A Rare Case of Autopsy Proven Achromobacter xylosoxidans Endocarditis Involving Tricuspid Valve: A Case Report

Infective endocarditis refers to infection of one or more valves of the heart, with Achromobacter xylosoxidans (A. xylosoxidans) being a rare cause. So far, 24 cases of A. xylosoxidans endocarditis were reported, with only one case describing tricuspid valvular involvement. Despite the rarity of A. xylosoxidans endocarditis, it is important for clinicians to be aware of atypical presentation and the high mortality associated with it. We present an autopsy-proven case of tricuspid valve endocarditis in the setting of A. xylosoxidans bacteremia in a 43-year-old female.


Introduction
This article was previously presented as a meeting abstract at the 2022 CHEST Annual Scientific Meeting in October 2022.
Achromobacter xylosoxidans (A. xylosoxidans) is a Gram-negative rod, usually present in aqueous environments, and has high mortality rates. This organism is more commonly associated with nosocomial infections and seldom causes endocarditis. The rarity of this organism and its high resistance pattern limit successful treatment modalities. While there is no current consensus on management, recommendations include a combination of antibiotic therapy and valve replacement surgery [1].

Case Presentation
A 43-year-old African American female with a past medical history significant for lymphedema and recent pulmonary embolism (low risk) on Apixaban presented in septic shock. Blood cultures were obtained on day one of admission to the medical intensive care unit; positive for A. xylosoxidans, which were susceptible to Meropenem, Piperacillin-Tazobactam, and Trimethoprim-Sulfamethoxazole. Imaging did not show any evidence of infection, and the echocardiogram was negative for vegetation. The source potentially responsible for septic shock was her lower extremity wounds. During her hospitalization of 10 days, four subsequent sets of blood cultures remained negative. She received a total of two weeks of Piperacillin-Tazobactam and Vancomycin and was subsequently discharged.
Two months later, the patient was re-admitted for chest pain and altered mental status. On initial presentation, vitals were temperature of 98.4°F, tachycardic at 132 bpm, blood pressure 70/48 mmHg, respiratory rate 25/min, and saturating at 100% on room air. Hypotension persisted even after aggressive fluid resuscitation and she was eventually started on a pressor medication. Significant laboratory data are shown in Table 1. On physical examination, the patient was confused, tachycardic with a regular rhythm, and lung auscultation revealed normal breath sounds. Skin examination showed lower extremity discoloration with healed wounds and pitting edema. Initially, the patient was started on Piperacillin-Tazobactam. Again, blood cultures grew A. xylosoxidans susceptible to Ceftazidime, Meropenem, Piperacillin-Tazobactam, and Trimethoprim-Sulfamethoxazole. Due to suspicion of meningitis, antibiotics were broadened to Meropenem for central nervous system (CNS) penetration. CT scan of the head was normal without any acute intracranial pathology. CT scan of her lower extremity showed diffuse soft tissue inflammation, suggestive of cellulitis. CT chest/abdomen/pelvis was performed to look for other sources of infection, negative except for septic pulmonary emboli. Echocardiography revealed a 13 mm x 9.6 mm echodensity on the anterior leaflet of the tricuspid valve (Video 1), with normal left and right ventricular systolic function without segmental wall motion abnormalities. For suspected tricuspid valve infective endocarditis secondary to A. xylosoxidans, Cardiovascular-Thoracic surgery was consulted. However, the patient was hemodynamically unstable for surgical intervention due to requiring intubation for airway protection, and increasing doses of vasopressor medications for blood pressure support. Despite the above aggressive measures, she remained acidotic, was started on continuous renal replacement therapy, and eventually succumbed to her disease. The source responsible for her bacteremia was still unknown as there were no procedures performed including central line placement. Autopsy showed a 1.0 cm vegetation on the tricuspid valve, bilateral acute pneumonia (right and left lower lobes), multiple septic emboli, and diffuse alveolar damage. Histopathology of the tricuspid valve showed acute inflammation, organized thrombus, and embedded bacterial colonies.

Discussion
Achromobacter xylosoxidans is an aerobic motile, Gram-negative rod that is usually associated with central line infections and seldom causes endocarditis. Literature has shown about 24 cases of infective endocarditis caused by A. xylosoxidans, with rare involvement of the tricuspid valve ( Table 2). Among the cases reported, mortality is high at about 48%, with risk factors being prosthetic devices and impaired immunity .   Common risk factors include the presence of a central venous catheter (CVC) or any indwelling catheter, tunneled hemodialysis catheters, immunocompromised state (cystic fibrosis, malignancy), pre-existing valvular disease, or the presence of a prosthetic device. The mode of transmission can be from contaminated water, contaminated IV contrast, disinfectants, ultrasound gels, poor hygiene among healthcare workers, and poor adherence to infection control protocols [25]. Achromobacter's nature to form biofilms on prosthetic material makes it exceedingly difficult to eradicate completely. Although the source of infection is unclear in our patient; recent hospitalization and contaminated medical equipment could be possibilities.
Although work-up is similar to any typical infective endocarditis including initial evaluation with modified Duke criteria along with blood cultures, electrocardiogram (EKG), transthoracic echocardiography (TTE), transesophageal echocardiography (TEE), the atypical presentations of Achromobacter make it difficult to diagnose despite repetitive imaging and evaluations. A review from 2012 reported the challenges in the diagnosis of Achromobacter endocarditis, which was identified on the 131st day after performing four separate TTEs and TEEs [12]. This highlights the atypical nature and the need for repetitive diagnostic evaluations if suspicion for infective endocarditis is high, as in our patient. Cardiac computed tomography angiography (CTA) and positron emission tomography with computed tomography (PET/CT) are recommended if echocardiographic evaluation is inconclusive [26]. Due to PET-CT being a functional and non-invasive modality, it is helpful in detecting infection prior to valvular structural damage, and in identifying embolic and extra-cardiac sources [27]. FDG PET-CT is usually preferred to radiolabeled white blood cell single-photon emission computed tomography (WBC SPECT), due to later's low sensitivity, time consumption, and increased expertise requirements [28]. However, a negative PET-CT cannot completely rule out the infection, as reported in a review by Tokuyasu et al. [12]. Additional imaging studies include CXR, CT chest, and CT/MRI head to rule out septic emboli.
Achromobacter is usually susceptible to antipseudomonal penicillins and Carbapenems. Studies have shown increasing resistance to bactrim and aminoglycosides [29]. Due to extensive drug resistance patterns, various regimens have been used; however, evidence on optimal regimens is still lacking [30]. In 2015, Abbott and Peleg recommended various monotherapies in comparison to combination therapies. This study also recommended the use of aminoglycosides like Gentamicin along with bactrim for a synergistic effect despite the prevalence of resistance [31]. Also, a review in 2018 described the rapid development of carbapenemase resistance due to a prolonged course of Meropenem, which led to poor outcomes [5]. A recent report in 2022 has successfully treated Achromobacter endocarditis using a Cefiderocol combination regimen [2]. In this study, the initial therapy used was a combination of Meropenem, Fosfomycin, and Trimethoprim-Sulfamethoxazole; however, due to persistent symptoms Meropenem was replaced with Cefiderocol. A significant increase in bactericidal activity was observed after this addition, which is due to Cefiderocol's activity against biofilm-forming pathogens.
Although there is no specific consensus on the duration of treatment, most cases reported a minimum duration of 6 weeks of treatment with close follow-ups. Despite this, there are reports of treatment failures leading to recurrent admissions and death [1]. Literature has also shown that treatment employing both antibiotics and surgical intervention demonstrated a decrease in mortality when compared to antibiotics alone, reinforcing the importance of early surgical consultation for interventions [1,5]. Catheter removal is recommended if CVC biofilms are the suspected source.

Conclusions
In summary, we presented a diagnostically challenging patient presenting with A. xylosoxidans endocarditis diagnosed after repetitive imaging and proven by autopsy. This case highlights the atypical presentation of patients with A. xylosoxidans bacteremia, especially endocarditis, and stresses the importance of a high suspicion in such cases. Knowledge about successful treatment of A. xylosoxidans is scarce, and more research is warranted for better management in the future.

Additional Information Disclosures
Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.