Abstract
Infective endocarditis (IE) due to Proteus mirabilis is rare. Given that cases of IE complicated with a left ventricular pseudoaneurysm (LVP) caused by P. mirabilis have not been reported thus far, here we report a case of IE complicated with an LVP caused by P. mirabilis. An 83-year-old woman was admitted to our hospital for urinary tract infection, and P. mirabilis was detected in blood cultures. Transesophageal echocardiography and electrocardiogram-gated computed tomography revealed mitral regurgitation and a mass protruding from the mitral annulus on the dorsal side. We made a diagnosis of an LVP due to IE and performed mitral valve replacement and patch plasty of the mitral annulus. Thus, P. mirabilis can cause bloodstream infections and lead to IE, which may result in LVPs.
<Learning objective:Proteus mirabilis commonly causes urinary tract infection in older adults and is also likely to cause bloodstream infections; however, it is rarely known to be the causative agent of infective endocarditis and left ventricular pseudoaneurysms. However, in clinical settings, clinicians should be aware that P. mirabilis can also cause IE with annular extension.>
Keywords: Endocarditis, Proteus mirabilis, Left ventricular pseudoaneurysm, Urinary tract infections, Bloodstream infections
Introduction
Proteus mirabilis has not been documented as a well-known cause of infective endocarditis (IE), although urinary tract infections (UTIs) due to P. mirabilis are common in older adults. Furthermore, IE complicated with a left ventricular pseudoaneurysm (LVP) caused by P. mirabilis has not been previously reported. Herein, we report a case of an LVP secondary to IE caused by P. mirabilis that was successfully managed surgically.
Case report
An 83-year-old woman with a history of hypertension and right total hip arthroplasty was hospitalized for UTI and septic shock 4 months prior to being referred to our hospital. P. mirabilis was detected in both urine and blood cultures. She was treated with intravenous (IV) meropenem 1 g once every 12 hours for 3 days, and IV ceftriaxone 1 g once every 12 hours for 13 days. Her general condition improved, and she was discharged with a slight fever and inflammation as indicated by a C-reactive protein (CRP) level of 3.68 mg/dL. However, 3 months later, she developed a fever and was readmitted to another hospital. This time, P. mirabilis was again detected in the urine culture, but the blood cultures were negative. Four days after admission, she had hypotension and was transferred to our hospital with a diagnosis of sepsis. Her body temperature at admission was 37.9°C and peaked at 39.5°C on the third day after admission. Blood tests on admission showed white blood cell counts of 11,200/μL, a CRP level of 17.6 mg/dL, a procalcitonin level of 6.21 ng/mL, a brain natriuretic peptide level of 466 pg/mL, and an estimated glomerular filtration rate of 31 mL/min/1.73 m2. Blood culture was negative, probably owing to the administration of antibiotics at the previous hospital. She was initially treated with IV ceftriaxone (1 g once every 12 hours); however, the high-grade fever and high CRP levels persisted. Transthoracic echocardiography (TTE) on day 6 revealed severe mitral regurgitation (Fig. 1A), moderate tricuspid regurgitation, and vegetation on the posterior leaflet of her mitral valve. Transesophageal echocardiography (TEE) further revealed a 10-mm mass at the posterior base of the anterior commissure of the mitral valve, a shunt flow from the left ventricle to the left atrium through the mass (Fig. 1B), and features indicative of a pseudoaneurysm on the dorsal side of the posterior mitral annulus (Fig. 1B). A moderate aortic stenosis was also observed with a valve area of 1.07 cm2. Electrocardiogram (ECG)-gated computed tomography (CT), which was performed to determine the exact location of the pseudoaneurysm and its orifice, revealed an irregularly shaped projection continuous with the posterior leaflet of the mitral valve toward the dorsal side of the heart (Fig. 2A, B, C). She fulfilled the modified Duke criteria for possible IE (evidence of endocardial involvement and temperature >38°C). Based on the above findings, we made a diagnosis of IE, severe mitral regurgitation, moderate aortic stenosis, and LVP. In line with the diagnosis of IE and based on the recommendations by the infection control team at our institution, the antibiotic regimen was changed to IV meropenem 1 g once every 8 hours, and IV daptomycin 450 mg once daily. We also planned to perform urgent surgery.
Fig. 1.
Preoperative transthoracic echocardiography and transesophageal echocardiography. (A) Transthoracic echocardiography shows severe mitral regurgitation. (B) Transesophageal echocardiography shows a 10-mm tumor at the posterior base of the anterior commissure of the mitral valve and a shunt in the tumor causing blood to flow from the left ventricle to the left atrium. The asterisk indicates a pseudoaneurysm.
LA, left atrium; LV, left ventricle; MR, mitral regurgitation.
Fig. 2.
Pre- and postoperative computed tomography (CT). (A) Preoperative axial CT. Left ventricular pseudoaneurysm (LVP) protruding laterally from the annulus of the posterior leaflet of the mitral valve. (B and C) Preoperative three-dimensional CT (3-D CT) showing a left ventricular pseudoaneurysm (LVP) protruding laterally from the left atrium. (D) Postoperative axial CT shows no LVP. (E and F) Postoperative 3-D CT confirming the absence of LVP.
LA, left atrium; LV, left ventricle.
During the surgery, a 1.2-cm vegetation was found on the P1 annulus of the mitral valve. Following excision of the anterior and posterior leaflets of the mitral valve, a 1.5 cm × 1.0 cm fistula was found just below the P1 annulus on the left ventricular side (Fig. 3), and this was considered to be the orifice of the LVP. The orifice was closed using a 2.5 cm × 2.5 cm autologous pericardial patch, and a bioprosthetic valve (25 mm Epic Mitral valve, Abbott, Chicago, IL, USA) was placed. The aortic valve had restricted mobility and was moderately calcified; however, there was no evidence of infection, such as vegetation. A 21-mm bioprosthetic valve (Carpentier-Edwards PERIMOUNT Magna Ease; Edwards Lifesciences, Irvine, CA, USA) was also implanted. The tissue resected during the operation was cultured, and the results were negative. The 16S ribosomal RNA (16S rRNA) gene was also sequenced [1]. The bacterial 16S rRNA gene sequence detected in the tissue was 99.93% (1390/1391 bp) identical to that of the type strain P. mirabilis.
Fig. 3.
Operative findings. Photograph taken after excision of the posterior leaflet of the mitral valve. A fistula is visible just below the P1 annulus of the posterior leaflet.
LA, left atrium; LV, left ventricle.
On the 5th postoperative day, the patient was weaned off the ventilator, and on the 8th postoperative day, she was discharged from the intensive care unit. On the 14th postoperative day, the antibiotic regimen was changed to IV 2 g ceftriaxone once every 12 hours. One month postoperatively, the regimen was changed to oral cefaclor 750 mg once daily, and this was continued for 2 months postoperatively. ECG-gated CT performed on the 90th postoperative day showed no signs of any LVP (Fig. 2D–F), and TTE on the 96th postoperative day showed no perivalvular leakage or residual shunt. On the 115th postoperative day, the patient was discharged; she did not require assistance while feeding or changing clothes and was wheelchair transferable.
Two years after discharge, the patient was still using a wheelchair and regularly visited the outpatient clinic without recurrence of IE or prosthetic valve endocarditis. The patient provided informed consent for the publication of this report and all accompanying images. The identity of the patient has been protected.
Discussion
We encountered a rare case of IE caused by P. mirabilis, complicated with an LVP that was successfully treated surgically.
P. mirabilis is a Gram-negative rod-shaped bacterium, belonging to the family Enterobacteriaceae. It causes UTIs, particularly in patients with urethral catheters in clinical settings [2]. UTIs caused by Proteus spp. bacteria are often severe; furthermore, recurrence, sequelae, and pyelonephritis have also been reported [3]. Since P. mirabilis can form biofilms easily and rapidly [4], it can likely cause bacteremia. Kwiecińska-Piróg et al. reported that P. mirabilis was isolated from 2.5% of all bloodstream infections, and among the Enterobacterales, P. mirabilis is the fourth most common Gram-negative bacterial species after Escherichia coli, Klebsiella pneumoniae, and Enterobacter spp. [5]. According to the same report, the mortality rate for bacteremia due to P. mirabilis was 28.9% [5]. According to the first systematic review of IE caused by Proteus species, only 16 cases had been identified since 1950, including 5 surgical intervention cases, and their overall mortality was as high as 43.8% (7 out of 16 cases) [4].
In their study, Graupner et al. reported that 78 (37%) of 211 patients with IE had annular extension, with an overall mortality rate of 35.9% [6], and identified aortic infection, prosthetic endocarditis, new atrioventricular block, and coagulase-negative staphylococci as independent risk factors for periannular complications. In our case, none of these risk factors was present. In addition, the patient did not use any immunosuppressants or steroids. However, the patient developed LVP, which was thought to be a sequela of a sealed rupture of a paravalvular abscess. Another case of prosthetic valve endocarditis due to P. mirabilis with aortic ring abscess and aorto-atrial fistula has also been reported [7]. Thus, P. mirabilis might be another risk factor of periannular complications in patients with IE.
Accurate and timely diagnosis is essential to effectively manage IE and its complications, such as valvular abscess and pseudoaneurysms. As TTE can be performed quickly and easily, it is an essential diagnostic modality. At the first hospitalization, a heart murmur was not detected by chest auscultation, and TTE was performed at the bedside of the emergency room. Older adults with persistent bacteremia and potentially weakened immunity are susceptible to IE; therefore, TEE should be performed promptly as a first-line screening measure, while paying attention to complications such as valve perforation and annulus abscess. Furthermore, ECG-gated cardiac CT is an effective modality for diagnosing an LVP and its orifice, as well as for evaluating coronary artery disease and the great vessels; it is also recommended in the latest Japanese guidelines for the prevention and treatment of IE (JCS 2017) [8].
In this case, P. mirabilis was identified from the surgical specimen by 16S rRNA sequencing. It is critical that the surgical sample, the preoperative urine sample, and the blood sample show similar findings of P. mirabilis. Ideally, 16S rRNA sequencing should be performed using both blood and urine samples for comparison, but this could not be performed in this case. However, it is reasonable to consider that the strains from the first blood and urine cultures and the second urine culture were the same given the findings of drug susceptibility tests, which showed intermediate susceptibility to imipenem and resistance to minocycline. Therefore, it is reasonable to assume that the same strain of P. mirabilis persisted to ultimately cause IE in our case.
Although our patient was determined to have possible IE based on the modified Duke criteria, we believe that she would have fulfilled the criteria for definite IE after surgery had DNA sequencing been included in the diagnostic criteria. DNA sequencing may be included in the diagnostic criteria for IE in the future.
In conclusion, we encountered a rare case of IE complicated with LVP caused by P. mirabilis. In clinical settings, we must be aware that P. mirabilis, a common causative agent of UTIs and bloodstream infections, can also cause IE with annular extension.
Declaration of Competing Interest
The authors declare that there is no conflict of interest.
Acknowledgments
We would like to thank Dr Risako Kakuta at the Department of Otolaryngology-Head and Neck Surgery, Tohoku University Graduate School of Medicine, and the echocardiographers at the Physiological Laboratory at Tohoku Medical and Pharmaceutical University Hospital.
Consent for publication: The patient provided informed consent for the publication of this report and any accompanying images. The identity of the patient has been protected.
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