Background: Fosfomycin is used as a combination partner for the treatment of severe non-urinary tract infections. Individualized dosing of fosfomycin based on therapeutic drug monitoring (TDM) has the potential to reduce drug-related adverse events (AEs). Methods: This retrospective study used routine data from patients receiving intravenous fosfomycin therapy. Plasma concentrations of fosfomycin were categorized into three different ranges: 128 mg/L. Subsequently, the influence of acute kidney injury (AKI) on reaching the specific plasma concentration ranges and the occurrence of AEs was analyzed. Results: The study included 143 patients (median age 73 years, 66.4% male) with fosfomycin plasma measurements. Beta-lactam antibiotics were most frequently used in combination (62.2%), followed by tetracyclines (12.2%), cotrimoxazole (8.1%), and other agents (17.5%). Fosfomycin concentrations were >128 mg/L in 45% (36/80) of patients with normal renal function, 70.4% (38/54) of patients with AKI stages I to III, and 77.8% (7/9) of patients with renal replacement therapy. AEs occurred in 54% (77/143), mainly hypernatremia (42.6%), hypokalemia (39.9%), and gastrointestinal symptoms (19.6%), with the median fosfomycin plasma concentration being significantly higher in patients with AEs (158 mg/L vs. 131 mg/L, p = 0.01). Multivariate logistic regression analysis revealed that patients aged ≥70 years (OR 3.70, 95% CI 1.24–11.5; p = 0.02) and patients with fosfomycin plasma concentrations > 128 mg/L (OR 3.30, 95% CI 1.09–10.4; p = 0.04) had a higher risk of AEs. Conclusions: There was a significant association between high plasma exposure and the occurrence of AEs. In particular, the impact of acute renal insufficiency on fosfomycin plasma concentrations should be considered. Individualized fosfomycin dosing based on TDM and the intensive monitoring of renal function contribute to reducing drug-related side effects.
Background: In recent years, there has been a significant increase in cases of tularemia, a rare zoonotic disease caused by Francisella tularensis, in Europe. Methods: To investigate the epidemiological, clinical, and therapeutic characteristics of tularemia patients in Germany, we performed a retrospective evaluation of tularemia cases treated between 2010 and 2025 at selected treatment centers of the Permanent Working Group of Competence and Treatment Centers for High Consequence Infectious Diseases (STAKOB) at the Robert Koch Institute. Results: A total of 65 patients (median age: 48.5 years; 66.2% male) were identified. Most common manifestation was ulceroglandular (70.7%), followed by oropharyngeal (13.8%), pulmonary (10.8%), oculoglandular (7.7%), typhoidal (4.6%), and meningitic (4.6%). Serological confirmation of the diagnosis was achieved in all patients (90.8% ELISA, 46.2% Western blot). PCR-based direct pathogen detection was successful in 26.2%. Bloodstream infection was detected in 4.6%. Median incubation period was 7 days (IQR: 4–10), with fever being the most common symptom in 96.9% and lymphadenopathy in 46.2%. Median time to recovery was 56 days (IQR: 37–80) in patients diagnosed and treated early (≤3 weeks after symptom onset), compared to 84 days (IQR: 66–182) in patients with late diagnosis (>3 weeks after symptom onset; p = 0.015). Empirical therapy with beta-lactam antibiotics was initiated in 49.2% of cases. Following suspicion of tularemia, 96.9% received recommended treatment with fluoroquinolones, tetracyclines, or aminoglycosides. Conclusions: Delayed diagnosis and inappropriate initial therapy can significantly prolong disease courses and increase morbidity. Early treatment with effective antibiotics, considering the intrinsic beta-lactam resistance of Francisella tularensis, leads to faster recovery.