Lacticaseibacillus rhamnosus Infection in a Liver Transplant Patient: A Case Report

Ahneez Abdul Hameed^1,2*, Bindu Mulakavalupil³, Francesca Trovato³ and Anita Verma^1
*Correspondence: Ahneez Abdul Hameed, Department of Pathology, Selayang Hospital, Selangor, Malaysia, Email:

Keywords

Lacticaseibacillus rhamnosus • liver transplant • liver • Immunocompromised

Introduction

Historically, Lactobacillus was first described in 1901; however, advancements in genetic sequencing methods have since uncovered new species. This prompted the International Journal of Systematic and Evolutionary Microbiology (IJSEM) to release new classifications and novel genera in April 2020. L. rhamnosus was renamed from L. rhamnosus, with lacti and casei meaning derived from milk and cheese Zheng J, et al. [1]. Lacticaseibacillus spp. have shown very low pathogenicity and beneficial effects on gut and vaginal microflora, such as preventing diarrhoea of varying etiology and vaginal candidiasis Mikucka A, et al. [2]. However, there have been an increasing number of reports on the isolation of Lacticaseibacillus spp., commonly Lacticaseibacillus casei and L. rhamnosus, in patients with bacteraemia and endocarditis. Some reported cases show organ or space infections due to Lacticaseibacillus spp , such as pneumonia, intra-abdominal infections, peritonitis, chorioamnionitis, and abscesses Mikucka A, et al. [2]; Salminen MK, et al. [3]. Less frequently, these bacteria have also been isolated in cases of pyelonephritis, endophthalmitis, liver disease, infected wounds, leukemia, transplantation, and vascular grafts Mikucka A, et al. [2]. Here, we describe the first case of L. rhamnosus infection in a Liver Transplant Recipient (LTR) and review of the literature.

Case Presentation

A 65-year-old man was electively admitted in January 2024 for are-do Liver Transplant (LTX) due to portal vein thrombosis and graft failure. His first transplant was performed in 2021 for hepatocellular carcinoma secondary to non-alcoholic steatohepatitis. Post re-do LTX, he experienced primary non-function graft and was super urgently re-listed, undergoing LTX surgery after 24 hours of anhepatic period. Following the transplant, he received broad-spectrum antibiotics piperacillin-tazobactam, vancomycin, and the antifungal anidulafungin, according to local protocol. On day 7, his antibiotic regimen was escalated to meropenem due to worsening inflammatory markers (Figure 1). His White Blood Cells (WBC) were rising, and he had elevated Procalcitonin (PCT) levels. His abdominal drains were removed 15 days post-op. On day 17 post-op, CT scan of the abdomen and pelvis was done because of abdominal distension and tenderness. There was significant collection in the right subhepatic and pelvic regions (Figure 2A), suggesting a possible colonic perforation. The patient underwent an emergency laparotomy with washout, primary repair of the colonic perforation, and defunctioning loop ileostomy. Cultures from abdominal wall tissue and peritoneal fluid grew L. rhamnosus despite being on meropenem. This isolate was only susceptible to metronidazole and resistant to other antibiotics tested. Metronidazole was added to the regimen on day 20. As his condition did not improve, a CT thorax, abdomen, and pelvis was repeated on day 44, showing less peritoneal collection than previous imaging but had large bilateral pleural effusions (Figures 2B and 2C). Pleural drainage was performed twice, on day 82 and day 99, with turbid and caramel-colored fluid drained both times. These pleural fluid cultures were positive for L. rhamnosus despite 60 days of metronidazole and meropenem treatment. On day 119 patient underwent right thoracotomy and decortication for the empyema. He received a total of 4 months of meropenem and metronidazole. The patient recovered from the described infection postoperatively but remained an inpatient for further management of his post LTX associated complications. The time line of infections and treatment are shown in Figure 3.

Results and Discussion

The pathogenesis of Lacticaseibacillus infection could be attributed to systemic dissemination or translocation sequealae following disturbances of the mucosa Sendil S, et al. [4]. In our patient infection was precipitated by colonic perforation post multiple abdominal surgeries. L. rhamnosus intarabdominal infection in our patient continued to progress to pleural empyema while on antibiotic for >3 months. The empyema was likely due to continuity with the intra-abdominal fluid. However after drainage of the empyema, repeat intra-abdominal wash out and continuation of long term antibiotics the infection resolved. Although this organism is of low pathogenicity, L. rhamnosus has been reported in most case series, as a significant cause of bacteraemia in both immunocompetent and immunocompromised patients (Table1) suggesting that this bacteria has greater pathogenic potential than initially thought [5]. Likely Due to its resistance pattern to commonly used antibiotics Falci DR, et al. [6]. Interestingly, Albarillo F, et al. [5] reported a case series of 47 patients that isolated L. rhamnosus from different samples, including blood cultures, wounds, urine, abdominal abscesses, and respiratory samples. Out of these, 35 patients were treated for the infection [5]. In most reported cases, patients had underlying chronic illnesses or were immunocompromised and the mortality as high as >55% Albarillo F, et al. [5]. The likely mortality was due to infection in critically ill patients with significant comorbidities, polymicrobial infections, and use of antibiotic therapies to which L. rhamnosus is intrinsically resistant [5].

Microbiologically, it is challenging isolating and performing antimicrobial susceptibility for L. rhamnosus because of their low significance and special growth requirements [7]. Standardized antimicrobial panels may not always be available or interpreted. The Clinical Laboratory Standards Institute (CLSI) M45 Ed3 guidelines for Lactobacillus spp. suggest testing for ampicillin, penicillin, imipenem, meropenem, vancomycin, daptomycin, erythromycin, Clindamycin, And Linezolid (CLSI, 2016), whilst, the European Committee on Antimicrobial Susceptibility Testing (EUCAST) recommends testing for ampicillin, gentamicin, streptomycin, and tetracycline. When it comes to the susceptibility pattern of Lactocaseibacillus species it can vary. For instance, penicillin and ampicillin are typically effective against L. rhamnosus, although resistance has been documented [3]. L. rhamnosus is intrinsically resistant to vancomycin, and resistance to ciprofloxacin, tetracycline, meropenem, metronidazole, and sulfonamides has been observed in some strains [4]. Despite known metronidazole resistance in some cases, in our case the organism was susceptible to metronidazole, and the patient responded positively when metronidazole was included in the treatment regimen. Treatment duration for Lactocaseibacillus infections is highly variable and depends on the patient's response and any underlying conditions. A study of 85 cases found that treatment durations can range from several days to weeks [3]. In our case, the infection disseminated despite the use of appropriate antibiotics, underscoring the critical need for source control in managing anaerobic infections. This case highlights several key considerations for treating invasive or severe Lactocaseibacillus infections, particularly in immunocompromised patients:

Tailored antimicrobial therapy

Due to the variability in resistance patterns, it is essential to base antimicrobial therapy on the specific susceptibility profile of the isolated strain.

Source control

Addressing the source of the infection is crucial, as antibiotics alone may not be sufficient to control the infection without effective source management.

Treatment duration

The duration of treatment should be individualized based on the patient's response and underlying conditions, which can range from several days to weeks.

Despite L. rhamnosus being generally of low virulence and pathogenicity, our case demonstrates that infections can disseminate and become severe, particularly in immunocompromised or transplant patients. Therefore, when Lactocaseibacillus is isolated in a clinical sample, it is important for clinical microbiologists and treating physicians to maintain a high index of suspicion for potential infection and to carefully consider appropriate treatment and source control measures [8-14].

Conclusion

In conclusion although L. rhamnosus is an opportunistic pathogen, but this and other reported cases emphasizes the necessity for increased awareness of it as a potential pathogen and its resistance in immunocompromised patients. For better outcome it is important to start customized early antimicrobial therapy with effective source control.

Funding

The clinical case was analysed and data collecting was performed during daily clinical practice of the Department of Infection Sciences and Liver intensive therapy unit at King’s College Hospital.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author Contributions

AAH, AV: drafting the initial manuscript and revising it critically for important intellectual content; AAH,AV,BM, FT: Reviewed and edited the draft. All authors approved the final manuscript.

Ethical Consideration

Not applicable.

Conflict of Interest Statement

The authors declare no conflict of interest.

References

1. Zheng, Jinshui, Stijn Wittouck, Elisa Salvetti and Charles MAP Franz, et al. "A taxonomic note on the genus Lactobacillus: Description of 23 novel genera, emended description of the genus Lactobacillus Beijerinck 1901, and union of Lactobacillaceae and Leuconostocaceae."Int J Syst Evol Microbiol 70 (2020): 2782-2858.

Google Scholar, Crossref, Indexed at

2. Mikucka, Agnieszka, Aleksander Deptuła, Tomasz Bogiel and Agnieszka Chmielarczyk, et al. "Bacteraemia caused by probiotic strains of Lacticaseibacillus rhamnosus—case studies highlighting the need for careful thought before using microbes for health benefits."Pathog11 (2022): 977.

Google Scholar, Crossref, Indexed at

3. Salminen, Minna K., Hilpi Rautelin, Soile Tynkkynen and Tuija Poussa, et al. "Lactobacillus bacteremia, species identification, and antimicrobial susceptibility of 85 blood isolates."Clin Infect Dis 42 (2006): e35-e44.

Google Scholar, Crossref, Indexed at

4. Sendil, Selin, Isha Shrimanker, Qurat Mansoora and John Goldman, et al. "Lactobacillus rhamnosus bacteremia in an immunocompromised renal transplant patient."Cureus12 (2020).

Google Scholar, Crossref, Indexed at

5. Albarillo, Fritzie S., Ushma Shah, Cara Joyce and David Slade. "Lactobacillus rhamnosus infection: A single-center 4-year descriptive analysis."J Glob Infect Dis 12 (2020): 119-123

Google Scholar, Crossref, Indexed at

6. Falci, D. R., M. H. Rigatto, V. V. Cantarelli and A. P. Zavascki. "Lactobacillus rhamnosus bacteremia in a kidney transplant recipient."Transpl Infect Dis17 (2015): 610-612.

Google Scholar, Crossref, Indexed at

7. Gouriet, F., M. Million, M. Henri and P-E. Fournier, et al. "Lactobacillus rhamnosus bacteremia: An emerging clinical entity."Eur J Clin Microbiol 31 (2012): 2469-2480.

Google Scholar, Crossref, Indexed at

8. Eze, Ujunwa J., Anthony Lal, Menatallah I. Elkoush and Marta Halytska, et al. "Recurrent Lactobacillus Rhamnoses Bacteremia and Complications in an Immunocompromised Patient With History of Probiotic Use: A Case Report."Cureus16 (2024).

Google Scholar, Crossref, Indexed at

9. Rubin, Ingrid Maria Cecilia, Lea Stevnsborg, Sarah Mollerup and Andreas Munk Petersen, et al. "Bacteraemia caused by Lactobacillus rhamnosus given as a probiotic in a patient with a central venous catheter: A WGS case report."Infect Prev Pract 4 (2022): 100200.

Google Scholar, Crossref, Indexed at

10. Karime, Christian, Maria S. Barrios, Nathaniel E. Wiest and Fernando Stancampiano. "Lactobacillus rhamnosus sepsis, endocarditis and septic emboli in a patient with ulcerative colitis taking probiotics" BMJ Case Rep CP15 (2022): e249020.

Google Scholar, Crossref, Indexed at

11. Aydoğan, Seda, Dilek Dilli, Ahmet Özyazici and Nesibe Aydin, et al. " Lactobacillus rhamnosus sepsis associated with probiotic therapy in a term infant with congenital heart disease."Fetal Pediatr Pathol 41 (2022): 823-827.

Google Scholar, Crossref, Indexed at

12. Lilitwat, W., S. Reeve, C. Womack and T. Kasemsri. "A Rare Bacteria: Lactobacillus Rhamnosus in Pediatric Lung Abscess." InD58. Lung Infection, Immunodeficiency. Ann Am Thorac Soc, (2020): A7171-A7171.

Google Scholar, Crossref

13. Jorgensen, James H. "Methods for antimicrobial dilution and disk susceptibility testing of infrequently isolated or fastidious bacteria; Approved guideline." (2010).

Google Scholar

14. Rossi, Franca, Carmela Amadoro and Giampaolo Colavita. "Members of the Lactobacillus Genus Complex (LGC) as opportunistic pathogens: A review."Microorganisms7 (2019): 126.

Google Scholar, Crossref, Indexed at