Lactobacillus Delbrueckii Urinary Tract Infection in a Male Patient: A Case Report

Abstract

Introduction: Lactobacilli are Gram-positive rods, commensals of the normal human flora. Generally, these lactic acid-producing bacteria are considered contaminants, however over the last years their clinical relevance is reevaluated. Lactobacillus delbrueckii is very rarely isolated and only a few cases of L. delbrueckii urinary tract infections (UTIs) have been reported, mainly in females. Case report: We report the case of a L. delbrueckii UTI in an 82-year-old male suffering from benign prostate hyperplasia with repeated episodes of acute urinary retention over the last month before presenting to our hospital. The catheter urine culture grew >10⁵ CFUs/mL of pure L. delbrueckii on Columbia CNA blood agar and on Trypticase soy agar. Identification was achieved by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS), using VITEK MS (bioMérieux, France). The patient was successfully treated with cefixime for ten days. A follow-up urine culture performed 7 days after antibiotic discontinuation was sterile. Conclusions: To our knowledge the present is the second case of L. delbrueckii urinary tract infection in a male patient. Further cases are required to confirm the clinical significance of these unusual pathogens and their involvement in human urinary tract infections.

Introduction

Lactobacilli are facultatively anaerobic, Gram-positive, non-spore forming rods, part of the commensal flora of the vagina, oropharynx and digestive tract. They are essential components of probiotics and can be found in fermented food products such as yogurt. Generally these lactic acid-producing bacteria are considered contaminants, however over the last years their clinical relevance is reevaluated and some species have been associated with bacteremia, endocarditis, meningitis, peritonitis, empyema, and urinary tract infections (UTIs) [1,2,3,4,5]. Lactobacillus delbrueckii is very rarely isolated and only a few cases of L. delbrueckii UTIs have been reported, mainly in females [1,2]. Here we report the second case of L. delbrueckii UTI in a male patient.

Case Report

An 82-year-old man was admitted to the Emergency Department of our hospital because of acute urinary retention. No fever was reported. His past medical and surgical history was significant for type 2 diabetes mellitus, hypertension, hypothyroidism, dementia, benign prostate hyperplasia, hyperuricemia and a laparoscopic surgery for inguinal hernia. No complications from the type 2 diabetes mellitus such as microangiopathy or nephropathy were present. No allergies, smoking, systematic yogurt, probiotics and alcohol intake were reported. A month ago he also had a previous urinary retention episode and visited a private urologist, who put a catheter (lasting for two weeks) and without taking any laboratory examinations administered him norfloxacin 400 mg orally every 12 hours for two weeks, with the presumptive diagnosis of acute bacterial prostatitis. Three weeks later a new episode of urinary retention occurred. He visited a hospital and an evacuated catheterization was performed. Although urinalysis was significant for pyuria, urine culture revealed no pathogen. Antibiotics were not administered and the patient returned home refusing to carry a catheter.

Five days later the patient visited our hospital with the new episode of urinary retention. He was catheterized and urinalysis revealed significant pyuria, many microorganisms and an acidic pH (5.5). Nitrite testing was negative. A urine sample was taken for culture. Empiric antibiotic therapy was immediately administered pending laboratory results with cefixime orally (400 mg/day), and the patient was released. The catheter urine culture grew >10⁵ CFUs/mL of pure L. delbrueckii on Columbia CNA blood agar and on Trypticase soy agar (TSA) after 48 h of incubation aerobically at 36 °C in a 5% CO₂-enriched atmosphere. The Drigalski agar that had also been used in the urine culture for selective isolation of possible Gram-negative pathogens was sterile. After the first day of incubation, the colonies on TSA and CNA blood agar were very tiny and incubation had to be prolonged for another 24 hours for a total of 48 h. Identification was achieved by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS), using VITEK MS (bioMérieux, France), according to manufacturer’s instructions. Antimicrobial susceptibility testing was performed by the E-test method. The results were interpreted according to the Clinical and Laboratory Standards Institute guidelines [6]. Minimum inhibitory concentrations (MICs) showed susceptibility to all suggested antibiotics namely: penicillin (0.032 μg/mL), ampicillin (0.047 μg/mL), imipenem (0.023 μg/mL), vancomycin (0.38 μg/mL), daptomycin (0.064 μg/mL), erythromycin (<0.016 μg/mL), clindamycin (<0.016 μg/mL), and linezolid (0.25 μg/mL). The gentamicin MIC was 0.75 μg/mL. The patient was receiving the antibiotic treatment at home. Due to the extension of incubation and the mediated weekend there was a delay in the results to become available. Because several days had already passed, and the strain was susceptible to all beta-lactams tested and since urination and the overall clinical status were good, the antibiotic therapy was not modified and was administered for a total of 10 days. After stopping antibiotic therapy, the catheter was removed. A follow-up urine culture performed 7 days after antibiotic discontinuation was sterile. The ultrasound of the kidneys, ureters and bladder (KUB) performed showed prostate hyperplasia without postvoiding residual urine and recommended the continuation of the already received treatment with finasteride and tamsulosin. The patient was taking this treatment for his benign prostate hyperplasia for the last two years. No other new clinical episode was reported the following four months.

Discussion

Lactobacilli are generally regarded as contaminants. To our knowledge, the first time a Lactobacillus spp. was considered as the etiologic agent of a UTI was in 1984 when Lactobacillus gasseri was isolated from both urine and blood samples of a 66-year-old diabetic patient who developed acute renal failure and sepsis in a setting of ureteral obstruction [4,7]. A second case was only reported in 2009 by Darbro et al. consisting in parallel the first time L. delbrueckii was considered the causative pathogen of a UTI [7]. The 85-year-old female suffered recurrent UTIs with severe symptomatology including painful urination, frequency, nocturia and urgency. Significant pyuria, negative leukocyte esterase test and many bacteria were constant findings of repeated urine studies. As predisposing conditions, a stage III cystocele with surgical repair and hypothyroidism were reported. Treatments with courses of ciprofloxacin failed to resolve the problem. Urine cultures grew multiple times >50,000 CFUs/mL of a Lactobacillus species, which was further identified as L. delbrueckii with the analysis of its 16S rRNA gene sequence. Appropriate therapy (clarithromycin at 250 mg BID for two weeks) was administered yielding in significant improvement in her symptomatology. Following the end of therapy, urine cultures were negative and a significant reduction in the number of urine WBCs was noted [7].

After this first case, a few additional cases were reported all referring to elderly women [8,9]. Hypothyroidism as a predisposing condition was found in those cases with a detailed medical history.

Maillet et al. in 2019 reported the first case of a L. delbrueckii UTI in a male patient [2]. The 49-year-old man with unremarkable medical history presented with a two-week history of lower urinary tract symptoms including dysuria, urinary frequency, urgency and pelvic pain with no fever. The clinical manifestations were attributed to acute bacterial prostatitis and a course of ofloxacin was administered. Urinalysis performed after two doses of ofloxacin showed significant hematuria and leukocyturia and the urine culture was negative [2]. Despite the antibiotic treatment the symptoms persisted. A urine dipstick test showed high amount of blood, leukocyte esterase and protein while negative for nitrate, ketone and glucose. A clean-cut urinalysis showed leukocyturia and abundant Gram-positive bacilli. Empirical intravenous cefotaxime was administered. The urine culture yielded approx. 10,000 CFU/mL of pure L. delbrueckii ssp. delbrueckii and cefotaxime was changed to oral amoxicillin for two weeks based on the susceptibility testing. The patient was asymptomatic on day 3. One week after discontinuation of therapy control urinalysis and the culture performed were negative.

To our knowledge, the present report is the second case of UTI by L. delbrueckii in a male patient. The pure monoculture of L. delbrueckii in high colony numbers is a clear and convincing evidence for L. delbrueckii being the cause of UTI in the patient. Advanced age, hypothyroidism and significant pyuria are common findings in cases of L. delbrueckii UTI. Moreover, negative nitrite testing along with acidic pH on urinalysis is consistent with infection from Lactobacillus species. Usually, there is a history of unsuccessful treatment with quinolones since L. delbrueckii is naturally resistant to this class of antibiotics [2]. Susceptibility data regarding clinical L. delbrueckii isolates are scarce. Lactobacilli are generally susceptible to penicillins, whereas their susceptibility to aminoglycosides is reduced perhaps due to low cell membrane permeability [10].

It should be mentioned that certain drugs that the patients may be chronically taking for other comorbidities could be associated with acute urinary retention. For instance, medications with anticholinergic properties, such as tricyclic antidepressants, or sympathomimetic drugs can in some cases lead to urinary retention. The patient was chronically receiving clonazepam, which could cause urinary retention. However, the fact that the KUB ultrasound showed no postvoiding residual urine is an indication that this medication was not associated with the episodes of urine retention.

Obstruction from any cause is a major risk factor for the development of UTI both in men and women, along with advanced age, catheterization, and significant comorbid conditions impairing immune response such as diabetes mellitus. However, the pathogenesis of the infection in our patient is unclear. It is possible that he was first colonized with L. delbrueckii and then developed the infection as a consequence of the benign prostate hyperplasia, which could predispose to UTI as a major cause of obstruction.

If a Lactobacillus spp. UTI is suspected the incubation of the urine culture should be prolonged due to its slow rate of growing. It is noteworthy that the use of specific chromogenic culture media such as UriSelect 4 facilitates the isolation and presumptive identification of Lactobacillus spp. responsible for UTIs [8].

Conclusions

In conclusion, L. delbrueckii should be considered as a possible cause of UTI in male patients with pure L. delbrueckii positive urine culture. More cases worldwide are needed to strengthen this conclusion.