Tuberculosis (TB) is a major global public health problem. Lymph node TB is the most common form of extrapulmonary tuberculosis. In 2022, a total of 3,927 cases of TB were reported in Spain, 27.4% of which corresponded to extrapulmonary forms of TB.1 Within this group, the incidence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) pulmonary tuberculosis reached 0.38 per 100,000 population.2

The patient is a 51-year-old male patient from Equatorial Guinea. He has a family history of health issues including a brother who died at the age of 18 from hepatitis, and a daughter who suffered from an autoimmune disease and was treated with corticosteroids and died in a traffic accident. His medical history included an episode of miliary tuberculosis, which was caused by a strain of Mycobacterium tuberculosis (M. tuberculosis) complex that was resistant to isoniazid. Following diagnosis in June 2009, the patient received an empirical four-drug regimen for TB, with a positive response.

Throughout 2018, kidney function progressively declined, which ultimately led to the initiation of hemodialysis (HD) in 2019. It was suspected that kidney function deterioration was secondary to an unbiopsied chronic glomerulonephritis or obesity-associated hyperfiltration. Concurrently with this period, the patient experienced febrile episodes and a persistent elevation of acute-phase reactants despite negative microbiological cultures. Further events included a history of multisystem involvement, including uveitis, arthralgia/arthritis, and autoimmune hepatitis. A CT angiography revealed increased density involving the celiac trunk, distal abdominal aorta, and the left common and internal iliac arteries, which raised suspicion of large-vessel vasculitis. However, positron emission tomography-computed tomography (PET/CT) excluded the presence of vascular metabolic abnormalities. The results of immunological testing (immunoglobulins, complement, background disease study (PDS), antineutrophil cytoplasmic antibodies (ANCA) and antibodies against the glomerular basement membrane (anti-GBM)) were negative. The patient responded to a regimen of colchicine and prednisone.

In 2021, the patient experienced a further episode of fever with accompanied by ankle arthralgias and arthritis concurrently and a latero-cervical mass. Upon suspicion of inflammatory polyarthritis, corticosteroid therapy was reinitiated and colchicine dosage was increased. In view of the patient's history of TB, further investigations were performed. These include blood cultures, a Mantoux test, a lymph node biopsy and a CT scan of the neck, chest and abdomen. The Mantoux test result was positive. Adenectomy revealed signs of TB, which was subsequently confirmed through the growth of M. tuberculosis resistant to streptomycin, isoniazid, rifampicin, ethambutol, pyrazinamide, and ethionamide.

These findings led to the initiation of a regimen of intravenous amikacin (at a starting dose of 10 mg/kg/day), oral linezolid (LZD) 600 mg daily, and oral levofloxacin 500 mg administered post-dialysis. The patient underwent extended HD for 4.5 hours three days a week via a Solacea dialyzer. Amikacin pharmacokinetic monitoring enabled the adjustment of the regimen to 1000 mg administered over a three-day period per week and, subsequently, to 250 mg with the same frequency. After two weeks, LZD was switched to tedizolid (TZD) owing to the development of anemia and thrombocytopenia, along with an episode of generalized tonic–clonic seizure. Since monitoring of plasma LZD levels was not performed, it remains unclear whether these adverse events were related to supratherapeutic LZD levels.

Two months later, the patient was admitted to our hospital with a diagnosis of COVID-19 pneumonia. During admission, tuberculostatic therapy was optimized by the administration of oral clofazimine 200 mg once daily and oral bedaquiline (400 mg daily for the first two weeks and 200 mg every 48 hours after HD sessions). Amikacin was discontinued due to dizziness and vestibular instability.

A follow-up CT scan performed in January 2022 revealed radiological improvement of necrotized laterocervical lymphadenopathies. In light of these findings, the tuberculostatic treatment comprising bedaquiline, clofazimine, levofloxacin and TZD was continued until completion of the full six-month course of treatment.

Following the initiation of the drug therapy, there was a progressive decrease in inflammation, resulting in improvements in the patient's general condition, appetite and anemia. As adverse events, the patient developed lower-extremity peripheral neuropathy possibly associated with TZD toxicity. No adverse events were observed in relation to bedaquiline.

Table 1 contains a timeline of treatment adjustments.

The patient remained under the care of the Department of Nephrology and continued on hemodialysis three times per week until his death from COVID-19 in June 2025.

It is widely acknowledge that the immune response to M. tuberculosis depends to a considerably extent on cellular immunity. Consequently, individuals suffering from cellular immunodeficiency are subject to a substantially increased risk of developing active TB. Dialysis patients represent a particularly vulnerable group due to a number of factors including older age, immunosuppressive treatment, and uremia3. This results in a 6.9- to 52.5-fold higher risk of developing active TB, compared with the general population. With regard to disease presentation, some authors have reported a higher incidence of miliary tuberculosis in patients receiving HD, as compared with the general population.4

Added to a challenging diagnosis, the increased variety of drug-resistant strains makes management more difficult. Strains are categorized into three groups according to their drug resistance: MDR-TB, pre-XDR-TB and XDR-TB. Strains resistant to two or more first-line medications are known as MDR-TB, whereas those resistant to first-line drugs and fluoroquinolones or to second-line injectable drugs (capreomycin, streptomycin or other aminoglycosides) are called pre-XDR-TB.5

Patients with MDR tuberculosis should receive an individualized treatment guided by antitubercular drug susceptibility tests.6 In this case, a regimen was started including LZD, levofloxacin and amikacin associated with bedaquiline. In patients receiving kidney replacement therapy, dose adjustment is required for both levofloxacin and amikacin, whereas modification of the linezolid regimen is not necessary. Bedaquiline was not included in the initial combination due to issues related to its procurement as a foreign medication. As a result of the development of drug-related adverse events, treatment was optimized to bedaquiline, TZD and clofazimine, with additional levofloxacin for six months.

LZD has been proven to be effective for the treatment of MDR tuberculosis. However, the high frequency of adverse events –most notably peripheral neuropathy and myelotoxicity– often requires reducing the dose from 600 mg to 300 mg. Nevertheless, this strategy is often insufficient, and treatment must eventually be discontinued.7 In this case, a tonic–clonic seizure associated with LZD required switching LZD to TZD, another oxazolidinone. Although TZD is not indicated for the treatment of tuberculosis, it has demonstrated activity against M. tuberculosis strains in vitro.8 In addition, there are case reports of TB patients successfully treated with TZD instead of LZD.9

Bedaquiline is a relatively novel mycobacterium-specific adenosine 5′-triphosphate (ATP) synthase inhibitor. This compound exhibits a high degree of plasma protein binding (>99%) and is therefore unlikely to undergo substantial clearance during hemodialysis. Furthermore, the urinary excretion of the drug is less than 0.001%, which means that there is no need for dose adjustment unnecessary for patients receiving kidney replacement therapy. However, patients with kidney failure may exhibit abnormal absorption, distribution or secondary metabolism of the active compound; therefore, close monitoring is recommended.5

The combination of these compounds with clofazimine –a medication used to treat leprosy– emerges as a novel treatment regimen for MDR-TB. This compound is administered orally at a dose of 100 mg–or 200 mg for severe forms. A study involving eight patients who received a dose of 200 mg prior to dialysis revealed a negligible reduction of clofazimine levels.10

The main limitation of this case report was the delayed initiation of bedaquiline therapy due to bureaucratic issues and the absence of plasma levels of the medications administered.

A comprehensive literature search on PubMed was conducted, leading to the conclusion that this is the first documented case of a patient with HD who has successfully undergone treatment for multidrug-resistant (MDR) lympb node tuberculosis. The treatment regimen involved the administration of bedaquiline, TDZ, clofazimine and levofloxacin for a period of six months, resulting in favourable outcomes and minimal adverse events. This treatment regimen could be considered for hemodialysis patients with MDR tuberculosis exhibiting an antibiotic susceptibility profile similar to that of the present case.

All authors contributed equally to the preparation, correction and approval of the final version of this manuscript.

Paula Novo González: Writing – review & editing, Writing – original draft. Irene Galindo Marín: Validation, Data curation, Conceptualization. Elena García Benayas: Validation, Supervision, Methodology, Formal analysis, Conceptualization. Carmen Mon Mon: Methodology, Investigation, Formal analysis. Rafael Torres Perea: Validation, Investigation. Sara Hernández Egido: Validation, Investigation, Data curation.

The authors declare that informed consent was obtained from the patient for the publication of this case.

The authors declare that this work was funded by AstraZeneca and Sanofi.