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              <p>Lactobacillus delbrueckii has been considered a very rare cause of human urinary tract infections (UTIs). However, little is known about its clinical significance and antimicrobial susceptibility, and genomic data from clinical isolates are lacking. This study aimed at analyzing clinical, microbiological, and genomic data of L. delbrueckii urinary isolates. All L. delbrueckii isolates collected from patients hospitalized in a French university hospital from 2014 to 2016 were included. Clinical and biological data were gathered. Species identification was performed by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry, and MICs were determined using the broth microdilution method. Whole genome sequencing (WGS) was conducted (Illumina MiSeq 2 x 300 bp), and genomes were compared using three approaches (multilocus sequence typing [MLST], average nucleotide identity [ANI], and core genome single nucleotide polymorphism [SNP]). From 2014 to 2016, 48 isolates of L. delbrueckii were recovered from the urine of 48 patients (mean age = 84 years; sex ratio M/F = 0.04). Nearly half (44%) of patients were diagnosed with a UTI, and all had significant cultures (&amp;gt;= 10(5) CFU/mL) with a positive direct examination in &amp;gt;90% of cases. The majority of isolates were susceptible to most antibiotics (especially beta-lactams), whereas they seemed intrinsically resistant to fosfomycin and metronidazole. Subspecies identification was consistent across the three approaches, showing that most L. delbrueckii isolates belonged to subspecies allosunkii (n = 40; 83%), followed by subspecies lactis (n = 8; 17%). Two isolates were resistant to tetracycline (MIC &amp;gt;16 mg/L) and both harbored the tet(W) gene. This study demonstrates the uropathogenic role of L. delbruekii subspecies allosunkii and lactis, particularly in elderly female patients. IMPORTANCE This largest case series of urinary tract infections (UTIs) caused by Lactobacillus delbrueckii clearly demonstrates the uropathogenic role of this species (especially the subspecies allosunkii) in human UTIs, particularly in elderly female patients and those with underlying comorbidities. This study may change practice in two ways: (i) clinical laboratories, which typically consider lactobacilli from urine samples as contaminants, may need to reassess this practice; (ii) patient care can be improved by prescribing appropriate antibiotics for these underdiagnosed UTIs. L. delbrueckii should be considered an actual pathogen when it is significantly found in the urine of predisposed patients with clinical and/or biological signs of infection. While matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry allows reliable identification of L. delbrueckii, there is also a need for better discrimination between subspecies (especially allosunkii and lactis). Since L. delbrueckii isolates are usually susceptible to many antibiotics, we recommend beta-lactams (especially aminopenicillins) for the treatment of those UTIs.</p>
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