Background Few data are reported in the literature about the outcome of patients with severe extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) infections treated with ceftolozane/tazobactam (C/T), in empiric or definitive therapy. Methods A multicenter retrospective study was performed in Italy (June 2016–June 2019). Successful clinical outcome was defined as complete resolution of clinical signs/symptoms related to ESBL-E infection and lack of microbiological evidence of infection. The primary end point was to identify predictors of clinical failure of C/T therapy. Results C/T treatment was documented in 153 patients: pneumonia was the most common diagnosis (n = 46, 30%), followed by 34 cases of complicated urinary tract infections (22.2%). Septic shock was observed in 42 (27.5%) patients. C/T was used as empiric therapy in 46 (30%) patients and as monotherapy in 127 (83%) patients. Favorable clinical outcome was observed in 128 (83.7%) patients; 25 patients were considered to have failed C/T therapy. Overall, 30-day mortality was reported for 15 (9.8%) patients. At multivariate analysis, Charlson comorbidity index >4 (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.9–3.5; P = .02), septic shock (OR, 6.2; 95% CI, 3.8–7.9; P < .001), and continuous renal replacement therapy (OR, 3.1; 95% CI, 1.9–5.3; P = .001) were independently associated with clinical failure, whereas empiric therapy displaying in vitro activity (OR, 0.12; 95% CI, 0.01–0.34; P < .001) and adequate source control of infection (OR, 0.42; 95% CI, 0.14–0.55; P < .001) were associated with clinical success. Conclusions Data show that C/T could be a valid option in empiric and/or targeted therapy in patients with severe infections caused by ESBL-producing Enterobacterales. Clinicians should be aware of the risk of clinical failure with standard-dose C/T therapy in septic patients receiving CRRT.

Background Our aim was to analyze mortality attributable to carbapenem-resistant (CR) Gram-negative bacilli (GNB) in patients with bloodstream infections (BSIs). Methods Prospective multicentric study including patients with GNB-BSI from19 Italian hospitals (June 2018-January 2020). Patients were followed-up to 30 days. Primary outcomes were 30-day mortality and attributable mortality. Attributable mortality was calculated in the following groups: KPC-producing Enterobacterales, metallo-β-lactamases (MBL)-producing Enterobacterales, CR-Pseudomonas aeruginosa (CRPA), CR-Acinetobacter baumannii (CRAB). A multivariable analysis with hospital fixed-effect was built to identify factors associated with 30-day mortality. Adjusted OR (aOR) were reported. Attributable mortality was calculated according to the DRIVE-AB Consortium. Results Overall,1276 patients with monomicrobial GNB BSI were included: 723/1276 (56.7%) carbapenem-susceptible (CS)-GNB, 304/1276 (23.8%) KPC-, 77/1276 (6%) MBL-producing CRE, 61/1276 (4.8%) CRPA, and 111/1276 (8.7%) CRAB BSI. Thirty-day mortality in patients with CS-GNB BSI was 13.7% compared to 26.6%, 36.4%, 32.8% and 43.2% in patients with BSI by KPC-CRE, MBL-CRE, CRPA and CRAB, respectively (p<0.001). On multivariable analysis, age, ward of hospitalization, SOFA score, and Charlson Index were factors associated with 30-day mortality, while urinary source of infection and early appropriate therapy resulted protective factors. Compared to CS-GNB, MBL-producing CRE (aOR 5.86, 95% CI 2.72-12.76), CRPA (aOR 1.99, 95% CI 1.48-5.95) and CRAB (aOR 2.65, 95% CI 1.52-4.61) were significantly associated with 30-day mortality. Attributable mortality rates were 5% for KPC-, 35% for MBL, 19% for CRPA, and 16% for CRAB. Conclusions In patients with BSIs, carbapenem-resistance is associated with an excess of mortality, with MBL-producing CRE carrying the highest risk of death.

No abstract

According to both definitions of US Centers for Disease Control and Prevention and World Health Organization, Neglected Tropical Diseases (NTDs) are a group of preventable and treatable parasitic, viral, and bacterial diseases that affect more than one billion people globally. They generally afflict the more indigent patients of the world and historically have not received as much attention as other diseases. NTDs tend to thrive in low-income regions, where water quality, sanitation and access to health care are substandard. They are common in several countries of Africa, Asia, and Latin America. In this literature review, we want to focus on Human African Trypanosomiasis (HAT), also known as “sleeping sickness”, one of the most common neglected diseases in Africa. It is caused by infection with the subspecies of the parasitic protozoan Trypanosoma brucei, and it is transmitted by the bite of the tsetse fly. It puts 70 million people at risk throughout sub-Saharan Africa and it is usually fatal if untreated or inadequately treated. This review covers several aspects of the disease. We focused our interests on most recent epidemiological data, novel diagnostic methods with their advantages and limitations, new improved treatment and orphan drugs and eradication programs, including vector control, according to a “One Health” approach, to achieve the new goals recently set by WHO.

Background This is a “proof-of-concept” study aiming to evaluate the impact of a multi-step bundles intervention in the management and outcome of patients with Gram-negative bloodstream infections (GN-BSIs). Methods This was a single-center, quasi-experimental design study. In the pre-phase (January 2019 to May 2020), patients were retrospectively enrolled. During the post-phase (June 2020 to September 2021), all patients were prospectively enrolled in a non-mandatory three steps bundles intervention arm including: i) step one: imaging to detect deep foci of infection, follow-up blood cultures and procalcitonin monitoring; ii) step two: early targeted antibiotic treatment and surgical source control; iii) step three: discontinuation of antibiotics within 7-10 days in case of uncomplicated BSI. Patients were followed up to 28-days from BSI onset. The primary outcome was 28-day mortality. Results A total of 271 patients were enrolled: 127 and 144 in the pre- vs post-phase, respectively. Full application of step one (67% vs 42%; p < .001), step two (83% vs 72%, p = .031), and step three (54% vs 2%, p < .001) increased in the pre-phase. Overall, the intervention reduced the 28-day mortality (22% vs 35% respectively, p = .016) and the median duration of total (11 vs 15 days, p < .001) and targeted (8 vs 12 days, p = .001) antibiotic therapy. Finally, the multivariate Cox regression confirmed the independent protective effect of the adherence to step one (aHR = 0.36, 95%CI = 0.20-0.63) and step two (aHR = 0.48, 95%CI = 0.29-0.81) on risk of 28-day mortality. Conclusions Clinical management and outcome of patients with GN-BSIs may be improved by providing a pre-established multi-step bundles intervention.