Lactobacillus paragasseri as a novel causative pathogen of cavernosal abscess

Highlights • L. paragasseri causes oligosymptomatic febrile spontaneous cavernosal abscesses.• Molecular identification methods alone can misidentify L. paragasseri as L. gasseri.• Molecular and microbial biochemistry methods can identify L. paragasseri.• Penicillins are optimal antimicrobials for treatment of L. paragasseri infections.• L. paragasseri cavernosal abscesses need drainage with appropriate antimicrobials.


Introduction
Lactobacillus species are gram-positive, non-sporing, and nonmotile rods, which are commensals of the gastrointestinal and genitourinary tract. Lactobacillus paragasseri is often confused with L. gasseri because of their molecular similarity. L. paragasseri was first described in 2018 as a sister taxon of L. gasseri based on wholegenome sequence analyses [1]. L. gasseri causes several infections, including bacteremia, dental caries, and empyema; however, the role of L. paragasseri remains unclear. L. paragasseri can often be misidentified as L. gasseri by matrix-assisted laser desorption ionization (MALDI) or 16S rRNA sequencing that shows 99.0% similarity between L. paragasseri and L. gasseri [1]. Hence, L. paragasseri infections reported in previously published case reports could have been misidentified as L. gasseri infections in the absence of appropriate microbial biochemical examinations.

Case report
A 63-year-old Japanese man with a history of foreign object insertion into the urethra one year prior presented with high-grade fever, general fatigue, loss of appetite, and spontaneous slight genital pain. The patient also presented with poorly managed diabetes and a left inguinal hernia.
The patient was alert, with body temperature of 40.2 °C, blood pressure 181/102 mmHg, heart rate 122 beats/min, respiratory rate 24 breaths/min, and oxygen saturation 95% in ambient air. Physical examination revealed general gingivitis, chronic periodontitis, and swelling of the area from the penile base to the scrotum with redness, warmth, and mild tenderness. Laboratory findings were as follows: white blood cell count 17,100/µL with 88.1% neutrophils, hemoglobin 14.0 g/dL, platelet count 28.0 × 10 4 /µL, albumin 3.2 g/dL, alanine transferase 26 U/L, lactate dehydrogenase 240 U/L, creatine kinase 120 U/L, blood urea nitrogen 7 mg/dL, creatinine 0.67 mg/dL, C-reactive protein 14.49 mg/dL, blood glucose 372 mg/dL, and hemoglobin A1c 11.5%. Computed tomography (CT) revealed a foreign body in the urethra, presenting bilateral hydronephrosis and an irregular low-density area with inflammation, which was consistent with an abscess in the corpus cavernosum (Fig. 1A). The foreign body, identified as a pearl with thread ( Fig. 1B), was manually removed and a catheter was placed in the bladder to relieve urinary retention. Two sets of blood cultures were performed, and intravenous meropenem (0.5 g) and clindamycin (600 mg) were administered every 12 h. The aerobic and anaerobic blood cultures showed presence of grampositive rods after 1-day incubation ( Fig. 2A). The isolates grew as circular, flat, and pinhead colonies, with an alpha-hemolytic zone on 5% sheep blood agar after additional 2 days of incubation under 5% CO 2 at 37 °C (Fig. 2B). The bacteria were identified as L. gasseri via MALDI with a high score of 2.32, whereas 16 S rRNA sequencing revealed the causative bacteria to be L. paragasseri, with identities of 100% (1487/1487) [2]. After additional microbial biochemical examinations, the bacteria were conclusively identified as L. paragasseri. The E-test showed penicillin and ampicillin to have minimum inhibitory concentrations of 0.047 and 0.094 µg/mL, respectively, indicative of susceptibility according to the Clinical and Laboratory Standards Institute criteria (Fig. 2C) [3].
Despite the antimicrobial therapy, the high-grade fever persisted, and the local pain was exacerbated. Enhanced CT on day 8 revealed progression toward multilocular abscesses in the corpus cavernosum. Therefore, the antimicrobials were switched to ampicillin/sulbactam (3 g every 8 h) based on the susceptibility testing. Furthermore, incisional drainage of the right corpus cavernosum was performed on day 9 (Fig. 3). The patient became apyrexial after the invasive procedure and antimicrobial change. Pus culture revealed the presence of L. paragasseri with consistent susceptibilities. Thereafter, ampicillin/sulbactam was changed to oral amoxicillin/ clavulanate (1875 mg daily). On day 40, the reduced abscess size was confirmed by CT findings, and amoxicillin/clavulanate was discontinued. Consequently, the patient remained disease-free without recurrence or sequelae during a 2-year follow-up period (Fig. 4).

Discussion
This report illustrates three main clinical issues: the potential of L. paragasseri to cause cavernosal abscess in a clinical setting, impaired capacity to distinguish L. paragasseri from the similar species L. gasseri, and a potential treatment strategy for L. paragasseri-induced cavernosal abscess.
L. gasseri is widely recognized as a commensal bacterium inhabiting the gastrointestinal and genitourinary tracts and can cause several infections, such as bacteremia, dental caries, empyema, and peritonitis [4][5][6][7]. However, to date, no reports have described cavernosal abscesses caused by L. paragasseri. Cavernosal abscesses can occur either spontaneously, or following intracavernosal injection, trauma, or foreign body insertion [8]. In the present case, odontogenic infections and the urethral foreign body may have led to the onset and exacerbation of the L. paragasseri-triggered cavernosal abscess. Cavernosal abscesses are commonly caused by Staphylococcus aureus, streptococci, Bacteroides and Fusobacterium species [9]; however, the most common pathogen is Neisseria gonorrhoeae, with infections generally occurring secondary to urethritis caused by sexually transmitted diseases (STDs) [8]. These microorganisms are easily identified using gram staining, leading to appropriate antimicrobial therapy based on local antibiograms. However, this report highlights that clinicians should pay attention to the potential of L. paragasseri involvement in cavernosal abscess cases with gram-positive rods identified by gram staining of pus or blood cultures.
Several strains, including the Japanese Collection of Microorganisms (JCM) 5343, JCM 5344, and JCM 1130, have been identified as L. gasseri American Type Culture Collection (ATCC) 33323. These strains show a 99.9% similarity to L. gasseri ATCC 33323 [1]. However, the average nucleotide identity and in silico DNA-DNA hybridization values of these three strains compared to L. gasseri ATCC 33323 were less than the widely accepted threshold to distinguish strains [1]. Therefore, JCM 5343, JCM 5344, and JCM 1130 were reclassified as L. paragasseri [1]. Moreover, these strains have different microbial biochemical characteristics compared with those of L. gasseri [1]. In this study, the isolate was identified as L. paragasseri JCM 5343 via 16S rRNA sequencing based on the GenBank Basic Local Alignment Search Tool database (www.ncbi.nlm.nih.gov/ genbank/) (Identities: 1487/1487; Gaps: 0/1487; Score: 2747 bits). In contrast, 16S rRNA sequencing also indicated L. gasseri ATCC 33323 with 99.0% identity (1485/1487). We confirmed L. paragasseri by performing microbial biochemical examinations, including API 50 CH assay (bioMérieux) ( Table 1) and growing the culture in the presence of NaCl. The findings were not consistent with the characteristics of L. gasseri, but instead with those of L. paragasseri JCM 5343, despite the identification of L. gasseri by MALDI.
The optimal antimicrobial therapy for L. paragasseri cavernosal abscesses has not been standardized owing to a lack of relevant of studies. However, most strains of L. gasseri are susceptible to penicillin and ampicillin [4]. Additionally, it is likely that previous cases of L. paragasseri infection were erroneously identified as L. gasseri, as L. paragasseri was first described in 2018 [1]. Our patient was successfully treated with ampicillin/sulbactam, which suggests that penicillin in an optimal antimicrobial for L. paragasseri infections. In general, anaerobes, including Bacteroides and Fusobacterium species, can cause cavernosal abscesses. Given the potential of anaerobic coinfection, ampicillin/sulbactam was administered as a definitive therapy because anaerobic transport devices and chambers were not available in our hospital. The optimal duration of antimicrobial therapy still needs to be optimized. Cavernosal abscesses may recur, and a case of total penectomy necessitated due to abscess recurrence has been reported [10,11]. In this case, the patient, who had poorly managed diabetes, progressed to multilocular abscesses despite removal of the foreign body and intravenous antimicrobial therapy. Hence, penicillins, to which L. paragasseri was susceptible, were continued for 6 weeks after the switch was made from the previous antimicrobials along with surgical incision and drainage. This treatment contributed to the disappearance of the abscess as confirmed by CT imaging, and no recurrence or sequelae were observed.
Surgical incision and drainage combined with appropriate antimicrobial administration should be considered as first-line treatment in such cases [9]; however, this approach can result in postoperative complications, such as penile deviation or erectile dysfunction [9]. Therefore, less invasive interventional techniques (e.g., image-guided aspiration) are performed in some cases [10]. In our case, surgical incision and drainage were performed, considering the difficulty of appropriate drainage because of multilocular abscesses.
In conclusion, oligosymptomatic cavernosal abscesses caused by L. paragasseri may occur without STDs. Additionally, Lactobacillus species present as gram-positive rods, which are distinct from microorganisms that commonly cause cavernosal abscesses, such as N. gonorrhoeae, S. aureus, streptococci, Bacteroides and Fusobacterium species. L. paragasseri can be identified using a combination of molecular and microbial biochemical examinations, despite its similarity to L. gasseri. Moreover, penicillins are optimal antimicrobials for L. paragasseri infections. Clinicians should pay special attention to the accurate identification and appropriate antimicrobial therapy for L. paragasseri infections. Enhanced CT imaging on day 8 revealed progression toward multilocular abscesses in the corpus cavernosum (yellow arrows). Incisional drainage of the right corpus cavernosum was performed on day 9. Pus culture also revealed L. paragasseri in the same way. Intravenous ampicillin/sulbactam was administered according to the susceptibility testing. Thereafter, ampicillin/sulbactam was changed to oral amoxicillin/ clavulanate on day 40 confirming reduced abscess size by CT imaging on day 39. Consequently, oral amoxicillin/clavulanate was discontinued, confirming the disappearance of the abscess without recurrence and sequelae.