Background Mycobacterium marinum is a nontuberculous mycobacterium that causes skin and soft tissue infections. Treatment consists of multiple antibiotics, sometimes combined with surgical... Show moreBackground Mycobacterium marinum is a nontuberculous mycobacterium that causes skin and soft tissue infections. Treatment consists of multiple antibiotics, sometimes combined with surgical debridement. There is little evidence for the choice of antibiotics, the duration of treatment, and the role of susceptibility testing. Methods We performed a retrospective cohort study of culture-confirmed M. marinum infections in the Netherlands in the 2011-2018 period. Clinical characteristics, in vitro susceptibility, extent of disease, treatment regimens, and outcomes were analyzed. Incidence was assessed from laboratory databases. Results Forty cases of M. marinum infection could be studied. Antibiotic treatment cured 36/40 patients (90%) after a mean treatment duration of 25 weeks. Failure/relapse occurred in 3 patients, and 1 patient was lost to follow-up. Antibiotic treatment consisted of monotherapy in 35% and 2-drug therapy in 63%. Final treatment contained mostly ethambutol-macrolide combinations (35%). Eleven patients (28%) received additional surgery. We recorded high rates of in vitro resistance to tetracyclines (36% of isolates). Tetracycline resistance seemed correlated with poor response to tetracycline monotherapy. The annual incidence rate was 0.15/100( )000/year during the study period. Conclusions Prolonged and susceptibility-guided treatment results in a 90% cure rate in M. marinum disease. Two-drug regimens of ethambutol and a macrolide are effective for moderately severe infections. Tetracycline monotherapy in limited disease should be used vigilantly, preferably with proven in vitro susceptibility. Show less
Substantial differences exist in virulence among Mycobacterium tuberculosis strains in preclinical TB models. In this study we show how virulence affects host responses in mice during the first... Show moreSubstantial differences exist in virulence among Mycobacterium tuberculosis strains in preclinical TB models. In this study we show how virulence affects host responses in mice during the first four weeks of infection with a mycobacterial strain belonging to the Beijing, East-African-Indian or Euro-American lineage. BALB/c mice were infected with clinical isolates of the Beijing-1585 strain or the East-African Indian (EAI)-1627 strain and host responses were compared to mice infected with the non-clinical H37Rv strain of the Euro-American lineage. We found that H37Rv induced a 'classical' T-cell influx with high IFN-gamma levels, while Beijing-1585 and EAI-1627 induced an influx of B-cells into the lungs together with elevated pulmonary IL-4 protein levels. Myeloid cells in the lungs appeared functionally impaired upon infection with Beijing-1585 and EAI-1627 with reduced iNOS and IL-12 expression levels compared to H37Rv infection. This impairment might be related to significantly reduced expression in the bone marrow of IFN-gamma, TNF-alpha and IFN-beta in mice infected with Beijing-1585 and EAI-1627, which could be detected from the third day post infection onwards. Our findings suggest that increased virulence of two clinical isolates compared to H37Rv is associated with a fundamentally different systemic immune response, which already can be detected early during infection. Show less
Uzorka, J.W.; Delfos, N.M.; Witte, A.M.C.; Scheper, H.; Soolingen, D. van; Arend, S.M. 2018
Animal studies have shown that the globally emerging Beijing genotype strains of Mycobacterium tuberculosis are more virulent than other strains. We examined whether Beijing strains increase... Show moreAnimal studies have shown that the globally emerging Beijing genotype strains of Mycobacterium tuberculosis are more virulent than other strains. We examined whether Beijing strains increase treatment failure in a prospective cohort study in Indonesia. Among 818 tuberculosis cases, positive sputum culture results after 6 months of treatment were more common among patients infected with Beijing strains (33.4%) than among those infected with non-Beijing strains (relative risk, 1.94 [95% confidence interval, 1.26-3.00]), even after adjustment for differences in drug resistance. These data suggest that M. tuberculosis Beijing genotype strains have a higher capacity to withstand tuberculosis treatment, even in the absence of drug resistance. Show less
Parwati, I.; Alisjahbana, B.; Apriani, L.; Soetikno, R.D.; Ottenhoff, T.H.; Zanden, A.G.M. van der; ... ; Crevel, R. van 2010
Animal studies have shown that the globally emerging Beijing genotype strains of Mycobacterium tuberculosis are more virulent than other strains. We examined whether Beijing strains increase... Show moreAnimal studies have shown that the globally emerging Beijing genotype strains of Mycobacterium tuberculosis are more virulent than other strains. We examined whether Beijing strains increase treatment failure in a prospective cohort study in Indonesia. Among 818 tuberculosis cases, positive sputum culture results after 6 months of treatment were more common among patients infected with Beijing strains (33.4%) than among those infected with non-Beijing strains (relative risk, 1.94 [95% confidence interval, 1.26-3.00]), even after adjustment for differences in drug resistance. These data suggest that M. tuberculosis Beijing genotype strains have a higher capacity to withstand tuberculosis treatment, even in the absence of drug resistance. Show less
Parwati, I.; Alisjahbana, B.; Apriani, L.; Soetikno, R.D.; Ottenhoff, T.H.; Zanden, A.G.M. van der; ... ; Crevel, R. van 2010
Animal studies have shown that the globally emerging Beijing genotype strains of Mycobacterium tuberculosis are more virulent than other strains. We examined whether Beijing strains increase... Show moreAnimal studies have shown that the globally emerging Beijing genotype strains of Mycobacterium tuberculosis are more virulent than other strains. We examined whether Beijing strains increase treatment failure in a prospective cohort study in Indonesia. Among 818 tuberculosis cases, positive sputum culture results after 6 months of treatment were more common among patients infected with Beijing strains (33.4%) than among those infected with non-Beijing strains (relative risk, 1.94 [95% confidence interval, 1.26-3.00]), even after adjustment for differences in drug resistance. These data suggest that M. tuberculosis Beijing genotype strains have a higher capacity to withstand tuberculosis treatment, even in the absence of drug resistance. Show less
