| 1. |
- Alpkvist, Helena, et al.
(författare)
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Clinical and Microbiological Factors Associated with High Nasopharyngeal Pneumococcal Density in Patients with Pneumococcal Pneumonia
- 2015
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Ingår i: PLOS ONE. - : Public Library Science. - 1932-6203. ; 10:10
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to study if certain clinical and/or microbiological factors are associated with a high nasopharyngeal (NP) density of Streptococcus pneumoniae in pneumococcal pneumonia. In addition, we aimed to study if a high NP pneumococcal density could be useful to detect severe pneumococcal pneumonia.Methods: Adult patients hospitalized for radiologically confirmed community-acquired pneumonia were included in a prospective study. NP aspirates were collected at admission and were subjected to quantitative PCR for pneumococcal DNA (Spn9802 DNA). Patients were considered to have pneumococcal etiology if S. pneumoniae was detected in blood culture and/ or culture of respiratory secretions and/or urinary antigen test.Results: Of 166 included patients, 68 patients had pneumococcal DNA detected in NP aspirate. Pneumococcal etiology was noted in 57 patients (84%) with positive and 8 patients (8.2%) with negative test for pneumococcal DNA (p<0.0001). The median NP pneumococcal density of DNA positive patients with pneumococcal etiology was 6.83 log(10) DNA copies/mL (range 1.79-9.50). In a multivariate analysis of patients with pneumococcal etiology, a high pneumococcal density was independently associated with severe pneumonia (Pneumonia Severity Index risk class IV-V), symptom duration >= 2 days prior to admission, and a medium/high serum immunoglobulin titer against the patient's own pneumococcal serotype. NP pneumococcal density was not associated with sex, age, smoking, co-morbidity, viral co-infection, pneumococcal serotype, or bacteremia. Severe pneumococcal pneumonia was noted in 28 study patients. When we studied the performance of PCR with different DNA cut-off levels for detection of severe pneumococcal pneumonia, we found sensitivities of 54-82% and positive predictive values of 37-56%, indicating suboptimal performance.Conclusions: Pneumonia severity, symptom duration similar to 2 days, and a medium/high serum immunoglobulin titer against the patient's own serotype were independently associated with a high NP pneumococcal density. NP pneumococcal density has limited value for detection of severe pneumococcal pneumonia.
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| 2. |
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| 3. |
- Alpkvist, H, et al.
(författare)
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High HMGB1 levels in sputum are related to pneumococcal bacteraemia but not to disease severity in community-acquired pneumonia
- 2018
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 13428-
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Tidskriftsartikel (refereegranskat)abstract
- During bacterial infections, damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs) activate immune cells. Here, we investigated whether plasma and sputum levels of High Mobility Group Box 1 (HMGB1), a prototypic DAMP, are associated with disease severity and aetiology in community-acquired pneumonia (CAP). In addition, in patients with pneumococcal CAP, the impact of the level of sputum lytA DNA load, a PAMP, was investigated. We studied patients hospitalised for bacterial CAP (n = 111), and samples were collected at admission. HMGB1 was determined by enzyme-linked immunosorbent assays, and pneumococcal lytA DNA load was determined by quantitative polymerase chain reaction. Plasma and sputum HMGB1 levels did not correlate to disease severity (pneumonia severity index or presence of sepsis), but high sputum HMGB1 level was correlated to pneumococcal aetiology (p = 0.002). In pneumococcal pneumonia, high sputum lytA DNA load was associated with respiratory failure (low PaO2/FiO2 ratio; p = 0.019), and high sputum HMGB1 level was associated with bacteraemia (p = 0.006). To conclude, high sputum HMGB1 was not associated with severe disease, but with pneumococcal bacteraemia, indicating a potential role for HMGB1 in bacterial dissemination. High sputum lytA was associated with severe disease.
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| 4. |
- Altun, O., et al.
(författare)
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Rapid identification of Streptococcus pneumoniae in blood cultures by using the ImmuLex, Slidex and Wellcogen latex agglutination tests and the BinaxNOW antigen test
- 2016
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Ingår i: European Journal of Clinical Microbiology and Infectious Diseases. - : Springer-Verlag New York. - 0934-9723 .- 1435-4373. ; 35:4, s. 579-585
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Tidskriftsartikel (refereegranskat)abstract
- Rapid identification of Streptococcus pneumoniae in blood culture (BC) bottles is important for early directed antimicrobial therapy in pneumococcal bacteraemia. We evaluated a new latex agglutination (LA) test on BC bottles, the ImmuLex™ S. pneumoniae Omni (Statens Serum Institut, Denmark), and compared the performance with the Slidex® pneumo-Kit (bioMérieux, France) and the Wellcogen™ S. pneumoniae (Remel, UK) LA tests, as well as the BinaxNOW® S. pneumoniae (Alere, USA) antigen test. The four tests were directly applied on 358 positive BC bottles with Gram-positive cocci in pairs or chains and on 15 negative bottles. Valid test results were recorded in all cases for ImmuLex and BinaxNOW and in 88.5 % (330/373) and 94.1 % (351/373) of cases for Slidex and Wellcogen, respectively. Based on bottles positive for S. pneumoniae by conventional methods, the sensitivity of ImmuLex was 99.6 %, similar to the other tests (range, 99.6-100 %). Based on bottles positive for non-pneumococcal pathogens, the specificity of ImmuLex was 82.6 %, in comparison to 97.6 % for Slidex (p < 0.01) and 85.4 % for Wellcogen (p = ns). The BinaxNOW test had a lower specificity (64.1 %) than any LA test (p < 0.01). On BC bottles positive for α-haemolytic streptococci, ImmuLex was positive in 12/67 (17.9 %) cases, Slidex in 2/59 (3.4 %) cases, Wellcogen in 11/64 (17.2 %) cases and BinaxNOW in 25/67 (37.3 %) cases. In conclusion, the ImmuLex test provides a valid and sensitive technique for the rapid detection of S. pneumoniae in BC bottles, similar to the other compared methods. However, the specificity was sub-optimal, since the test may cross-react with other Gram-positive bacteria.
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| 5. |
- Athlin, Simon, 1971-, et al.
(författare)
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Association between serotype-specific antibody response and serotype characteristics in patients with pneumococcal pneumonia, with special reference to degree of encapsulation and invasive potential
- 2014
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Ingår i: Clinical and Vaccine Immunology. - : American Society for Microbiology. - 1556-6811 .- 1556-679X. ; 21:11, s. 1541-1549
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Tidskriftsartikel (refereegranskat)abstract
- We studied the immunoglobulin (Ig) response to causative serotype-specific capsular polysaccharides in adult pneumococcal pneumonia patients. The serotypes were grouped according to their degree of encapsulation and invasive potential. Seventy patients with pneumococcal pneumonia, 20 of whom were bacteremic, were prospectively studied. All pneumococcal isolates from the patients were serotyped, and the Ig titers to the homologous serotype were determined in acute- and convalescent-phase sera using a serotype-specific enzyme-linked immunosorbent assay. The Ig titers were lower in bacteremic cases than in nonbacteremic cases (P < 0.042). The Ig titer ratio (convalescent/acute titer) was ≥2 in 33 patients, 1 to 1.99 in 20 patients, and <1 in 17 patients. Patients ≥65 years old had a lower median Ig titer ratio than did younger patients (P < 0.031). The patients with serotypes with a thin capsule (1, 4, 7F, 9N, 9V, and 14) and medium/high invasive potential (1, 4, 7F, 9N, 9V, 14, and 18C) had higher Ig titer ratios than did patients with serotypes with a thick capsule (3, 6B, 11A, 18C, 19A, 19F, and 23F) and low invasive potential (3, 6B, 19A, 19F, and 23F) (P < 0.05 for both comparisons after adjustment for age). Ig titer ratios of <1 were predominantly noted in patients with serotypes with a thick capsule. In 8 patients with pneumococcal DNA detected in plasma, the three patients with the highest DNA load had the lowest Ig titer ratios. In conclusion, a high antibody response was associated with serotypes with a thin capsule and medium/high invasive potential, although a low antibody response was associated with serotypes with a thick capsule and a high pneumococcal plasma load.
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| 6. |
- Athlin, Simon, 1971-, et al.
(författare)
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Comparison of the ImmuView and the BinaxNOW antigen tests in detection of Streptococcus pneumoniae and Legionella pneumophila in urine
- 2017
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Ingår i: European Journal of Clinical Microbiology and Infectious Diseases. - : Springer. - 0934-9723 .- 1435-4373. ; 36:10, s. 1933-1938
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Tidskriftsartikel (refereegranskat)abstract
- The use of urinary antigen tests (UATs) may provide early etiology in pneumonia, and facilitates rapid and directed antibiotic treatment. In this study, we evaluated the novel lateral flow ImmuView Streptococcus pneumoniae and Legionella pneumophila UAT, which detects pneumococcal and L. pneumophila serogroup 1 antigens in a combined test. We compared the ImmuView UAT with the BinaxNOW S. pneumoniae UAT and the BinaxNOW L. pneumophila UAT in 147 patients with pneumococcal bacteremia (n = 48), non-pneumococcal non-Legionella bacteremia (n = 93) and Legionella infections in the lower airways (L. pneumophila, n = 5; L. bozemanii, n = 1). In three cases, the ImmuView test was invalid before and after boiling while the BinaxNOW tests were valid in all cases. In 144 cases, the three UATs demonstrated a very good inter-assay agreement for detection of pneumococcal antigen (kappa = 0.86) and L. pneumophila antigen (kappa = 1.00). The ImmuView and BinaxNOW S. pneumoniae tests had similar sensitivities (62% vs 60%; p = ns) in 48 cases with pneumococcal bacteremia and both tests had specificities of 97% in 96 cases with non-pneumococcal infections. Furthermore, the ImmuView and BinaxNOW L. pneumophila tests were positive for Legionella antigen in five patients with confirmed L. pneumophila serogroup 1 infections, and negative in all non-L. pneumophila cases. The ImmuView and BinaxNOW tests performed similarly when evaluated on urine samples from bacteremic and non-bacteremic patients with identified etiology.
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| 7. |
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| 8. |
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| 9. |
- Athlin, Simon, 1971-, et al.
(författare)
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Management of community-acquired pneumonia in immunocompetent adults : updated Swedish guidelines 2017
- 2018
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Ingår i: Infectious Diseases. - : Informa UK Limited. - 2374-4235 .- 2374-4243. ; 50:4, s. 247-272
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Forskningsöversikt (refereegranskat)abstract
- Based on expert group work, Swedish recommendations for the management of community-acquired pneumonia in adults are here updated. The management of sepsis-induced hypotension is addressed in detail, including monitoring and parenteral therapy. The importance of respiratory support in cases of acute respiratory failure is emphasized. Treatment with high-flow oxygen and non-invasive ventilation is recommended. The use of statins or steroids in general therapy is not found to be fully supported by evidence. In the management of pleural infection, new data show favourable effects of tissue plasminogen activator and deoxyribonuclease installation. Detailed recommendations for the vaccination of risk groups are afforded.
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| 10. |
- Athlin, Simon, 1971-, et al.
(författare)
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Pneumococcal urinary antigen testing for antimicrobial guidance in community-acquired pneumonia : A register-based cohort study
- 2022
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Ingår i: Journal of Infection. - : Elsevier. - 0163-4453 .- 1532-2742. ; 85:2, s. 167-173
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 11. |
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| 12. |
- Athlin, Simon, 1971-, et al.
(författare)
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The Binax NOW Streptococcus pneumoniae test applied on nasopharyngeal aspirates to support pneumococcal aetiology in community-acquired pneumonia.
- 2013
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 45:6, s. 425-31
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The use of nasopharyngeal secretions to enhance diagnostic yields of pneumococcal aetiology in community-acquired pneumonia (CAP) is of interest. We evaluated the Binax NOW Streptococcus pneumoniae immunochromatographic test (ICT) on nasopharyngeal aspirates (NPA) in order to support pneumococcal aetiology in CAP.METHODS: The NPA ICT was applied on 180 adult CAP patients and 64 healthy controls. The rate of pneumococcal detection in the nasopharynx was compared to rates for lytA polymerase chain reaction (PCR) and culture on NPA.RESULTS: According to blood and sputum culture and urine ICT, the test sensitivity in 59 patients with a pneumococcal aetiology was 81%. The specificity was suboptimal, with 72% negative tests among CAP patients without a pneumococcal aetiology. However, the test was positive in only 11% of patients with atypical pneumonia and in 4.7% of healthy controls. The positivity rate was higher for NPA ICT compared to culture on NPA in all CAP patients, and to both PCR and culture on NPA in non-pneumococcal non-atypical CAP patients. In 113 (63%) patients with β-lactam monotherapy, cure without treatment alteration was noted more often in cases with positive compared to negative NPA ICT at admission (91% vs 69%; p < 0.01).CONCLUSIONS: The high sensitivity and the low positivity rates in patients with atypical pneumonia and healthy controls, in combination with the correlation between positive test results and clinical cure with β-lactam therapy, may support a pneumococcal aetiology in CAP in populations with low pneumococcal carriage rates.
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| 13. |
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| 14. |
- Athlin, Simon, 1971-, et al.
(författare)
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The UniGold(TM) Streptococcus pneumoniae urinary antigen test : an interassay comparison with the BinaxNOW (R) Streptococcus pneumoniae test on consecutive urine samples and evaluation on patients with bacteremia
- 2015
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Ingår i: European Journal of Clinical Microbiology and Infectious Diseases. - : Springer. - 0934-9723 .- 1435-4373. ; 34:8, s. 1583-1588
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Tidskriftsartikel (refereegranskat)abstract
- The performance of the recently commercialized UniGoldTM Streptococc-us pneurnonfac test for the detection of pneumococcal antigen in urine was studied in a multicenter study. First, we studied the interassay agreement between UniGoldTm and the BinaxNOVs," S. pneumoniae urinary antigen test on 337 consecutive urine samples sent to the laboratory for the detection of pneumococcal antigen. The two tests performed similarly (K-0.82): both tests positive in 27 cases, both tests negative in 299 cases, and with divergent test results in 11 cases. Secondly, the tests were run on urine samples from 203 patients with bacteremia, including 51 patients with pneumococcal bacteremia. The sensitivities and specificities were 67 and 86 A for Uni-GoldTm, and 57 % and 94 % for BinaxNOW, respectively. The false-positivity rate was significantly higher for Uni-GoldTm compared with BinaxNOW in patients with Escherichia colt bacteremia (15 vs. 2.1 %. p=0.04), and tended to be higher in patients with bacteremia with alpha-hemolytic streptococci (32 vs. 11 %, p=0.13). When cases with E. coli and alphahemolytic streptococci were excluded from the analysis, the overall false-positivity rate was 9/85 (11 A) for Uni-GoldTm and 6/85 (7.1 %) for BinaxNOW. In conclusion, the study showed that UniGold(TM) was not inferior to BinaxNOW (R) for the detection of pneumococcal urinary antigen in patients with pneumococcal bacteremia. The specificity of UniGold(TM) was suboptimal due to false-positive results in cases with E. colt and alpha-hemolytic streptococci bacteremia. However, in patient populations usually subjected to testing for pneumococcal urinary antigen, such as pneumonia and meningitis patients, bacteremia with these pathogens is uncommon. The diagnostic usefulness of the UniGoldTM test should be further evaluated.
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| 15. |
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| 16. |
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| 17. |
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| 18. |
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| 19. |
- Brodin, Daniel, et al.
(författare)
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Inhaled ciclesonide in adults hospitalised with COVID-19 : a randomised controlled open-label trial (HALT COVID-19)
- 2023
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 13:2
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 20. |
- Edlund, Charlotta, et al.
(författare)
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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
- 2022
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Ingår i: The Lancet - Infectious diseases. - : Elsevier. - 1473-3099 .- 1474-4457. ; 22:3, s. 390-400
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 21. |
- Hammarström, Helena, et al.
(författare)
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Treatment with reduced dose trimethoprim-sulfamethoxazole is effective in mild to moderate Pneumocystis jirovecii pneumonia in patients with hematologic malignancies
- 2023
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Ingår i: Clinical Infectious Diseases. - : University of Chicago Press. - 1058-4838 .- 1537-6591. ; 76:3, s. e1252-e1260
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 22. |
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| 23. |
- Kättström, Magdalena, 1974-, et al.
(författare)
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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
- 2023
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Ingår i: Vaccine. - : Elsevier. - 0264-410X .- 1873-2518. ; 41:9, s. 3128-3136
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 24. |
- Larsson, E., et al.
(författare)
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Evaluation of the ImmuView RSV Test for Rapid Detection of Respiratory Syncytial Virus in Adult Patients with Influenza-Like Symptoms
- 2021
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Ingår i: Microbiology Spectrum. - : American Society for Microbiology. - 2165-0497. ; 9:3
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Tidskriftsartikel (refereegranskat)abstract
- Rapid antigen tests may enhance the diagnostic yield of respiratory syncytial virus (RSV) infections, but studies have shown low sensitivity in adults. We evaluated the novel ImmuView RSV test in adult patients with influenza-like symptoms who were prospectively enrolled at three emergency departments in two Swedish hospitals during two influenza seasons, 2017 to 2018 and 2018 to 2019. The ImmuView RSV test was performed on nasopharyngeal swabs and results were compared to those of the BinaxNOW RSV test. In the first season, tests were performed on frozen samples, while unfrozen samples were used in the second season. For comparison, tests were also performed on selected samples from children. Of 333 included adult patients, the sensitivity of ImmuView and BinaxNOW was 27% for both tests and specificities were 98% and 100%, respectively. The interassay agreement was good (κ = 0.61). There was no significant difference in test performance between frozen and unfrozen samples. In samples from children, the sensitivities of ImmuView and BinaxNOW were 67% and 70%, respectively. In conclusion, the ImmuView RSV test showed low sensitivity and high specificity for identifying RSV in adult patients with influenza-like symptoms, comparable with the BinaxNOW RSV test. Rapid RSV testing is of limited value for diagnosing RSV infection in adults. IMPORTANCE: By timely RSV diagnosis among patients with influenza-like symptoms, especially when influenza diagnostics turn negative, it is possible to prevent unnecessary antibiotic usage as well as reduce diagnostic testing, nosocomial transmission, and hospital stay. Previous rapid RSV tests have demonstrated poor sensitivity in adults, and we could demonstrate that the novel ImmuView RSV test similarly showed limited value for diagnosing RSV infection in adult patients. However, in contrast to many other studies, we investigated patient characteristics in cases with false-positive tests and we compared the performance between unfrozen and frozen samples. Thus, our results are important, as they generate new knowledge about rapid antigen tests.
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| 25. |
- Littorin, Nils, et al.
(författare)
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Serotypes With Low Invasive Potential Are Associated With an Impaired Antibody Response in Invasive Pneumococcal Disease
- 2018
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Ingår i: Frontiers in Microbiology. - : Frontiers Media S.A.. - 1664-302X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Pneumococcal polysaccharide vaccines may elicit a hyporesponse under certain conditions. There is limited knowledge, however, on the type of specific antibody response in individuals with invasive pneumococcal disease (IPD). The aim of this study was to investigate the functional antibody response in patients with IPD caused by different serotypes. Pre-immune and convalescent sera from 40 patients (age 14-91 years) with IPD caused by serotypes with low (serotype 3, 19F, and 23F) and high (1, 4, 7F, and 14) invasive potential were investigated. For each patient, the homologous serotype-specific antibody concentration was determined. The functionality of induced antibodies post-IPD was evaluated in an opsonophagocytic assay (OPA). Undetectable or decreased pneumococcal killing in OPA following IPD, i.e., a nonfunctional antibody response, was observed in 24 of 40 patients (60%). Patients with nonfunctional antibody responses had lower serotype specific IgG antibody ratios post-IPD than patients with increased OPA titres. A nonfunctional antibody response was associated with low invasive serotypes (3, 19F, and 23F, p = 0.015). In conclusion, a nonfunctional antibody response may follow IPD, and was in our cohort associated to serotypes with low invasive potential. These findings need to be confirmed in a larger material.
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| 26. |
- Nordenskjöld, Anna M., 1977-, et al.
(författare)
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Prevalence and prognostic implications of myocardial injury in patients with influenza
- 2022
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Ingår i: European Heart Journal Open. - : Oxford University Press. - 2752-4191. ; 2:5
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 27. |
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| 28. |
- Olofsson, Emma, 1981-, et al.
(författare)
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Evaluation of the Sofia S. pneumoniae FIA for Detection of Pneumococcal Antigen in Patients with Bloodstream Infection
- 2019
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Ingår i: Journal of Clinical Microbiology. - : American Society for Microbiology. - 0095-1137 .- 1098-660X. ; 57:8
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Tidskriftsartikel (refereegranskat)abstract
- The usefulness of pneumococcal urinary antigen tests (UATs) in severe pneumococcal infection relies heavily on the performance in bacteremic patients. Fluorescence technology and automatic reading of test results may improve UAT performance. We evaluated the automatically read Sofia S. pneumoniae FIA for diagnosing pneumococcal bloodstream infection (BSI) in hospitalized adult patients. First, the Sofia FIA was evaluated on 97 patients with pneumococcal (n = 47) and nonpneumococcal (n = 50) BSI and compared with results by the visually read BinaxNOW S. pneumoniae immunochromatographic test (ICT) and ImmuView S. pneumoniae and Legionella pneumophila ICT. In four cases (4.1%), the Sofia FIA showed invalid test results, three of which showed invalid results by the ImmuView ICT previously. Based on 93 valid cases, the Sofia FIA showed similar sensitivity (for both comparisons: 68% versus 62%; P = 0.45) and specificity (for both comparisons: 91% versus 93%; P = 1.00) as the visually read UATs. Second, the Sofia FIA was prospectively evaluated on 82 consecutive nonfrozen urine samples, detecting pneumococcal antigen in 10 of 14 (sensitivity, 71%) pneumococcal BSI patients, similarly to the visually and automatically read BinaxNOW ICT (both 12 of 14; sensitivity, 86%; P = 0.50). Of five nonpneumococcal BSI cases, the Sofia FIA showed an invalid test result in one case, but no positive UAT results were obtained. Thus, the sensitivity and specificity of the Sofia FIA were similar to the performance rates of other UATs in patients with BSI, but invalid test results are of concern for the usefulness in pneumococcal BSI.
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| 29. |
- Olsson, Henrik, et al.
(författare)
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Household air pollution and pneumococcal density related to nasopharyngeal inflammation in mothers and children in Ethiopia: A cross-sectional study
- 2024
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- 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-1 beta, IL-6 and VEGF-A) and children (CCL4, CXCL8, IL-1 beta, 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.
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| 30. |
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| 31. |
- Schagatay, Felix, et al.
(författare)
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Serum concentration of extracellular cold-inducible RNA-binding protein is associated with respiratory failure in COVID-19
- 2022
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 32. |
- Shine, Sisay, et al.
(författare)
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Pregnant women's perception on the health effects of household air pollution in Rural Butajira, Ethiopia : a phenomenological qualitative study
- 2023
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Ingår i: BMC Public Health. - : BioMed Central (BMC). - 1471-2458. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 33. |
- Uddén, Fabian, et al.
(författare)
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Corrected and Republished from : A Nonfunctional Opsonic Antibody Response Frequently Occurs after Pneumococcal Pneumonia and Is Associated with Invasive Disease
- 2020
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Ingår i: mSphere. - : ASM. - 2379-5042. ; 5:6
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Tidskriftsartikel (refereegranskat)abstract
- Naturally acquired opsonic antipneumococcal antibodies are commonly found in nonvaccinated adults and confer protection against infection and colonization. Despite this, only limited data exist regarding the adaptive immune response after pneumococcal exposure. To investigate the dynamics of naturally acquired antipneumococcal immunity in relation to an episode of infection, opsonic antibody activity was studied with paired acute-phase and convalescent-phase sera obtained from 54 patients with pneumococcal community-acquired pneumonia (CAP) using an opsonophagocytic assay (OPA). Results were compared with clinical characteristics and anticapsular immunoglobulin (Ig) concentrations. Interestingly, a nonfunctional opsonic antibody response (characterized by a decreased convalescent-phase serum OPA titer compared to that of the acute-phase serum or undetectable titers in both sera) was observed in 19 (35%) patients. The remaining individuals exhibited either an increased convalescent-phase OPA titer (n = 24 [44%]) or a detectable, but unchanged, titer at both time points (n = 11 [20%]). Invasive pneumococcal disease (i.e., bacteremia) was significantly more common among patients with a nonfunctional convalescent-phase response than in patients with other convalescent-phase responses. Anticapsular Ig concentrations were higher among patients with detectable convalescent-phase OPA titers (P = 0.003), and the greatest Ig concentration increase was observed among patients with an increased convalescent-phase response (P = 0.002). Our findings indicate that an episode of pneumococcal infection may act as an immunizing event. However, in some cases when patients with CAP also suffer from bacteremia, a nonfunctional opsonic antibody response may occur. Furthermore, the results suggest that factors other than anticapsular Ig concentrations determine opsonic antibody activity in serum.IMPORTANCE: Numerous reports on the dynamics of antipneumococcal immunity in relation to immunization with pneumococcal vaccines and on the prevalence of naturally acquired immunity in various populations have been published. In contrast, studies on the dynamics of the humoral immune response triggered by pneumococcal infection are scarce. This study provides valuable information that will contribute to fill this knowledge gap. Our main results indicate that a functional immune response may fail after CAP, predominantly among patients with simultaneous bacteremia.
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| 34. |
- Wong, Alicia Yoke Wei, et al.
(författare)
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Comparison of Four Streptococcus pneumoniae Urinary Antigen Tests Using Automated Readers
- 2021
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Ingår i: Microorganisms. - : MDPI. - 2076-2607. ; 9:4
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Tidskriftsartikel (refereegranskat)abstract
- Streptococcus pneumoniae urinary antigen tests (UATs) may be interpreted using automatic readers to potentially automate sample incubation and provide standardized results reading. Here, we evaluated four UATs the BinaxNOW S. pneumoniae Antigen Card (Abbott, Chicago, IL, USA), ImmuView S. pneumoniae and Legionella (SSI Diagnostica, Hillerød, Denmark), STANDARD F S. pneumoniae Ag FIA (SD Biosensor, Gyeonggi, South Korea), and Sofia S. pneumoniae FIA (Quidel Corporation, San Diego, CA, USA) with their respective benchtop readers for their ability to detect S. pneumoniae urinary antigen. We found that these assays had a sensitivity of 76.9–86.5%, and specificity of 84.2–89.7%, with no significant difference found among the four UATs. The assays had a high level of agreement with each other, with 84.5% of samples testing consistently across all four assays. The automatically and visually read test results from the two immunochromatographic assays, BinaxNOW and ImmuView, were compared and showed excellent agreement between the two types of reading. Immunofluorescent-based assays, Sofia and STANDARD F, had significantly less time to detect compared to the two immunochromatographic assays due to having less assay setup procedures and shorter sample incubation times. In conclusion, the four UATs performed similarly in the detection of S. pneumoniae urinary antigen, and readers can bring increased flexibility to running UATs in the clinical routine.
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| 35. |
- Wong, Alicia Y. W., et al.
(författare)
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Evaluation of Four Lateral Flow Assays for the Detection of Legionella Urinary Antigen
- 2021
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Ingår i: Microorganisms. - : MDPI. - 2076-2607. ; 9:3
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Tidskriftsartikel (refereegranskat)abstract
- Urinary antigen tests (UATs) are often used to diagnose Legionnaires' disease as they are rapid and easy to perform on readily obtainable urine samples without the need for specialized skills compared to conventional methods. Recently developed automated readers for UATs may provide objective results interpretation, especially in cases of weak result bands. Using 53 defined patient urine samples, we evaluated the performance of the BinaxNOW Legionella Antigen Card (Abbott), ImmuView S. pneumoniae and Legionella (SSI Diagnostica), STANDARD F Legionella Ag FIA (SD Biosensor), and Sofia Legionella FIA (Quidel) simultaneously with their respective automated readers. Automatic and visual interpretation of result bands were also compared for the immunochromatography-based BinaxNOW and ImmuView UATs. Overall sensitivity and specificity of Legionella UATs were 53.9-61.5% and 90.0-94.9%, respectively. All four UATs successfully detected all samples from L. pneumophila serogroup 1-positive patients, but most failed to detect samples for Legionella spp., or other serogroups. Automatic results interpretation of results was found to be mostly concordant with visual results reading. In conclusion, the performance of the four UATs were similar to each other in the detection of Legionella urinary antigen with no major difference between automated or visual results reading.
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