Clinical characteristics and factors affecting disease severity in hospitalized tick-borne encephalitis patients in Norway from 2018 to 2022.

PURPOSE: To describe the clinical characteristics and factors associated with disease severity in a Norwegian cohort of hospitalized patients with tick-borne encephalitis (TBE). METHODS: This observational multicenter study included hospitalized patients with TBE in the endemic area in the southeastern region of Norway from 2018 to 2022. Clinical signs and findings from laboratory tests, EEG, CT and MRI scans were recorded. Patient characteristics were compared among those with mild, moderate, and severe TBE, and factors associated with disease severity were identified. RESULTS: Nearly all eligible patients were included in the final cohort (153/189 participants, 81%). The median age was 56 years, 63% were men, and 7% were vaccinated against TBE; no participants were fully vaccinated. TBE presented as mild (meningeal) disease in 31% of patients and as moderate or severe (encephalitic) disease in 54% and 14% of patients, respectively. We found that 46% of the patients had a monophasic course, 64% had hyponatremia, and 7% presented with central nervous system (CNS) symptoms without pleocytosis in cerebrospinal fluid (CSF). Dysesthesia, a symptom previously not described, was reported in 10% of the patients. Most objective findings were related to the CNS. Preexisting comorbidities, CRP and CSF protein levels were predictors of more severe disease. CONCLUSION: This novel presentation of a large Norwegian cohort supports TBE as a serious disease in the southeastern region of Norway. The majority of hospitalized patients presented with encephalitis, and fewer presented with meningitis. Comorbidities, CRP and CSF protein levels were associated with more severe disease. TRIAL REGISTRATION: Prosjekt #2,296,959 - The Norwegian Tick-borne Encephalitis Study - NOTES. Acute phase characteristics and long-term outcomes. - Cristin.

The efficacy of pivmecillinam in oral step-down treatment in hospitalised patients with E. coli bacteremic urinary tract infection; a single-arm, uncontrolled treatment study.

BACKGROUND: The role of oral beta-lactam antibiotics in treating febrile urinary tract infections (UTI) is not yet definite. Today, fluoroquinolones together with trimethoprim-sulfamethoxazole (TMP-MTX) are considered standard of care and often the only available evidence-based oral treatment for febrile UTI. This study clarifies the efficacy and safety of pivmecillinam (PIV) used as step-down therapy for bacteremic urinary tract infection (UTI). METHODS: A single-arm, uncontrolled treatment trial was conducted in the period September 2017-March 2020. Candidates for inclusion were men and women suffering from E. coli bacteremia due to UTI and were consecutively included in a Norwegian hospital. Exclusion criteria were among others: other ongoing bacterial infection, septic shock, pyonephrosis/abscess and pregnancy. After 3 days of parenteral antibiotic, the treatment was converted to the study drug; oral PIV 400 mg QID for 1 week. Primary endpoint was a combination of three elements; afebrility, no need for retreatment and improvement in self-reported health status. Test Of Cure (TOC) was 1 week post-treatment. Secondary endpoints included among others microbiological efficacy and CRP value < 30 mg/L. RESULTS: Of 476 screened subjects, 53 patients were included. Median age was 67 years, 28 (56%) were women. 50 patients were evaluated for per-protocol analysis. 44 of 50 patients (88%) (95% CI [75.7-95.5]) reached the primary endpoint on TOC. 14 of 48 patients (29.2%) had significant growth (> 103 CFU/mL) of E.coli on TOC. CRP-level was strongly associated to treatment outcome, (OR 0.006 [95% CI 0.00-0.11], p < 0.001). CONCLUSIONS: This trial documents that PIV 400 mg QID given for 1 week following 3 days of parenteral antibiotics, is a suitable treatment option in patients suffering from bacteremic UTI due to E. coli. Randomised clinical trials studying the efficacy of PIV vs standard of care of febrile UTI are warranted. Trial registration The trial was registered at ClinicalTrials.gov under the identifier: NCT03282006 13/09/2017 and approved by The Regional Committees for Medical Research Ethics South East Norway (2015/2384/REK sør-øst) and the Norwegian Medicines Agency (SLV; reference No 16/06018-09; EudraCT No 2016-000984-18) before initiation.