To Örebro University

oru.seÖrebro University Publications
Change search
Link to record
Permanent link

Direct link
Publications (10 of 35) Show all publications
Olsson, H., Tamire, M., Samuelsson, E., Addissie, A., Andersson, R., Skovbjerg, S. & Athlin, S. (2024). Household air pollution and pneumococcal density related to nasopharyngeal inflammation in mothers and children in Ethiopia: A cross-sectional study. PLOS ONE, 19(1), Article ID e0297085.
Open this publication in new window or tab >>Household air pollution and pneumococcal density related to nasopharyngeal inflammation in mothers and children in Ethiopia: A cross-sectional study
Show others...
2024 (English)In: PLOS ONE, E-ISSN 1932-6203, Vol. 19, no 1, article id e0297085Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Three billion people in low- and middle-income countries are exposed to household air pollution as they use biomass fuel for cooking. We investigated the associations between solid fuel use and nasopharyngeal (NP) inflammation, as well as the associations between high pneumococcal density and NP inflammation, in mothers and children in rural and urban Ethiopia.

MATERIALS AND METHODS: Sixty pairs of mothers (median age, 30 years; range, 19-45 years) with a child (median age, 9 months; range, 1-24 months) were included from rural Butajira (n = 30) and urban Addis Ababa (n = 30) in Ethiopia. The cohort was randomly selected from a previous study of 545 mother/child pairs included 2016. Questionnaire-based data were collected which included fuel type used (solid: wood, charcoal, dung or crop waste; cleaner: electricity, liquefied petroleum gas). Nasopharyngeal (NP) samples were collected from all mothers and children and analyzed for the levels of 18 cytokines using a Luminex immunoassay. Pneumococcal DNA densities were measured by a real-time multiplex PCR and a high pneumococcal density was defined as a cyclic threshold (Ct) value ≤ 30.

RESULTS: Mothers from rural areas had higher median CXCL8 levels in NP secretions than those from urban areas (8000 versus 1900 pg/mL; p < 0.01), while rural children had slightly higher IL-10 levels than those from the urban area (26 vs 13 pg/mL; p = 0.04). No associations between fuel type and cytokine levels were found. However, a high pneumococcal density was associated with higher levels of cytokines in both mothers (CCL4, CXCL8, IL-1β, IL-6 and VEGF-A) and children (CCL4, CXCL8, IL-1β, IL-6 and IL-18).

CONCLUSIONS: No significant associations were found between solid fuel use and NP inflammation in Ethiopian mothers and children, but the inflammatory activity was higher in individuals living in the rural compared to the urban area. In addition, high cytokine levels were associated with high pneumococcal density in both mothers and children, indicating a significant impact of NP pathogens on inflammatory mediator levels in upper airways.

Place, publisher, year, edition, pages
Public Library of Science (PLoS), 2024
National Category
Occupational Health and Environmental Health
Identifiers
urn:nbn:se:oru:diva-111224 (URN)10.1371/journal.pone.0297085 (DOI)38271409 (PubMedID)2-s2.0-85183480183 (Scopus ID)
Funder
Swedish Research Council, 2020-04653Region Örebro County, 807831
Available from: 2024-01-31 Created: 2024-01-31 Last updated: 2024-02-05Bibliographically approved
Kättström, M., Uggla, B., Tina, E., Kimby, E., Norén, T. & Athlin, S. (2023). Improved plasmablast response after repeated pneumococcal revaccinations following primary immunization with 13-valent pneumococcal conjugate vaccine or 23-valent pneumococcal polysaccharide vaccine in patients with chronic lymphocytic leukemia. Vaccine, 41(9), 3128-3136
Open this publication in new window or tab >>Improved plasmablast response after repeated pneumococcal revaccinations following primary immunization with 13-valent pneumococcal conjugate vaccine or 23-valent pneumococcal polysaccharide vaccine in patients with chronic lymphocytic leukemia
Show others...
2023 (English)In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 41, no 9, p. 3128-3136Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Patients with chronic lymphocytic leukemia (CLL) show an immune dysfunction with increased risk of infections and poor response to vaccination. Streptococcus pneumoniae is a common cause of morbidity and mortality in CLL patients. In a previous randomized clinical trial, we found a superior immune response in CLL patients receiving conjugated pneumococcal vaccine compared to non-conjugated vaccine. The response to revaccination in CLL patients is scarcely studied. In this study, early humoral response to repeated revaccinations with pneumococcal vaccines was evaluated, by determination of B cell subsets and plasmablast dynamics in peripheral blood.

METHOD: CLL patients (n = 14) and immunocompetent controls (n = 31) were revaccinated with a 13-valent pneumococcal conjugate vaccine (PCV13) after previous primary immunization (3-6 years ago) with PCV13 or a 23-valent pneumococcal polysaccharide vaccine (PPSV23). Eight weeks after the first revaccination, all CLL patients received a second revaccination with PCV13 or PPSV23. B cell subsets including plasmablasts were analyzed in peripheral blood by flow cytometry, before and after the first and the second revaccination.

RESULTS: None of the CLL patients, but all controls, had detectable plasmablasts at baseline (p < 0.001). After the first revaccination with PCV13, the plasmablast proportions did not increase in CLL patients (p = 0.13), while increases were seen in controls (p < 0.001). However, after a second revaccination with PCV13 or PPSV23, plasmablasts increased compared to baseline also in CLL patients (p < 0.01). If no response was evident after first revaccination, only a second revaccination with PCV13 increased plasmablasts in contrast to PPSV23 revaccination. Patients with hypogammaglobulinemia and ongoing/previous CLL specific treatment responded poorly, also to a second revaccination.

CONCLUSION: In CLL patients, pneumococcal revaccination induced minor early plasmablast response compared to controls, but the response improved using a strategy of repeated doses with of conjugated T cell dependent pneumococcal vaccine.

Place, publisher, year, edition, pages
Elsevier, 2023
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-105539 (URN)10.1016/j.vaccine.2023.04.016 (DOI)000990402500001 ()37061372 (PubMedID)2-s2.0-85152584628 (Scopus ID)
Funder
Region Örebro CountyNyckelfonden
Note

Funding agency:

Uppsala-Örebro Regional Research Council

Available from: 2023-04-17 Created: 2023-04-17 Last updated: 2023-06-01Bibliographically approved
Brodin, D., Tornhammar, P., Ueda, P., Krifors, A., Westerlund, E., Athlin, S., . . . Andersson, D. P. (2023). Inhaled ciclesonide in adults hospitalised with COVID-19: a randomised controlled open-label trial (HALT COVID-19). BMJ Open, 13(2), Article ID e064374.
Open this publication in new window or tab >>Inhaled ciclesonide in adults hospitalised with COVID-19: a randomised controlled open-label trial (HALT COVID-19)
Show others...
2023 (English)In: BMJ Open, E-ISSN 2044-6055, Vol. 13, no 2, article id e064374Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: To assess the efficacy of inhaled ciclesonide in reducing the duration of oxygen therapy (an indicator of time to clinical improvement) among adults hospitalised with COVID-19.

DESIGN: Multicentre, randomised, controlled, open-label trial.

SETTING: 9 hospitals (3 academic hospitals and 6 non-academic hospitals) in Sweden between 1 June 2020 and 17 May 2021.

PARTICIPANTS: Adults hospitalised with COVID-19 and receiving oxygen therapy.

INTERVENTION: Inhaled ciclesonide 320 µg two times a day for 14 days versus standard care.

MAIN OUTCOME MEASURES: Primary outcome was duration of oxygen therapy, an indicator of time to clinical improvement. Key secondary outcome was a composite of invasive mechanical ventilation/death.

RESULTS: Data from 98 participants were analysed (48 receiving ciclesonide and 50 receiving standard care; median (IQR) age, 59.5 (49-67) years; 67 (68%) men). Median (IQR) duration of oxygen therapy was 5.5 (3-9) days in the ciclesonide group and 4 (2-7) days in the standard care group (HR for termination of oxygen therapy 0.73 (95% CI 0.47 to 1.11), with the upper 95% CI being compatible with a 10% relative reduction in oxygen therapy duration, corresponding to a <1 day absolute reduction in a post-hoc calculation). Three participants in each group died/received invasive mechanical ventilation (HR 0.90 (95% CI 0.15 to 5.32)). The trial was discontinued early due to slow enrolment.

CONCLUSIONS: In patients hospitalised with COVID-19 receiving oxygen therapy, this trial ruled out, with 0.95 confidence, a treatment effect of ciclesonide corresponding to more than a 1 day reduction in duration of oxygen therapy. Ciclesonide is unlikely to improve this outcome meaningfully.

TRIAL REGISTRATION NUMBER: NCT04381364.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2023
Keywords
COVID-19, clinical trials, respiratory infections
National Category
Anesthesiology and Intensive Care Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:oru:diva-104438 (URN)10.1136/bmjopen-2022-064374 (DOI)000944467100011 ()36813503 (PubMedID)2-s2.0-85148548652 (Scopus ID)
Available from: 2023-02-23 Created: 2023-02-23 Last updated: 2023-08-28Bibliographically approved
Shine, S., Tamirie, M., Kumie, A., Addissie, A., Athlin, S., Mekonnen, H., . . . Kaba, M. (2023). Pregnant women's perception on the health effects of household air pollution in Rural Butajira, Ethiopia: a phenomenological qualitative study. BMC Public Health, 23(1), Article ID 1636.
Open this publication in new window or tab >>Pregnant women's perception on the health effects of household air pollution in Rural Butajira, Ethiopia: a phenomenological qualitative study
Show others...
2023 (English)In: BMC Public Health, E-ISSN 1471-2458, Vol. 23, no 1, article id 1636Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Household air pollution is the major public health problem in developing countries. Pregnant women spent the majority of their time at home and are the most affected population by household air pollution. Exploring the perception of pregnant women on adverse health effects is important to enhance the mitigation strategies. Therefore, this study aim to explore the pregnant women's perceptions about health effects of household air pollution in rural Butajira, Ethiopia.

METHODS: A phenomenological qualitative study design was conducted among 15 selected pregnant women. All interviews were carried out at the participants´ house and audio-recorded while housing and cooking conditions were observed and appropriate notes were taken for each. The collected data were transcribed verbatim and translated into the English language. Then, the data were imported into Open code software to manage the overall data coding processes and analyzed thematically.

RESULTS: Study participants perceived that respiratory problems such as coughing, sneezing and asthma and eye problem were the major health problem caused by household air pollution among pregnant women. Study participants also mentioned asphyxiated, abortion, reduces weight, and hydrocephalus was caused by household air pollution on the foetus. Study participants perceived that financial inability, spouse negligence, autonomy and knowledge level of the women were the barriers to tackling household air pollution. Study participant also suggested that opening the door and window; using improved cookstove and reduce workload were the perceived solution for household air pollution.

CONCLUSIONS: This study explores pregnant women's perceptions on health effects of household air pollution. The finding of this study was important to deliver suitable intervention strategies to mitigate household air pollution. Therefore, educating the women on way of mitigating household air pollution, improving existing structure of the house and minimize the time to stay in the kitchen is important to mitigate household air pollution exposure.

Place, publisher, year, edition, pages
BioMed Central (BMC), 2023
Keywords
Butajira, Ethiopia, Household air pollution, Pregnant mother perception, Qualitative study
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:oru:diva-107862 (URN)10.1186/s12889-023-16578-8 (DOI)001054758500004 ()37626318 (PubMedID)2-s2.0-85168720429 (Scopus ID)
Note

Funding agency:

Addis Ababa University

Available from: 2023-08-28 Created: 2023-08-28 Last updated: 2023-09-26Bibliographically approved
Hammarström, H., Krifors, A., Athlin, S., Friman, V., Golestani, K., Hällgren, A., . . . Blennow, O. (2023). Treatment with reduced dose trimethoprim-sulfamethoxazole is effective in mild to moderate Pneumocystis jirovecii pneumonia in patients with hematologic malignancies. Clinical Infectious Diseases, 76(3), e1252-e1260
Open this publication in new window or tab >>Treatment with reduced dose trimethoprim-sulfamethoxazole is effective in mild to moderate Pneumocystis jirovecii pneumonia in patients with hematologic malignancies
Show others...
2023 (English)In: Clinical Infectious Diseases, ISSN 1058-4838, E-ISSN 1537-6591, Vol. 76, no 3, p. e1252-e1260Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Recent studies have reported that reduced dose trimethoprim-sulfamethoxazole (TMP-SMX) may be effective in the treatment of Pneumocystis jirovecii pneumonia (PJP) but data is lacking for patients with hematologic malignancies.

METHODS: This retrospective study included all adult hematologic patients with PJP between 2013 and 2017 at six Swedish University Hospitals. Treatment with 7.5-15 mg TMP/kg/day (reduced dose) was compared with >15-20 mg TMP/kg/day (standard dose), after correction for renal function. The primary outcome was the change in respiratory function (ΔPaO2/FiO2) between baseline and day 8. Secondary outcomes were clinical failure and/or death at day 8 and death at day 30.

RESULTS: Out of a total of 113 included patients, 80 patients received reduced dose, and 33 patients received standard dose. The overall 30-day mortality in the whole cohort was 14%. There were no clinically relevant differences in ΔPaO2/FiO2 at day 8 between the treatment groups, neither before nor after controlling for potential confounders in an adjusted regression model (-13,6 mmHg [95% CI -56,7-29,5] and -9,4 mmHg, [95% CI -50.5-31.7], respectively). Clinical failure and/or death at day 8 and 30-day mortality did not differ significantly between the groups, 18% vs. 21% and 14% vs. 15%, respectively. Among patients with mild to moderate pneumonia, defined as PaO2/FiO2>200 mmHg, all 44 patients receiving reduced dose were alive at day 30.

CONCLUSION: In this cohort of 113 patients with hematologic malignancies, reduced dose TMP-SMX was effective and safe for treating mild to moderate PJP.

Place, publisher, year, edition, pages
University of Chicago Press, 2023
Keywords
Pneumocystis pneumonia, Hematologic malignancies, Treatment Outcome, trimethoprim-sulfamethoxazole
National Category
Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-99105 (URN)10.1093/cid/ciac386 (DOI)000819031800001 ()35594562 (PubMedID)2-s2.0-85147783441 (Scopus ID)
Note

Funding agencies:

Swedish National Health Services through Örebro University

National Health Services

Available from: 2022-05-23 Created: 2022-05-23 Last updated: 2023-03-15Bibliographically approved
Athlin, S., Magnuson, A., Spindler, C., Hedlund, J., Strålin, K. & Nauclér, P. (2022). Pneumococcal urinary antigen testing for antimicrobial guidance in community-acquired pneumonia: A register-based cohort study. Journal of Infection, 85(2), 167-173
Open this publication in new window or tab >>Pneumococcal urinary antigen testing for antimicrobial guidance in community-acquired pneumonia: A register-based cohort study
Show others...
2022 (English)In: Journal of Infection, ISSN 0163-4453, E-ISSN 1532-2742, Vol. 85, no 2, p. 167-173Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: To evaluate the effect of pneumococcal urinary antigen test (UAT) usage on broad-spectrum antibiotic treatment in community-acquired pneumonia (CAP).

METHODS: Patients admitted to 32 Swedish hospitals between 2011 and 2014 were retrospectively included from the Swedish National Quality Register of CAP. Using propensity score matched data, stratified by CRB-65 score, we studied the effect of performing UAT and of positive test results on treatment with broad-spectrum β-lactam monotherapy (BSBM) and antibiotics with coverage for atypical bacteria compared to narrow-spectrum β-lactam monotherapy (NSBM).

RESULTS: UAT was performed for 4,995/14,590 (34.2%) patients, 603/4,995 (12.1%) of whom had positive test results. At day three, performing UAT was not associated with decreased use of BSBM (OR 1.07, 95% CI 0.94-1.23) but was associated with increased atypical coverage among patients with CRB-65 score 2 (OR 1.47, 95% CI 1.06-2.02). A positive UAT was associated with decreased BSBM use (OR 0.39, 95% CI 0.25-0.60) and decreased atypical coverage (OR 0.25, 95% CI 0.16-0.37), predominantly in non-severe CAP. At day one, performing UAT was associated with atypical coverage among patients with CRB-65 scores 2 (OR 2.60, 95% CI 1.69-3.98) and 3-4 (OR 3.69, 95% CI 1.55-8.79), and a positive test reduced the odds of BSBM treatment among CRB-65 score 3-4 patients (OR 3.49, 95% CI 1.02-12.0).

CONCLUSIONS: Performing UAT had no overall effect on decreasing the use of BSBM treatment by day three of hospitalization, yet non-severely ill patients with positive UAT results were less likely to be treated with BSBM and antibiotics with atypical coverage.

Place, publisher, year, edition, pages
Elsevier, 2022
Keywords
Antibiotic stewardship, Broad-spectrum antibiotics, Community-acquired pneumonia, Pneumococcus, Streptococcus pneumoniae, Urinary antigen test
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:oru:diva-99517 (URN)10.1016/j.jinf.2022.05.021 (DOI)000829326000013 ()35618153 (PubMedID)2-s2.0-85131539827 (Scopus ID)
Funder
Region Örebro County, OLL-524181; OLL-689581Region StockholmSwedish Society of Medicine
Available from: 2022-06-14 Created: 2022-06-14 Last updated: 2022-08-22Bibliographically approved
Nordenskjöld, A. M., Johansson, N., Sunnefeldt, E., Athlin, S. & Fröbert, O. (2022). Prevalence and prognostic implications of myocardial injury in patients with influenza. European Heart Journal Open, 2(5), Article ID oeac051.
Open this publication in new window or tab >>Prevalence and prognostic implications of myocardial injury in patients with influenza
Show others...
2022 (English)In: European Heart Journal Open, E-ISSN 2752-4191, Vol. 2, no 5, article id oeac051Article in journal (Refereed) Published
Abstract [en]

Aims: Influenza may cause myocardial injury and trigger acute cardiovascular events. The aim of this study was to investigate the prevalence and prognostic implications of elevated high-sensitivity cardiac troponin I (hs-cTnI) in patients with influenza.

Methods and results: In this prospective cohort study, we consecutively enrolled patients with influenza-like illness from two emergency departments in Sweden during three seasons of influenza, 2017-20. Ongoing Influenza infection was diagnosed by polymerase chain reaction and blood samples were collected for later analysis of hs-cTnI. All patients were followed-up for a composite endpoint of major adverse cardiovascular events (MACE) including death, myocardial infarction, unstable angina, heart failure, atrial fibrillation, and stroke within 1 year. Of the 466 patients with influenza-like symptoms, 181 (39%) were positive for influenza. Fifty (28%) patients were hospitalized. High-sensitivity cTnI was elevated in 11 (6%) patients and 8 (4%) experienced MACE. In univariate analyses, MACE was associated with age [hazard ratio (HR): 1.14, 95% confidence interval (CI): 1.05-1.23], hypertension (HR 5.56, 95%CI: 1.12-27.53), estimated glomerular filtration rate (HR: 0.94, 95%CI: 0.91-0.97), and elevated hs-cTnI (HR: 18.29, 95%CI: 4.57-73.24), N-terminal prohormone of brain natriuretic peptide (HR: 14.21, 95%CI: 1.75-115.5), hs-CRP (HR: 1.01, 95%CI: 1.00-1.02), and white blood cell count (HR: 1.12, 95%CI: 1.01-1.25). In multivariate analysis, elevated hs-cTnI was independently associated with MACE (HR: 4.96, 95%CI: 1.10-22.41).

Conclusion: The prevalence of elevated hs-cTnI is low in unselected patients with influenza. Elevated hs-cTnI was associated with poor prognosis. A limitation is that the estimated associations are uncertain due to few events.

Place, publisher, year, edition, pages
Oxford University Press, 2022
Keywords
Cardiac troponin, Influenza, Prognosis
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:oru:diva-101416 (URN)10.1093/ehjopen/oeac051 (DOI)36105869 (PubMedID)2-s2.0-85153401496 (Scopus ID)
Available from: 2022-09-23 Created: 2022-09-23 Last updated: 2024-01-16Bibliographically approved
Schagatay, F., Diamant, K., Lidén, M., Edin, A., Athlin, S., Hultgren, O., . . . Cajander, S. (2022). Serum concentration of extracellular cold-inducible RNA-binding protein is associated with respiratory failure in COVID-19. Frontiers in Immunology, 13, Article ID 945603.
Open this publication in new window or tab >>Serum concentration of extracellular cold-inducible RNA-binding protein is associated with respiratory failure in COVID-19
Show others...
2022 (English)In: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 13, article id 945603Article in journal (Refereed) Published
Abstract [en]

Uncontrolled release of damage-associated molecular patterns (DAMPs) is suggested to be a major trigger for the dysregulated host immune response that leads to severe COVID-19. Cold-inducible RNA-binding protein (CIRP), is a newly identified DAMP that aggravates inflammation and tissue injury, and induces respiratory failure in sepsis. Whether CIRP contributes to the pathogenesis of respiratory failure in COVID-19 has not yet been explored.

Aim: To investigate if the concentration of extracellular CIRP (eCIRP) in serum associates with respiratory failure and lung involvement by chest computed tomography (CT) in COVID-19.

Methods: Herein we report a prospective observational study of patients with COVID-19 included at two University Hospitals in Sweden between April 2020 and May 2021. Serum from hospitalized patients in Örebro (N=97) were used to assess the association between eCIRP and the level of respiratory support and its correlation with pulmonary involvement on chest CT and inflammatory biomarkers. A cohort of hospitalized and non-hospitalized patients from Umeå (N=78) was used as an external validation cohort. The severity of disease was defined according to the highest degree of respiratory support; mild disease (no oxygen), non-severe hypoxemia (conventional oxygen or high-flow nasal oxygen, HFNO <50% FiO2), and severe hypoxemia (HFNO ≥50% FiO2, mechanical ventilation). Unadjusted and adjusted linear regression was used to evaluate peak eCIRP day 0-4 in respect to severity, age, sex, Charlson comorbidity score, symptom duration, and BMI.

Results: Peak eCIRP concentrations were higher in patients with severe hypoxemia and were independently associated with the degree of respiratory support in both cohorts (Örebro; p=0.01, Umeå; p<0.01). The degree of pulmonary involvement measured by CT correlated with eCIRP, rs=0.30, p<0.01 (n=97).

Conclusion: High serum levels of eCIRP are associated with acute respiratory failure in COVID-19. Experimental studies are needed to determine if treatments targeting eCIRP reduces the risk of acute respiratory failure in COVID-19.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2022
Keywords
CIRP, COVID-19, DAMPs, eCIRP, inflammation, severity
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:oru:diva-100684 (URN)10.3389/fimmu.2022.945603 (DOI)000840651100001 ()35967397 (PubMedID)2-s2.0-85136034592 (Scopus ID)
Funder
Region Örebro County, OLL-938628 OLL-961416Knut and Alice Wallenberg Foundation, VC-2020-0015Umeå UniversityRegion VästerbottenSwedish Heart Lung FoundationSwedish Research Council, 2020-06235
Note

Funding agency:

Centrum for klinisk forskning (CKF) Region Västmanland

Available from: 2022-08-16 Created: 2022-08-16 Last updated: 2024-01-17Bibliographically approved
Edlund, C., Ternhag, A., Skoog Ståhlgren, G., Edquist, P., Östholm Balkhed, Å., Athlin, S., . . . Hanberger, H. (2022). The clinical and microbiological efficacy of temocillin versus cefotaxime in adults with febrile urinary tract infection, and its effects on the intestinal microbiota: a randomised multicentre clinical trial in Sweden. The Lancet - Infectious diseases, 22(3), 390-400
Open this publication in new window or tab >>The clinical and microbiological efficacy of temocillin versus cefotaxime in adults with febrile urinary tract infection, and its effects on the intestinal microbiota: a randomised multicentre clinical trial in Sweden
Show others...
2022 (English)In: The Lancet - Infectious diseases, ISSN 1473-3099, E-ISSN 1474-4457, Vol. 22, no 3, p. 390-400Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Use of third-generation cephalosporins, such as cefotaxime, is associated with an increased risk of selection for antimicrobial resistance, so alternative antibiotics need to be considered. The aim of the present study was to evaluate intestinal colonisation with third-generation cephalosporin-resistant pathogens following use of temocillin-an alternative antibiotic to cefotaxime that is potentially less prone to disturbing the intestinal microbiota-in empirical treatment of febrile urinary tract infection (UTI).

METHODS: We did a randomised, multicentre, superiority, open-label phase 4 trial in patients who had been admitted to inpatient care in 12 Swedish hospitals with suspected or diagnosed febrile UTI (complicated or uncomplicated). To meet inclusion criteria, a patient was required to have at least one sign or symptom of pyelonephritis (ie, flank pain; costovertebral angle tenderness; and changes to urinary frequency or urgency or dysuria), a fever of 38·0°C or higher, and a positive urine dipstick (for nitrites, white blood cells, or both). Participants were also required to have an indication for intravenous antibiotic treatment. Participants were randomly assigned (1:1) to receive either 2 g temocillin or 1-2 g cefotaxime, by local investigators opening consecutive sealed randomisation envelopes that were generated centrally in advance. Both drugs were administered intravenously every 8 h. The trial was open label for investigators and patients, but those doing the microbiological analyses were masked to the groups. Participants were treated with antibiotics for 7-10 days (or up to 14 days if they had bacteraemia), at least 3 days of which were on the study drug; at day 4 and later, participants who were showing improvement could be given an oral antibiotic (ciprofloxacin, ceftibuten, cefixime, or co-trimoxazole). Patients not showing improvement were regarded as having treatment failures. Rectal swabs were collected at three timepoints: at baseline (before the first dose), after the last dose of study drug, and 7-10 days after treatment stopped. The composite primary outcome was colonisation with Enterobacterales with reduced susceptibility to third-generation cephalosporins, or colonisation with toxin-producing Clostridioides difficile, or both, to evaluate disturbance of the intestinal microbiota. The study is registered in the EU Clinical Trials Register (EudraCT 2015-003898-15).

FINDINGS: Between May 20, 2016, and July 31, 2019, 207 patients were screened for eligibility, of whom 55 patients were excluded. 152 participants were randomly assigned to groups: 77 (51%) patients received temocillin, 75 (49%) patients received cefotaxime. The composite primary endpoint was met by 18 (26%) of 68 participants receiving temocillin versus 30 (48%) of 62 patients receiving cefotaxime (risk difference -22% [95% CI -42% to -3%]), showing superiority of temocillin versus cefotaxime (ie, less disturbance of the intestinal microbiota). 43 adverse events were reported in 40 (52%) of 77 patients in the temocillin group, versus 46 adverse events in 34 (45%) of 75 patients in the cefotaxime group. Most events were of mild to moderate severity. 21 (27%) patients in the temocillin and 17 (23%) patients in the cefotaxime group had an adverse event that was considered to be associated with the study drug.

INTERPRETATION: Temocillin was found to be less selective than cefotaxime of Enterobacterales with reduced susceptibility to third-generation cephalosporins, and it could therefore be a favourable alternative in the empirical treatment of febrile UTI. Use of this antibiotic could reduce hospital transmission and health-care-associated infections by these pathogens.

Place, publisher, year, edition, pages
Elsevier, 2022
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:oru:diva-95387 (URN)10.1016/S1473-3099(21)00407-2 (DOI)000762437600034 ()34756180 (PubMedID)2-s2.0-85124969462 (Scopus ID)
Funder
Public Health Agency of Sweden
Available from: 2021-11-11 Created: 2021-11-11 Last updated: 2024-01-17Bibliographically approved
Larsson, C. (Ed.). (2022). Örebro University’s Nobel Day Festivities: Book of abstracts 2022. Örebro: Örebro Universitet
Open this publication in new window or tab >>Örebro University’s Nobel Day Festivities: Book of abstracts 2022
Show others...
2022 (English)Collection (editor) (Other academic)
Place, publisher, year, edition, pages
Örebro: Örebro Universitet, 2022. p. 29
National Category
Other Medical Sciences
Research subject
Biomedicine; Medicine; Surgery; Caring sciences; Occupational therapy; Public health; Disability research; Sports Science
Identifiers
urn:nbn:se:oru:diva-105783 (URN)978-91-87789-74-8 (ISBN)
Available from: 2023-05-02 Created: 2023-05-02 Last updated: 2024-01-04Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-8730-6955

Search in DiVA

Show all publications