IJTLD OPEN 1(4):160–165

http://dx.doi.org/10.5588/ijtldopen.23.0466

Characteristics of and treatment outcomes in

rifampicin-intolerant patients
R. Mangat,1 S.K. Brode,2,3 H.K. Mah,1 M.S. Brar,4 N.F. Sabur3,5
1
West Park Healthcare Centre, York, ON, 2Department of Respirology, Toronto Western Hospital, West Park Healthcare Centre,
Toronto, ON, Departments of 3Medicine, and 4Surgery, University of Toronto, Toronto, ON, 5Department of Respirology, St. Michael’s
Hospital, West Park Healthcare Centre, Toronto, ON, Canada
SUMMARY

BACKGROUND: Rifampicin (RIF) is considered the to transaminitis (25%), cytopenia (14.5%), rash (17.1%)
backbone of TB treatment, but adverse effects often limit and gastro-intestinal intolerance (7.8%). Twenty patients
its use. were subsequently challenged with rifabutin, and this was
M E T H O D S : This retrospective cohort study examined successful in 70%. The mean treatment duration was
patients treated for TB disease at our institution, and significantly longer in patients who were intolerant to RIF
compared those who received RIF to those who were (335 vs. 270 days; P , 0.001). There was no significant
intolerant to RIF. difference in treatment outcomes.
R E S U L T S : A total of 829 patients were included. C O N C L U S I O N : RIF intolerance is more common in older
Seventy-six patients (9%) were intolerant to RIF. Patients patients, females, and those with concurrent diabetes
with RIF intolerance were significantly older (median age: mellitus. Patients who could not tolerate RIF had a longer
67 years, IQR 50–78 vs. 48 years, IQR 31–70; P , duration of therapy, but no difference in treatment out-
0.0001), and were more likely to be female (57% vs. comes. When attempted, rifabutin was well tolerated in
41%; P ¼ 0.01) and have concurrent diabetes mellitus most patients with a previous RIF-related adverse event.
(37.3% vs. 19%; P , 0.0001) compared to those who K E Y W O R D S : tuberculosis treatment; treatment intoler-
tolerated RIF. RIF intolerance was most commonly due ance; RIF; rifabutin; adverse effects

According to the WHO, an estimated 10.6 million available regarding the use of RFB in patients who are
people were diagnosed with TB in 2021.1 TB continues intolerant of RIF.
to be a leading infectious cause of death worldwide Prior to the introduction of standardised shorter
with mortality rates of up to 50% if untreated. multidrug-resistant TB (MDR-TB) treatment regi-
Adherence to a treatment regimen is critical for curing mens, the World Health Organization recommended a
TB disease, limiting the spread of infection, and total treatment duration of 18–20 months in indi-
preventing the development of drug resistance.2 viduals with RIF-resistant TB,7 and clinical practice
Rifamycins, a class of antibiotics including rifam- guidelines published by the American Thoracic
picin (RIF), rifabutin (RFB) and rifapentine, are of Society/US Centers for Disease Control/European
significant importance in the treatment of TB given Respiratory Society/Infectious Diseases Society of
their substantial sterilising activity, which is critical to America recommend a total treatment duration of
the prevention of relapse; they also have moderate 15–21 months for RIF-resistant/MDR-TB.8 Similarly,
early bactericidal activity and play an important role in the Canadian Tuberculosis Standards recommend
the prevention of drug resistance.3 RIF is the most extending therapy to 12–18 months if a rifamycin is
commonly used rifamycin and is part of the recom- not included in the treatment of drug-susceptible TB.3
mended standard first-line treatment regimen in Although critically important to the TB treatment
combination with isoniazid, pyrazinamide and eth- regimen, RIF intolerance if fairly common,9 resulting
ambutol. RIF inhibits bacterial RNA polymerase in a in exclusion from the TB treatment regimen and
concentration dependent manner.4 Its use is often substantially longer treatment courses that are asso-
limited by drug–drug interactions via induction of the ciated with greater toxicity and poorer adherence.10,11
cytochrome p450 enzyme system and P-glycoprotein In our tertiary TB referral centre, where many
multidrug efflux transporters,5 or by adverse effects, patients are elderly and medically complex, RIF
including dermatologic events, cytopenias, trans- intolerance is relatively common. We sought to
aminitis and gastrointestinal intolerance. RFB has a compare characteristics and outcomes between
similar mechanism of action, but has fewer drug–drug patients who received RIF throughout treatment and
interactions,6 and has been widely used in patients those who were RIF-intolerant. We reviewed reasons
with HIV co-infection. However, limited data are for RIF discontinuation, identified risk factors for RIF

Correspondence to: Natasha F Sabur, St Michael’s Hospital, Rm 6-045, 30 Bond St, Toronto ON, M5B 1W8, Canada. email:
natasha.sabur@unityhealth.to
Article submitted 24 September 2023. Final version accepted 23 February 2024.
 Rifampicin-intolerant patients 161

intolerance, and evaluated the patients who were attained for use in MDR-TB in Canada during the
successfully treated with RFB in place of RIF. study period and was therefore not used in this
population.
METHODS Data collection
West Park Healthcare Centre is a provincially desig- Patient demographics at the time of treatment initia-
nated treatment centre for TB and is one of three adult tion, including age, weight, and country of birth/
TB clinics in the city of Toronto, ON, Canada, which origin; clinical details including location of disease
service a population of approximately 2.96 million and comorbidities; and TB characteristics, including
people, and a broader population of 6.4 million in the smear positivity and microbiologic features were
Greater Toronto Area.12 Approximately 300 new retrospectively abstracted from patient charts.
cases of TB disease are reported each year in Subsequent treatment details including medications
Toronto.13 received, duration of each treatment, laboratory
We conducted a retrospective cohort study of all abnormalities, and patient reported adverse events
patients with TB disease treated at our institution over the course of treatment were also abstracted.
between 1 January 2010 and 31 August 2020. The Drugs given for .8 consecutive weeks were considered
study was approved by the West Park Healthcare included as part of the treatment regimen. Clinical
Centre Research Ethics Board, Toronto, ON, Canada. outcomes over a minimum 2-year follow-up period
were recorded.
Study inclusion and exclusion criteria
We included patients who met the following criteria: Adverse events and clinical outcomes: definitions
age .18 years; diagnosis of TB disease (by nucleic acid Adverse events were defined as any clinical or labo-
amplification testing, culture, or clinical diagnosis); ratory abnormality requiring treatment alteration (at
received RIF initially as part of the intended treatment the discretion of the treating clinician). Blood work
regimen; and initiated treatment between 1 January was monitored weekly in inpatients and at least
2010 and 31 August 2020. Patients were excluded monthly in outpatients. End of treatment outcomes
from the study if they had RIF resistance or if they were defined according to previous WHO definitions,
never received RIF as part of their initial treatment. and included success (cure/treatment completion),
treatment failure, death during treatment, and loss to
Institutional approach to drug intolerance follow up/not evaluated.15 The definition for treat-
We are a referral site for complex TB and as such, our ment failure was modified slightly from the WHO such
patient population has significant co-morbid disease that a regimen change due to adverse events alone was
and medical complexity. Medications are frequently not considered a failure. All patients who had outcomes
stopped and restarted in the early phases of treatment evaluated without loss to follow up were followed for a
as a regimen is being established. Medications are minimum of 2 years post-treatment completion to assess
taken on an empty stomach. When gastro-intestinal for relapse.
(GI) intolerance is encountered, antibiotics are divided
over the day and anti-nausea medications are Statistical analysis
administered. For other adverse events, therapy is Descriptive statistics were calculated for baseline
stopped and sequential rechallenge attempted until an variables and treatment characteristics. Categorical
alternative regimen is constructed. Minor drug tox- variables were expressed as number (percentage) and
icity is often overcome with supportive care during the mean (standard deviation [SD]) using the v2 test
drug rechallenge period. Once the culprit drug/drugs or Fisher’s exact test; continuous variables were
are identified, new drugs are introduced until the expressed as median (interquartile range [IQR]) using
regimen is felt to be adequate by the treating physician. the Mann–Whitney U-test. For binary treatment
outcomes, exact binomial confidence intervals were
Definition of rifampicin intolerance reported. Risk factors associated with intolerance on
Patients were considered RIF intolerant if they re- univariate analysis were included in a logistic regres-
ceived RIF for ,8 consecutive weeks. Eight weeks was sion model. Statistical significance was set at P ,0.05.
chosen as a cut-off since most adverse events with RIF All analyses were performed using Stata v15 (Stata-
are known to occur during the early weeks of treat- Corp, College Station, TX, USA).
ment.14 Eight weeks is also the duration of the in-
tensive phase of TB treatment and an important time
RESULTS
point in TB treatment.
Alternative medications used included fluo- Patient characteristics and treatment details
roquinolones (moxifloxacin or levofloxacin), clofazi- Patient characteristics are detailed in Table 1. Nine
mine, amikacin, para-aminosalicylic acid, cycloserine, hundred and twelve patients had a diagnosis of TB and
ethionamide and linezolid. Bedaquiline could only be were screened for inclusion into the study; 75 patients
162 IJTLD OPEN

Table 1. Baseline patient characteristics.

RIF-tolerant RIF-intolerant
(n ¼ 753) (n ¼ 76)
n/N (%) n/N (%) P-value
Female sex 312/753 (41) 43/76 (57) 0.01
Age, years, median [IQR] 48 [31–70] 67 [50–78] ,0.001
BMI, kg/m2, median [IQR] 21.4 [18.8–24.6] 22.1 [18.9–24.6] 0.61
Region of origin 0.51
Africa 97 (12.9) 8 (10.5)
Americas 130 (17.3) 5 (6.6)
Europe 36 (4.8) 5 (6.6)
South-East Asia 475 (63.2) 56 (73.7)
Eastern Mediterranean 14 (1.9) 1 (1.3)
Western Pacific 0 1 (1.3)
TB location
Pulmonary 404 (53.7) 48 (63.2)
Extrapulmonary 133 (17.7) 10 (13.2)
Both 216 (28.7) 18 (23.7)
TB characteristics
AFB smear-positive 360 (48.2) 39 (52) 0.25
Cavitary disease 234 (31.1) 25 (32.9) 0.75
Bilateral disease 334 (44.7) 42 (55.3) 0.08
Comorbidities
HIV 15 (2.2) 3 (4.3) 0.28
Diabetes mellitus 143 (19.0) 28 (37.3) ,0.001
Smoking 136 (18.8) 6 (8.3) 0.08
Alcohol use 256 (35.3) 14 (19.4) 0.02

RIF ¼ rifampicin; IQR ¼ interquartile range; BMI ¼ body mass index; AFB ¼ acid-fast bacilli.

had RIF resistance, and 8 patients were started directly RIF tolerance; however, this was not statistically
on RFB due to expected drug-drug interactions. significant.
Therefore, over the study period, a total of 829 patients Details of treatment are described in Tables 2 and 3.
met inclusion criteria; 43% were female and 83% had Table 2 outlines the medications used in patients who
pulmonary involvement. did not tolerate RIF. Isoniazid (68%), ethambutol
Seventy-six patients (9%) were intolerant to RIF. (68%), a fluoroquinolone (moxifloxacin or levo-
The median time to RIF discontinuation in those who floxacin) (53%) and pyrazinamide (45%) were most
were intolerant was 14 days (IQR 7–33). On univariate commonly used. The majority of patients (76%) were
analysis, patients with RIF intolerance were significantly established on a 3 or 4 drug treatment regimen in the
older (median age: 67 years, IQR 50–78 vs. 48 years, absence of RIF (Table 3).
IQR 31–70; P , 0.0001), and were more likely to be
female (57% vs. 41%; P ¼ 0.01) and have concurrent Adverse events
diabetes mellitus (DM) (37.3% vs. 19%; P , 0.0001)
Adverse events attributed to RIF and RFB are outlined
than those who tolerated RIF. These associations
in Table 4. RIF intolerance was most commonly due to
remained significant on multivariate analysis. There was
transaminitis (25%), followed by rash (17.1%), GI
a higher rate of alcohol use in patients who tolerated RIF
intolerance (7.8%) and thrombocytopenia (7.8%).
than those who did not (35.3% vs. 19.4%; P ¼ 0.02) and
Cytopenia (leukopenia, thrombocytopenia or pancy-
a trend towards a higher rate of smoking in patients with
topenia) occurred in 11 patients (14.5%).
Of the RIF-intolerant patients, 20 (26.3%) patients
Table 2. Drugs included in treatment regimens in patients with
RIF intolerance.
were challenged with RFB, and of these, 70% were
challenged successfully (i.e., did not experience an
Drugs included in adverse event prompting RFB discontinuation). RFB
treatment regimen (RIF-intolerant) (n ¼ 76)
was not tolerated in 6 patients due to rash (n ¼ 2),
Isoniazid 52 (68.4)
Ethambutol 52 (68.4) Table 3. Number of drugs included in treatment regimen in
Fluoroquinolone* 40 (52.6) patients with rifampicin intolerance.*
Pyrazinamide 34 (44.7)
Rifabutin 14 (18.4) (n ¼ 57)
Clofazimine 9 (11.8) Number of drugs used n (%)
Amikacin 6 (7.9)
Para-aminosalicylic acid 3 (3.9) 2 6 (10.5)
Cycloserine 3 (3.9) 3 22 (38.6)
Ethionamide 1 (1.3) 4 21 (36.8)
Linezolid 1 (1.3) 5 6 (10.5)
6 2 (3.5)
* Moxifloxacin or levofloxacin were used in all patients who received a
fluoroquinolone. * Drugs included only if documented to have been given for .8 weeks
RIF ¼ rifampicin. consecutively.
 Rifampicin-intolerant patients 163

Table 4. Adverse events related to RIF and RFB use. that alternative treatment regimens could be
RIF RFB constructed despite RIF-related adverse events in our
Adverse events leading (n ¼ 76) (n ¼ 20) population. We found no significant difference in
to drug discontinuation n (%) n (%) treatment outcomes between RIF-tolerant and RIF-
Transaminitis 19 (25) 1 (5) intolerant patients, although those who were unable to
Rash 13 (17.1) 2 (10) tolerate RIF had a significantly longer duration of
Thrombocytopenia 6 (7.9) 2 (10)
GI intolerance 6 (7.9)
therapy. Although our sample size was limited, we
DRESS syndrome 5 (6.6) found that when attempted, RFB was well tolerated in
Anaphylaxis 5 (6.6) 1 (5) the majority of patients with a previous RIF-related
Hyperbilirubinemia 5 (6.6)
Confusion 4 (5.3)
adverse event.
Renal failure 3 (3.9) RIF has excellent sterilising activity and is consid-
Drug interaction 3 (3.9) ered the backbone of standard TB treatment.2
Leukopenia 3 (3.9)
Pancytopenia 2 (2.6)
Guidelines recommend prolonged courses of TB
Eosinophilia 1 (1.3) treatment in the absence of rifamycins. However, RIF
Hypertension 1 (1.3) intolerance is common, and historically, has been
RIF ¼ rifampicin; RFB ¼ rifabutin; GI ¼ gastrointestinal; DRESS ¼ drug reaction described in 2-4% of patients.9 A previous study
with eosinophilia and systemic symptoms. conducted in New York City, NY, USA, assessed rates
and risk factors of RIF discontinuation in patients with
thrombocytopenia (n ¼ 2), transaminitis (n ¼ 1) and TB, and determined that while RIF was discontinued
anaphylaxis (n ¼ 1). Three patients had the same in 2% of patients, only 1% of discontinuations were
adverse event with RFB as that experienced with RIF done for appropriate reasons, including serious
(one patient with rash, one with thrombocytopenia adverse reactions such as thrombocytopenia, kidney
and one with anaphylaxis). injury, hyperbilirubinemia or drug-induced rash/
fevers.24 We had a substantially higher rate of RIF
Treatment outcomes intolerance (9% of all patients), however as we are a
The mean treatment duration was 270 days (SD �187) tertiary TB centre, many of our patients are referred
in patients who tolerated RIF, compared to 335 days with complex disease, significant comorbidities or
(SD �200, P , 0.001) in those with RIF intolerance. with already established drug intolerance. In our
There was no significant difference in treatment out- cohort, transaminitis, cytopenia, serious drug rash and
comes between the two groups (P ¼ 0.52) (Table 5). refractory GI intolerance were the most common
reasons for RIF to be discontinued. Similar to other
studies in the literature, patients in our cohort who did
DISCUSSION
not tolerate RIF typically received 3–4 drugs during
Our study demonstrates that RIF intolerance is more their treatment, and had a prolonged treatment
common in older patients, in females, and in those course.14
with concurrent DM. Our findings are in keeping with Treatment regimens for drug susceptible TB are
a number of case series in the literature describing significantly prolonged in the absence of rifamycin
higher rates of medication-related adverse events in therapy, and there has been longstanding interest in
both drug-susceptible and MDR-TB in elderly using RFB in place of RIF due to better tolerability
patients,16,17 and in those with DM.18,19 Although TB and fewer drug–drug interactions.25,26 Although a
is more commonly diagnosed in males, and males Cochrane review published in 2019 found no differ-
are known to have more unfavourable treatment ence in adverse events between RFB and RIF,27 many
outcomes and higher mortality,20,21 several studies case reports and case series in the published literature
suggest that drug intolerance is more commonly describe improved tolerability of RFB, and its
experienced by female patients.22,23 We found that successful use in place of RIF, including in the
females were more likely to have intolerance to RIF, HIV-infected population,28 the elderly,29 and in those
but there was no difference in treatment outcomes with prior adverse events with rifampin.30–32 A ret-
between males and females in our cohort, indicating rospective study published in 2011 examined a cohort

Table 5. Treatment outcomes.

RIF-tolerant RIF-intolerant
n (%) n (%) P-value
Total treatment duration, days, mean � SD 270 � 187 335 � 200 ,0.001
Treatment outcomes
Success 522 (69.3) 48 (63.2) 0.52
LTFU/not evaluated 202 (26.8) 24 (31.6)
Death 29 (3.9) 4 (5.3)
RIF ¼ rifampicin; SD ¼ standard deviation; LTFU ¼ loss to follow-up.
164 IJTLD OPEN

of TB patients in Seattle, WA, USA, and out of References

100 patients with an adverse effect from RIF, 57 were 1 World Health Organization. Global tuberculosis report, 2022.
challenged with RFB. Of these, 72% completed Geneva, Switzerland: WHO, 2022.
treatment successfully with RFB. In this cohort, those 2 Nahid P, et al.; Official American Thoracic Society/Centers for
Disease Control and Prevention/Infectious Diseases Society of
with a dermatologic reaction to RIF were less likely to America Clinical Practice Guidelines: Treatment of drug-
tolerate RFB.33 Our cohort excluded patients who susceptible tuberculosis. Clin Infect Dis 2016;63(7):e147–
were started on RFB at TB treatment initiation, and e195.
3 Johnston JC, Cooper R, Menzies D. Chapter 5: Treatment of
this included many of our HIV-infected patients and
tuberculosis disease. Can J Respir Crit Care Sleep Med 2022;6(1):
those with known RIF-related drug–drug interactions, 66–76.
including those on methadone and direct oral anti- 4 Campbell EA, et al. Structural mechanism for rifampicin inhibition
coagulants. In our group, 26% of patients with an of bacterial rna polymerase. Cell 2001;104(6):901–912.
5 Baciewicz AM, et al. Update on rifampin and rifabutin drug in-
adverse event to RIF were challenged with RFB, and
teractions. Am J Med Sci 2008;335(2):126–136.
this was successful in 70% of patients. Similar to our 6 Tuloup V, et al. Model-based comparative analysis of rifampicin
group, a cohort from Taiwan demonstrated that 72% and rifabutin drug-drug interaction profile. Antimicrob Agents
of patients who were intolerant to RIF were able to Chemother 2021;65(9):e0104321.
7 World Health Organization. WHO consolidated guidelines on
tolerate RFB.30 In our cohort, 13 patients with a prior drug-resistant tuberculosis treatment. Geneva, Switzerland:
cutaneous reaction to RIF were challenged with RFB, WHO, 2019.
and only a single patient had a similar reaction to RFB. 8 Nahid P, et al. Treatment of drug-resistant tuberculosis. An Of-
There are several limitations to our study. Over the ficial ATS/CDC/ERS/IDSA Clinical Practice Guideline. Am J Respir
Crit Care Med 2019;200(10):e93–e142.
10-year study period, treatment varied widely in 9 A controlled clinical trial of daily and intermittent regimens of
patients who did not tolerate first-line regimens. Our rifampicin plus ethambutol in the retreatment of patients with
study was retrospective in nature. Because only a pulmonary tuberculosis in Hong Kong. A Hong Kong Tubercu-
limited number of patients were challenged with RFB, losis Treatment Services/Brompton Hospital/British Medical Re-
search Council investigation. Tubercle 1974;55(1):1–27.
we were unable to analyse for predictors of RFB 10 Mase SR, Chorba T. Treatment of drug-resistant tuberculosis. Clin
intolerance in patients who were intolerant to RIF. Chest Med 2019;40(4):775–795.
Our treatment success rates were lower than those of 11 Zhu QQ, et al. Factors associated with non-adherence for pre-
other Canadian centres, which are reported to scribed treatment in 201 patients with multidrug-resistant and
rifampicin-resistant tuberculosis in Anhui Province, China. Med
be .90%.34 There are several reasons for this. TB care Sci Monit 2022;28:e935334.
in Ontario is decentralised, such that the majority of 12 City of Toronto. Toronto at a glance. Toronto, ON, Canada: City
straightforward pulmonary TB is treated in the of Toronto, 2023. https://www.toronto.ca/city-government/
data-research-maps/toronto-at-a-glance/ Accessed September
community. As we are a tertiary care centre for TB, 2023.
patients referred to our site tend to be more medically 13 City of Toronto. Programs and services for tuberculosis. Toronto,
complex with significant comorbid illness, higher rates ON, Canada: City of Toronto, 2023. https://www.toronto.ca/
of drug resistance/intolerance, and more disseminated/ community-people/health-wellness-care/health-programs-advice/
tuberculosis-tb/programs-services-for-tuberculosis-tb/ Accessed
multi-organ disease. Once patients are established on September 2023.
appropriate treatment, their care is often transferred 14 Kim HJ, et al. Real-world experience of adverse reactions-
back to the original care provider, leading to a high necessitated rifampicin-sparing treatment for drug-susceptible
number of lost to follow up outcomes in our cohort. pulmonary tuberculosis. Sci Rep 2023;13(1):11275.
15 World Health Organization. Definitions and reporting framework
Data on final drug treatment regimen and duration for tuberculosis - 2013 revision. Geneva, Switzerland: WHO,
were consequently also missing for many patients. 2013.
We describe our experience with RIF intolerance in 16 Tabernero E, et al. TB in the elderly: clinical features and out-
a low-incidence/high-resource setting. Our study comes. Int J Tuberc Lung Dis 2022;26(9):842–849.
17 Chopra KK, Matta S, Arora VK. Drug resistant tuberculosis
highlights the high rate of adverse events from RIF in among elderly: Challenges. Indian J Tuberc 2022;69 Suppl 2:
older patients, females, and those with DM, and adds S202–S204.
to the limited but growing body of literature reporting 18 Siddiqui AN, Khayyam KU, Sharma M. Effect of diabetes mellitus
successful use of RFB in the treatment of TB in patients on tuberculosis treatment outcome and adverse reactions in
patients receiving directly observed treatment strategy in India:
who are intolerant to RIF. We believe that more a prospective study. Biomed Res Int 2016;2016:7273935.
patients can be challenged with RFB after RIF intol- 19 Munoz-Torrico M, et al. Diabetes is associated with severe ad-
erance, as many of these patients will be able to verse events in multidrug-resistant tuberculosis. La diabetes se
asocia con reacciones adversas graves en la tuberculosis multi-
successfully complete a rifamycin-based treatment
rresistente. Arch Bronconeumol 2017;53(5):245–250. [Article in
regimen. Further research in this field including the use English, Spanish]
of prospective studies would be beneficial. 20 Deshmukh S, et al. Sex differences in TB clinical presentation,
drug exposure, and treatment outcomes in India. Chest 2023;
163(4):778–789.
Acknowledgements 21 Chidambaram V, et al. Male sex is associated with worse mi-
crobiological and clinical outcomes following tuberculosis
The authors would like to thank H Song, J McNamee and P Derkatch treatment: a retrospective cohort study, a systematic review of
for their contributions. the literature, and meta-analysis. Clin Infect Dis 2021;73(9):
Conflicts of interest: none declared. 1580–1588.
 Rifampicin-intolerant patients 165

22 Thontham A, Polsook R. Symptom experience of adverse drug associated tuberculosis. A single-blind randomized evaluation in
reaction among male and female patients with newly diagnosed Ugandan patients with HIV-1 infection and pulmonary tuber-
pulmonary tuberculosis in Thailand. Belitung Nurs J 2021;7(3): culosis. Tuberc Lung Dis 1995;76(3):210–218.
195–202. 29 Morimoto K, et al. [Clinical experience using rifabutin for treating
23 Resende LS, Santos-Neto ET. Risk factors associated with adverse infection with Mycobacterium tuberculosis in elderly Japanese
reactions to antituberculosis drugs. J Bras Pneumol 2015;41(1): patients]. Kekkaku 2013;88(8):625–628. [Japanese]
77–89. 30 Chien JY, et al. Safety of rifabutin replacing rifampicin in the
24 Cook SV, Fujiwara PI, Frieden TR. Rates and risk factors for treatment of tuberculosis: a single-centre retrospective cohort
discontinuation of rifampicin. Int J Tuberc Lung Dis 2000;4(2): study. J Antimicrob Chemother 2014;69(3):790–796.
118–122. 31 Tattevin P, et al. A regimen containing rifabutin for the treatment
25 McGregor MM, et al. Efficacy and safety of rifabutin in the of tuberculosis in patients intolerant to rifampin. Clin Infect Dis
treatment of patients with newly diagnosed pulmonary tuber- 2003;36(1):127–128.
culosis. Am J Respir Crit Care Med 1996;154(5):1462–1457. 32 Lehloenya RJ, et al. Therapeutic trial of rifabutin after rifampicin-
26 Burman WJ, Gallicano K, Peloquin C. Comparative pharmaco- associated DRESS syndrome in tuberculosis-human immunode-
kinetics and pharmacodynamics of the rifamycin antibacterials. ficiency virus coinfected patients. Open Forum Infect Dis 2016;
Clin Pharmacokinet 2001;40(5):327–341. 3(3):ofw130.
27 Davies GR, Cerri S, Richeldi L. Rifabutin for treating pulmonary 33 Horne DJ, Spitters C, Narita M. Experience with rifabutin
tuberculosis (Review). Cochrane Database Syst Rev 2007; replacing rifampin in the treatment of tuberculosis. Int J Tuberc
2007(4):CD005159. Lung Dis 2011;15(11):1485–1489, i.
28 Schwander S, et al. A pilot study of antituberculosis combinations 34 Campbell JR, et al. Costs of tuberculosis at 3 treatment centers,
comparing rifabutin with rifampicin in the treatment of HIV-1 Canada, 2010–2016. Emerg Infect Dis 2022;28(9):1814–1823.

R ÉS U M É

CONTEXTE: La rifampicine (RIF) est généralement con- une cytopénie (14,5%), une éruption cutanée (17,1%) et
sidérée comme le pilier du traitement de la TB, cependant, une intolérance gastro-intestinale (7,8%). Vingt patients
ses effets indésirables limitent fréquemment son utilisation. ont ensuite été soumis à un test de provocation à la
M ÉT H O D E S : Dans cette étude de cohorte rétrospective rifabutine, avec un taux de succès de 70%. La durée
nous avons examiné les patients traités pour la TB dans moyenne du traitement était significativement plus lon-
notre institution et avons comparé ceux qui ont reçu la gue chez les patients intolérants au RIF (335 vs. 270 jours ;
RIF à ceux qui n’ont pas pu la tolérer. P < 0.001). Aucune différence significative n’a été observée
R ÉS U L T A T S : Au total, 829 patients ont été inclus. dans les résultats du traitement.
Soixante-seize patients (9%) étaient intolérants au RIF. C O N C L U S I O N : L’intolérance au RIF est plus courante
Les patients intolérants au RIF étaient significativement chez les patients plus âgés, les femmes et les patients
plus âgés (âge médian : 67 ans, IQR 50–78 vs. 48 ans, atteints de diabète sucré. Les patients qui n’ont pas pu
IQR 31–70 ; P < 0,0001), et étaient plus susceptibles tolérer le RIF ont suivi un traitement plus long, mais cela
d’être des femmes (57% vs. 41% ; P ¼ 0,01) et d’avoir un n’a pas entrainé de différence dans les résultats du
diabète sucré concomitant (37,3% vs. 19% ; P < 0,0001) traitement. Lorsqu’elle a été tentée, la rifabutine a été bien
par rapport à ceux qui toléraient le RIF. L’intolérance au tolérée par la plupart des patients ayant déjà présenté un
RIF était principalement due à une transaminite (25%), effet indésirable lié au RIF.

IJTLD OPEN welcomes the submission of research articles on all aspects of TB and respiratory diseases such as
asthma, bronchiectasis, COVID-19, COPD, child lung health and the hazards of tobacco and air pollution.

This is an open access article published by The Union under the terms of the Creative Commons Attribution License CC-BY.

For information on IJTLD OPEN see: https://theunion.org/our-work/journals/ijtld-open or contact: journal@theunion.org