Characteristics of and treatment outcomes in rifampicin-intolerant patients.

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

CONTEXTE: La rifampicine (RIF) est généralement considérée comme le pilier du traitement de la TB, cependant, ses effets indésirables limitent fréquemment son utilisation. MÉTHODES: Dans cette étude de cohorte rétrospective nous avons examiné les patients traités pour la TB dans notre institution et avons comparé ceux qui ont reçu la RIF à ceux qui n'ont pas pu la tolérer. RÉSULTATS: Au total, 829 patients ont été inclus. Soixante-seize patients (9%) étaient intolérants au RIF. Les patients intolérants au RIF étaient significativement plus âgés (âge médian : 67 ans, IQR 50­78 vs. 48 ans, IQR 31­70 ; P < 0,0001), et étaient plus susceptibles d'être des femmes (57% vs. 41% ; P = 0,01) et d'avoir un diabète sucré concomitant (37,3% vs. 19% ; P < 0,0001) par rapport à ceux qui toléraient le RIF. L'intolérance au RIF était principalement due à une transaminite (25%), une cytopénie (14,5%), une éruption cutanée (17,1%) et une intolérance gastro-intestinale (7,8%). Vingt patients ont ensuite été soumis à un test de provocation à la rifabutine, avec un taux de succès de 70%. La durée moyenne du traitement était significativement plus longue chez les patients intolérants au RIF (335 vs. 270 jours ; P < 0.001). Aucune différence significative n'a été observée dans les résultats du traitement. CONCLUSION: L'intolérance au RIF est plus courante chez les patients plus âgés, les femmes et les patients atteints de diabète sucré. Les patients qui n'ont pas pu tolérer le RIF ont suivi un traitement plus long, mais cela n'a pas entrainé de différence dans les résultats du traitement. Lorsqu'elle a été tentée, la rifabutine a été bien tolérée par la plupart des patients ayant déjà présenté un effet indésirable lié au RIF.

Phenotypic amikacin resistance may not indicate poor response to amikacin in Mycobacterium avium complex pulmonary disease.

When using amikacin to treat Mycobacterium avium complex pulmonary disease (MAC-PD), a minimum inhibitory concentration resistance breakpoint of ≥64 mcg/mL is recommended. We explored whether amikacin resistance characterized by phenotypic drug susceptibility testing was associated with clinical outcomes or mutational resistance in a retrospective cohort of patients with MAC-PD. Despite little aminoglycoside exposure, amikacin resistance was common in our MAC-PD patients but was not associated with worse outcomes or rrs gene mutations.

The epidemiologic relationship between tuberculosis and non-tuberculous mycobacterial disease: a systematic review.

SETTING: Tuberculosis (TB) rates are decreasing in many areas, while non-tuberculous mycobacteria (NTM) infection rates are increasing. The relationship between the epidemiology of TB and NTM infections is not well understood. OBJECTIVE: To understand the epidemiologic relationship between TB and NTM disease worldwide. DESIGN: A systematic review of Medline (1946-2014) was conducted to identify studies that reported temporal trends in NTM disease incidence. TB rates for each geographic area included were then retrieved. Linear regression models were fitted to calculate slopes describing changes over time. RESULTS: There were 22 studies reporting trends in rates of NTM disease, representing 16 geographic areas over four continents: 75% of areas had climbing incidence rates, while 12.5% had stable rates and 12.5% had declining rates. Most studies (81%) showed declining TB incidence rates. The proportion of incident mycobacterial disease caused by NTM was shown to be rising in almost every geographic area (94%). CONCLUSION: We found an increase in the proportion of mycobacterial disease caused by NTM in many parts of the world due to a simultaneous reduction in TB and increase in NTM disease. Research into the interaction between mycobacterial infections may help explain this inverse relationship.