Polymicrobial Clostridioides difficile lung empyema

Abstract

Clostridioides (Clostridium) difficile is a well-known cause of enteritis and antibiotic-associated diarrhea. Extraintestinal C. difficile infection is uncommon, with most extraintestinal infections involving the intra-abdominal cavity and anatomic structures adjacent to the colon. Empyema secondary to C. difficile is especially rare, with only a handful of cases reported in the medical literature. A standard antibiotic treatment regimen for C. difficile empyema does not currently exist, and data chronicling successful treatment is limited. We present the case of an 80-year-old woman with a polymicrobial C. difficile empyema who was successfully treated with multiple chest tube insertions and intravenous vancomycin.

Case Presentation

An 80-year-old woman presented to a community hospital with a 2-day history of dyspnea and chills on the background of a 1-month history of malaise and anorexia. Comorbidities included a remote small bowel resection following multiple small bowel obstructions (20 years prior to presentation), a 20-pack year smoking history, a remote appendectomy, hypertension, dyslipidemia, macular degeneration, and cataracts. She was diagnosed with a large left pleural effusion and a possible underlying left lung mass on chest X-ray and admitted to a community hospital. She was started on levofloxacin 500 mg daily for possible pneumonia. She was transferred to our tertiary care facility 2 days later to facilitate intravenous access and advanced imaging studies. Upon arrival to our hospital, she was afebrile and hemodynamically stable. She was tachycardic at 107 beats per minute. She was tachypneic at 24 breaths per minute, and her oxygen saturation was 94% on 2 L by nasal prongs. She was noted to be in mild respiratory distress and had decreased air entry to the left lung. Investigations revealed a leukocyte count of 26.8 × 10⁹/L (normal range 5.0–10.0 × 10⁹/L), hemoglobin 116 g/L (normal range 121–151 g/L), and platelet count 321 × 10^9/L (normal range 150–400 × 10⁹/L). A venous blood gas revealed a pH of 7.28 (normal range 7.31–7.41), PCO₂ 54 mmHg, and HCO₃ of 25 mmol/L. She was found to have an acute kidney injury, with a creatinine of 224 µmol/L (normal range 60–110 µmol/L). She underwent insertion of a chest tube by an interventional radiologist. The pleural fluid analysis revealed an exudative effusion with a cell count of 11,000 nucleated cells, mostly monocytes. The pH of the pleural fluid was 6.9, the lactate dehydrogenase was >1,800 U/L (serum 173 U/L), the glucose was 0.1 mmol/L (serum 5.9 mmol/L), and the pleural fluid protein was 38 g/L (serum 63 g/L). A culture of the first pleural fluid was ordered, but a sample did not make it to the microbiology laboratory. Computed tomography (CT) of the chest with intravenous contrast following chest tube insertion revealed a decrease in the size of a left pleural effusion and a left lung nodule suspicious for primary lung cancer. Her chest tube fell out accidentally after 2 days, and another was inserted. Microbiology from the insertion of the second chest tube revealed growth of Enterococcus faecalis, Enterococcus faecium, and Clostridioides difficile. As there was no history of antecedent diarrhea, a stool sample for C. difficile was not sent.

She was initially treated with levofloxacin, which was changed to moxifloxacin (formulary substitution) for a total of 7 days upon her arrival at our tertiary care centre. She was then switched to ceftriaxone by her hospitalists. After assessment by infectious diseases, she was switched to intravenous vancomycin monotherapy for 4 weeks following her second chest tube insertion. She achieved clinical and radiographic resolution of her empyema at her follow-up infectious diseases clinic visit. She underwent a CT abdomen and pelvis, which did not reveal the presence of an enteric-pleural fistula to account for her polymicrobial empyema. A lung biopsy revealed a diagnosis of primary lung adenocarcinoma.

Discussion

Clostridioides difficile is an anaerobic, spore-forming gram-positive bacillus (1–6). C. difficile was first isolated in the early 1930s, though its significance as a human pathogen was not determined for decades afterward (4,7,8). It was not until the 1970s that C. difficile was found to cause pseudomembranous colitis and antibiotic-associated diarrhea (1,4,7,8). Cases of extraintestinal C. difficile in the medical literature have predated reports of enteritis by more than a decade (5,8,9).

C. difficile recovered from extraintestinal sites represents less than 1% of all isolates (1,5,10). Intra-abdominal and peri-anal structures are the most frequently described sites involved in extraintestinal C. difficile infection (2,10). Since the 1960s, C. difficile has also been implicated in bacteremias, osteomyelitis, reactive arthritis, pyelonephritis, splenic and brain abscesses, and empyemas (3,7,10,11).

Of the clostridial species, Clostridium perfringens is the most likely to infect the pleural space (4,7,8,12). Only a few reports of lung empyemas secondary to C. difficile have been published (7,8,11). Proposed mechanisms for infection of the pleuropulmonary space by C. difficile include aspiration and inoculation from contaminated chest tubes and drains (4,5,7,8,11). Seeding of the pleural space as the result of transient bacteremia has also been proposed as a potential mechanism of infection; however, this premise has been met with contention as there has yet to be a record of a C. difficile bacteremia complicated by an empyema or any report of a concurrent C. difficile bacteremia and empyema (4,5,7). The virulence factor(s) of C. difficile that allow it to infect extraintestinal sites remain unknown (5,10).

There are several differences between intestinal and extraintestinal diseases. Unlike with enteritis, extraintestinal C. difficile is not usually preceded by diarrhea (1,2,5). More than half of the isolates involved in extraintestinal disease were from non-toxigenic strains; they were devoid of C. difficile toxin A (cdA), B (cdB), and combined toxin (cdT) (1,2,4,10). The overwhelming majority of extraintestinal C. difficile infections are polymicrobial, with Escherichia coli and Enterococcus faecalis and faecium as the most frequently encountered co-pathogens (1–6,9). The presence of C. difficile has been described to increase the pathogenicity of other organisms in polymicrobial infections (13).

Risk factors for C. difficile carriage and ultimately developing extraintestinal infection include prolonged antimicrobial use, hospitalization, being elderly, alcohol abuse, and serious medical comorbidities (1,4–7,9,10,13).

Empyemas secondary to C. difficile behave similarly to empyemas caused by other organisms (8). The mainstays of therapy include source control measures such as chest tube insertion or decortication in conjunction with antimicrobial therapy (5,12). There is no standard antimicrobial treatment regimen (agent or duration) for the treatment of C. difficile lung empyema, though the use of intravenous vancomycin, metronidazole, and cefepime has been described (3,6–8,10–12). Antibiotic therapy is usually tailored to agents with activity against the co-pathogens that are recovered alongside C. difficile (3,6). Reports of successful treatment of C. difficile empyema are rare, and this report adds to this sparse existing literature. Another unique element to our case is that our patient’s empyema (and possibly the C. difficile) was community acquired, although inoculation of the pleural space by C. difficile at the time of chest tube insertion cannot be excluded. Her underlying lung malignancy likely served as a risk factor for the development of this infection.

Extraintestinal C. difficile infection is rare, and most extraintestinal strains are different from those that cause C. difficile enteritis. Many authors contend that the isolation of C. difficile from extraintestinal sites should be interpreted cautiously, as it could represent colonization or contamination in many contexts (1,5,8,9).

Ethics Approval:

N/A

Informed Consent:

Informed consent was obtained by the patient for submission of her case for publication.

Funding:

No funding was received for this work.

Disclosures:

The authors have nothing to disclose.

Peer Review:

This article has been peer reviewed.

Animal Studies:

N/A