100,000 individuals in that patient group [7]. Similarly, C. ramosum was isolated in only 1.5% of anaerobic blood cultures in another large retrospective study [8].

We reviewed all case reports of C. ramosum infection in the English-language literature as well as sources in the non-English literature (Table 1). Generally, patients with C. ramosum infections fall into one of two groups. The first group consists of pediatric patients who present with chronic or acute otitis media. The second group includes older adults, often with co-morbidities that pre-dispose to infection, such as diabetes mellitus. Unlike several other clostridial species, C. ramosum is not known to have many virulence factors. Its primary virulence factor is its extended IgA protease [9]. Although in healthy adults this protease might not be sufficient to allow the organism to proliferate or translocate, in children without fully developed gut flora or gut-associated lymphoid tissue, or in adults with immunosuppressive co-morbidities, the IgA protease of C. ramosum may be sufficient to allow it to become pathogenic. It is important to consider the possibility of C. ramosum infection in immunosuppressed patients who develop intra-abdominal infection. Antimicrobial resistance is not widespread among C. ramosum, and avoidance of rifampin or tetracycline and obtaining of source control in treating infections in which it is identified can be expected to provide a successful outcome.

Table 1.

Case Reports of Clostridium ramosum Infection

Reference	Age/gender	Co-morbidities	Source	Co-infecting organisms	Anti-biogram
Brook et al. 1979 [15]	2M	None	Inner ear	Group A beta-hemolytic streptococci	Not reported
Brooke 1995 [14]	3F	None	Blood	None	Not reported
Brooke 1995 [14]	3M	None	Inner ear	None	Not reported
Brook et al. 1979 [15]	4F	None	Inner ear	Eubacterium limosum	Not reported
Set et al. 2001 [16]	5M	Chronic otitis	Cerebellar abscess	None	Not reported
Turkoglu et al. 2005 [19]	7M	None	Intracranial cyst	Echinococcus granulosus	Not reported
van der Vorm et al. 1999 [17]	11F	Acute lymphatic leukemia	Blood	Candida albicans	Susceptible to penicillin
Langdale et al. 1988 [21]	28F	None	Perinephric abscess	Bacteroides fragilis, Peptostreptococcus spp.	Not reported
Nanda et al. 2006 [23]	49M	DM	Blood	None	Susceptible to ampicillin-sulbactam, metronidazole, penicillin and vancomycin. Resistant to cefoxitin and clindamycin
Muakkassa et al. 1983 [3]	53M	Renal transplant recipient	Blood	None	Susceptible to penicillin, chloramphenicol, clindamycin. Resistant to tetracycline, erythromycin
Miret et al. 1998 [22]	59M	Chronic EtOH abuse, HTN, gout	Intracranial abscess	Peptostreptococcus spp.	Susceptible to penicillin, clindamycin, cephalosporins, andimipenem-cilastatin. Resistant to metronidazole
Lavigne et al. 2003 [20]	74M	Prostate adenoma	Disk space aspirate	None	None
Alcade-Vargas et al. 2012 [18]	79F	Not reported	Blood	None	Susceptible to penicillin and metronidazole
Forrester et al. 2012	80F	Pancreatic adenocarcinoma, DM	Blood	Bacteroides fragilis	Susceptible to ampicillin-sulbactam, clindamycin, meropenem, metronidazole, and penicillin
Mohandas et al. 2001 [10]	91F	HTN, DM	Blood	None	Not reported

DM=diabetes mellitus; EtOH=ethanol; HTN=hypertension.

Although it is a common commensal organism, C. ramosum causes infection rarely and rarely shows resistance to antibiotics. The organism is more likely to cause infection in several specific sub-groups than in others. These include children with acute otitis media, immunosuppressed adults, and patients with bowel perforation and abscess formation.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

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