Abstract
Urethritis is a frequent lower urinary tract infection often linked to sexually transmitted infections (STIs). While Neisseria gonorrhoeae and Chlamydia trachomatis are the main pathogens, other microorganisms such as Mycoplasma genitalium, Trichomonas vaginalis, and Ureaplasma urealyticum may also be involved. In over half of non-gonococcal urethritis (NGU) cases, no causative agent is identified. We present the case of a 37-year-old man with scrotal pain, painful ejaculation, dysuria, and urethral discharge following a single unprotected sexual encounter. Initial STI PCR was positive for Ureaplasma urealyticum, and azithromycin was prescribed. Symptoms persisted, and a urethral culture revealed Streptococcus urinalis, confirmed by MALDI-TOF MS and 16S rRNA sequencing. Gram staining showed numerous leukocytes and Gram-positive cocci in chains. A second urethral swab yielded the same organism. The isolate was fully susceptible to all tested antibiotics. Although S. urinalis has been described in urinary tract infections and sepsis, to our knowledge, this is the first reported case suggesting a possible role in male urethritis. While prostatitis or epididymitis cannot be ruled out, the repeated isolation of S. urinalis and persistent symptoms support its potential pathogenicity. This case adds to growing evidence implicating S. urinalis in genitourinary tract infections.
Keywords
Urethritis is an infection of the lower urinary tract that causes inflammation of the urethra in both men and women. It is commonly associated with sexually transmitted infections (STIs) and is typically classified as gonococcal or non-gonococcal. Neisseria gonorrhoeae and Chlamydia trachomatis are the primary microorganisms involved in this infection. 1 However, other microorganisms, such as Mycoplasma genitalium, Trichomonas vaginalis, and Ureaplasma urealyticum, can also cause urethritis. 2 In more than 50% of cases, no infectious cause can be identified. 3
We present the case of a 37-year-old man who presented to the primary care clinic with spontaneous scrotal pain, painful ejaculation, dysuria, and urethral discharge following a single unprotected sexual encounter. Of note, one year earlier the patient had sought medical care for hypogastric pain, scrotal pain, and testicular discomfort with right testicular swelling, although no definitive cause was identified. Due to the suspicion of a sexually transmitted infection, an STI PCR test was performed at Miguel Servet University Hospital. The result was positive for Ureaplasma urealyticum and negative for Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Herpes simplex virus, Treponema pallidum, and Trichomonas vaginalis. The patient received treatment with azithromycin 1 g daily for five days. Despite treatment, symptoms persisted, and the patient returned for further evaluation one week later. A new round of testing was ordered at Lozano Blesa University Clinical Hospital, including STI PCR on urine and urethral swab samples, urethral culture, and serological tests for syphilis, hepatitis B and C, and HIV. All PCR results were negative for Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, and Mycoplasma genitalium. Additionally, serological tests were all negative.
A direct Gram stain of the urethral swab showed >25 leukocytes/×1000 magnification field and Gram-positive cocci in chains, that were visible both extracellular and inside polymorphonuclear leukocytes (Figure 1(a)). After 48 hours of incubation, predominant growth of numerous transparent colonies measuring approximately 1 mm in diameter, was observed on chocolate agar (Figure 1(b) and (c)). These colonies were identified by MALDI-TOF MS as Streptococcus urinalis (LSV 2.49; Streptococcus equi ssp zooepidemicus LSV 1.93 as the second top-scoring species) and confirmed by PCR and 16S rRNA gene sequencing (GenBank accession number: LR134323.1). (a) Direct gram stain of the first urethral smear showing a polymorphonuclear leukocyte with a chain of gram positive cocci inside (*); (b) transparent colonies growth after 24–48 hours of incubation are visible on chocolate agar (
Susceptibility testing was performed by MicroStrep PLUS 6 panel -Beckman®-. Following the antibiotic susceptibility breakpoints for either viridans group streptococci or hemolytic streptococci of groups A, B, C, and G (EUCAST 2023 version 13.0), the isolate showed susceptibility to: penicillin (MIC: <=0.03 mg/L), ampicillin (MIC: <=0.06 mg/L), amoxicillin-clavulanic acid (MIC: <=1/0.5 mg/L), cefuroxime (MIC: <=0.25 mg/L), cefotaxime (MIC: <=0.25 mg/L), ceftriaxone (MIC: <=0.25 mg/L), cefepime (MIC: <=0.25 mg/L), meropenem (MIC:<=0.25 mg/L), vancomycin (MIC: 0.5 mg/L), daptomycin (MIC: <=0.25 mg/L), linezolid (MIC: < =4 mg/L), erythromycin (MIC: <=0.06 mg/L), clarithromycin (MIC: <=0.12 mg/L), azithromycin (MIC: <=0.12 mg/L), clindamycin (MIC: <=0.06 mg/L), tetracycline (MIC: <=1 mg/L) and minocycline (MIC: <=0.05 mg/L).
Due to the uncertain clinical significance of the isolate, a subsequent sample was requested. The patient continued to experience symptoms but did not receive any empirical antibiotic treatment before sample collection. A second urethral swab was collected 7 days after the first one. The Gram staining, again, showed Gram-positive cocci in chains, both intra- and extracelular (Figure 1(d)) and S. urinalis was isolated in chocolate agar. A single oral dose of azithromycin was then prescribed but unfortunately, follow-up samples could not be obtained due to missed medical appointments.
Discussion
Non-gonococcal urethritis (NGU) accounts for a significant proportion of urethritis cases. It is well established that Mycoplasma genitalium is responsible for 15%–25% of NGU cases 4 and that Trichomonas vaginalis is also an important cause of NGU in men. 5 Other microorganisms are less commonly implicated in urethritis; for instance, Ureaplasma urealyticum has been associated with NGU in certain cases and should be considered when detected in the absence of other etiological agents.2,6 In our case, although Ureaplasma urealyticum was initially detected by STI PCR and treated with azithromycin, the urethral culture subsequently grew Streptococcus urinalis, and the patient continued to experience urethral discomfort. This clinical evolution suggests that Streptococcus urinalis may have played a pathogenic role in the development of urethritis.
There is limited data on viral causes of urethritis; however, herpes simplex virus (HSV) and adenovirus have been recognized as potential pathogens.7,8 Evidence also suggests that Gram-negative bacilli may cause urethritis in cases of insertive anal sex, while respiratory tract pathogens such as Haemophilus spp., Neisseria meningitidis, Moraxella catarrhalis, and Streptococcus pneumoniae have been associated with urethritis in the context of insertive oral sex. 9
Species of Streptococcus are commonly found in urethral samples and are typically regarded as commensals. 3 S. urinalis has been associated with urinary tract infections and sepsis10,11; however, to our knowledge, it has not previously been described as a causative agent of urethritis. Consistent with previous reports of S. urinalis in infections,10,11 our isolate exhibited susceptibility to all tested antibiotics.
Although in our case a concurrent clinical process such as prostatitis or epididymitis cannot be definitively excluded as a cause of the patient’s associated symptoms, the persistence of Streptococcus urinalis may underscore its potential clinical significance. Gram staining remains an essential tool for the accurate interpretation of bacterial cultures, particularly when dealing with microorganisms of uncertain pathogenicity. This case may contribute to the emerging body of evidence supporting S. urinalis as a potential pathogen in genitourinary tract infections.
Footnotes
Author contributions
Declaration of conflicting interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
Informed consent
Informed consent was obtained from the patient for publication of this manuscript.
