| 1. |
- Hedin, Wilhelm, et al.
(författare)
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A Rough Colony Morphology of Mycobacterium abscessus Is Associated With Cavitary Pulmonary Disease and Poor Clinical Outcome
- 2023
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press. - 0022-1899 .- 1537-6613. ; 227:6, s. 820-827
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Mycobacterium abscessus complex (MABC) is a difficult to treat mycobacterium with two distinct morphologies: smooth and rough. As the clinical implications are unclear, we explored the morphology of MABC in relation to disease and outcome.Methods: We performed a retrospective multicenter cohort study including patients with confirmed MABC in Sweden, 2009-2020, with treatment outcome as the primary outcome. MABC colony morphology was determined by light microscopy on Middlebrook 7H10 agar plates.Results: Of the 71 MABC isolates, a defined morphology could be determined for 63 isolates, of which 40 were smooth (56%) and 23 were rough (32%). Immunosuppression, pulmonary disease, and cavitary lesion on chest radiographs were significantly associated with a rough isolate morphology. Participants with smooth isolates had more favorable treatment outcomes (12/14, 86%) compared to those with rough isolates (3/10, 30%). In an age-adjusted logistic regression, rough morphology of MABC was associated to lower odds of clinical cure compared to smooth morphology (adjusted odds ratio, 0.12; P = .049).Conclusions: Study participants with rough MABC colony morphology of isolates had a worse clinical outcome compared to those with smooth isolates. The biological mechanisms should be further characterized and colony morphology of MABC taken into account during clinical management.
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| 2. |
- Venkatesan, Meera, et al.
(författare)
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Polymorphisms in Plasmodium falciparum chloroquine resistance transporter and multidrug resistance 1 genes : parasite risk factors that affect treatment outcomes for P. falciparum malaria after artemether-lumefantrine and artesunate-amodiaquine.
- 2014
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Ingår i: The American journal of tropical medicine and hygiene. - : American Society of Tropical Medicine and Hygiene. - 1476-1645 .- 0002-9637. ; 91:4, s. 833-43
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Tidskriftsartikel (refereegranskat)abstract
- Adequate clinical and parasitologic cure by artemisinin combination therapies relies on the artemisinin component and the partner drug. Polymorphisms in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multidrug resistance 1 (pfmdr1) genes are associated with decreased sensitivity to amodiaquine and lumefantrine, but effects of these polymorphisms on therapeutic responses to artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) have not been clearly defined. Individual patient data from 31 clinical trials were harmonized and pooled by using standardized methods from the WorldWide Antimalarial Resistance Network. Data for more than 7,000 patients were analyzed to assess relationships between parasite polymorphisms in pfcrt and pfmdr1 and clinically relevant outcomes after treatment with AL or ASAQ. Presence of the pfmdr1 gene N86 (adjusted hazards ratio = 4.74, 95% confidence interval = 2.29 - 9.78, P < 0.001) and increased pfmdr1 copy number (adjusted hazards ratio = 6.52, 95% confidence interval = 2.36-17.97, P < 0.001 : were significant independent risk factors for recrudescence in patients treated with AL. AL and ASAQ exerted opposing selective effects on single-nucleotide polymorphisms in pfcrt and pfmdr1. Monitoring selection and responding to emerging signs of drug resistance are critical tools for preserving efficacy of artemisinin combination therapies; determination of the prevalence of at least pfcrt K76T and pfmdr1 N86Y should now be routine.
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