Purpose: To investigate the susceptibility of carbapenemase-producing Enterobacterales (CPE) to mecillinam based on the recently updated European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints for uncomplicated Urinary Tract Infection (uUTI).Methods: The challenge collection consisted of 105 molecularly characterized Enterobacterales [Klebsiella spp. (N = 49), Escherichia coli (N = 30), Enterobacter cloacae (n = 13), Citrobacter freundii (N = 9), Proteus mirabilis (N = 3), and Raoultella ornithinolytica (N = 1)]. Isolates produced OXA-48 (N = 18), OXA-48-like (N = 18), VIM (N = 22), NDM (N = 22), KPC (N = 12), IMI (N = 9), IMP (N = 6), GES (N = 1), OXA-58 (N = 2) or combinations thereof (N = 5). MICs of carbapenems were determined by agar gradient diffusion (AGD). MICs of mecillinam were assessed by agar dilution (reference method) and compared to disk diffusion (DD) and AGD.Results: Overall 23/105 CPE (21.9%) were susceptible to mecillinam. Susceptibility was observed in E. coli (N = 12), E. cloacae (N = 7), and Klebsiella pneumoniae (N = 4) producing IMI, OXA-48, OXA-48-like, and NDM-1 carbapenemases. MIC50 for mecillinam in all isolates was 128 mg/L while MIC50 for meropenem was 8 mg/L. Lower MICs for mecillinam were found in IMI (MIC50 8 mg/L) and OXA-48-like (MIC50 16 mg/L) producers. The comparison of the different susceptibility methods showed very major errors of 12.2% with AGD and 8.5% with disk diffusion when compared to the reference method.Conclusion: Mecillinam susceptibility was restricted to isolates producing IMI-, OXA-48-like, and NDM-1 carbapenemases and was documented despite high carbapenem MICs in some isolates. Mecillinam could be a promising oral antimicrobial in uUTI caused by E. coli and E. cloacae isolates carrying IMI- and OXA-48-like carbapenemases; however, susceptibility testing by AGD and disk diffusion remains problematic.

Brain metastases deriving from esophageal cancer are very rare with scarce data available concerning these patients’ outcome. We, therefore, evaluated outcome after surgical resection followed by radiotherapy of brain metastasis from esophageal cancer. A retrospective analysis was conducted on consecutive patients undergoing resection of brain metastasis from esophageal cancer in 2 neuro-oncological centers between 2008 and 2018. Clinical and demographic data were retrieved from electronic patient charts. Post-treatment survival was calculated using Kaplan–Meier estimates. Twenty-five patients were identified. Treatment for primary disease comprised neo-adjuvant radio-chemotherapy followed by surgery (64.0%), surgery and adjuvant radio-chemotherapy (8.0%), radio-chemotherapy only (24.0%), and 1 patient receiving esophageal stenting only. Median time interval since initial diagnosis was 16 (range 0–110) months. All but 1 brain lesion were neurologically symptomatic and median Karnofsky performance score improved postoperatively from 70 to 80. After resection of brain metastases patients received whole-brain (n = 13 (52.0%)) or local fractionated (n = 9 (36.0%)) radiotherapy. In 2 patients adjuvant treatment was impeded by clinical deterioration; 1 patient refused radiotherapy. By the time of analysis 22 patients had died. Median survival after brain metastasis was 6 (95% CI 0.5–11.6) months. Survival after resection of metastasis from esophageal cancer is poor compared to other tumor entities. Nevertheless, resection of symptomatic brain metastases may improve clinical status in the context of a palliative concept.

Background With increasing resistance to common antibiotics the treatment of urinary tract infections has become challenging and alternative therapeutic options are needed. In the present study, we evaluate the activity of three older and less frequently used antibiotics against MDR Enterobacterales. Methods Susceptibility of mecillinam, temocillin and nitroxoline was assessed in Enterobacterales isolated from urinary specimens with elevated MICs of third-generation cephalosporins. Susceptibility was determined by the recommended reference MIC methods and additionally by disc diffusion. All isolates were characterized for common β-lactamases by phenotypic and molecular assays. Results In total 394 Enterobacterales were included. The most common resistance mechanisms were ESBLs (n = 273), AmpC (n = 132), carbapenemases [n = 12, including OXA-48-like (n = 8), VIM (n = 2), KPC (n = 1) and NDM (n = 1)] or others (n = 2). Resistance was observed in 59% of isolates to ceftazidime, in 41% to piperacillin/tazobactam and in 54% to ciprofloxacin. In comparison, resistance was less frequent against mecillinam (15%), temocillin (13%) or nitroxoline (2%). Mecillinam showed higher activity in Enterobacter spp., Escherichia coli and in OXA-48-like-producing isolates compared with temocillin, which was more active in Proteus mirabilis and in ESBL-producing isolates. Activity of nitroxoline was high against all isolates, including carbapenemase-producing isolates. Correlation between disc diffusion and MIC methods was good for mecillinam and moderate for temocillin and nitroxoline. Conclusions Mecillinam, temocillin and nitroxoline show good to excellent in vitro activity in MDR Enterobacterales. The activity of mecillinam and temocillin was higher in certain species and restricted depending on β-lactamase production while nitroxoline showed universally high activity irrespective of species or β-lactamase present.