Case Report: A rare case of prosthetic valve infective endocarditis caused by Aerococcus urinae

Infective endocarditis (IE) is a serious and life-threatening cardiac condition, most commonly caused by staphylococci, Streptococcus viridans, and enterococci. However, in special settings, IE can be caused by rare organisms. Here we present a case of IE caused by Aerococcus urinae in a 75-year-old man with a bioprosthetic aortic valve. Aerococcus urinae is a gram-positive, catalase-negative microorganism and is usually an isolate of complicated urinary tract infections in the elderly male population. Improvements in diagnostic testing including use of matrix-assisted laser desorption ionization– a time of flight mass spectrometry (MALDI-TOF MS) have played an important role in recognition of Aerococcus urinae.


Case report
A 75-year-old Caucasian man presented to his local hospital with malaise, fever, and nausea for five days. He had a bio prosthetic aortic valve replacement for mixed aortic valve disease 12 years ago; further significant past medical history included placement of a permanent pacemaker for complete heart block, right total hip replacement, hypertension and benign prostatic hyperplasia (BPH). The patient had no history of smoking, alcohol consumption or illicit drug use. The patient had no recent surgeries or dental work, and the review of systems was unremarkable. The physical exam revealed vital parameters of HR 97 bpm regular, BP 134/87, the temperature of 101.5°F, respiratory rate of 18 per minute and oxygen saturation of 96% on room air. On precordial auscultation, a systolic and a diastolic murmur were heard in the aortic area, mild bi-basal crackles, but no jugular venous distention or peripheral edema. The rest of the physical exam was unremarkable. The labs showed a normal white cell count (WCC) of 9.9 × 10 6 /L, elevated C-reactive protein to 214.9 mg/L (normal <5 mg/l) and a hemoglobin of 11.2 g/dl), the other labs were unremarkable. His mid-stream urine showed WCC < 20; red cell count (RCC) of 20-50 and it grew mixed organisms, all considered part of the normal flora. Chest X-ray, CT scan of the brain, thorax, abdomen, and pelvis did not show any source of infection.

Amendments from Version 2
We rephrased the remaining, unclear points, according to Dr. Christensen's feedback. We provided the reference that Aerococcus urinae was first reported in 1967. This also clarified that Aerococcus urinae has been increasingly identified due to advancement in detection and identification techniques. We also stated that partial 16S rRNA gene sequencing analysis would be the most time-efficient method but is not performed frequently due to cost and lack of expertise. Finally, we corrected our text to say that MALD-TOFI has improved recognition, and not isolation as previously stated. Despite prompt initiation of appropriate antibiotic treatment and intensive clinical monitoring, the patient failed to improve this hospitalization and developed sudden pulmonary edema and worsening aortic regurgitation on repeat transthoracic echo and unfortunately died due to rapid deterioration before surgery. As per family's wishes, an autopsy was not performed.

Discussion
Aerococcus urinae is a gram-positive, catalase-negative coccus which grows in clusters. It is mostly associated with urinary tract infections in elderly men, especially in the setting of structural abnormalities, e.g. BPH, urethral strictures and nephrolithiasis. It has been associated with culture-negative infective endocarditis 4 . It is reported to be sensitive to penicillins/cephalosporins and resistant to sulfonamides and aminoglycosides 5 . By now, more than 40 cases of IE caused by Aerococcus urinae have been reported 6 likely due to improvements in diagnostics.
Despite the fact that Aerococcus urinae is rare organism causing infective endocarditis, most cases respond well to antibiotic theray and surgery is often not needed 3 . The indications for surgical intervention for PVE include severe prosthetic dysfunction, severe heart failure, large vegetation, and abscess or peri-valvular involvement 7 .
This case highlights the importance of source control by expediting prosthesis removal in the presence of overt symptoms of worsening cardiac failure and worsening prosthesis dysfunction (regurgitation in this case), as medical therapy alone may not be sufficient to effectively treat Aerococcus urinae IE despite appropriate sensitivities. Early identification is crucial and can be life-saving. The current diagnostic testing for microorganisms -whereas partial 16S rRNA gene sequencing analysis would be the most time-efficient method, it's rarely done, as the expertise is limited and costs are high. Recently, there is good evidence for the use of MALDI-TOF 8,9 due to increased detection rates, even in direct comparison to 16s sequencing.
In conclusion, Aerococcus urinae has been increasingly identified as the cause of infective endocarditis due to advancement in detection and identification methods. Therefore establishing a concise and broadly acknowledged protocol for diagnosis up to patient management is critical.

Consent
Written informed consent for publication of their clinical details was obtained from the patient. Permission was also granted from a next of kin for publication of the manuscript.

Competing interests
No competing interests were disclosed.

Grant information
The author(s) declared that no grants were involved in supporting this work.

2. Introduction
Please rephrase "secondary to Aerococcus urinae" Please give a reference on initial recognition of A. urinae. Is the year 1967 correct? As can be seen in this case can be deleted. Case report Give entity on C-reactive protein Blood-culture system used is missing MALDI-TOF MS details are missing Antibiotic susceptibility testing system used is missing Discussion The main problem… and the rest of the section: Thank you very much for your helpful feedback. We rephrased the suggested points throughout the article. Unfortunately we were not able to assess the points listed in the case report in our patient, however our aim was to underline the need for new techniques (like MALDI-TOF) in order to make the correct diagnosis in a timely manner. A fatal case of IE caused by Aerococcus urinae, in a 75-year-old man with a bioprosthetic aortic valve is presented and discussed. Very precise and covering comments have been given by reviewer 1. Microbiological data should be examined thouroughly and extended. Language correction seems indicated. The following comments can be added.

1) Abstract:
It is always important to also having focus on more rare etiologies of IE. In the abstract it is stated that the mortality rate is high. This is suggested to be modified to: Initial descriptions of collections of IE cases with A. urinae demonstrated a high morbidity and mortality rate, whereas a recent Swedish epidemiological study could not retrieve this. IE. A poor prognosis is claimed in the abstract, introduction and discussion. This claim must urinae be modified based on the findings by Sunnerhagen . et al

A new reference was added to the introduction about favourable outcome to IE caused by Aerococcus urinae
2. A diagnosis of IE is established through the Dukes criteria, I suggest a reference to Li is given . Symptoms and chest X-ray are irrelevant for the diagnostic process. Please modify introduction.

A new reference was added to diagnose IE based on Dukes criteria or their modifications
3. In the case description it is twice stated that the patient has sepsis. Sepsis-3 criteria are not fulfilled. Please rephrase.

The cultures grew
How was the species determination performed? How many A. urinae. cultures? MIC for ampicillin and gentamycin should be given.

MICs for ampicillin and gentamicin added, description added about blood cultures
5. It is claimed that TEE demonstrates a "moderate aortic regurgitation due to a large mobile vegetation". It is important if the regurgitation was paravalvular or through the valves. Maximum size of the vegetation is also crucial since this is important for establishing the indication for operation. Left ventricular function should also be commented on as well as if there were signs of vegetations on the pacemaker cable.

Transesophgeal echo description expanded, commented on LV and pacemaker lead.
6. It is claimed that ampi+genta was commenced according to local guidelines. For which bacterial species are these guidelines meant. The use of aminoglycosides in this condition is controversial .
Hospital guidelines for suspected/possible IE were followed 7. How was "progressive aortic regurgitation verified? Could pacemaker failure have played a role? Repeat transthoracic echo showed worsening of regurgitation; this is added to the case 8. Why was the patient not moved for emergency surgery when he deteriorated? This seem like an avoidable fatality! Deterioration was sudden and rapid, arrangements were made but patient died before the surgery 9. In the discussion it is claimed that there are only 20 reports. This is not true . Cases up until 2015 are summarized in a review .

Updated number of Aerococcus urinae IE reported
10. Surgical intervention is claimed to be common in the discussion with a quote to Wang. Please read and quote Sunnerhagen instead . Surgery is relatively rarely needed.

Reference added to show that surgery in most cases is not indicated
11. "Large persistent vegetation" is claimed as an indication for surgery. Large is enough.

"
The presence of vegetation on the valve created a consistent source of bacteria that could embolize and can serve as a source of sepsis." This statement has nothing to do with the current case and should be omitted.

"
The main problem is current diagnostic testing for microorganisms-whereas 16s sequencing would be the most time-efficient method, it's rarely done, as the expertise is limited and costs… and so on" This is irrelevant for the case since the reason to operate is not dependent on microbiological diagnostics. Irrespective of the causative pathogen this patient would have been saved by timely heart surgery. This is kept; we wish our readers to know that improved methods of isolation are important and could help with management 14. The claim "In conclusion, Aerococcus urinae used to be a rare cause of IE but rates have been increasing significantly within the last 10 years." Lacks support and should be deleted.
has been increasingly REPORTED as a cause of IE but incidence is likely A. urinae unchanged.
This is now added that that increase in reported cases is due to better isolation methods.
15. In discussing Duke criteria in the case presentation one must keep in mind that in 2/2 A. urinae cultures (4/4 bottles) only fulfill Duke criteria if the cultures were taken with 1 3 1 I have read this submission. I believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.
Author Response 13 Feb 2018 , Yale University, USA Carina Dehner 1) Abstract: -It is always important to also having focus on more rare etiologies of IE. In the abstract it is stated that the mortality rate is high. This is suggested to be modified to: Initial descriptions of collections of IE cases with A. urinae demonstrated a high morbidity and mortality rate, whereas a recent Swedish epidemiological study could not retrieve this. New reference to the introduction was added to highlight the better outcome 2) Introduction: -Dukes criteria should be mentioned.

-New references added to mention Duke's criteria or its modifications
-There is not a species named Streptococcus viridans.

·
Recent diagnostic improvements should be included, especially MALDI-TOF mass spectrometry. Added in abstract -a gram-positive, catalase-negative Correction made 3) Case description: Specific description of PM electrode findings should be given.

Included in description, PM lead was not involved.
Microbiological data are very scarce. Blood-culture system and number of positive bottles should be given. Likewise identification criteria and susceptibility methods and results, including MIC values of relevant antibiotics should be given.