No abstract

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: Experience in real clinical practice with ceftazidime-avibactam for the treatment of serious infections due to gram−negative bacteria (GNB) other than carbapenem-resistant Enterobacterales (CRE) is very limited. Methods: We carried out a retrospective multicenter study of patients hospitalized in 13 Italian hospitals who received ≥72 h of ceftazidime-avibactam for GNB other than CRE to assess the rates of clinical success, resistance development, and occurrence of adverse events. Results: Ceftazidime-avibactam was used to treat 41 patients with GNB infections other than CRE. Median age was 62 years and 68% of them were male. The main causative agents were P. aeruginosa (33/41; 80.5%) and extended spectrum beta lactamase (ESBL)-producing Enterobacterales (4/41, 9.8%). Four patients had polymicrobial infections. All strains were susceptible to ceftazidime-avibactam. The most common primary infection was nosocomial pneumonia (n = 20; 48.8%), primary bacteremia (n = 7; 17.1%), intra-abdominal infection (n = 4; 9.8%), and bone infection (n = 4; 9.8%). Ceftazidime-avibactam was mainly administered as a combination treatment (n = 33; 80.5%) and the median length of therapy was 13 days. Clinical success at the end of the follow-up period was 90.5%, and the only risk factor for treatment failure at multivariate analysis was receiving continuous renal replacement therapy during ceftazidime-avibactam. There was no association between clinical failures and type of primary infection, microbiological isolates, and monotherapy with ceftazidime-avibactam. Only one patient experienced recurrent infection 5 days after the end of treatment. Development of resistance to ceftazidime-avibactam was not detected in any case during the whole follow-up period. No adverse events related to ceftazidime-avibactam were observed in the study population. Conclusions: Ceftazidime-avibactam may be a valuable therapeutic option for serious infections due to GNB other than CRE.

The emerging outbreak of the coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread worldwide. We prescribed some promising medication to our patients with mild to moderate pneumonia due to SARS-CoV-2, however such drugs as chloroquine, hydrossichloroquine, azithromycin, antivirals (lopinavir/ritonavir, darunavir/cobicistat) and immunomodulating agents (steroids, tocilizumab) were not confirmed as effective against SARS-CoV2. We, therefore, started to use auto-hemotherapy treated with an oxygen/ozone (O 2 /O 3 ) gaseous mixture as adjuvant therapy. In Udine University Hospital (Italy) we performed a case–control study involving hospitalized adult patients with confirmed COVID-19 with mild to moderate pneumonia. Clinical presentations are based upon clinical phenotypes identified by the Italian Society of Emergency and Urgency Medicine (SIMEU—Società Italiana di Medicina di Emergenza-Urgenza) and patients that met criteria of phenotypes 2 to 4 were treated with best available therapy (BAT), with or without O 3 -autohemotherapy. 60 patients were enrolled in the study: 30 patients treated with BAT and O 2 /O 3 mixture, as adjuvant therapy and 30 controls treated with BAT only. In the group treated with O 3 -autohemotherapy plus BAT, patients were younger but with more severe clinical phenotypes. A decrease of SIMEU clinical phenotypes was observed (2.70 ± 0.67 vs. 2.35 ± 0.88, p = 0.002) in all patients during hospitalization but this clinical improvement was statistically significant only in O 3 -treated patients (2.87 ± 0.78 vs. 2.27 ± 0.83, p < 0.001), differently to the control group (2.53 ± 0.51 vs. 2.43 ± 0.93, p = 0.522). No adverse events were observed associated with the application of O 2 /O 3 gaseous mixture. O 2 /O 3 therapy as adjuvant therapy could be useful in mild to moderate pneumonia due to SARS-CoV-2. Randomized prospective study is ongoing [Clinical Trials.gov ID: Z7C2CA5837].

No abstract

Introduction: The Italian Society of Anti-Infective Therapy (SITA) and the Italian Society of Pulmonology (SIP) constituted an expert panel for developing evidence-based guidance for the clinical management of adult patients with coronavirus disease 2019 (COVID-19) outside intensive care units. Methods: Ten systematic literature searches were performed to answer ten different key questions. The retrieved evidence was graded according to the Grading of Recommendations Assessment, Development, and Evaluation methodology (GRADE). Results and Conclusion: The literature searches mostly assessed the available evidence on the management of COVID-19 patients in terms The Italian Society of Anti-infective Therapy (SITA) and the Italian Society of Pulmonology (SIP) Collaborators members are listed in the Acknowledgements section.

Newly approved and investigational drugs for the treatment of VAP are expected to offer many advantages for the management of patients with respiratory infections caused by MDR. Promising characteristics of new compounds include high activity against both methicillin-resistant Staphylococcus aureus and MDR Gram-negative bacteria and a favorable safety profile.

Purpose of review In recent years, traditional β-lactams have dramatically reduced their effectiveness against gram-negative bacteria mainly because of their ability to express multiple β-lactamase or carabapenemases that are not hydrolyzed by the old β-lactam inhibitors (BLIs) such as clavulanic acid, tazobactam, and sulbactam. New BLIs molecules have been developed to face the need of compounds that are active against multidrug or pandrug resistant gram-negative pathogens. The aim of this review is to summarize the new generation of BLIs and β-lactams combinations. Recent findings A number of new molecules with activity against Ambler class A (e.g., extended-spectrum β-lactamases, serine carbapenemases), class C (e.g., AmpC), or class D (e.g., oxacillinase-48) have been recently approved in combination with old β-lactams for the treatment of multidrug-resistant bacteria, and other agents are under investigation. These new compounds include diazabicyclooctanones non-β-lactam inhibitors (e.g., avibactam, relebactam, nacubactam) and boronic acid inhibitors (e.g., vaborbactam). Summary Newly approved and investigational new BLIs are expected to offer many advantages for the management of patients with multidrug-resistant gram-negative pathogens. Promising characteristics of new compounds include high activity against multi drug resistance gram-negative bacteria and a favorable safety profile.