Lactococcus lactis bacteraemia in a patient on probiotic supplementation therapy
- 1 Department of Medicine, Brown University Warren Alpert Medical School, Providence, Rhode Island, USA
- 2 Division of Infectious Diseases, Brown University Warren Alpert Medical School, Providence, Rhode Island, USA
- 3 Division of Hospital Medicine, Brown University Warren Alpert Medical School, Providence, Rhode Island, USA
- Correspondence to Dr Arkadiy Finn; afinn1@lifespan.org
Abstract
A 59-year-old woman presented with fever and malaise and was found to have Lactococcus lactis bacteraemia. L. lactis infection is rare in humans with few reported cases, with most associated with dairy food product ingestion. The patient reported use of a multistrain over-the-counter probiotic supplement. After isolation of L. lactis from blood culture, the patient was treated empirically with ertapenem and amoxicillin and displayed clinical improvement. She remained well after completion of antibiotic regimen and discontinued probiotic supplementation use. We review the clinical presentation of L. lactis infection including diagnosis, identification and treatment.
Background
Lactococcus lactis is a bacterium that is classified by United States Food and Drug Administration (US FDA) as generally regarded as safe (GRAS) status. It is essentially regarded as non-virulent, making it able to be added to specific foods for production of lactic acid in food processing. It can be found in cheese, yoghurt and milk and in many probiotics, and has been found in the gastrointestinal tract of healthy patients. Few case reports exist about symptomatic infection by L. lactis. The majority of studied cases of infection feature introduction of this organism via dairy food product ingestion, often in patients who are immunocompromised.
Case presentation
A 59-year-old woman with a history of chronic kidney disease, medullary sponge kidney, interstitial cystitis requiring bilateral ureterolysis, right ileal ureter replacement, and ileal loop diversion with multiple revisions presented to hospital with acute malaise, fevers, bilateral flank pain and headache. Her medical history was notable for self-catheterisation into her urinary stoma, recurrent urinary tract infections, and colonisation with multidrug resistant organisms including extended spectrum beta lactamase producing Escherichia coli. She reported fever to 39.4°C, diminished oral intake, and generalised malaise. She denied dysuria and malodorous or discoloured urine. She also denied ingestion of any dairy products including milk, yoghurt and cheese, largely due to personal preference.
Medications at home included nitrofurantoin daily as urinary infection prophylaxis and a daily over-the-counter probiotic supplement. The patient did not use tobacco products, alcohol, or any other substances. Her occupation was counselling psychologist.
On examination, the patient was found to have a temperature of 37.7°C, a pulse rate of 85 beats/min, and a blood pressure 90/55 mm Hg. In general, she was alert, fatigued and in no distress. Abdominal examination revealed a soft abdomen without tenderness or guarding. She had mild flank tenderness and urostomy site with a urinary catheter draining clear yellow urine. The rest of the examination was unremarkable.
Investigations
The patient’s white blood cell count was 8.8×109/L, with a differential including 72% neutrophils. Her blood urea nitrogen (BUN) was 29 mg/dL, creatinine 1.6 mg/dL with a previously noted baseline creatinine of 1.3 mg/dL. The urinalysis was negative for nitrites and positive for leucocyte esterase, and microscopy revealed >180 white blood cells per high powered field, squamous epithelial cells, and bacteria. Urine cultures grew normal urogenital flora.
A CT scan of the abdomen and pelvis showed stable hydronephrosis of the renal collecting systems, with diffuse urothelial enhancement bilaterally, which was a chronic finding.
Two sets of peripheral blood cultures, one set of two bottles drawn at 24 hours and one set of two bottles drawn at 30 hours, all grew gram positive cocci suggestive of streptococci vs enterococci. These were ultimately speciated as L. lactis.
Differential diagnosis
Following the gram stain results, the most likely causal organism seemed to be enterococcus given its predilection for the genitourinary tract, with a streptococcal strain also on the differential. After speciation to L. lactis, several explanations remained for the patient’s presentation. It is possible that the L. lactis could be contaminant, although this is unlikely as it was present in both of the two blood cultures. A urinary tract infection was also considered given the presence of fever, flank pain and pyuria. However, the patient’s urinary culture was negative. The source of L. lactis bacteraemia was difficult to ascertain. The patient routinely used an over-the-counter probiotic. The ingredient list for this probiotic did not specify the presence of L. lactis but a complete list of ingredients was not provided. Additionally, a history of antibiotic use and surgically altered gastrointestinal and genitourinary tract anatomy may have predisposed the patient to L. lactis colonisation and subsequent contiguous spread of the bacteria, for example, through the wall of her ileal conduit or peristomal hernia.
Treatment
The patient was admitted to hospital for treatment of sepsis and fever and received intravenous ertapenem as an empiric treatment of extended-spectrum beta-lactamase producing organism causing urinary tract infection . Following speciation to L. lactis and clinical improvement, she was discharged with a 14-day course of amoxicillin.
Outcome and follow-up
The patient’s sepsis resolved with antibiotics and she was discharged home in improved condition. At 2-week outpatient follow-up, she remained free of fevers, with good urine output and no signs of urinary or systemic infection. She had also discontinued her probiotic.
Discussion
L. lactis is a facultative, anaerobic Gram-positive coccus used widely in the production of fermented dairy products.1–3 Although generally considered to be non-pathogenic to humans, reports of L. lactis infection have increased over the past two decades.1–4 Identification of this organism is complicated by requirement for specialised media and prolonged incubation, likely leading to under-reporting of infection.1–4
Thirty-eight cases of clinically significant infection in humans with L. lactis have been reported, and all but two of these cases have been reported in the last two decades.1 5–10 In patients with L. lactis bacteraemia, presenting problems and findings may include fever, chills, diaphoresis, leukocytosis and neutrophilia. Reported sites of infection include endocarditis, cholangitis, peritonitis, pneumonia, soft tissue and joint infection, brain abscess and bacteraemia.1–10 Colonisation of the gastrointestinal and genitourinary tracts, as well as consumption of pasteurised and unpasteurised dairy products including yoghurt, buttermilk and cheese, have been implicated as sources of exposure to L. lactis. According to one report, exposure to L. lactis through food products was documented in 33 of 36 reported cases.1
Our report is the first to our knowledge in which L. lactis bacteraemia was associated with an over-the-counter probiotic supplement, as our patient denied all dairy consumption. An alternative explanation may be colonisation of the GI tract with L. lactis and translocation into the blood stream through the wall of the ileal conduit. Many cases of L. lactis infection are associated with an immunosuppressed state such as presence of malignancy or HIV infection, which in our patient may be attributed to abnormal genitourinary tract anatomy and frequent exposure to broad spectrum antibiotic therapy.1 3–7 10
L. lactis has been used as a dairy additive in the production of fermented dairy products such as yoghurt and buttermilk for centuries.11 The US FDA, which evaluates product safety for human consumption, rates L. lactis with ‘generally recognised as safe’ status. As a lactic acid fermenter, this bacterium imparts flavour and preservative qualities in food production. Additionally, modern bacterial science has greatly expanded the uses of L. lactis as a molecular factory to produce various industrial enzymes and compounds.12 L. lactis is an attractive choice as a probiotic supplement ingredient as it is able to survive in the human digestive tract, produces bacteriocins molecules which may be inhibitory to pathogenic gut bacteria, and possess anti-inflammatory and antioxidant properties.11 12 Studies to confirm clinical benefit are lacking. It is difficult to determine how widespread the use of L. lactis in the consumer probiotic supplement industry. Our patient’s probiotic supplement was purchased from a major commercial internet vendor.
Unlike other bacteria used in food preparation, L. lactis is not affected by digestion due to its high tolerance of low pH environments, L. lactis and may gain access to the bloodstream or gut immune system.13 The pathogenicity of L. lactis is not well identified but may be similar to Enterococcus, although with a lower virulence. L. lactis includes three subspecies: L. lactis subspecies lactis, L. lactis subspecies cremoris and L. lactis subspecies hordniae.14–17 L. lactis subspecies lactis and L. lactis subspecies cremoris have been identified to cause infection in humans. They have few phenotypic and genotypic differences and may be difficult to tell apart.1 13 17 Identification methods include bacterial culture which requires nutritionally rich media, matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS)—a method which analyses whole-cell protein patterns, and 16S rRNA sequencing.17
Treatment of L. lactis bacteraemia is centred on eradication from blood cultures and investigation for another site of infection. In our case, CT of the abdomen and pelvis was performed. Standardised antibiotic treatment for L. lactis infection has not been established due to low incidence of infection.1 13 In reported cases, therapeutic regimen was based on the result of susceptibility tests and included penicillins and other beta-lactams, in combination with beta-lactamase inhibitors, fluoroquinolones, cephalosporins with aminoglycosides, and vancomycin.2–10 13 Our isolate was not analysed for susceptibility. Our patient was treated with empiric ertapenem while hospitalised and amoxicillin after discharge home.
In conclusion, clinicians should remain aware of possible L. lactis infection, particularly in the setting of altered immune system function or exposure to dairy food products and/or probiotics.
Learning points
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L. lactis is a bacteria that is generally regarded and United States Food and Drug Administration approved as safe for use in the production of commercial probiotics and dairy products.
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Nevertheless, clinicians should be mindful of possible L. lactis infection, especially in patients with altered immune system function or exposure to dairy food products and/or probiotics.
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L. lactis bacteraemia can lead to metastatic septic complications.
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L. lactis is usually susceptible to penicillins and other beta-lactam antibiotics.
Ethics statements
Footnotes
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Contributors AF and AG were responsible for primary manuscript writing and data gathering. TO and JMG were responsible for manuscript editing and data gathering.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Competing interests None declared.
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Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.
References
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