# Brevibacterium Bacteremia in the Setting of Pyogenic Liver Abscess: A Case Report with Accompanying Literature Review

Authors: Sarah Hossain; Afif Hossain; Aldo Barajas-Ochoa; Michael A. Jaker
Journal: Case Reports in Infectious Diseases
 (2021)

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## Abstract

A 71-year-old Pakistani man with poorly controlled type 2 diabetes mellitus presenting with worsening mental status, abdominal pain, and oral intake for the past seven days was found to have pyogenic hepatic abscess with unculturable bacteria and subsequently found to have rareBrevibacterium bacteremia.


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## Body

## 1. Introduction

Brevibacterium is a short coryneform species found in dairy products and known colonizers of the human skin. Early in its life cycle, Brevibacterium exhibits typical features of coryneform bacteria. However, as it matures, it takes on an appearance similar to cocci or coccobacilli [1]. The most common species isolated from humans is Brevibacterium casei [2], which appears as a catalase-positive, non-spore-forming, short, club-shaped rod on gram staining. Most commonly, bacteremia is associated with indwelling intravascular catheters in the immunocompromised [3]. However, there are rare cases leading to meningitis, cholangitis, salpingitis, peritonitis, endocarditis, and osteomyelitis. The treatment of choice for serious infections is vancomycin as the bacteria show some resistance to B-lactams, fluoroquinolones, clindamycin, and macrolide antibiotics [4]. To date, there are only 16 published case reports of Brevibacterium bacteremia [5].


## 2. Case Presentation

A 71-year-old Pakistani man presented to University Hospital in Newark, NJ, in May of 2020 after being brought in by emergency medical services from home for worsening mental status over the last seven days. The patient had a history of triple vessel coronary artery disease after percutaneous coronary intervention and stenting to the acute marginal branch of the right coronary artery in June, 2018, balloon angioplasty to the proximal and middle right coronary artery in 2011, and stenting of the left anterior descending artery in 2011, poorly controlled type 2 diabetes mellitus, hypertension, and hyperlipidemia. According to the patient’s family, he had worsening mental status, decreased oral intake, and worsening abdominal pain over the last week, with a sharp decline over the past two days.At baseline, the patient was able to perform all activities of daily living independently, was able to hold full conversations in English and Urdu, and had no issues with ambulation. He had no other symptoms prior to arrival. Furthermore, the patient was not taking his medications regularly, including insulin. For diabetes, the patient was previously prescribed insulin, metformin, glimepiride, canagliflozin, and sitagliptin. However, it was unclear which of these medications he was indeed taking as he had not been seen outpatient in over 10 years. Of note, the patient had traveled to Pakistan and Dubai within the last year but did not have any sick contacts.In the emergency room, the patient was found to be febrile to 101.8⁰F, tachycardic to 128, normotensive, tachypneic to 20, and saturating 99% on room air. On exam, he was disoriented and confused, speaking incoherently in one-word sentences, had poor dentition with dry mucous membranes, tachycardic, and had diffuse abdominal tenderness to minimal palpation, worse in the right upper quadrant but without rebound or guarding. Admission labs were significant for a leukocytosis of 12, hemoglobin of 8.3 from a baseline of 12 with a mean corpuscular volume of 63.1, sodium of 124, bicarbonate of 18, glucose of 399 but negative acetone, anion gap of 18 with lactic acidosis to 3.5, HbA1c 12.2, procalcitonin 8.16, c-reactive protein 50, negative cardiac enzymes, and normal liver enzymes. Given his altered mental status and severe sepsis, the patient had computed tomography of the abdomen and pelvis with intravenous contrast carried out (Figure1), showing multiple colonic diverticula without diverticulitis and a 6 by 4.6 centimeter rim-enhancing lesion with surrounding satellite lesions, likely representing a liver abscess.Figure 1
Computed tomography of the abdomen and pelvis with intravenous contrast in the transverse section showing rim-enhancing fluid-filled collections in hepatic segments 4A and 4B, 6 cm by 4.6 cm in size in the greatest axial dimensions. There are several smaller, localized satellite lesions. Findings are highly suspicious for a liver abscess.The patient was started on aggressive intravenous fluid resuscitation, morphine for pain control, and intravenous Flagyl (metronidazole) and cefepime for 2 days. Vancomycin was later added to cover forEnterococcus but discontinued after three doses, so no level was checked. COVID-19 testing, interferon-γ release assay, Entamoeba histolytica, and Echinococcus serologies were all negative. During his hospital course, the patient had uncontrollable blood sugars and ultimately required 65 units of Lantus daily, 8 units of lispro with meals, and an additional 20–25 units of coverage daily. Abscess drainage by interventional radiology was performed on admission and then again 6 days later. Two sets of body fluid cultures were sent, which grew Gram-positive cocci in pairs and chains but could not be speciated. Blood cultures eventually speciated Brevibacterium from aerobic bottles twice. Unfortunately, real-time polymerase chain reaction was unable to identify speciation for the causative organism for either set of body fluid cultures or blood cultures. Infectious Disease was consulted, and the patient was switched to ampicillin-sulbactam (Unasyn) 3 g every six hours for a minimum 3-week course with a plan for repeat imaging after 3 weeks of intravenous antibiotics. After a 10-day hospital stay and improvement in his condition, the patient was safely transferred to subacute rehabilitation for continued antibiotic therapy.


## 3. Discussion and Literature Review

To date, there are only 18 publications mentioningBrevibacterium bacteremia, with 16 of those cases published as case reports [5]. The earliest publication, dating back to 1973, involved pediatric patients undergoing carious extraction for moderate to severe dental pathology [6]. Blood cultures were drawn several times pre- and postoperatively, with one of thirty-four patients testing positive for Brevibacterium. In Saudi Arabia, a 2004 study found Brevibacterium bacteremia in four critically ill patients, highlighting its involvement in serious infections in the immunocompromised [7]. From the published case reports, 11 speciated Brevibacterium casei, 1 Brevibacterium epidermidis, 1 Brevibacterium paucivorans, 1 Brevibacterium massiliense, and 2 were not specified. Seven patients had underlying malignancy, two had AIDS, five had chronic medical comorbidities, one had a congenital abnormality of metabolism, and one was not mentioned. 13 patients had some form of indwelling catheter, 2 were not specified, and 1 had no indwelling catheter present. The majority of patients were given broad-spectrum antibiotics, including vancomycin, teicoplanin, aminoglycosides, extended-spectrum beta lactams, and/or fluoroquinolones. 14 patients improved, 6 patients had recurrence, and 2 patients died. See Table 1 for further details.Table 1
Clinical summaries ofBrevibacterium bacteremia case reports.
Author (year)SexAgeBrevibacterium speciesUnderlying conditionClinical courseTreatment regimen (duration)Presence of an indwelling catheterOutcomeMcCaughey and Damani (1991) [8]M40epidermidisZollinger–Ellison SyndromeVomiting, weight loss, recurrent duodenal ulceration, pyloric outflow obstructionErythromycin, TLCa removalYes- indwelling subclavian TLCa for TPNbSurvivedLina et al. (1994) [9]M19Not specifiedLymphoblastic LymphomaFever, retroocular pain; recurrence after 1 monthIV teicoplanin, amikacin for 20 days; teicoplanin x21 days, TLCa removalYes- for chemotherapy; type not specifiedRecurrence; survivedReinert et al. (1995) [10]M25caseiTesticular choriocarcinomaFever, pancytopeniaIV piperacillin, teicoplanin for 10 days; piperacillin, tobramycin for 10 daysYes- TLCa for chemotherapyRecurrence; survivedKaukoranta-Tolvanen et al. (1995) [11]F56caseiNon-Hodgkin lymphomaFever, pancytopenia, CRPc 42 mg/dLNot specifiedYes- TLCa for chemotherapyRecurrence; survivedCastagnola et al. (1997) [12]------caseiNeuroblastomaFever, ANCd>1000 cm3Not specified; TLCa removedYes- Broviac® for chemotherapySurvivedBrazzola et al. (2000) [13]F18caseiAcquired Immunodeficiency Syndrome (AIDS)Fever, dehydrationIV Unasyn, switched to ciprofloxacin for 14 days; TLCa removedYes- Port-A Cath® for PPNeSurvivedOgunc et al. (2002) [14]---60Not specifiedChronic Lymphocytic Leukemia (CLL)Fever following fludarabine chemotherapy, anemiaIV ceftazidime, amikacin; switched to vancomycinNot specifiedSurvivedJanda et al. (2003) [7]M34caseiAcquired Immunodeficiency Syndrome (AIDS)CD4<50, known CMV retinitis, oropharyngeal candidiasis, neutropenic fever, malaiseIV vancomycin for 8 days, ceftazidime (stopped); TLCa removedYes- Hickman® catheter for long-term gancylovir infusionSurvivedBeukinga et al. (2004) [15]F43caseiCrohn’s DiseaseChronic fistulae, total colectomy, fever, WBCf 3300, CRPc 5.8 mg/dLIV vancomycin for 15 days, TLCa remained; IV Unasyn, Merrem, amikacin, TLCa removedYes- Port-A Cath® for PPNeRecurrence (at 5 months); diedBeukinga et al. (2004) [15]M31caseiNot specifiedFever, WBCf 4700, CRPc (-)IV vancomycin for 15 days, TLCa remained; same treatmentYes- Hickman® catheter for hemodialysisRecurrence (at 5 months); survivedUlrich et al. (2006) [3]F62caseiSevere pulmonary hypertensionFlu-like symptoms, productive cough, chills, fever, hypoxemia, CRPc 38 mg/dLIV vancomycin for 10 days, then moxifloxacin for 20 days, TLCa removedYes- TLCa for iloprost infusionSurvivedBal et al. (2015) [16]M6caseiAcute Lymphoblastic Leukemia (ALL), B cell typeHerpes zoster infection, pancytopenia, neutropenic fever, ANCd 387 mm3/uL, CRPc 6.1 mg/dLIV Zosyn, vancomycin for 10 days, TLCa remainedYes- Hickman® catheter for chemotherapySurvivedBonavila Juan et al. (2017) [17]M60caseiChild–Pugh C alcoholic cirrhosis, aortic stenosis; development of aortic valve endocarditis and insufficiency with recurrenceTremor, altered mental status, fever, pustular rash; decompensated cirrhosis, coagulopathy, thrombocytopenia, 1.5 cm aortic valve vegetation seen on TEEg; right arm weakness, septic emboliOral Levaquin for 10 days, then norfloxacin; IV vancomycin for 4 weeks; IV vancomycin for 10 days, daptomycin for 6 daysNot specifiedRecurrence (30 days, 90 days); diedVecten et al. (2017) [18]M4massilienseCongenital methylmelonic acidemiaFever, cough, emesis, left ear discharge, WBCf 9400uL, CRPc (-), oxalic acid 0.020 mmol/LIntra-auricular ofloxacin for 8 daysYes- gastrostomy tube presentSurvivedMagi et al. (2018) [19]F48CaseiBilateral breast cancer requiring mastectomy, chemotherapy, radiation, and salpingoophorectomyFever, myalgia, CRPc 5.97 mg/dLIV teicoplanin for 7 days, linezolid for 7 days, TLCa removedYes- transjugular Port-A-Cath® from prior chemotherapy treatmentSurvivedAsai et al. (2019) [5]F94paucivoransType 2 diabetes mellitus, congestive heart failureFever, decreased oral intake, appetite loss, thrombocytopenia, CRPc (-)IV Merrem, teicoplanin for 14 daysNot presentSurvivedOur CaseM71Unable to speciatePoorly controlled type 2 diabetes mellitus, pyogenic liver abscessAltered mental status, abdominal pain, decreased oral intake, WBCf 12,000, anemia, hyponatremia, hyperglycemia, HbA1c 12.2, acetone (-), CRPc 50 mg/dL, procalcitonin 8.16IV Unasyn for 3 weeks, abscess drainageNot presentSurvivedM = male, F = female;aTLC = triple lumen catheter; bTPN = total parenteral nutrition, cCRP = c-reactive protein, dANC = absolute neutrophil count, ePPN = partial parenteral nutrition, fWBC = white blood cell, gTEE = transesophageal echocardiogram.As mentioned previously,Brevibacterium are nonmotile, non-spore-forming, non-acid-fast, obligate aerobes. They are Gram-positive bacilli in singlets, pairs, or short chains which transform into cocci approximately 48 hours after inoculation. Characteristic features include positivity for lipase, catalase, DNAse, litmus milk, oxidase variability, urease negativity, and reduction of nitrates to nitrites [1]. Though there are various strains, Brevibacterium casei is the most common clinically relevant pathogen [2]. Brevibacterium species are typically innocuous bacteria found in cheeses, poultry, and human skin flora. However, in the immunocompromised and, especially, those with indwelling catheterization [3], they can function as devastating opportunistic pathogens. In addition to the aforementioned bacteremia cases, they rarely can cause brain abscess, meningitis, endocarditis, pericarditis, peritonitis, cholangitis, salpingitis, mastitis, and osteomyelitis. Although vancomycin is used most frequently, ultimately the antibiotic chosen depends on the infection site and severity of infection [4].In this case report, a patient with pyogenic liver abscess was found to have concomitantBrevibacterium bacteremia. To our knowledge, this is the first instance of such a phenomenon and one of the only cases without central-line-associated infection. It is unclear if our patient had bacterial translocation from colonic diverticula leading to hepatic abscess. Another potential source is yogurt and cheese consumed by the patient while abroad in Pakistan and/or Dubai, which is a common delicacy with most meals. Despite very poorly controlled diabetes, the patient showed improvement in his condition after abscess drainage and treatment with intravenous Unasyn.Despite prior notions thatBrevibacterium species pose little to no harm clinically, evolving evidence points towards the contrary. Given the severity of bacteremia cases in the immunosuppressed, Brevibacterium can function as a serious and deadly causative opportunistic agent. Utilization and maintenance of long-term indwelling catheters requires close adherence to sterile technique. Earlier case reports highlight non-specific symptomatology, with an often indolent presentation, which later manifests as florid septicemia. In these cases, prompt initiation of broad-spectrum, empiric antibiotics can be lifesaving but should later be deescalated based on the source of infection and susceptibilities in accordance with proper antibiotic stewardship.


## 4. Conclusions

Brevibacterium infection is an uncommon but potentially fatal cause of bacteremia in the immunocompromised. This risk is increased with prolonged use of indwelling catheters and implanted devices. Infections are often indolent initially but can rapidly escalate if left untreated. Though initial treatment typically includes broad-spectrum antibiotics, treatment can be de-escalated based on the source of infection and susceptibilities with favorable outcomes. Our report hopes to provide further insight into the management of Brevibacterium bacteremia, specifically in the setting of pyogenic liver abscesses, for which there are no documented cases.



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