A mouse model displays host and bacterial strain differences in Aerococcus urinae urinary tract infection

ABSTRACT In recent years, the clinical significance of Aerococcus urinae has been increasingly recognized. A. urinae has been implicated in cases of urinary tract infection (UTI; acute cystitis and pyelonephritis) in both male and female patients, ranging from children to older adults. Aerococcus urinae can also be invasive, causing urosepsis, endocarditis, and musculoskeletal infections. Mechanisms of pathogenesis in A. urinae infections are poorly understood, largely due to the lack of an animal model system. In response to this gap, we developed a model of A. urinae urinary tract infection in mice. We compared A. urinae UTI in female C3H/HeN and C57BL/6 mice and compared four clinical isolates of A. urinae isolated from patients with UTI, urgency urinary incontinence, and overactive bladder. Our data demonstrate that host genetic background modulates A. urinae UTI. Female C57BL/6 female mice rapidly cleared the infection. Female C3H/HeN mice, which have inherent vesicoureteral reflux that flushes urine from the bladder up into the kidneys, were susceptible to prolonged bacteriuria. This result is consistent with the fact that A. urinae infections most frequently occur in patients with underlying urinary tract abnormalities or disorders that make them susceptible to bacterial infection. Unlike uropathogens such as E. coli, which cause infection and inflammation both of the bladder and kidneys in C3H/HeN mice, A. urinae displayed tropism for the kidney, persisting in kidney tissue even after clearance of bacteria from the bladder. Aerococcus urinae strains from different genetic clades displayed varying propensities to cause persistent kidney infection. Aerococcus urinae infected kidneys displayed histological inflammation, neutrophil recruitment and increased pro-inflammatory cytokines. These results set the stage for future research that interrogates host-pathogen interactions between A. urinae and the urinary tract.

Validation of a Gradient Diffusion Method (Etest®) for Antimicrobial Susceptibility Testing of Aerococcus urinae to Fluoroquinolones

Aerococcus urinae is a urinary pathogen with well-described resistance to fluoroquinolones. This study aimed to validate the gradient diffusion (GD) method (Etest®) on cation-adjusted Mueller-Hinton agar with 5% sheep blood for Aerococcus urinae antimicrobial susceptibility testing (AST) to ciprofloxacin and levofloxacin and compare it to the broth microdilution (BMD) method from CLSI M45-A3. Agar dilution (AD), as recommended by EUCAST, was used as an alternate reference method to arbitrate discrepancies or address technical issues. Aerococcus urinae isolates from urinary specimens were prospectively collected between June 2016 and December 2017 from six Quebec hospitals (Canada) and identifications were confirmed using Vitek MS® with IVD 3.0 database. Of the 207 isolates tested using BMD, 37 (17.9%) showed trailing and 19 (9.2%) showed insufficient growth and were tested using AD. Also, 38 isolates (18.4%) for ciprofloxacin and 13 isolates (6.3%) for levofloxacin showed a lack of essential or categorical agreement between Etest® and BMD and were also tested by AD. Using a combined reference method (BMD or AD), susceptibility rate of Aerococcus urinae was 82.6% and 81.6% for ciprofloxacin and levofloxacin, respectively. Categorial agreement between GD and the combined reference methods was 95.2% for ciprofloxacin and 97.1% for levofloxacin, with no very major error identified. Major and minor error rates were 0.6% and 4.3% for ciprofloxacin, and 1.2% and 1.9% for levofloxacin, respectively. Overall, AST using Etest® on sheep blood agar showed a good agreement with reference methods and can be considered by clinical laboratories wishing to perform AST on Aerococcus urinae isolates.

Aerococcus urinae causing Infective endocarditis in a patient with Down’s syndrome with ventricular septal defect

Aerococcus urinae is rare in infective endocarditis. The best known risk factors are urogenital comorbidities. We report the case of a 46-year-old male with Down’s syndrom with infective endocarditis. The patient underwent successful treatment with amoxicillin and heart surgery with valve replacement.He had an unknown ventricular septal defect

Actinotignum schaalii and Aerococcus urinae as Etiology of Infected Kidney Cyst: A Diagnostic Challenge

The case presented here illustrates a sometimes complex disease presentation where interdisciplinary teamwork is essential. A 74-years-old woman with stable chronic obstructive pulmonary lung disease and a composite graft aortic valve implant was admitted to hospital with an episode of acute lower back pain combined with long-term fever. The final diagnoses of a left-sided, infected and radiologically evident kidney cyst caused by the urinary tract pathogens Actinotignum schaalii and Aerococcus urinae was established by the use of partial 16S/18S rRNA gene sequence analysis on kidney cyst drainage material taken after four weeks of relevant antibiotic therapy.

The clinical relevance of pathogen Aerococcus urinae identification by MALDI-TOF mass spectrometry: a case of sepsis in 86-year-old Caucasian male

The infrequency of urinary tract and blood stream infections caused by Aerococcus urinae is most probably due to the difficulties in the identification of this bacterium using standard microbiological methods. With the introduction of more sensitive and accurate techniques in clinical microbiology, such as genetic approaches and Matrix-Assisted Laser Desorption/Ionization-Time Of Flight (MALDI-TOF) mass spectrometry (MS), the incidence of infections due to A. urinae increased. Herein, we described a case of urinary tract and bloodstream infection caused by A. urinae, which occurred in an 86-year-old Caucasian man with a previous history of prostate cancer. The identification of A. urinae was performed by MALDI-TOF MS, since this microorganism cannot be identified by biochemical reactions. In this report, we highlight the need to consider MALDI-TOF MS as technique of choice for A. urinae identification in the presence of subjects with predisposing factors, such as old age, male gender, and genitourinary tract pathologies.