Anaerobic pericarditis due to Clostridium ramosum: First known case report

Abstract

Anaerobic pathogens are uncommon etiologies of pericardial infections. Clostridium ramosum, an obligate anaerobic gram-positive bacillus and member of the normal gastrointestinal flora, is generally considered of low virulence but has been implicated in invasive infections in elderly or immunocompromised individuals. We report the first documented case of Clostridium ramosum pericarditis. An 85-year-old male with atrial fibrillation, hypertension, hyperlipidemia, splenomegaly with bicytopenia, and depression was found to have a moderate pericardial effusion on transthoracic echocardiography. Follow-up imaging revealed a reduced ejection fraction, progressive aortic dilation, and early tamponade physiology. Despite being asymptomatic, he underwent pericardiocentesis, which yielded 400 mL of fluid. Gram stain demonstrated gram-positive bacilli, later identified on anaerobic culture as Clostridium ramosum. Blood cultures remained negative. He was treated with intravenous ampicillin-sulbactam followed by oral metronidazole, with resolution of the effusion and no recurrence on follow-up. This case highlights that anaerobic pericarditis can occur in the absence of systemic symptoms or sepsis, particularly in elderly patients with comorbidities that predispose to bacterial translocation. Timely drainage and targeted antimicrobial therapy are essential for favorable outcomes. Importantly, routine anaerobic cultures of pericardial fluid should be considered to avoid missed diagnoses. Recognition of rare anaerobic pathogens in pericardial infections expands the understanding of their pathogenic potential and informs future diagnostic and therapeutic approaches.

Introduction

Pericardial infections are uncommon but potentially life-threatening, with bacterial etiologies representing a small subset of cases [1], [2]. The most frequently implicated organisms include Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus species, and Mycobacterium tuberculosis [3], [4], [5], [6]. Anaerobic pericarditis is particularly rare and typically arises from contiguous spread from intra-abdominal, esophageal, or mediastinal sources, or less commonly via hematogenous dissemination [7], [8], [9]. Reported anaerobic pathogens include Bacteroides fragilis group, Peptostreptococcus, Fusobacterium, Actinomyces, and Clostridium species [8], [9]. Clostridium ramosum (also known as Erysipelatoclostridium ramosum) is a gram-positive, obligate anaerobic, spore-forming bacillus that is part of the normal human gastrointestinal flora [10]. Although generally regarded as a low-virulence strain, it has been implicated in invasive infections, particularly among elderly or immunocompromised patients [11]. These infections include bacteremia [12], intra-abdominal abscesses [12], osteomyelitis [13], and soft tissue or necrotizing infections such as Fournier’s gangrene [15]. In a systematic review of invasive C. ramosum infections, the organism was most often isolated from blood or sterile body fluids, with consistent susceptibility to metronidazole, β-lactam/β-lactamase inhibitor combinations, and carbapenems [15]. To our knowledge, C. ramosum pericarditis has not been previously described. This case therefore represents the first reported instance of C. ramosum involving the pericardium. It underscores the importance of including anaerobic cultures in the diagnostic evaluation of pericardial effusions and considering empiric antimicrobial coverage for anaerobic organisms in appropriate clinical contexts.

Case

An 85-year-old male with medical history of recently diagnosed atrial fibrillation (not yet anticoagulated), hypertension, hyperlipidemia, splenomegaly with associated bicytopenia, and depression was evaluated by his primary care provider for a newly detected murmur and ectopic beats on examination. Holter monitoring and a transthoracic echocardiogram (TTE) were ordered. The Holter revealed new-onset paroxysmal atrial fibrillation with a burden of less than 1 %. The TTE showed a preserved ejection fraction (EF) of 50–55 %, grade II diastolic dysfunction, aortic root dilation measuring 4.1 cm, and a moderate pericardial effusion without signs of tamponade. He was managed conservatively as an outpatient, with close follow-up and repeat imaging planned. Approximately one week later, a follow-up TTE demonstrated significant changes: the EF had declined to 35 % with global hypokinesis, the aortic root had further dilated to 5.4 cm, and new findings suggestive of early tamponade physiology (Fig. 1A). Given this progression, he was urgently transferred to the emergency department (ED) for further evaluation.

Fig. 1.

(A) Transthoracic echocardiography image showing large pericardial effusion with early tamponade physiology. (B) Computed tomography angiogram of the chest showing ascending aortic ectasia (4.6 cm) without dissection. (C) Image of hemorrhagic fluid drained from the pericardiocentesis on hospital day two. (D) Gram stain of pericardial fluid sample collected from pericardiocentesis showing numerous large gram-positive rods with blunt ends with some appearing in pairs or short chains.

On presentation to the ED, the patient remained asymptomatic. He denied fever, chills, chest pain, dyspnea, palpitations, dizziness, or diaphoresis. There were no signs of volume overload, such as worsening peripheral edema, orthopnea, or weight gain. He reported no constitutional symptoms such as night sweats or unintentional weight loss but did endorse new-onset loose stools with lower abdominal discomfort that was a change from his baseline. His gastrointestinal history included a normal colonoscopy 20 years prior and a negative Cologuard test five years earlier. Vital signs were stable with normal oxygen saturation, and telemetry showed atrial fibrillation with a controlled ventricular response. A chest computed tomography angiogram (CTA) confirmed an ectatic ascending aorta measuring 4.6 cm without evidence of dissection (Fig. 1B). Abdominal CT revealed potential rectal inflammation, with circumferential rectal wall thickening and presacral fat stranding.

Initial laboratory work-up showed a white blood cell count of 9.2 K/μL on admission, which progressively rose to 29.5 K/μL by hospital day four. He had a hemoglobin of 10.8 g/dL and platelet count of 89 K/μL, consistent with his chronic bicytopenia. While his haptoglobin was < 8 mg/dL and LDH was elevated to 168 U/L, his hepatic function and peripheral smear were not suggestive of hemolysis. His C-reactive protein was elevated at 104 mg/L without systemic signs of infection. Given evidence of early tamponade physiology on TTE, pericardiocentesis was performed on hospital day two, despite hemodynamic stability. The procedure was uncomplicated and yielded approximately 400 mL of fluid. Pericardial fluid analysis revealed mildly elevated nucleated cell count (623 per mm³) with a mononuclear-predominant differential (68 %), normal glucose, low protein levels, and 824 red blood cells per mm³ (Fig. 1C). Gram stain identified gram-positive bacilli (Fig. 1D), raising early suspicion for an anaerobic or unusual pathogen. Initial empiric antimicrobial coverage was started with intravenous vancomycin. Anaerobic cultures later identified the organism as Clostridium ramosum, prompting narrowing of antimicrobial therapy to intravenous ampicillin-sulbactam (Unasyn) on hospital day four. Antimicrobial susceptibility testing, interpreted according to Clinical and Laboratory Standards Institute (CLSI) guidelines, demonstrated the following minimum inhibitory concentrations (MICs): clindamycin 4 µg/mL (intermediate), meropenem 0.38 µg/mL (susceptible), metronidazole 0.38 µg/mL (susceptible), and penicillin 0.25 µg/mL (susceptible). Notably, blood cultures remained negative, and no additional infectious foci were identified.

Given the patient's chronic bicytopenia, splenomegaly, and persistent leukocytosis, hematology was consulted to evaluate for an underlying bone marrow disorder, such as chronic myelomonocytic leukemia (CMML), myelodysplastic syndrome (MDS), leukemia, lymphoma, or multiple myeloma. A bone marrow biopsy was recommended but declined by the patient. The gastroenterology team was consulted due to CT findings suggesting rectal inflammation and a potential gastrointestinal source. Colonoscopy revealed diverticulosis in the left and right colon, with multiple 3–7 mm polyps in the transverse colon, ascending colon, and cecum. No overt source of infection was identified, although occult diverticulitis remained a possibility. Throughout hospitalization, the patient remained clinically stable without fever, chills, chest discomfort, or worsening dyspnea. He completed five days of intravenous Unasyn and was discharged in stable condition on a four-week course of oral metronidazole. On follow-up, repeat transthoracic echocardiogram (TTE) showed no residual pericardial effusion and the patient remained hemodynamically stable, without fever or systemic signs of sepsis.

Discussion

Bacterial pericarditis is a rare but serious infection, most often caused by aerobic organisms such as Staphylococcus aureus, Streptococcus pneumoniae, and Mycobacterium tuberculosis [6], [7]. Anaerobic bacterial pericarditis is even less common, typically arising from direct extension of infection from adjacent foci, including esophageal perforation, subdiaphragmatic abscesses, or postoperative mediastinal contamination, with hematogenous seeding being less frequent [2], [8]. These cases often present with purulent pericardial effusion and systemic sepsis, with mortality rates approaching 40–50 % despite prompt drainage and antimicrobial therapy [1], [2]. Reported anaerobic pathogens include Bacteroides fragilis, Peptostreptococcus, Fusobacterium nucleatum, Actinomyces israelii, and Clostridium perfringens [7], [9].

Clostridium ramosum is an obligate anaerobic, spore-forming, gram-positive rod residing in the normal gastrointestinal microbiota, now classified under the genus Erysipelatoclostridium [10], [11]. A systematic review by Forrester and Spain identified 12 cases of invasive C. ramosum infection, primarily presenting as bacteremia or intra-abdominal abscesses, often in patients with gastrointestinal malignancies, prior abdominal surgery, or structural abnormalities [15]. Other reported manifestations included osteomyelitis, soft-tissue infections, and, rarely, central nervous system abscesses [13], [14], [15]. Notably, none of the cases in this review involved pericardial infection, underscoring the novelty of our report. C. ramosum infections are typically seen in older or immunocompromised patients, highlighting its opportunistic nature [11], [12]. Historically, identification was challenging due to slow growth and subtle biochemical features, often resulting in misclassification as other Clostridium species. Advances in MALDI-TOF MS and 16S rRNA sequencing now allow more reliable detection, suggesting that prior reports of “unspecified Clostridium” infections may have included unrecognized C. ramosum. Unlike previously reported cases, our patient had no obvious intra-abdominal source or prior gastrointestinal procedures, although factors such as advanced age, chronic bicytopenia, and splenomegaly may have facilitated bacterial translocation, with occult diverticular disease representing a plausible portal of entry.

This case highlights the importance of considering anaerobic pathogens, including C. ramosum, in the differential diagnosis of pericardial infections, even in the absence of classic septic features. Advances in rapid proteomic identification, early anaerobic cultures, and prompt targeted therapy may reveal that these infections are more common than previously recognized. Given the fastidious nature of anaerobic organisms and their frequent omission from standard culture protocols, increased awareness and empiric broad-spectrum antibiotics with anaerobic coverage are essential, particularly in patients with atypical presentations or risk factors such as malignancy, recent surgery, or chronic immunosuppression.

Conclusion

We present what we believe to be the first reported case of anaerobic pericarditis caused by Clostridium ramosum. This case highlights the importance of sending anaerobic cultures on pericardial fluid, particularly in elderly or immunocompromised patients, and of maintaining a broad differential when managing pericardial infections. Early drainage and appropriate antibiotic therapy are critical to successful outcomes. Reporting such rare infections expands our understanding of the pathogenic potential of anaerobic gut flora in extra-abdominal infections and may help guide future recognition and management strategies.

CRediT authorship contribution statement

Rohan Mylavarapu: Writing – review & editing, Writing – original draft, Investigation, Data curation, Conceptualization. Moamen Al Zoubi: Writing – review & editing, Writing – original draft, Supervision, Formal analysis, Data curation, Conceptualization.

Ethics statement

The IRB has conducted an administrative review. This case report was approved via administrative review by the MHC Office of Research. While there is no requirement for IRB approval for a case report, HIPAA Privacy Rules and restrictions must be followed in order to protect all identifiable personal health information.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.