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Schön, Thomas
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Publications (10 of 64) Show all publications
Koeser, C. U., Miotto, P., Ismail, N., Anthony, R. M., Utpatel, C., Merker, M., . . . Schön, T. (2024). A composite reference standard is needed for bedaquiline antimicrobial susceptibility testing for Mycobacterium tuberculosis complex [Letter to the editor]. European Respiratory Journal, 64(1), Article ID 2400391.
Open this publication in new window or tab >>A composite reference standard is needed for bedaquiline antimicrobial susceptibility testing for Mycobacterium tuberculosis complex
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2024 (English)In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 64, no 1, article id 2400391Article in journal, Letter (Other academic) Published
Place, publisher, year, edition, pages
EUROPEAN RESPIRATORY SOC JOURNALS LTD, 2024
Identifiers
urn:nbn:se:liu:diva-207224 (URN)10.1183/13993003.00391-2024 (DOI)001282815900029 ()38991722 (PubMedID)
Note

Funding Agencies|German Ministry of Health [ZMVI1-2519GHP708]; Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's ' s Excellence Strategy [EXC 2167]; Leibniz Science Campus Evolutionary Medicine of the Lung (EvoLUNG); Belgian Science Policy Office; Flemish government [G0B0222N]; US National Institutes of Health (NIH) [NIAID R01-AI176498, R01-AI155765]; Heart and Lung Foundation (Oscar II Jubilee Foundation) [20220148]; Swedish Research Council [2022-00865, 2022-05263]; Swedish Research Council [2022-05263, 2022-00865] Funding Source: Swedish Research Council

Available from: 2024-09-05 Created: 2024-09-05 Last updated: 2025-04-18
Rudolf, F., Abate, E., Moges, B., Gomes, V. F., Mendes, A. M., Sifna, A., . . . Schön, T. (2024). A structured 2-week follow-up visit in the cascade of care for TB increases case detection. The International Journal of Tuberculosis and Lung Disease, 28(3), 148-153
Open this publication in new window or tab >>A structured 2-week follow-up visit in the cascade of care for TB increases case detection
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2024 (English)In: The International Journal of Tuberculosis and Lung Disease, ISSN 1027-3719, E-ISSN 1815-7920, Vol. 28, no 3, p. 148-153Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: Delayed detection in TB due to structural and diagnostic shortcomings is pivotal for disease transmission, morbidity and mortality. We investigated whether an inclusive screening, followed by a structured clinical follow-up (FU) could improve case -finding. METHODS: Patients were recruited from health centres in Bissau, Guinea-Bissau, and Gondar, Ethiopia. A routine FU was done at Week 2. If persisting symptoms were found, patients were investigated using chest X-ray (CXR) and Xpert (R) MTB/RIF, followed by a medical consultation. The main outcome were additional TB patients diagnosed by applying the FU strategy. RESULTS: Of 3,571 adults, 3,285 (95%) were examined at Week 2 FU, where 2,491 (72%) were asymptomatic. Screening patients presenting with cough > 2 weeks alone contributed to the diagnosis of 93 patients (45% of all patients diagnosed here), whereas a TBscore > 3 increased this by 18 (9%); adding a Week 2 FU yielded an additional 94 (46%) patients. Among the 794 (24%) with persisting symptoms, 25 were diagnosed using Xpert and 69 at clinical FU, which constituted 46% (94/205) of the total TB patients diagnosed. CONCLUSION: A Week 2 FU visit, which can be nested into routine healthcare, increased the diagnosis of TB patients by two -fold and avoids diagnostic gaps in the cascade -of -care.

Place, publisher, year, edition, pages
INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D), 2024
Keywords
epidemiology; tuberculosis; case-finding; cascade of care; TBscore
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:liu:diva-203796 (URN)10.5588/ijtld.23.0435 (DOI)001222158500012 ()38454179 (PubMedID)
Note

Funding Agencies|Novo Nordisk Foundation; Scandinavian Society for Anti- microbial Chemotherapy Foundation (Stockholm, Sweden); Swedish Research Council (Stockholm, Sweden); Gondar University (Gondar, Ethiopia)

Available from: 2024-05-31 Created: 2024-05-31 Last updated: 2025-02-05
Dahl, V. N., Burke, A., Floe, A., Bruchfeld, J., Schön, T., Wejse, C. M., . . . Forsman, L. D. (2024). Advantages and limitations of virtual multi-disciplinary team meetings on difficult-to-treat mycobacteria [Letter to the editor]. The International Journal of Tuberculosis and Lung Disease, 28(4), 212-213
Open this publication in new window or tab >>Advantages and limitations of virtual multi-disciplinary team meetings on difficult-to-treat mycobacteria
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2024 (English)In: The International Journal of Tuberculosis and Lung Disease, ISSN 1027-3719, E-ISSN 1815-7920, Vol. 28, no 4, p. 212-213Article in journal, Letter (Other academic) Published
Place, publisher, year, edition, pages
INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D), 2024
Keywords
non-tuberculous mycobacteria; clinical management; telemedicine; digital health
Identifiers
urn:nbn:se:liu:diva-204368 (URN)10.5588/ijtld.23.0551 (DOI)001229576200005 ()38563342 (PubMedID)
Available from: 2024-06-12 Created: 2024-06-12 Last updated: 2025-02-05
Phelan, J. E., Utpatel, C., Ismail, N., Cortes, T., Niemann, S., Cirillo, D. M., . . . Koser, C. U. (2024). Careful classification of potential bedaquiline resistance mutations is critical when analysing their clinical impact. The International Journal of Tuberculosis and Lung Disease, 28(6), 312-313
Open this publication in new window or tab >>Careful classification of potential bedaquiline resistance mutations is critical when analysing their clinical impact
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2024 (English)In: The International Journal of Tuberculosis and Lung Disease, ISSN 1027-3719, E-ISSN 1815-7920, Vol. 28, no 6, p. 312-313Article in journal, Editorial material (Other academic) Published
Place, publisher, year, edition, pages
INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D), 2024
Keywords
Mycobacterium tuberculosis; TB; antimicrobial susceptibility testing; BDQ
Identifiers
urn:nbn:se:liu:diva-206731 (URN)10.5588/ijtld.24.0083 (DOI)001246134100011 ()38822482 (PubMedID)
Available from: 2024-08-26 Created: 2024-08-26 Last updated: 2025-02-05
Damgaard, T., Woksepp, H., Brudin, L., Bonnedahl, J., Nielsen, E. I., Schön, T. & Hällgren, A. (2024). Estimated glomerular filtration rate as a tool for early identification of patients with insufficient exposure to beta-lactam antibiotics in intensive care units. Infectious Diseases, 56(6), 451-459
Open this publication in new window or tab >>Estimated glomerular filtration rate as a tool for early identification of patients with insufficient exposure to beta-lactam antibiotics in intensive care units
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2024 (English)In: Infectious Diseases, ISSN 2374-4235, E-ISSN 2374-4243, Vol. 56, no 6, p. 451-459Article in journal (Refereed) Published
Abstract [en]

<bold>Background: </bold>Only about 50% of intensive care unit (ICU) patients reach a free trough concentration above MIC (100% fT > MIC) of beta-lactam antibiotics. Although dose adjustments based on therapeutic drug monitoring (TDM) could be beneficial, TDM is not widely available. We investigated serum creatinine-based estimated GFR (eGFR) as a rapid screening tool to identify ICU patients at risk of insufficient exposure. <bold>Method: </bold>Ninety-three adult patients admitted to four ICUs in southeast Sweden treated with piperacillin/tazobactam, meropenem, or cefotaxime were included. Beta-lactam trough concentrations were measured. The concentration target was set to 100% fT > MICECOFF (2, 4, and 16 mg/L based on calculated free levels for meropenem, cefotaxime, and piperacillin, respectively). eGFR was primarily determined via Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) and compared to three other eGFR equations. Data was analysed using logistic regression and receiver operative characteristic (ROC) curves. <bold>Results: </bold>With intermittent standard dosing, insufficient exposure was common in patients with a relative eGFR >= 48mL/min/1.73m(2) [85%, (45/53)], particularly when treated with cefotaxime [96%, (24/25)]. This eGFR cut-off had a sensitivity of 92% and specificity of 82% (AUC 0.871, p < 0.001) in identifying insufficient exposure. In contrast, patients with eGFR <48mL/min/1.73m(2) had high target attainment [90%, (36/40)] with a wide variability in drug exposure. There was no difference between the four eGFR equations (AUC 0.866-0.872, cut-offs 44-51 ml/min/1.73m(2)). <bold>Conclusion: </bold>Serum creatinine-based eGFR is a simple and widely available surrogate marker with potential for early identification of ICU patients at risk of insufficient exposure to piperacillin, meropenem, and cefotaxime.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2024
Keywords
Beta lactam; glomerular filtration rate; exposure; intensive care units; drug dose
National Category
Infectious Medicine
Identifiers
urn:nbn:se:liu:diva-201835 (URN)10.1080/23744235.2024.2323002 (DOI)001179603100001 ()38436273 (PubMedID)2-s2.0-85186899082 (Scopus ID)
Note

Funding Agencies|Region Kalmar County

Available from: 2024-03-25 Created: 2024-03-25 Last updated: 2025-02-20Bibliographically approved
Kuhlin, J., Forsman, L. D., Osman, A., Skagerberg, M., Jonsson, J., Groenheit, R., . . . Bruchfeld, J. (2024). Increased risk of adverse drug reactions by higher linezolid dose per weight in multidrug-resistant tuberculosis. International Journal of Antimicrobial Agents, 64(4), Article ID 107302.
Open this publication in new window or tab >>Increased risk of adverse drug reactions by higher linezolid dose per weight in multidrug-resistant tuberculosis
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2024 (English)In: International Journal of Antimicrobial Agents, ISSN 0924-8579, E-ISSN 1872-7913, Vol. 64, no 4, article id 107302Article in journal (Refereed) Published
Abstract [en]

Objectives: Linezolid treatment has a high risk of toxicity and adverse drug reactions (ADR) are frequent. Few studies have investigated risk factors of major ADRs separately, therefore, we aimed to evaluate major ADRs including peripheral neuropathy in relation to risk factors and drug concentration levels of linezolid in a high-resource setting for multidrug-resistant tuberculosis (MDR-TB). Methods: We conducted a retrospective cohort study including participants treated with a linezolid-containing MDR-TB regimen in Sweden 1992-2018. Data was collected from medical records. ADRs were classified according to Common Terminology Criteria for Adverse Events (version 5.0). Results: Of all participants (n = 132), 43.2% were female and the median age 28 y. The median linezolid treatment was 6.5 months (IQR 3.0-12.7) with a median daily dose of 9.6 mg/kg/d. Any ADR was seen in 58.3% (n = 77) of participants, with 35.6% having peripheral neuropathy (n = 47), 27.3% anaemia (n = 36), 22.0% leukopenia (n = 36) while 6.1% (n = 8) had optic neuritis. The median time for peripheral neuropathy was 3.6 months (IQR 2.1-5.9) and 8.3 months (6.2-10.7) for optic neuritis. A >2.0 mg/L trough concentration (n = 40) was associated with anaemia (P = 0.0038) and thrombocytopenia (P = 0.009) but not with peripheral neuropathy. In multivariable analysis, a dose >= 12 mg/kg/d was associated with time to peripheral neuropathy (HR 2.89, 95% CI 1.08-7.74, P = 0.035), anaemia (HR 6.62, 95% CI 2.22-19.8, P = 0.001) and leukopenia (HR 5.23, 95% CI 1.48-18.5, P = 0.010). Conclusions: Linezolid ADRs were frequent in a high-resource setting. Structured, regular follow-up for ADRs and adjusting dosing according to body weight followed-up by monitoring of drug concentrations early may reduce toxicity. (c) 2024 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )

Place, publisher, year, edition, pages
ELSEVIER, 2024
Keywords
MDR-TB; adverse drug reactions; Linezolid; Peripheral neuropathy; Leukopenia; Anaemia; Thrombocytopenia; Drug concentrations
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:liu:diva-207970 (URN)10.1016/j.ijantimicag.2024.107302 (DOI)001309786300001 ()39146999 (PubMedID)
Note

Funding Agencies|Swedish Heart-Lung Foundation [20190229, 20210407, 20220859, 20150237, 20190226]; Swedish research council [2016-02043, 2018-1256]; ALF in Region Ostergotland, Sweden [987589]

Available from: 2024-10-03 Created: 2024-10-03 Last updated: 2025-04-23
Pandey, S., Vilcheze, C., Werngren, J., Bainomugisa, A., Mansjo, M., Groenheit, R., . . . Koser, C. U. (2024). Loss-of-function mutations in ndh do not confer delamanid, ethionamide, isoniazid, or pretomanid resistance in Mycobacterium tuberculosis. Antimicrobial Agents and Chemotherapy, 68(1), Article ID e0109623.
Open this publication in new window or tab >>Loss-of-function mutations in ndh do not confer delamanid, ethionamide, isoniazid, or pretomanid resistance in Mycobacterium tuberculosis
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2024 (English)In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 68, no 1, article id e0109623Article in journal (Refereed) Published
Abstract [en]

Results from clinical strains and knockouts of the H37Rv and CDC1551 laboratory strains demonstrated that ndh (Rv1854c) is not a resistance-conferring gene for isoniazid, ethionamide, delamanid, or pretomanid in Mycobacterium tuberculosis. This difference in the susceptibility to NAD-adduct-forming drugs compared with other mycobacteria may be driven by differences in the absolute intrabacterial NADH concentration.

Place, publisher, year, edition, pages
AMER SOC MICROBIOLOGY, 2024
Keywords
Mycobacterium tuberculosis; delamanid; ethionamide; isoniazid; pretomanid
National Category
Microbiology
Identifiers
urn:nbn:se:liu:diva-200671 (URN)10.1128/aac.01096-23 (DOI)001139943000011 ()38038476 (PubMedID)
Note

Funding Agencies|National Institute of Health Grant [ANR-20-PAMR-0005]; PNG National Tuberculosis Programme [AI26170]; National Institute of Health

Available from: 2024-02-06 Created: 2024-02-06 Last updated: 2025-02-05
Spreco, A., Schön, T. & Timpka, T. (2022). Corruption should be taken into account when considering COVID-19 vaccine allocation [Letter to the editor]. Proceedings of the National Academy of Sciences of the United States of America, 119(19)
Open this publication in new window or tab >>Corruption should be taken into account when considering COVID-19 vaccine allocation
2022 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 119, no 19Article in journal, Letter (Other academic) Published
Place, publisher, year, edition, pages
Proceedings of the National Academy of Sciences, 2022
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-192370 (URN)10.1073/pnas.2122664119 (DOI)001011165900004 ()2-s2.0-85129437852 (Scopus ID)
Funder
Swedish Research Council, 2021-05608
Available from: 2023-03-13 Created: 2023-03-13 Last updated: 2025-04-03
Dahl, V. N., Mølhave, M., Fløe, A., van Ingen, J., Schön, T., Lillebaek, T., . . . Wejse, C. (2022). Global trends of pulmonary infections with nontuberculous mycobacteria: a systematic review. International Journal of Infectious Diseases, 125, 120-131
Open this publication in new window or tab >>Global trends of pulmonary infections with nontuberculous mycobacteria: a systematic review
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2022 (English)In: International Journal of Infectious Diseases, ISSN 1201-9712, E-ISSN 1878-3511, Vol. 125, p. 120-131Article, review/survey (Refereed) Published
Abstract [en]

Objectives: To describe the global trends of pulmonary nontuberculous mycobacteria (NTM) infection and disease.

Methods: A systematic review of studies including culture-based NTM data over time. Studies reporting on pulmonary NTM infection and/or disease were included. Information on the use of guideline-based criteria for disease were collected, in which, infection is defined as the absence of symptoms and radiological findings compatible with NTM pulmonary disease. The trends of change for incidence/prevalence were evaluated using linear regressions, and the corresponding pooled estimates were calculated.

Results: Most studies reported increasing pulmonary NTM infection (82.1%) and disease (66.7%) trends. The overall annual rate of change for NTM infection and disease per 100,000 persons/year was 4.0% (95% confidence interval [CI]: 3.2-4.8) and 4.1% (95% CI: 3.2-5.0), respectively. For absolute numbers of NTM infection and disease, the overall annual change was 2.0 (95% CI: 1.6-2.3) and 0.5 (95% CI: 0.3-0.7), respectively. An increasing trend was also seen for Mycobacterium avium complex infection (n = 15/19, 78.9%) and disease (n = 10/12, 83.9%) and for Mycobacterium abscessus complex (n = 15/23, 65.2%) infection (n = 11/17, 64.7%) but less so for disease (n = 2/8, 25.0%).

Conclusion: Our data indicate an overall increase in NTM worldwide for both infection and disease. The explanation to this phenomenon warrants further investigation.

Place, publisher, year, edition, pages
Elsevier, 2022
Keywords
Chronic lung disease; Incidence; Nontuberculous mycobacteria; Respiratory infections; Systematic review
National Category
Infectious Medicine Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:liu:diva-192100 (URN)10.1016/j.ijid.2022.10.013 (DOI)000965649700010 ()36244600 (PubMedID)
Note

Funding: Department of Public Health, Aarhus University; Fonden, Skibsreder Per Henriksen, R. og hustrus fond; Region Midtjyllands Sundhedsvidenskabelige Forskningsfond; Christian Larsen og dommer Ellen Larsens Legat; Helga og Peter Kornings Fond; Beckett-Fonden

Available from: 2023-03-02 Created: 2023-03-02 Last updated: 2024-05-05
Woksepp, H., Karlsson, L., Ärlemalm, A., Hällgren, A., Schön, T. & Carlsson, B. (2022). Simultaneous Measurement of 11 Antibiotics for use in the Intensive Care Unit by Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry. Therapeutic Drug Monitoring, 44(2), 308-318
Open this publication in new window or tab >>Simultaneous Measurement of 11 Antibiotics for use in the Intensive Care Unit by Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry
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2022 (English)In: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 44, no 2, p. 308-318Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Recent studies indicate that a high proportion of patients in the intensive care unit (ICU) fail to attain adequate antibiotic levels. Thus, there is a need to monitor the antibiotic concentration to ensure effective treatment. Herein, the authors aimed to develop an ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the simultaneous quantification of antimicrobials to assess individualized therapeutic drug monitoring (TDM).

METHODS: A UHPLC-MS/MS method with 11 antibiotics (ciprofloxacin, moxifloxacin, benzylpenicillin, levofloxacin, linezolid, rifampicin, meropenem, cloxacillin, cefotaxime, clindamycin, and piperacillin) was developed. Chromatographic separation was performed using a Kinetex biphenyl reversed-phase column, with gradient elution using 0.1% formic acid (FA) and methanol with 0.1% FA. Sample preparation was performed using methanol protein precipitation. The total run time was 5 min.

RESULTS: For all analytes, the inter-assay inaccuracies for calibrators were ≤5%. The inter-day inaccuracies for the quality controls (QCs) were ≤5% for all analytes. The inter-assay precision for calibration standards ranged between 1.42% and 6.11%. The inter-assay imprecision for QCs of all antibiotics and concentrations ranged between 3.60% and 16.1%. Inter-assay inaccuracy and imprecision for the QCs and calibration standards were ≤15% for all drugs, except benzylpenicillin.

CONCLUSION: A rapid UHPLC-MS/MS method was developed for the simultaneous quantification of 11 different antibiotics. Minimal sample preparation was required to ensure a rapid turnaround time. The method was applied to clinical samples collected from four ICUs.

Place, publisher, year, edition, pages
Philadelphia, PA, United States: Lippincott Williams & Wilkins, 2022
Keywords
UHPLC-MS/MS; Antibiotics; Therapeutic drug monitoring; Critically ill patients; Clinical application
National Category
Analytical Chemistry
Identifiers
urn:nbn:se:liu:diva-183609 (URN)10.1097/ftd.0000000000000911 (DOI)000769195300007 ()34224537 (PubMedID)
Note

Funding: Research Council of South-East Sweden (FORSS); Swedish Research CouncilSwedish Research CouncilEuropean Commission; Marianne and Marcus Wallenberg Foundation [DNR 2014/236-31]

Available from: 2022-03-14 Created: 2022-03-14 Last updated: 2024-05-05Bibliographically approved
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