Cefiderocol is a new cephalosporin displaying against extensively resistant (XDR) Gram-negative bacteria. We report our experience with cefiderocol-based combination therapies as “rescue” treatments in immunocompromised or critically ill patients or in patients with post-surgical infections who had failed previous regimens. A total of 13 patients were treated from 1 September 2020 to 31 March 2021. In total, 5/13 (38%) patients were classified as critically ill, due to severe COVID-19 lung failure; 4/13 (31%) patients had post-surgical infections and 4/13 (31%) had severe infections in immunocompromised subjects due to solid organ transplantation (2/4) or hematological malignancy (2/4). Overall, 10/13 infections were caused by carbapenem-resistant Acinetobacter baumannii, one by KPC-positive ceftazidime/avibactam-resistant Klebsiella pneumonia and two by Pseudomonas aeruginosa XDR. Based on clinical, microbiological and hematobiochemical evaluation, cefiderocol was associated with different companion drugs, particularly with fosfomycin, high-dose tigecycline and/or colistin. Microbiological eradication was achieved in all cases and the 30-day survival rate was 10/13; two patients died due to SARS-CoV-2 lung failure, whereas one death was attributed to subsequent infections. No recurrent infections within 30 days were reported. Finally, we hereby discuss the therapeutic potential of cefiderocol and the possible place in the therapy of this novel drug.

The long-term consequences of the coronavirus disease 19 (COVID-19) are likely to be frequent but results hitherto are inconclusive. Therefore, we aimed to define the incidence of long-term COVID signs and symptoms as defined by the World Health Organization, using a systematic review and meta-analysis of observational studies. A systematic search in several databases was carried out up to 12 January 2022 for observational studies reporting the cumulative incidence of long COVID signs and symptoms divided according to body systems affected. Data are reported as incidence and 95% confidence intervals (CIs). Several sensitivity and meta-regression analyses were performed. Among 11,162 papers initially screened, 196 were included, consisting of 120,970 participants (mean age: 52.3 years; 48.8% females) who were followed-up for a median of six months. The incidence of any long COVID symptomatology was 56.9% (95% CI 52.2–61.6). General long COVID signs and symptoms were the most frequent (incidence of 31%) and digestive issues the least frequent (7.7%). The presence of any neurological, general and cardiovascular long COVID symptomatology was most frequent in females. Higher mean age was associated with higher incidence of psychiatric, respiratory, general, digestive and skin conditions. The incidence of long COVID symptomatology was different according to continent and follow-up length. Long COVID is a common condition in patients who have been infected with SARS-CoV-2, regardless of the severity of the acute illness, indicating the need for more cohort studies on this topic.

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The impact on time to results (TTR) and clinical decisions was evaluated for mono-microbial positive blood cultures (BC) processed using the BD Kiestra Work Cell Automation (WCA) system. Positive BC were processed by the WCA system by full-automatic subculture on solid media and digital imaging after 8 h of incubation (8-h method) followed by identification (ID) and antimicrobial susceptibility testing (AST). To evaluate the accuracy of the 8-h method, ID and AST from 8-h and overnight incubated colonies were compared for the same organisms. To evaluate its clinical impact, results from 102 BC processed by the 8-h method (cases) were compared with those from 100 BC processed by overnight incubation method (controls) in a comparable period. Identification after 8-h and overnight incubation gave concordant results in 101/102 (99.0%) isolates. Among a total of 1379 microorganism-antimicrobial combinations, categorical agreement was 99.4% (1371/1379); no very major error, 7 major errors, and one minor error were observed. TTR in cases (32.8 h ± 8.3 h) was significantly (p < 0.001) shorter than in controls (55.4 h ± 13.3 h). A significant reduction was observed for duration of empirical therapy (cases 54.8 h ± 23.3 h vs controls 86.9 h ± 34.1 h, p < 0.001) and 30-day crude mortality rate (cases 16.7% vs controls 29.0%, p < 0.037). Automation and 8-h digital reading of plates from positive BC, followed by ID and AST, greatly reduce TTR and shorten the duration of antimicrobial empiric therapy, possibly improving outcome in patients with mono-microbial bloodstream infections.

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Objectives: The aim of this study was to describe our experience of a combination treatment including meropenem/vaborbactam (M/V) plus aztreonam (ATM) for bloodstream infections (BSIs) due to ceftazidime/avibactam-resistant Klebsiella pneumoniae (CAZ/AVI-R-Kp), for which gene typing was not available at the time the blood culture (BC) results were obtained. Methods: Between 20 July and 22 August 2021, in our hospital laboratory, the molecular test for carbapenemase gene typing was not available. All Gram-negative bloodstream infections were recorded, and characteristics of patients were analysed. Among them, three patients had positive BCs for CAZ/AVI-R-Kp, and the empirical therapy was switched to M/V plus ATM pending phenotypic testing of sensitivity to M/V. Therapy was subsequently targeted on the basis of the results of this test. Results: KPC and NDM represent the most prevalent carbapenemases in our polyclinic. Three patients with CAZ/AVI-R-Kp sepsis were treated with M/V plus ATM not knowing the carbapenemase gene. Two had an NDM-Kp infection for which, upon obtaining the result of sensitivity to M/V, combination therapy was maintained. The third had KPC-Kp infection for which ATM was discontinued, after the acquisition of an antibiogram reporting full sensitivity to M/V (MIC = 0.25 mg/L). One patient with NDM-Kp infection died due to complications of the underlying disease for which he was hospitalised. Conclusions: Meropenem/vaborbactam plus ATM and subsequent de-escalation could represent a possible therapeutic strategy in severe CAZ/AVI-R-Kp infections when carbapenemase gene typing is not rapidly available.