Aspiration Pneumonia Leading to Bacteremia in a Neutropenic Patient: Case Report and Management Strategy

Introduction

Clostridium ramosum is an anaerobic, spore-producing, gram-positive rod, enteric pathogen that can be difficult to detect given its spore-like qualities and poor gram stain variability [1–3]. Clostridium species bacteremia is rarely pathogenic [4] and reported in only 1% of blood culture pathogens [1]. There have been case reports of Clostridium ramosum bacteremia in the setting of bowel perforation, colorectal tumors, mucositis, osteomyelitis, soft-tissue infections, lung abscesses, endocarditis, and Fournier’s gangrene [1–3,5,6]. Although rare, Clostridium ramosum bacteremia has been found in elderly patients and in patients with the following comorbidities: on hemodialysis, active malignancy, diabetes mellitus, and status after organ transplant [1–3,7]. Clostridium ramosum is likely underdiagnosed given difficulty with isolation and identification and the often polymicrobial presentation [1–4]. We report a case of Clostridium ramosum bacteremia in an immunocompromised patient who presented with fever.

Case Report

A 65-year-old man presented to the emergency room with a fever. He had been diagnosed with follicular lymphoma 4 months prior and received his first cycle of MATRix therapy without methotrexate (cytarabine, thiotepa, rituximab) 8 days prior to admission. His additional medical comorbidities included sigmoid bowel perforation, which required emergent limited sigmoid colectomy 2 months prior to admission, paroxysmal atrial fibrillation on chronic anticoagulation, type 2 diabetes mellitus, coronary artery disease status after 4 stents, and provoked deep venous thrombosis (DVT) and pulmonary embolism. He reported feeling well up until day 8 of post cycle 1 when he developed a nonproductive cough, generalized fatigue, weakness, and confusion. Aside from a fever of 38.3°C, his other vitals were within normal limits (respirations 20/min, blood pressure 129/74 mmHg, SpO2 94% on room air, and heart rate 94/min). His physical examination was unremarkable with the exception of +2 bilateral lower-extremity pitting edema. His laboratory results were remarkable for hemoglobin 6.7 g/dL, platelets 22×109/L, and white blood cells 0.3×109/L, with absolute neutrophil count (ANC) of 0.35×109/L. The chest X-ray and urinalysis were unremarkable. He was given 1 unit of packed red blood cells and started on intravenous (IV) vancomycin and aztreonam. At 13 hours, 2/2 anaerobic peripheral blood culture bottles (right arm and left arm) demonstrated gram-variable bacilli (gram stain on anaerobic culture medium) with eventual speciation to Clostridium ramosum via MALDITOF (matrix-assisted laser desorption/ionization-time of flight) after being plated to a CDC agar plate. No species identification was performed via PCR and no additional cultures, other than blood, were taken. Minimum inhibitor concentration (MIC) tests were performed (Table 1) and the patient was started on intravenous piperacillin-tazobactam as it was susceptible to Clostridium ramosum at ≤16/4 mcg/mL.

He eventually defervesced by day 4 of hospitalization. Both sets of blood cultures from admission grew isolated Clostridium ramosum with susceptibility to piperacillin-tazobactam, followed by negative blood cultures. CT abdomen/pelvis with IV contrast demonstrated left lower-lung consolidation with a peripherally enhancing fluid collection (2.6×1.8 cm) (Figure 1) and new small loculated left pleural effusion (not present on admission chest X-ray). CT chest with contrast demonstrated possible infarct verses abscess in the left lower lung, lower-lobe ground-glass opacities, and segmental/subsegmental pulmonary emboli despite apixaban use. Pulmonology and Infectious Diseases were consulted and recommended a 14-day course of IV piperacillin-tazobactam for pneumonia followed by repeat CT chest after treatment completion. The patient deferred repeat inpatient chest imaging. However, 2 weeks after discharge, an outpatient PET-CT was performed and was negative for left lower-lung pathology.

Discussion

The genus Clostridium accounts for only 1% of bacteremia isolates [1]. In a retrospective population-based surveillance study of the Calgary Health Region from 2000 to 2006, Clostridium ramosum only accounted for 9% of all Clostridium species bacteremia [7]. Clostridium ramosum is likely underdiagnosed given difficulty in isolation and accurate identification due to some stains appearing gram-negative or gram-variable, spores being difficult to delineate, and Clostridium ramosum often being part of a polymicrobial presentation given its enteric origin [1–4]. Due to gram stain variability, the lab may utilize various identification strategies to identify Clostridium ramosum, such as ability to ferment maltose, glucose, mannose, lactose, and mannitol, and ability to cleave IgA1 and IgA2 (IgA protease) [2]. The IgA proteases are hypothesized to allow mucosal penetration through the GI tract [2,3], allowing Clostridium ramosum to reproduce and translocate [4].

Risk factors for Clostridium ramosum bacteremia include older age, malignancy, bowel perforation, and immunosuppression [1]. Our patient’s risk factors for Clostridium ramosum included his age, diabetes mellitus, and immunocompromised status. He was successfully treated with penicillin-based antibiotics. The mechanism of his Clostridium ramosum bacteremia was suspected to be secondary to aspiration pneumonia. Pneumonia as a source of Clostridium ramosum bacteremia uncommon, but is likely explained by aspiration pneumonia in this case report. Despite being immunocompromised, this patient who presented with neutropenic fever had a favorable outcome with resolution of pneumonia as well as bacteremia on an appropriate antibiotic regimen. Future research is required to improve lab identification, which will lead to increased data regarding morbidity and mortality of Clostridium ramosum bacteremia.

Conclusions

In conclusion, immunocompromised patients are at risk of Clostridium ramosum bacteremia. It is necessary to consider Clostridium ramosum as a potential pathogenic bacterium in these patients given its often polymicrobial presentation and elusive identification.