Native Aortic Valve Endocarditis Caused by Rothia mucilaginosa, Initially Misidentified as Neisseria sicca

Introduction

Rothia spp. are gram-positive, cocci-shaped bacteria found in the oropharynx and respiratory tract that only recently became recognized as an opportunistic pathogen in humans [1]. Reports of Rothia infections are rare and mostly involve benign oral and dental infections. Serious infections such as endocarditis and meningitis are very uncommon and occur primarily in immunocompromised hosts [2]. In cases of Rothia causing endocarditis, the organism often affects prosthetic valves and rarely native ones. A complication seen in Rothia spp. endocarditis cases is septic emboli [1]. Prompt administration of broad-spectrum antimicrobial therapy is recommended as soon as endocarditis is suspected. Once blood cultures and sensitivities are definitive, medication regimens can be tailored to those results. We report a case of native aortic valve endocarditis caused by R. mucilaginosa, initially misidentified as Neisseria sicca, in an immunocompromised middle-aged patient.

Case Report

A 54-year-old man with histories of hemochromatosis, type 2 diabetes mellitus, hypertension, alcohol abuse, and smokeless tobacco use presented to the Emergency Department with a 7-day history of fever, intermittent cough, headache, and a new systolic murmur. He was previously seen at 2 urgent care centers where he had negative influenza, streptococcus, coronavirus, and urine tests done. He took a 3-day course of amoxicillin-clavulanate without improvement. Imaging at our facility consisted of computed tomography (CT) of the brain and CT chest, abdomen, and pelvis, both of which were negative. Notably, the CT scan showed gallbladder thickening, and given that the patient was found to have right upper-quadrant abdominal pain, there was concern for acute cholecystitis. He received intravenous ceftriaxone and metronidazole before cholecystitis was ruled out by a hepatobiliary iminodiacetic acid scan. Blood cultures initially were thought to grow gram-positive cocci in clusters, so the antibiotics were changed to intravenous vancomycin and cefazolin. However, blood cultures from the same sample were repeated and identified as Neisseria sicca. He was subsequently placed on intravenous cefazolin and gentamicin. Transesophageal echocardiogram (on day 6 of admission) revealed a mobile 0.8×0.8-cm vegetation on the left coronary cusp of the aortic valve (Figure 1). Of note, the patient was receiving daily prophylactic enoxaparin but refused doses on days 5 and 7 of admission. Given the positive blood cultures and echocardiogram findings, he was diagnosed with subacute infective endocarditis using the Duke criteria. He was eventually discharged with the plan to complete 6 weeks of intravenous ceftriaxone at home through a peripherally inserted central catheter.

One day after discharge and on day 8 after initial symptom presentation, he presented to another facility with a new fever (temperature 39.2°C) and fatigue. A chest X-ray (CXR) revealed pneumonia, most likely hospital-acquired (Figure 2). He received piperacillin-tazobactam and doxycycline. During this time, the outside facility re-identified the causative organism of the initial blood isolates as Rothia mucilaginosa. There was no microbiological evidence of any polymicrobial infections. He was continued on ceftriaxone because of the antibiotic’s broad coverage for gram-positive and gram-negative bacteria. While an inpatient, he developed bilateral lower extremity stiffness, pain, and difficulty walking. He subsequently had a magnetic resonance imaging (MRI) scan of the brain with and without contrast, which revealed a small, 1.1-cm focus of intraparenchymal hemorrhage involving the left thalamus and 2 small bland embolic infracts measuring up to 0.5-cm involving the right caudate head and right cerebral cortex (Figure 3). Computed tomography angiography (CTA) of the head and neck with and without contrast was obtained and showed a new small hemorrhagic infarction in the right posterior temporal lobe not shown by the previous MRI (Figures 4, 5). He was transferred to a third facility, where he was evaluated by Neurosurgery, who deferred surgical intervention at the time. After completing the course of ceftriaxone, he eventually recovered to baseline.

Discussion

Rothia spp. are rarely the sources of infections, especially bacterial endocarditis. In 2020, a systematic literature review of 4,465 published cases of Rothia spp. infections found 51 cases of Rothia infective endocarditis described since 1978 [1]. From these cases, 13 were caused by R. mucilaginosa (26%), of which 9 involved pre-existing valvular disease and 3 had immunodeficiency [1]. One case was associated with orodental abnormalities [1]. R. mucilaginosa comprises 74% of Rothia species in saliva [3]. Therefore, dental portal entry from poor oral hygiene could be a route of disease transmission and explain how our patient developed R. mucilaginosa endocarditis. We postulate that our immunocompromised patient’s daily smokeless tobacco use was the potential infectious source. The use of smokeless tobacco could have contributed to broken barriers in the oral mucosa, thus increasing his susceptibility to serious diseases such as endocarditis.

Infective endocarditis can have subacute onset of symptoms. Our patient initially presented with nonspecific concerns that gradually progressed. He did not have any classic presentations of endocarditis such as subungual hemorrhages, Janeway lesions, Osler nodes, or Roth spots. He did, however, have a systolic murmur not heard on prior exams. He was diagnosed with R. mucilaginosa infective endocarditis based on positive blood cultures and transesophageal echocardiogram, which fulfilled 2 major Duke criteria. Rothia spp. are considered microorganisms that occasionally or rarely causes infective endocarditis, and isolating nontypical organisms from 3 or more blood culture sets satisfies the major microbiological criterion [4].

The patient’s blood cultures collected at his initial presentation revealed N. sicca, which are gram-negative, diplococci organisms, on day 4 of admission. However, new cultures completed 8 days after symptom onset using the same blood sample showed gram-positive R. mucilaginosa, which also appear as cocci. The repeat cultures, which used the blood sample from day 1 of admission, grew only R. mucilaginosa and not any other species such as N. sicca. Therefore, we believe he was misdiagnosed with N. sicca as opposed to having 2 distinct infections.

In most cases, empiric antibiotic therapy for Rothia spp. involves a beta-lactam antibiotic combined with either an aminoglycoside (42%) or vancomycin (25%) [1]. Often, after susceptibility testing results, treatment consists of a beta-lactam antibiotic alone (39%) for an average of 6 weeks [1]. Our patient initially received a cephalosporin and an aminoglycoside because N. sicca was thought to be the source of infection at the time, and previous reported cases were treated as such [5,6]. Since he became asymptomatic during his first hospital stay, he was discharged on intravenous ceftriaxone. He remained on ceftriaxone even after the organism was re-identified as R. mucilaginosa because a beta-lactam antibiotic alone has been the most frequently used after antimicrobial susceptibility testing results.

Systemic complications (eg, neurologic, cardiac and endovascular, extracerebral embolic) of Rothia spp. infective endocarditis occurred in 57% of reported cases [1]. For R. mucilaginosa endocarditis, 15% of cases had neurological complications (n=2) [1]. Interestingly, our patient did not develop focal neurological deficits and remained largely asymptomatic despite having several septic emboli noted on imaging.

Conclusions

Our report demonstrates that atypical organisms can cause infective endocarditis in immunocompromised patients without the typical risk factors associated with the disease, such as history of valvular disease. This case also highlights the importance of acknowledging and responding appropriately to a misdiagnosis by following treatment guidelines.