Polymicrobial bacteraemia with Clostridioides difficile and Pseudomonas aeruginosa in an elderly man following antibiotic use

Background

Clostridioides difficile (formerly Clostridium difficile) is a spore-forming Gram-positive bacteria notorious for causing infectious diarrhoea due to pseudomembranous colitis following antibiotic use both in healthcare facilities and the community. Although a recent publication demonstrated that the national burden of C. difficile infections (CDI) has in fact decreased in recent years, largely on account of infection prevention and antibiotic stewardship efforts, CDI remains a significant cause of morbidity and mortality in the USA.1 Extraintestinal manifestations of CDI in general are rare, with bacteraemia being one of the least common. One retrospective study found that among 18 570 cases of C. difficile colitis, only 31 (0.17%) were also characterised by extra-intestinal infection2; another similarly found that among 2034 C. difficile isolates identified, only 21 (1.08%) were collected from extraintestinal sites.3 The most common extraintestinal manifestations were wound infections and intra-abdominal infections including peritonitis, but abscesses of the brain and liver, osteomyelitis, mycotic aneurysms, urinary tract infections and even prosthetic device infections have been described, among other presentations.2–7 We present a case of polymicrobial bacteraemia associated with C. difficile colitis.

Case presentation

A male patient in his 90s, a former smoker, with a medical history of hypertension, hypothyroidism, prostate cancer with metastases to bone on enzalutamide/leuprolide, and no prior history of CDI who was sent to the emergency department (ED) from his oncologist’s office with hypotension (blood pressure 90/50 mmHg) in the setting of 2 days of acute fevers and chills concerning for sepsis. On arrival, he further endorsed several days of loose stools. He denied cough, shortness of breath, abdominal pain or dysuria. Approximately 10 days prior to presentation, he had completed a 7-day course of oral ciprofloxacin and metronidazole for asymptomatic diverticulitis incidentally found on surveillance positron emission tomography/computed tomography (PET/CT) scan.

His vital signs in the ED were significant for persistent hypotension (blood pressure 89/51 mmHg) with a normal temperature, heart rate, and peripheral oxygen saturation on room air. On physical examination, he was slightly diaphoretic, his lungs were clear to auscultation, and his abdomen was mildly tender to palpation in the right upper and left lower quadrants without rebound or guarding.

His labs were notable for an acute kidney injury (creatinine of 1.38 mg/dL, up from baseline 1.1 mg/dL) and a leucocytosis (white blood cell count 12.5×10⁹/L with 89% neutrophils). His urinalysis was unremarkable. His CT abdomen/pelvis demonstrated sigmoid diverticulosis (seen on prior imaging) with wall thickening suggestive of colitis, but without a discrete collection or extraluminal gas. Blood cultures were collected prior to administration of antibiotics. Given the clinical picture of sepsis with concern for an intra-abdominal source, he was started on empiric piperacillin/tazobactam, as per our institution’s antimicrobial norm.

Investigations

Blood cultures from admission resulted on hospital day (HD) 1 with Gram-positive rods (GPR) in one of four bottles (anaerobic bottle of one of two sets) and Pseudomonas aeruginosa in two of four bottles. Stool PCR testing for C. difficile toxin was positive. On HD 4, the GPR from admission were identified as C. difficile. While all blood cultures after HD 1 were negative for P. aeruginosas, follow-up blood cultures from HDs 3 and 4 each grew C. difficile in one of two bottles (anaerobic bottle of one set). Glutamate dehydrogenase (GDH) testing and susceptibility testing of C. difficile were not performed.

Differential diagnosis

When the initial blood cultures resulted positive for GPR and P. aeruginosa, we considered the differential for GPRs, which includes Bacillus, Clostridium, Listeria, Corynebacterium and Cutibacterium (formerly Propionibacterium), among others. Although Clostridium perfringens bacteraemia seemed unlikely in the absence of trauma or skin changes, we did consider the possibility of C. difficile bacteraemia in the setting of colitis and recent antibiotic use. Cutibacterium acnes, a common skin coloniser and frequent contaminant, also seemed likely. The patient did not report any recent food exposures which would have predisposed him to either Bacillus or Listeria infection such as fried rice for the former, or unpasteurised dairy, deli meats, and raw vegetables for the latter. He also lacked any obvious respiratory or cutaneous symptoms, as well as any devices or prostheses, which would raise concern for Corynebacterium infection.

Treatment

Once the Gram-positive isolate was identified as C. difficile, the patient was initially started on intravenous vancomycin. Following infectious diseases consultation, he was switched to intravenous metronidazole 500 mg every 8 hours, with the plan to transition to oral metronidazole on discharge for an anticipated 4–6 weeks course with close outpatient infectious diseases follow-up. For his C. difficile colitis, he was continued on oral vancomycin while on piperacillin/tazobactam, and for an additional 10 days post-completion of systemic antibiotics. He received a total of 10 days of piperacillin/tazobactam from the first negative blood culture for Pseudomonas bacteraemia.

Outcome and follow-up

The patient’s sepsis resolved. He remained afebrile throughout his admission. His blood cultures from HD 5 and subsequent days all remained negative for C. difficile. The polymicrobial bacteraemia was thought to have most likely developed as a result of bacterial translocation in the setting of CDI caused by his prior treatment with a fluoroquinolone. Transthoracic echocardiogram did not demonstrate any obvious vegetations. Given his lack of risk factors for endocarditis, as well as the higher risk for complications from anaesthesia with advanced age, transoesophageal echocardiogram was deferred. PET/CT was considered to evaluate for possible seeding, but ultimately not pursued due to the likelihood of the results being difficult to interpret in the setting of metastatic cancer. The patient was discharged on HD 12 with outpatient infectious diseases follow-up. He remained clinically well on follow-up and successfully completed a 4-week course of intravenous, followed by oral metronidazole. His subsequent blood cultures remained negative.