Fluoroquinolones for the treatment of latent Mycobacterium tuberculosis infection in liver transplantation

Table 1 Risk factors and indications of latent tuberculosis infection treatment in the liver transplant setting (adapted from Meije et al[20] and Bosh et al[22])

Risk factors include:
Residence in a high-endemicity area
Age greater than 50 years
Homelessness or incarceration
Personal or donor history of TB
Diabetes mellitus, malnutrition, HIV infection, end-stage liver disease
Chest radiography or CT scan showing abnormalities
Intensification of immunosuppression for rejection; use of everolimus, sirolimus and T-cell-depleting antibodies
LTBI treatment should be prescribed to candidates with compensated cirrhosis or to recipients with normal liver allograft function and at least one of the following criteria:
TST (initial or after a booster effect) with an induration of ≥ 5 mm1
Positive IGRA result1
Recent change in the TST result
Personal or donor history of untreated or incorrectly treated TB
History of contact with a smear-positive TB patient
Residual TB lesions in an untreated patient

¹Only if the candidate or the recipient has not been previously treated for latent tuberculosis infection or active tuberculosis. CT: Computed tomography; HIV: Human immunodeficiency virus; IGRA: Interferon-γ release assay; LTBI: Latent tuberculosis infection; TB: Tuberculosis; TST: Tuberculin skin test.

Table 2 Reported fluoroquinolone-induced adverse events and outcomes associated with treatment of latent mycobacterium tuberculosis infection in liver transplantation

Author [ref.]	Type of patients	Treatment prescribed	Musculosk-eletal (joint pain, tendinopa-thy)	Gastrointe-stinal (diarrhea, vomiting)	Constitu-tional (fatigue, malaise)	Hepatotoxi-city	C. difficile-associated diarrhea	Permanent withdrawal of FQ	Completed treatment
	n (%)		n (%)	n (%)	n (%)	n (%)	n (%)	n (%)	n (%)
Torre-Cisneros et al[46]	33 LT candidates	Levofloxacin	6 (18.2)	3 (9.0)	0 (0.0)	2 (6.1)	1 (3.0)	11 (33.0)1	18 (54.5)
Tien et al[47]	25 LT candidates and 6 additional LT recipients	Levofloxacin or moxifloxacin	5 (16.1)	4 (12.9)	4 (12.9)	0 (0.0)	2 (6.4)	2 (6.4)2	21 (67.7)
Grim et al[48]	8 LT and LT/KT candidates	Moxifloxacin	NA	NA	NA	NA	NA	NA	2 (25)3
Sgarabotto et al[49]	35 LT recipients	Levofloxacin plus ethambutol	NA	NA	NA	NA	NA	4 (11.4)4	NA

¹Fluoroquinolone treatment was primarily stopped due to tenosynovitis (5 patients [45.4%]) and hepatotoxicity [2 patients (18.2%)].

²Treatment was withdrawn due to tenosynovitis [1 patient (50.0%)] and severe constitutional symptoms [1 patient (50.0%)].

³Data not available on the other 6 patients.

⁴Prophylaxis was stopped due to tenosynovitis [2 patients (50.0%)], hepatotoxicity [one patient (25.0%)], and transient optical neuritis [one recipient (25.0%)]. FQ: Fluoroquinolone; KT: Kidney transplant; LT: Liver transplant; NA: Data not available.