Recurrent endocarditis due to Brevibacterium casei: Case presentation and a review of the literature

Brevibacterium casei (B. casei) is an aerobic, gram-positive bacillus to which the aroma and colour of cheese is attributed, and until not long ago it was postulated to be a cutaneous saprophyte¹ with no pathogenic ability. There are few cases of infections caused by this genus and they are mainly reported as a pathogen in immunocompromised patients,² catheter-related infections^2,3 and peritoneal dialysis-related infections.⁴

We wish to present the case of a patient with a history of chronic liver disease who developed B. casei-induced endocarditis.

A 60-year-old male patient was seen for tremor and decreased level of consciousness, with a medical history of moderate aortic stenosis and Child Pugh C11 alcoholic chronic liver disease with only one prior hospital admission.

When admitted to the ward, he started with a low-grade fever of 37.6 °C, for which blood cultures were extracted. During the examination, a pustular skin lesion in a scabby phase was noted on his forehead along with a grade IV/VI panfocal, systolic ejection murmur with carotid irradiation. After three days, two blood cultures (MALDI-TOF MS (Bruker)) were reported to be positive for B. casei (sensitive to gentamicin, tetracycline (MIC < 1), vancomycin (MIC < 0.5), and levofloxacin (MIC < 2) and antibiotic therapy was started with oral levofloxacin 500 mg/24 h for 10 days. The patient remained afebrile, and as the lesion on his forehead was suggested to be the route of entry, he was discharged with oral norfloxacin 400 mg/24 h.

After 30 days the patient returned to the emergency department due to decompensation with jaundice and ascites, coagulopathy, thrombocytopaenia and hyponatraemia, hypochloraemia, reported instability while walking, diffuse abdominal discomfort with feelings of nausea, with no fever measured.

He was admitted to the ward and diagnostic paracentesis was performed, where despite not meeting the criteria for spontaneous bacterial peritonitis and given the presence of protein in the ascitic fluid under 1 g/dL and total bilirubin >4 g/L, primary prophylaxis was initiated with intravenous ceftriaxone 2 g/24 h.

The patient again started to have low-grade fever with blood cultures repeatedly positive for B. casei (sensitive to gentamicin, tetracycline (MIC < 1), vancomycin (MIC < 0.5), levofloxacin (MIC < 2), and resistant to norfloxacin and ciprofloxacin), therefore treatment was initiated with vancomycin adjusted for kidney function and levofloxacin, while ceftriaxone was suspended. Forty-eight hours after starting the antibiotic therapy, two series of negative blood cultures were obtained.

A transthoracic echocardiogram was performed which showed moderate aortic stenosis and a severely dilated left atrium. No vegetation was observed. The testing was therefore completed with a transoesophageal ultrasound which revealed 15 mm vegetation on the aortic valve with perforation of the non-coronary cusp and aortic insufficiency, probably moderate. The patient was diagnosed with infective endocarditis. The case was discussed with cardiac surgery, and due to the high surgical risk and the patient's clinical stability, surgery was ruled out.

The patient completed 4 weeks of antibiotic treatment with intravenous vancomycin and his kidney function was monitored with no repercussions (initially 1 g/12 h which was adjusted according to his levels until completing 19 days at a dose of 450 mg/12 h). Primary prophylaxis for bacterial peritonitis was maintained with norfloxacin.

Follow-up blood cultures were obtained three days after ending the antibiotic treatment. The cultures were negative and the transthoracic echocardiogram was repeated with no deterioration versus the previous one.

Two weeks after finishing the intravenous antibiotic, the patient presented loss of strength in his right arm. A cerebral NMRI was performed which showed two recently bleeding foci in the posterior left temporal lobe, compatible with septic embolisms given the patient's history. In the following days, he again presented with a low-grade fever with positive blood cultures for B. casei (sensitive to gentamicin, tetracycline (MIC < 1), vancomycin (MIC < 0.5), and intermediate to levofloxacin (MIC 4), resistant to norfloxacin and ciprofloxacin). Intravenous vancomycin therapy was restarted at doses of 1000 mg/12 h in combination with 4 days of oral doxycycline 100 mg/12 h. As the fever persisted after three days, daptomycin 500 mg every 48 h was added for the last 6 days. The blood cultures became negative and the patient remained afebrile. He gradually progressed to liver failure and his kidney function deteriorated which did not respond to terlipressin. He was declared dead after 10 days.

The genus Brevibacterium is composed of strictly aerobic, immobile, non-haemolytic, gram-positive bacilli, with optimal growth between 30 and 37 °C.^5,6 There are 45 different species in total, but only nine have been isolated in clinical samples and B. casei is the species that most frequently causes disease.^7,8 Generally it is rarely virulent, but infections caused by this species can be severe and fatal.

B. casei has been identified in multiple infections such as meningitis, brain abscesses,⁷ peritonitis⁹ and catheter-related sepsis,¹⁰ and is generally associated with states of immunosuppression.

We have only found one case of infective endocarditis caused by the genus Brevibacterium in the literature, specifically by B. otitidis.¹¹ The patient was a 68-year-old woman with a prosthetic valve indicated for rheumatic valvular heart disease with no other history of interest. The patient was treated with vancomycin for six weeks (with gentamicin for the first two) and afterwards, arbitrarily, as recognised by the authors, with continuous oral azithromycin (250 mg/day) with a good response after one year of follow-up. In our case, initially the treatment was maintained for 4 weeks, probably due to the lack of data from the literature and the early negative cultures. It may be that one of the reasons our interventions failed was the short duration of the antibiotic treatment, assuming that it was a vegetation and therefore a large amount of inoculum which would have been difficult to remove without surgery.

Or perhaps thinking that it was an non-aggressive germ meaning combination therapy was not required, as initiated afterwards during the relapse after observing that resistance to levofloxacin had increased.

We should also keep in mind that the levels we typically use with vancomycin as a guide in clinical practice may not be the optimal levels for B. casei.

Bacteria such as B. casei, to date understood to be a saprophyte of the skin, have gone from being innocuous microorganisms to potential pathogens, mainly being reported as the causative agents of infection in immunocompromised subjects. The presented case is an advanced-stage cirrhotic patient who developed a rare complication, native-valve infective endocarditis, treated for four weeks, and who relapsed with a fatal outcome.