There is existing controversy regarding the efficacy of tigecycline (TG) in treating complicated urinary tract infections (cUTIs) because of its pharmacokinetic concerns. We present three patients with cUTIs caused by carbapenem-resistant gram-negative (GN) pathogens successfully treated with high-dose tigecycline (HDT)based regimens, as cefiderocol and aztreonam were not available in our country. The first case describes a 67-year-old patient with diabetes, prostate cancer, and double J ureteral stenting who was hospitalized with a febrile, complicated urinary tract infection (cUTI). Urine and blood cultures were positive for metallo-betasusceptible). The synergy between TG and colistin using the in vitro E-test was demonstrated, and the patient was started on this regimen using HDT. Clinical and microbiological cures were achieved, and the patient was discharged home. The second case presents a 70-year-old patient with urethral pathology who was hospitalized with the diagnosis of a lower cUTI caused by an MBL-producing pan-drug-resistant (PDR) Klebsiella pneumoniae. The in vitro E-test showed synergy between TG and colistin, and our patient was successfully treated with this HDT-based combination. The third case emphasizes a 63-year-old patient with insulin-dependent diabetes, Child B cirrhosis, and a right double J ureteral stent who was hospitalized with a febrile cUTI. Urine and blood cultures were positive for carbapenem-resistant XDR Acinetobacter baumannii (susceptible to colistin and TG). Colistin was administered for only 96 hours because of stage II acute kidney injury, and we continued the treatment with HDT in monotherapy. The patient was discharged home, and no urinary tract infection relapse was seen for six months. Favorable clinical and microbiological outcomes were achieved with TG-based regimens in our cUTI cases. We highlight the role of antibiotic synergy determined by the in vitro E-test in two cases of MBL-producing XDR/PDR Klebsiella pneumoniae.

The rate of thrombotic complications in COVID-19 patients is high and could be associated with the risk of unfavourable outcomes. Moreover, pulmonary thrombotic events can occur even in patients already on anticoagulant treatment. We present the case of a patient with severe COVID-19 pneumonia, without traditional risk factors for thrombosis, who developed massive pulmonary thrombosis (PT) despite therapeutic anticoagulation. The diagnosis was challenging, and the case raised concerns about the protective role of conventional anticoagulant treatment in COVID-19 pneumonia. Thus, we searched for literature reports on COVID-19 patients who developed PT despite being under anticoagulation therapy. We identified 13 cohort studies including 4058 patients of which 346 (8.5%) developed PT and nine case reports/series enrolling 14 patients. Four cohorts were further analysed, which reported data on risk factors for thrombosis, outcomes and biological characteristics. We found that there were no differences between patients with and without PT regarding the classical risk factors for thrombosis. PT occurred regardless of the anticoagulation regimen, and the risk factor identified was severe COVID-19 pneumonia and a stay in an intensive care unit (ICU). Pulmonary thrombotic events in patients with COVID-19 are rather inflammation-related than correlated with traditional thromboembolic risk factors, and the therapeutic approach must take into consideration this aspect.