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Prevotella bivia cardiac implantable electronic device related endocarditis

Cases of Gram-negative, anaerobic rod bacteremia and endocarditis have been increasingly recognized in recent years. This increase has been primarily observed in patients at risk for polymicrobial infections, such as those who use injection drugs and patients with diabetes mellitus. Despite a growing incidence, there are few published case reports of cardiac implantable electronic device related endocarditis secondary to Gram negative, anaerobic organisms. We present a unique case of Prevotella bivia cardiac implantable electronic device related endocarditis in a middle-aged woman with no history of injection drug use. This case highlights the increasing incidence of polymicrobial infections and anaerobic endocarditis. Additionally, it demonstrates how Prevotella bivia has the potential to cause native valve infective endocarditis as well as cardiac implantable electronic device related endocarditis.


Introduction
Cardiac implantable electronic device (CIED) related endocarditis is a rare but life-threatening condition that is associated with significant morbidity, prolonged hospitalizations, and high financial costs [1,2]. Unfortunately, the incidence of CIED related infections has increased out of proportion to the rate of pacemaker and implantable cardiac defibrillator (ICD) placements [2][3][4][5]. According to Tarakji et al., the rate of CIED related infections following primary implantation is approximately 0.5%, while the rate of infections following secondary interventions can be as high as 7% [2]. The most common organisms associated with CIED related endocarditis are Staphylococcus genus, most notably Staphylococcus aureus and coagulase-negative Staphylococcus [2,6]. More recently, there has been an increase in Gram-negative, anaerobic rod bacteremia and infective endocarditis [7,8]. According to Brook, infectious endocarditis secondary to anaerobic bacteria accounts for approximately 2-16% of infective endocarditis cases. The growing incidence of Gram-negative, anaerobic rod infective endocarditis has been attributed to a rise in polymicrobial infections, primarily in patients who use injection drugs [7]. Despite this rise, CIED related endocarditis secondary to Gram negative, anaerobic organisms remains rare. We present a unique case of Gram-negative, anaerobic rod tricuspid valve and CIED related endocarditis secondary to Prevotella bivia (P. bivia).

Investigations
A 60-year-old female presented to the emergency department with four-day history of back pain after falling secondary to leg weakness. She denied loss of consciousness, head injury, or any preceding symptoms. She complained of persistent, sharp back pain radiating across her lower back. On further questioning, she reported multiple similar falls due to weakness and feeling as though her legs were giving out. She also noted a recent sore throat, earache, chills, and a mildly productive cough. Her medical history was significant for atrioventricular node dysfunction requiring dual-chamber pacemaker placement, hypercoagulable state with prior pulmonary emboli, type two diabetes mellitus, and hypertension. On initial examination, she appeared ill but in no acute distress. Her blood pressure was 102/51 mm Hg, heart rate 72 beats per minute, temperature 97.2 degrees Fahrenheit, and she was breathing 16 breaths per minute with an oxygen saturation of 100% on room air. Pertinent exam findings included a 2/6 systolic murmur best heard over the lower left sternal border and moderate right lumbar paraspinal tenderness which was reproducible with hip flexion. Dental examination revealed overall poor dentition with multiple dental caries. Relevant laboratory findings included a lactic acid of 2.9 mmol/L (reference range: 0.5-2.2 mmol/L), procalcitonin of > 100 (reference range: 0.00-0.50 ng/mL), platelet count of 57 (reference range: 150-450 K/uL), and a creatinine of 1.44 (reference range: 0.57-1.00 mg/dL). Initial blood cultures demonstrated growth of Gram-positive cocci in chains. Computed tomography (CT) scan of the lumbar spine with contrast demonstrated a small abscess in right psoas muscle. Transthoracic echocardiogram followed by transesophageal echocardiogram demonstrated a mobile echodensity attached to the tricuspid valve and a mobile echodensity on the pacemaker lead in the right ventricle concerning for endocarditis ( Figs. 1-3).

Diagnosis
Her positive blood cultures and echocardiogram findings confirmed infective endocarditis. She was prescribed empiric antimicrobials: vancomycin and cefepime. Cardiology and Infectious Diseases were consulted. Initial blood cultures ultimately grew Streptococcus agalactiae (Group B streptococcus), and antibiotics were de-escalated to ceftriaxone. Following pacemaker extraction and temporary pacing wire placement, the patient became hypotensive and required transfer to the cardiovascular intensive care unit for hemodynamic support with vasopressors. Interestingly, the cultures of her cardiac device as well as her repeat blood cultures demonstrated growth of Gram-negative, anaerobic rods, which were not present on initial blood cultures. Given her acute decompensation in the setting of polymicrobial bacteremia her antibiotics were broadened to meropenem. The Gram-negative rods were later identified as Prevotella bivia.

Treatment
With new findings of P. bivia CIED related endocarditis and her known Streptococcus agalactiae bacteremia, antimicrobial therapy was changed to ertapenem. She underwent placement of a new pacemaker device upon clearance of her P. bivia bacteremia without complications. Her right psoas muscle abscess was evaluated by Interventional Radiology and deemed too small for percutaneous drainage.

Follow-up and outcomes
She was safely discharged home with home health. She completed a 6-week course of intravenous ertapenem and has followed up regularly without complications or adverse events.

Discussion
The diagnosis and management of Gram-negative, anaerobic rod endocarditis is poorly characterized in the literature and has remained a challenge for many healthcare professionals [8,9]. Currently, Bacteroides fragilis is the most common Gram-negative, anaerobic rod causing infective endocarditis [7]. However, as the number of polymicrobial infections increases, so does the diversity of anaerobic organisms causing infective endocarditis. Initial studies demonstrate that patients with anaerobic endocarditis have both higher mortality rates (21-43%) and a higher incidence of thromboembolic events compared to those with aerobic infections [7,10,11]. However, more recent studies argue that patients with nonstaphylococcal CIED-related endocarditis, including Gram-negative, anaerobic rods, have relatively low virulence and mortality rates [12]. These discrepancies in mortality rates may be related to the advancements in antibiotic therapy and the widely accepted early initiation of broad-spectrum antimicrobials. However, additional studies are needed to fully evaluate morality rates and outcomes of patients with nonstaphylococcal CIED-related endocarditis, particularly Gram-negative, anaerobic rods.   Despite the recent increase in polymicrobial bacteremia and infective endocarditis, CIED related endocarditis secondary to nonstaphylococcal species, including Gram negative, anaerobic rods, is quite rare [7]. These organisms are inherently less likely to hematogenously seed or adhere to endothelialized cardiac devices when compared to Gram positive organisms [4]. Multiple risk factors and comorbid conditions, in addition to injection drug use, have been identified as risk factors for nonstaphylococcal CIED-related endocarditis such as hypertension, congestive heart failure, coronary artery disease, diabetes mellitus and liver disease [7,12]. Our patient's history of diabetes mellitus certainly increased her risk for nonstaphylococcal CIED-related endocarditis. Given that our patient had growth of Streptococcus agalactiae on initial blood cultures this case can be considered a polymicrobial infection. However, while Streptococcus agalactiae is considered a co-pathogen with P. bivia and possibly the cause of the patient's native tricuspid valve endocarditis, it was not isolated on the patients CIED cultures. Like P. bivia, Streptococcus agalactiae is a rare cause of endocarditis [13]. While our patient did not use injection drugs, her history of diabetes also placed her at risked for a polymicrobial infection.
P. bivia, a member of the Prevotellaceae family, is characterized as a Gram-negative, obligatory anaerobic bacillus that is primarily found in the female urogenital tract as well as the respiratory and digestive tracts [14,15]. P. bivia is a common cause of urogenital infections such as bacterial vaginosis [14,15]. Less commonly, P. bivia has been found to cause other infections such as osteomyelitis, septic arthritis, and abscesses [16,17]. P. bivia has also been identified as a rare cause of infective endocarditis [17]. According to Brook, patients with head and neck infections, pulmonary infections, diabetes, and a history of drug use are at risk for Prevotella endocarditis. [7] We suspect our patient's bacteremia may have been secondary to her recent upper respiratory tract infection or poor dentition with multiple dental caries. There are very few published case reports of endocarditis secondary to P. bivia. In 1994, Kentos et al. reported a case of P. bivia endocarditis in a 60-year-old man who presented with peripheral emboli, multiple abscesses, and tricuspid valve vegetations [17]. To our knowledge there are no prior published case reports of P. bivia CIED related endocarditis. Our case highlights how P. bivia has the potential to cause both native valve endocarditis, as previously reported in the literature, and hematogenously seed cardiac devices.
More recently, the management and treatment of Gram-negative, anaerobic rod endocarditis has become more complex due to an increasing resistance against several antimicrobials including betalactams and metronidazole [7]. This growing resistance has led to an increase in the use of carbapenems in the treatment of Gram-negative, anaerobic rod endocarditis [18]. Recent reports have described alarming carbapenem resistance in some Prevotella species [18]. Fortunately, our patient responded well to carbapenem therapy and recovered from her P. bivia CIED related endocarditis. Our case demonstrates that although rare, P. bivia is a serious and evolving cause of Gram-negative, anaerobic rod CIED related endocarditis.

CRediT authorship contribution statement
All authors reviewed the literature and helped write the manuscript. Benjamin Fogelson, DO, James Livesay, DO, Michael Rohrer, DO, Megan Edwards, MD, and Jeffrey B. Hirsh, MD performed critical revisions of the article and approved the final version of manuscript.

Data availability
The Authors declare that data supporting the findings of this study are available within the article.