Introduction A major knowledge gap in the treatment of complicated Staphylococcus aureus bacteraemia (SAB) is the optimal duration of antibiotic therapy. Safe shortening of antibiotic therapy has... Show moreIntroduction A major knowledge gap in the treatment of complicated Staphylococcus aureus bacteraemia (SAB) is the optimal duration of antibiotic therapy. Safe shortening of antibiotic therapy has the potential to reduce adverse drug events, length of hospital stay and costs. The objective of the SAFE trial is to evaluate whether 4 weeks of antibiotic therapy is non-inferior to 6 weeks in patients with complicated SAB.Methods and analysis The SAFE-trial is a multicentre, non-inferiority, open-label, parallel group, randomised controlled trial evaluating 4 versus 6 weeks of antibiotic therapy for complicated SAB. The study is performed in 15 university hospitals and general hospitals in the Netherlands. Eligible patients are adults with methicillin-susceptible SAB with evidence of deep-seated or metastatic infection and/or predictors of complicated SAB. Only patients with a satisfactory clinical response to initial antibiotic treatment are included. Patients with infected prosthetic material or an undrained abscess of 5 cm or more at day 14 of adequate antibiotic treatment are excluded. Primary outcome is success of therapy after 180 days, a combined endpoint of survival without evidence of microbiologically confirmed disease relapse. Assuming a primary endpoint occurrence of 90% in the 6 weeks group, a non-inferiority margin of 7.5% is used. Enrolment of 396 patients in total is required to demonstrate non-inferiority of shorter antibiotic therapy with a power of 80%. Currently, 152 patients are enrolled in the study.Ethics and dissemination This is the first randomised controlled trial evaluating duration of antibiotic therapy for complicated SAB. Non-inferiority of 4 weeks of treatment would allow shortening of treatment duration in selected patients with complicated SAB. This study is approved by the Medical Ethics Committee VUmc (Amsterdam, the Netherlands) and registered under NL8347 (the Netherlands Trial Register). Results of the study will be published in a peer-reviewed journal. Show less
Background: Recurrent urinary tract infections (UTIs) are common, especially in women. When oral antimicrobial prophylaxis is ineffective or not possible due to allergies or antimicrobial... Show moreBackground: Recurrent urinary tract infections (UTIs) are common, especially in women. When oral antimicrobial prophylaxis is ineffective or not possible due to allergies or antimicrobial resistance, intravesical aminoglycoside instillations (IAIs) are a non-systemic alternative.Objectives: To assess treatment satisfaction, long-term safety and efficacy of IAIs for recurrent UTI.Methods: We conducted a cohort study using data collected between January 2013 and June 2022 at the Leiden University Medical Center. Adult patients with recurrent UTI who received prophylactic IAI were eligible for inclusion. Treatment satisfaction was assessed through a survey. Data on serum aminoglycoside concentrations, cystoscopy results and number of recurrences were obtained through chart review. Number of recurrences and UTI characteristics were compared between patients on and off IAI using Poisson and logistic mixed effects models.Results: Forty-four patients were included (median follow-up time 976 days) and 323 UTIs occurred during follow-up. Overall treatment satisfaction was high (median 79.2/100). All but one patient had undetectable serum aminoglycoside levels and no malignancies were found on follow-up cystoscopy. IAI increased the time to first recurrence (102 days versus 36 days, P = 0.02), reduced the number of recurrences (rate ratio 0.75, 95% CI 0.56-0.99, P = 0.04) and the necessity for systemic antibiotics (OR 0.33, 95% CI 0.13-0.86, P = 0.02). Conclusions: In patients with recurrent UTI, IAI was associated with high treatment satisfaction, and was found to be a safe and effective alternative to oral antimicrobial prophylaxis. Show less
Stalenhoef voerde een een gerandomiseerd onderzoek uit op de Spoedeisende Hulp-afdelingen van het LUMC en geaffilieerde ziekenhuizen onder leiding van prof. Jaap van Dissel (Infectieziekten), over... Show moreStalenhoef voerde een een gerandomiseerd onderzoek uit op de Spoedeisende Hulp-afdelingen van het LUMC en geaffilieerde ziekenhuizen onder leiding van prof. Jaap van Dissel (Infectieziekten), over de toepassing van een klinische beslisregel om het risico in te schatten bij patiënten die zich presenteren met pyelonefritis, acute prostatitis of urosepsis.Het onderzoek waaraan 370 patiënten deelnamen, toonde aan dat het aantal ziekenhuisopnames met de toepassing van deze beslisregel significant werd verlaagd. Het aantal thuis behandelde patiënten dat op een later moment toch werd opgenomen, was hierbij hoger dan verwacht. Dit kwam mede doordat er bij een aantal patiënten toch een andere diagnose werd gesteld op het moment dat de kweekuitslagen bekend werden. Verder onderzoek richt zich op verbetering van de beslisregel door deze te combineren met een biomarker die de acute immuunrespons reflecteert. Show less
Stalenhoef, J.E.; Nieuwkoop, C. van; Menken, P.H.; Bernards, S.T.; Elzevier, H.W.; Dissel, J.T. van 2019