A Rare Case of Brevibacterium luteolum Bacteremia in a Patient With Acute Promyelocytic Leukemia

Abstract

The Brevibacterium genus is a group of nonmotile, catalase-positive, and aerobic bacteria that form part of the skin flora. Brevibacterium species are an emerging opportunistic bacteria with an unknown pathogenic potential; hence, further research is needed. Most Brevibacterium bacteremia cases have been treated successfully with vancomycin, but there is still no consensus on the duration of treatment or the removal of the infected hardware. We describe a unique case of Brevibacterium luteolum bacteremia in a geriatric male patient undergoing chemotherapy for acute promyelocytic leukemia.

Introduction

The Brevibacterium genus is a nonacid-fast, obligate aerobe, and Gram-positive coccobacilli. ¹ They are often seen in raw milk (contributing to its color and scent) and surface-ripened cheese. However, this catalase-positive microorganism can also be found in the skin microflora, genital hair, and otorrhea.^2,3 There have been 20 reported cases of Brevibacterium species (spp.)-associated infections since 1969, 14 of which resulted in bacteremia, and 10 out of 14 had an indwelling catheter (central venous catheter or port) as a nidus of infection.^2,4 Most of these patients were immunocompromised due to cancer, cancer-directed therapy, organ transplantation, or HIV/AIDS. ² Intravenous vancomycin provides empiric coverage for Brevibacterium spp.-associated infections and coverage can be prolonged once a diagnosis is confirmed.^5,6 This case adds to the limited literature on Brevibacterium spp. catheter-associated bloodstream infections. Herein, we present a rare case of port-a-cath-related bacteremia caused by Brevibacterium luteolum in a male patient with chronic hepatitis C, HIV disease, and acute promyelocytic leukemia (APML). This is the third case of B. luteolum bacteremia reported in the English literature. ⁴

Case Summary

A 68-year-old male with a medical history of polysubstance use disorder, chronic hepatitis C on sofosbuvir/velpatasvir, compensated cirrhosis, HIV disease (CD4 count 1027, viral load <20), and APML treated with all-trans retinoic acid and arsenic trioxide presented to the emergency department (ED) from an infusion center for high fever and chills. Per the nurse at the infusion center, the patient came in shivering, and a sublingual temperature check revealed a fever of 38.6 °C. The patient was then sent to the ED for evaluation.

In the ED, the patient’s mentation was intact, and he was conversant. He reported a 2-day history of subjective fever, chills, and numbness in the fingertips. He denied starting new medications or recent international travel. He also denied nausea, vomiting, headache, acute vision changes, cough, shortness of breath, chest pain, abdominal pain, diarrhea, dysuria, polyuria, urinary frequency, or tenderness over the right-tunneled central venous catheter. The vital signs were significant for elevated blood pressure (197/103 mmHg) and a fever of 102.92 °F. On examination, the patient appeared diaphoretic but in no acute distress. There was no tenderness, erythema, edema, or discharge at the port-a-cath site. The rest of the exam was unremarkable. Triage blood tests were notable for leukocytosis (11.1 × 10³/mm³) and hyperglycemia (174 mg/dL). The rest of the blood test results were within normal ranges. We ordered a sepsis workup, including a multiplex polymerase chain reaction-based pneumonia and viral respiratory panel, urinalysis, urine culture, (1,3)-beta-D-glucan, and procalcitonin. We also sent blood cultures from the peripheral line and port-a-cath site.

As part of the sepsis bundle, the patient received doses of intravenous vancomycin and piperacillin-tazobactam in the ED. On admission, antimicrobial therapy was adjusted to intravenous vancomycin 1250 mg every 12 hours, cefepime 2 g every 8 hours, and intravenous metronidazole 500 mg every 8 hours to lower risk of kidney injury and gut dysbiosis. One of 2 blood cultures drawn from the central venous catheter grew B. luteolum, and the antibiotics were narrowed to intravenous vancomycin monotherapy. The peripheral blood culture set remained negative. In total, the patient completed 5 days of cefepime and metronidazole therapy. Starting on the day of negative blood cultures, vancomycin monotherapy was extended over 10 days to ensure bacterial clearance and the port-a-cath was removed. Although only 1 bottle grew B. luteolum and the catheter tip was negative, the patient’s systemic signs and symptoms, growth from catheter-drawn blood culture, and response to treatment were suggestive of an acute infection. The lack of an alternative source of bloodstream infection makes central line-associated bloodstream infection more plausible. The patient was diagnosed with probable B. luteolum bacteremia and treated accordingly. The repeat blood cultures and surveillance cultures at the end of vancomycin therapy returned negative.

Contrast-enhanced computerized tomography of the chest, abdomen, and pelvis showed a right-sided port-a-cath with no evidence of an abscess at the port level or along the catheter tract. Transthoracic echocardiography showed a normal left ventricular ejection fraction of 60% to 65% and no vegetations or valvulopathy. Bone marrow aspiration/biopsy showed that the patient was in molecular remission. Two months after discharge, the patient was seen in the infectious disease clinic, and he remained afebrile and without complications.

Discussion

Brevibacterium spp. are nonspore-forming, aerobic, catalase-positive, nonmotile, Gram-positive rods with pathogenic potential.^7,8 Brevibacterium have an irregular morphology and form yellow to gray-white colonies. ⁷ They are also nonhemolytic and can withstand a hypertonic salt medium. ⁷ The genus Brevibacterium has 50 different species, but only 9 (Brevibacterium casei, Brevibacterium massiliense, Brevibacterium sanguinis, Brevibacterium paucivorans, Brevibacterium otitis, Brevibacterium mcbrellneri, Brevibacterium iodinum, Brevibacterium epidermis, and Brevibacterium linens) are known to colonize human tissues.^1,4 B. casei is the most isolated species in clinical samples^1,7 and likely the most pathogenic. Brevibacterium spp. are commensal bacteria that can also be found in milk and milk products, ⁸ enhancing the color and aroma of surface-ripened cheeses. ⁹ This is the third case of B. luteolum bacteremia/infection reported in the literature (Table 1). ⁴

Table 1.

A Summary of Brevibacterium luteolum Bacteremia Cases Reported in the English Literature.

Author(s)	Age/sex	Year	Pathogen	Comorbidities	Treatment	Outcome
Barton et al 10	67/M	2017	B. luteolum	Unknown	Cefazolin and metronidazole	Successfully treated
Munshi et al 4	64/M	2022	B. luteolum	Type 2 diabetes mellitus, hypothyroidism, nephrolithiasis, pancreatic cancer (recently completed chemotherapy)	Vancomycin 14-day course	Successfully treated
Our case	68/M	2024	B. luteolum	Chronic hepatitis C, cirrhosis, HIV disease, acute promyelocytic leukemia (on chemotherapy)	Vancomycin 10-day course	Successfully treated

In 1969, Fleurette described the first case of postsurgical meningitis and persistent fever due to B. fermentans. ⁷ Since then, several Brevibacterium-associated bloodstream infections have been reported. We present a case of port-a-cath-related bacteremia caused by B. luteolum in a male patient with chronic hepatitis C, HIV disease, and APML. Barton et al ¹⁰ were the first to report a case of B. luteolum bacteremia in 2017 in a patient with calcaneal fracture. Four years later, Munshi et al ⁴ described the second case of B. luteolum bacteremia in a patient with pancreatic cancer (Table 1). ⁴

Brevibacterium spp. colonize the skin and mucous membranes and are often seen as contaminants in clinical specimens.^1,8 To date, few cases of Brevibacterium spp.-associated endocarditis, meningitis, cholangitis, and bloodstream infections have been reported, especially in immunocompromised patients.^1,11 Brevibacterium spp. form biofilms, ¹¹ which may explain their affinity for catheters and other medical devices. Implanted devices such as prosthetic valves, peritoneal dialysis catheters, and port-a-cath serve as nidus for the bacteria, ¹ predisposing patients to bloodstream infections. A study at the Mayo Clinic from 2014 through 2019 isolated Brevibacterium spp. from 48 patients admitted to the institution. ¹² A third of the patients were found to have some form of cancer; 15% were recipients of stem cell or solid organ donation, whereas 20% had received chemotherapy in the past month. ¹²

Due to its rarity, there is a paucity of data on Brevibacterium spp.-associated catheter-associated bloodstream infections. Intravenous vancomycin is often used for empiric Gram-positive coverage; however, there is no consensus regarding catheter removal to prevent reinfection. ¹¹ Munshi et al ⁴ reported a case of B. luteolum bacteremia that was successfully treated with a 14-day course of intravenous vancomycin. ⁴ Similarly, our patient completed a 10-day course of intravenous vancomycin and was asymptomatic at discharge. In cases where the implanted hardware cannot be removed, a combination of intravenous antibiotics and an antibiotic lock have proven equally effective.^4,8

Conclusion

Herein, we describe a unique case of B. luteolum bacteremia in a geriatric male patient on chemotherapy for APML. The patient was successfully treated with a 10-day course of intravenous vancomycin, and the port-a-cath removed due to an active infection. B. luteolum is a commensal bacterium with pathogenic potential in immunocompromised patients. Clinicians must be aware of this pathogen as prompt treatment can avert further complications.