Douglas Gordon MD, Christopher J Peterson MD, MS, Kirit S Vattikonda DO, Yunan D Wang MD
Corresponding author: Christopher Peterson
Contact Information: Cjpeterson1@carilionclinic.org
DOI: 10.12746/swrccc.v12i53.1385
Leuconostoc mesenteroides is a Gram-positive bacterium in the Lactobacillaceae family. This species is rarely encountered clinically and in the past was regarded as a contaminant when cultured. Recently it is being recognized as a pathogen responsible for opportunistic infections in immunocompromised patients. Compared to other Gram-positive cocci, Leuconostoc spp. carry intrinsic resistance to vancomycin. It is not common for clinical microbiology laboratories to isolate this organism and instead incorrectly report enterococcus and streptococcus organisms. Here, we present a case of bacteremia resulting in febrile illness and pneumonia in an 81-year-old woman with a history of rheumatoid arthritis and a notable lapse between immunomodulator therapy exposure. She was successfully treated when this organism was identified, and her antibiotic therapy was switched from vancomycin to ampicillin-sulbactam. This case highlights the importance of considering L. mesenteroides as a source of infection in patients predisposed to an immunocompromised state despite this organism’s being a rare pathogen.
Keywords: Leuconostoc mesenteroides, rheumatoid arthritis, immunomodulators; vancomycin resistance
Infections with rare pathogens can be both a diagnostic and therapeutic challenge for physicians. Particularly challenging is the use of specialized diagnostic methods to identify the pathogen and inherent resistance patterns that may not be anticipated by those unfamiliar with the organisms. Leuconostoc mesenteroides is such a bacterium, often requiring advanced culture techniques, historically mistaken for other organisms, and inherently resistant to vancomycin. Infections attributed to this organism are rare and usually occur in patients who have undergone transplants, have indwelling catheters, take immunomodulator therapy, or received vancomycin.1 However, a wide variety of presentations have been reported, including endocarditis, urinary tract infections, intrabdominal infections, meningitis, empyema, and catheter-associated bloodstream infections.1 Furthermore, although L. mesenteroides is frequently associated with oncology patients,2–4 infections may occur in patients with other forms of immunocompromise. We present a case of bacteremia caused by this organism in an 81-year-old woman with severe immunodeficiency as a result of her immunomodulator therapies for rheumatoid arthritis.
An 81-year-old woman presented to the emergency department for a near syncopal episode after arising from a seated position. Her past medical history included hypertension, seropositive rheumatoid arthritis (RA), and osteopenia. Her RA was diagnosed in 2012 with a positive cyclic citrullinated peptide (CPP) antibody, and she has been treated with multiple disease-modifying anti-rheumatic drugs (DMARDs), including methotrexate, hydroxychloroquine, leflunomide, adalimumab, certolizumab, golimumab, abatacept, tocilizumab, and sulfasalazine. Prior to her admission, she was recently treated with rituximab for 7 years but stopped 7 months ago and switched to hydroxychloroquine. Evaluations by a rheumatology consultant had discovered persistent lymphopenia and hypogammaglobinemia, which was considered residual effects of rituximab.
The patient was initially found to be orthostatic and treated with conservative measures but subsequently developed a febrile illness and hypoxic respiratory failure with radiographic evidence of pneumonia. Treatment was initiated with ceftriaxone and azithromycin for community-acquired pneumonia. Despite treatment, she remained febrile (101–102°F), and treatment was broadened to cefepime and metronidazole. The following day, blood cultures grew a Gram-positive organism in pairs and chains. Polymerase chain reaction testing was negative for multiple organisms, including Staphylococcus, Streptococcus, Listeria, and Enterococcus. Subsequent send-out testing identified L. mesenteroides as the organism with susceptibility to all antimicrobials tested (penicillin, ampicillin, chloramphenicol). She was switched to ampicillin-sulbactam and underwent a transesophageal echocardiogram, which was negative for vegetations. She completed a 14-day course of ampicillin-sulbactam with defervescence and clearance of blood cultures and was discharged with a plan for follow-up in pulmonology and rheumatology clinics.
Leuconostoc mesenteriodes is a Gram-positive, nonmotile, catalase-negative, lactic acid-producing bacterium found on plant and vegetable matter and is used in the food industry for dairy product fermentation.5 It is a rare and typically opportunistic pathogen in humans, with the first pathogenic case identified in 1985.6 Risk factors include an immunocompromised immune status, indwelling catheters, bacteremia, pre-mature birth weight, underlying enteric disease, parenteral nutrition, compromised gastrointestinal mucosa, and previous vancomycin exposure.1,7–9 Leuconostoc spp. are often associated with patients with underlying malignancy,10 likely secondary to immunocompromised host defenses and indwelling catheters. L. mesenteroides are also variable biofilm producers, which may allow their colonization of indwelling catheters.11 Hospital outbreaks of L. mesenteroides have been reported. In one such outbreak, parenteral nutrition was the suspected source.9 L. mesenteroides can also colonize the human gastrointestinal tract, with disruption of the GI mucosal membrane as the proposed means of entry.12,13 In one case, a patient with poor dentition consumed unpasteurized milk resulting in L. mesenteroides bacteremia.14 In this case, no definitive source was determined. The most likely source was the lungs, given her pneumonia, but sputum cultures did not grow L. mesenteroides.
Leuconostoc spp. may result in a variety of presentations, such as endocarditis,15 prosthetic joint infection,16 urinary tract infection,17 empyema,18 meningitis,19 brain abscess,13 odontogenic infection,20 osteomyelitis,21 and endophthalmitis;22 bacteremia and catheter infection are usually the most common.9 Identification of L. mesenteroides can be challenging. They may be misidentified as Streptococcal, Enterococcus, or Lactobacillus species.23 Identification of a vancomycin-resistant streptococcal species should prompt testing for other bacterial species such as Leuconostoc,20 which may include advanced microbiological testing or molecular methods, such as 16S rRNA sequencing.13 Microbiological criteria include catalase-negative organism, resistance of vancomycin, negative for pyrolidonyl arylamidase production, negative leucine aminopeptidase production, dioxide production from glucose, and no growth in broth with 6.5% NaCl.3,10,24 Treatment for Leuconostoc spp. includes penicillin, clindamycin carbapenems, ampicillin, and aminoglycosdies.25 Central venous catheters should be removed.2,26 Echocardiography should be considered given the potential for Leuconostoc spp. to cause endocarditis.15,24,27–29 In one single-center study, fatalities related to L. mesenteroides was 7.1%, but many of the patients in this study had significant underlying disorders.9
Immunosuppression is a known risk factor for L. mesenteroides infection, as is the case here with hydroxychloroquine use and recent rituximab use. Immune reconstitution after stopping rituximab usually begins at six months and is completed at 9 to 12 months;30 her persistent lymphopenia and hypogammaglobinemia are consistent with this. However, Leuconostoc infection in patients with rheumatological diseases is infrequent. Indeed, there are only 3 cases of L. mesenteroides infection in rheumatoid arthritis patients. Patients with rheumatological diseases, such as rheumatoid arthritis receiving immunosuppressive therapy, are at risk for a variety of infections.31 The global disease burden of rheumatoid arthritis is projected to increase to 31.7 million by 2050 (from 17.6 million in 2020). Furthermore, the increasing prevalence of immunosuppression,32 including increased use of disease-modifying anti-rheumatic drugs (DMARDs),33 means physicians may encounter infections with unusual bacteria, such as L. mesenteroides, in patients without malignancy, active chemotherapy, or indwelling ports.
In conclusion, L. mesenteroides is a rare cause of human infection. While often associated the malignancy, it can also be associated with other forms of immunocompromised host defenses. In this case, we report the third instance of L. mesenteroides infection in a patient with RA. Immunosuppression was not readily apparent given her discontinuation of rituximab, though it is possible her immune system was not fully reconstituted at the time of infection. With an increase in the use of immune-modulating agents to treat cancers and autoimmune diseases, more patients could be susceptible to infection from traditionally rare pathogens like L. mesenteroides. Physicians should consider Leuconostoc infection in patients with known risk factors and isolation of a vancomycin-resistant Streptococcus.
Article citation: Gordon D, Peterson CJ, Vattikonda KS, Wang YD. Lock, stock, and Leuconostoc: An unusual presentation of a rare pathogen. The Southwest Respiratory and Critical Care Chronicles 2024;12(53):54–57
From: Department of Internal Medicine, Virginia Tech Carilion School of Medicine, Roanoke, VA
Submitted: 6/27/2024
Accepted: 9/11/2024
Conflicts of interest: none
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