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Aims This study assessed comparative effectiveness of glargine 300 U/mL (Gla-300) versus degludec 100 U/mL (Deg-100) in insulin-naïve patients with T2D. Methods This is a retrospective, multicenter, non-inferiority study based on electronic medical records. All patients initiating Gla-300 or Deg-100 were 1:1 propensity score-matched (PSM). Linear mixed models were used to assess the changes in continuous endpoints. Incidence rates (IR) of hypoglycemia were compared using Poisson’s regression models. Results Nineteen centers provided data on 357 patients in each PSM cohort. HbA1c after 6 months (primary endpoint) decreased by − 1.70% (95%CI − 1.90; − 1.50) in Gla-300 group and − 169% (95%CI − 1.89; − 1.49) in Deg-100 group, confirming non-inferiority of Gla-300 versus Deg-100. Fasting blood glucose (BG) decreased by ~60 mg/dl in both groups; body weight remained unchanged. In both groups, the mean starting dose was 12U (0.15U/kg) and it was slightly titrated to 16U (0.20U/kg). IR (episodes per patient-months) of BG ≤70 mg/dl was 0.13 in Gla-300 group and 0.14 in Deg-100 group (p=0.87). IR of BG p=0.49). No severe hypoglycemia occurred. Conclusion Initiating Gla-300 or Deg-100 was associated with similar improvements in glycemic control, no weight gain and low hypoglycemia rates, without severe episodes during 6 months of treatment.

Pivotal trials documented glycemic benefits of fixed-ratio combination of insulin glargine 100 U/mL and lixisenatide (iGlarLixi), with no weight gain and low hypoglycemia risk in type 2 diabetes (T2D). This study aimed at assessing effectiveness and patterns of use of iGlarLixi in a real-world setting.This was a retrospective, multicenter, study, based on electronic medical records. All patients initiating iGlarLixi from May 2018 to July 2020 were considered.Overall, 25 centers provided data on 675 patients initiating iGlarLixi with the following characteristics: age 66.4 ± 10.1 years, 54.2% men, T2D duration 15.5 ± 11.5 years, HbA1c 8.6 ± 1.4%, body mass index (BMI) 30.8 ± 5.3 kg/mIn adults with T2D, effectiveness and safety of iGlarLixi were documented in a real-world setting; appropriateness of use and adequate titration should be urgently improved so that clinical practice outcomes become more comparable to clinical trials results. Further real-world studies on the effect of iGlarLixi therapy are warranted.

Introduction Following pivotal trials, real-world evidence is important to assess the impact of new drugs in everyday clinical practice. The RESTORE-1 study aimed to compare effectiveness and safety of the second-generation basal insulins (2BI), i.e., insulin glargine 300 U/ml (Gla-300) vs. degludec 100 U/ml (IDeg-100), in type 1 diabetes (T1D). Methods Retrospective, non-inferiority, multicenter study, based on electronic medical records. All patients switching to Gla-300 or IDeg-100 from first-generation basal insulins (1BI) were 1:1 propensity score matched (PSM). Changes during 6 months in HbA1c (primary endpoint), fasting plasma glucose (FPG), body weight, and insulin doses were assessed using linear mixed models for repeated measures. Incidence rates (IR) of hypoglycemic events were assessed. Results Overall, 19 centers provided data on 585 patients in each PSM cohort. For both groups, statistically significant reductions in HbA1c from baseline to 6 months were documented: − 0.20%; (95% CI − 0.32; − 0.08) in the Gla-300 group and − 0.14%; (95% CI − 0.24; − 0.04) in the IDeg-100 group. The non-inferiority of Gla-300 vs. IDeg-100 was confirmed (non-inferiority margin of 0.30%; upper 95% CI at 6 months, 0.09%). No statistically significant between-group differences emerged in FPG and body weight. Dose changes of basal and short-acting insulin were small in both groups, but higher in the Gla-300 group than in the Deg-100 group (p

Introduction Primary aim was to provide real-world evidence of the outcomes after the switch to glargine 300 U/ml (Gla-300) from other basal insulins (first or second generation) in Italy. Methods Multicenter, observational, retrospective study based on electronic medical records. Results Overall, 953 T2DM insulin ± OAD treated people switched to Gla-300 or Gla-100 from January 2015 to July 2018. Three clinically relevant cohorts were identified: patients switching to Gla-300 from first-generation basal insulin (cohort 1), patients switching to Gla-300 from degludec-100 (Deg-100) (cohort 2), and those switching to Gla-100 from any basal insulin (cohort 3). The three cohorts differed in terms of age, diabetes duration, and metabolic control. HbA1c changes after 6 months from the switch were − 0.27% (95% CI − 0.38; − 0.16), − 0.06% (95% CI − 0.31; 0.19), and − 0.30% (95% CI − 0.51; − 0.09) in the three cohorts, respectively. FPG significantly decreased in cohort 1 (− 14.07 mg/dl, 95% CI − 20.25; − 7.89), while body weight significantly decreased in cohort 2 (− 1.47 kg, 95% CI − 2.55; − 0.39). Doses of insulin marginally changed during the follow-up (+ 0.89 U in basal insulin daily dose in cohort 1 and + 2.07 U in short-acting insulin daily dose in cohort 2). Conclusions Switching to Gla-300 from first-generation basal insulin in the real world is associated with improvements in metabolic control despite a suboptimal titration of both basal and short-acting insulins. Inertia in insulin titration documented in the Gla-100 cohort is also observed with the second-generation basal insulin. The switch to Gla-300 from Deg-100 was associated with a decrease in body weight of − 1.47 kg despite a slight increase in short-acting insulin daily doses of about + 2 U.

Data on second generation basal insulin (2BI) in people with type 2 diabetes (T2D) generated by clinical trials still need confirmation in real-world clinical settings. This study aimed at assessing the comparative effectiveness of 2BI [Glargine 300 U/mL (Gla-300) vs. Degludec 100 U/mL (Deg-100)] in T2D Italian patients switching from first generation basal insulins (1BI).This was a retrospective, non-inferiority, multicenter study. Patients switching to Gla-300 or Deg-100 from 1BI were 1:1 propensity score matched (PSM). Changes during 6 months in continuous endpoints were assessed through linear mixed models. Incidence rates (IR) of hypoglycemia (episodes per patient-months) were compared using Poisson regression. Each PSM cohort included 593 patients. HbA1c decreased from baseline (8.7%) to 6 months by -0.58% (95%CI -0.69;-0.47) in Gla-300 group and -0.50% (95%CI -0.61;-0.39) in Deg-100 group, confirming the non-inferiority of Gla-300 vs. Deg-100. No between-group differences emerged: FBG was reduced by about 20 mg/dl with both 2BI, mean dose of 2BI (24.5 U, 0.3 U/Kg at the first prescription) was suboptimally titrated during 6 months (+1.34 U in Gla-300 and + 1.76 U in Deg-100), body weight showed minor changes. IR of hypoglycemia54 mg/dl was 0.32 (95%CI 0.21; 0.49) in Gla-300 group and 0.19 (95%CI 0.11; 0.33) in Deg-100 group (p = 0.14).In subjects with T2D, switching to 2BI from 1BI was associated with similar improvements in glycemic control, low hypoglycemia rates and no weight gain in real-life setting. Clinical inertia, represented by late treatment intensification and suboptimal titration, represents a major issue in Italy.

Randomized clinical trials (RCT) showed benefits of FRC of basal insulin (BI) and GLP1-RAs in terms of glycemic target, no weight gain, low risk of hypoglycemia, and gastrointestinal side effects. Real-world evidence (RWE) complements RCT to assess effectiveness and safety of drugs in clinical practice. The study evaluated the impact of iGlarLixi [once-daily FRC of basal insulin glargine 100 U/mL and GLP1-RA lixisenatide] in T2D. This was a retrospective, multicenter study, based on electronic medical records. All subjects initiating iGlarLixi in May 2018-July 2020 were analyzed. Overall, 25 centers provided data on 675 subjects with the following baseline characteristics (mean and standard deviation or proportion): age: 66.4±10.1 years, 54.2% men, T2DM duration 15.5±11.5 years, HbA1c 8.6±1.4%, and BMI 30.8±5.3 Kg/m2. Before starting iGlarLixi, 67.3% of subjects were treated with BI and 9.9% with GLP1-RA (5.5% as free combinations). Drugs associated with iGlarLixi were not only metformin and SGLT2 inhibitors, as by summary of product characteristics (SmPC); off-label combinations were found in 32.4% of patients (21.4% sulphonylureas). Effectiveness data (N=184) showed that HbA1c decreased by -0.77% [95%CI -1.00;-0.54] after 6 months and by -0.92% [95%CI -1.22;-0.62] in patients treated as by SmPC. Weight significantly decreased by 1.21 Kg. iGlarLixi dose increased by 5.14 U. Rates of blood glucose ≤70 and Disclosure R. Candido: None. M. Modugno: None. E. Gabellieri: None. A. Nicolucci: Advisory Panel; Self; AstraZeneca, Research Support; Self; Novo Nordisk, Pikdare, Sanofi, Shionogi & Co., Ltd., SOBI. M. Rossi: Research Support; Self; Novo Nordisk, Sanofi, Shionogi & Co., Ltd., Swedish Orphan Biovitrum AB. M. Larosa: Employee; Self; Sanofi. On behalf of ensure study group: n/a. Funding Sanofi

Second generation basal insulin (2BI) provide similar/improved efficacy with better safety compared to first generation BI. Real-world data on 2BI in patients with type 2 diabetes (T2D) are still limited. The study aimed at comparing effectiveness of 2BI (Gla-300 vs. iDeg-100) in insulin-naïve T2D. This was a retrospective, non-inferiority, multicenter study, from electronic medical records. All patients initiating Gla-300 or iDeg-100 in January 2017-2020 were 1:1 propensity score matched. Linear mixed models for repeated measures were applied to assess changes during 6 months in HbA1c, fasting blood glucose (FBG), body weight, and insulin doses. Incidence rates (IR) of hypoglycemic events were compared using Poisson regression models. Overall, 19 centers provided data on 357 patients in each PSM cohort. Estimated mean baseline levels of HbA1c were 9.2%. Marked reductions in HbA1c after 6 months were documented: -1.70%; (95%CI -1.90; -1.50) in Gla-300 group and -1.69%; (95%CI -1.89; -1.49) in IDeg-100 group (between group mean difference: 0.01; 95%CI -0.29; 0.27), confirming non-inferiority of Gla-300 vs. IDeg-100. FBG was reduced by about 60 mg/dl in both groups; minor changes in body weight were documented. In both groups, the mean prescribed dose was about 12 U (0.15 U/Kg) and was slightly titrated during 6 months up to +4U (0.20 U/Kg). IR (episodes per patient-months) of BG≤70 mg/dl was 0.13 (95%CI 0.07;0.26) in Gla-300 group and 0.14 (95%CI 0.07;0.27) in IDeg-100 group (p=0.87). IR of BG Disclosure G. Fadini: Board Member; Self; Novo Nordisk, Sanofi, Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Novo Nordisk, Sanofi. R. Buzzetti: None. A. Nicolucci: Advisory Panel; Self; AstraZeneca, Research Support; Self; Novo Nordisk, Pikdare, Sanofi, Shionogi & Co., Ltd., SOBI. M. Rossi: Research Support; Self; Novo Nordisk, Sanofi, Shionogi & Co., Ltd., Swedish Orphan Biovitrum AB. M. Larosa: Employee; Self; Sanofi. D. Cucinotta: None. On behalf of restore-2 study group: n/a. Funding Sanofi

Aims The Italian Titration Approach Study (ITAS) demonstrated comparable HbA1c reductions and similarly low hypoglycaemia risk at 6 months in poorly controlled, insulin-naïve adults with T2DM who initiated self- or physician-titrated insulin glargine 300 U/mL (Gla-300) in the absence of sulphonylurea/glinide. The association of patient characteristics with glycaemic and hypoglycaemic outcomes was assessed. Methods This post hoc analysis investigated whether baseline patient characteristics and previous antihyperglycaemic drugs were associated with HbA1c change and hypoglycaemia risk in patient- versus physician-managed Gla-300 titration. Results HbA1c change, incidence of hypoglycaemia (any type) and nocturnal rates were comparable between patient- and physician-managed arms in all subgroups. Hypoglycaemia rates across subgroups (0.03 to 3.52 events per patient-year) were generally as low as observed in the full ITAS population. Small increases in rates of 00:00–pre-breakfast and anytime hypoglycaemia were observed in the ≤ 10-year diabetes duration subgroup in the patient- versus physician-managed arm (heterogeneity of effect; p Conclusions Comparably fair glycaemic control and similarly low hypoglycaemia risk were achieved in almost all patient subgroups with patient- versus physician-led Gla-300 titration. These results reinforce efficacy and safety of Gla-300 self-titration across a range of phenotypes of insulin-naïve people with T2DM. Clinical trial registration EudraCT 2015-001167-39

Background and aims To evaluate the economic impact of using 2nd generation basal insulin analogs, Glargine 300 Units/ml (Gla-300) vs Degludec 100 Units/ml (IDeg-100), in patients with type 2 diabetes (T2D). Methods and results An economic analysis was conducted using findings from the BRIGHT study (the first controlled, head-to-head study comparing Gla-300 vs IDeg-100), and costs for the Italian National Healthcare Service (NHS). A cost-minimization analysis (CMA) and a budget impact analysis (BIA) were conducted. Only pharmacological costs were included in the analysis. The CMA estimated patient treatment costs at 24 weeks and 1 year; the BIA assessed the economic impact of treating the overall Italian population of T2D insulin-naive patients, who initiated insulin treatment during the period September 2017–August 2018 (N = 55 318). In the BIA, four different scenarios were compared: i) all patients receive IDeg-100 (Scenario A); ii) 61% of patients receive Gla-300, 39% IDeg-100 (Scenario B); iii) 80% of patients receive Gla-300, 20% IDeg-100 (Scenario C); iv) all patients treated with Gla-300 (Scenario D). The average treatment costs per patient were lower with Gla-300 vs IDeg-100 (at 24 weeks: €129 vs €161; at 1 year: €324 vs €409, respectively). Results of the BIA showed that comparing Scenario D vs Scenario A, total savings would amount to €1.76 million at 24 weeks, €4.73 million at 1 year, €5.53 million at 2 years. Conclusion A larger use of Gla-300 vs IDeg-100 for the treatment of T2D patients would lead to a relevant reduction of therapy costs in Italy.

Beginning on April 2007, a prospective multicenter study was performed to investigate prevalence and epidemiology of microbial pathogens causing bloodstream infections (BSIs). Twenty microbiology laboratories participated to the survey over a 1-year period. A total of 11 638 episodes of BSI occurred in 11 202 patients, with 8.5% ( n = 985) of episodes being polymicrobial. Of 12 781 causative organisms, aerobic Gram-negative bacteria were 47.4% ( n = 6058), whereas Gram-positives accounted for 43.9% ( n = 5608). The remaining organisms included fungal species ( n = 924, 7.2%) and anaerobes ( n = 191, 1.5%). The most prevalent agents were Escherichia coli (21.7%), Staphylococcus aureus (14.9%), Staphylococcus epidermidis (8.2%), Pseudomonas aeruginosa (7.0%), and Enterococcus faecalis (6.3%). Isolates recovered from patients admitted to medical, surgical, and intensive care units accounted for 62.9%, 17.7%, and 19.4% of cases, respectively. BSIs were classified as hospital-acquired in 67.2% of cases. Compared with previous studies, our data show an increasing role of Gram-negative bacteria among both hospital- and community-acquired blood isolates.

Background: The therapeutic strategy for antibiotic treatment of community-acquired pneumonia (CAP) and assessments of the efficacy of such treatments are usually based on microbiologic, clinical, and chest radiographic findings. However, all these techniques have several limitations, particularly evaluation of pulmonary lesions on chest radiographs (CXRs), which is still based only on semiquantitative criteria. Objective: The aim of the present study was to use a novel computerized mathematical-statistical method of digital imaging for the quantitative evaluation of standard CXRs as an additional tool to assess and compare the efficacy of different antimicrobial treatments in patients with CAP. Methods: In this prospective, multicenter (10 centers), randomized, double-blind trial, hospitalized patients with CAP received intramuscularly either ceftazidime 1 g BID for 7 days or ceftriaxone 1 g QD (plus an injection of an inert solution every 12 hours to maintain the double-blind provision) for 7 days. CXRs were obtained before, during, and at the end of treatment in both groups. The computerized digital imaging of CXRs and their consequent mathematical-statistical analyses were performed at a central institute. The clinical outcome was also evaluated by the treating physicians using a semiquantitative, 4-level scale at baseline, in the interim, and 1 to 3 days after the end of treatment. Results: Sixty-eight patients were enrolled; 33 patients received ceftazidime and 35 received ceftriaxone. The standardized analysis of CXR digital imaging showed a significantly faster regression of the original pulmonary lesions ( P = 0.024) in the ceftazidime group, although no differences were observed in clinical outcome between the 2 treatment groups. Conclusions: Some quantitative and reproducible indices that enable a comparison of the radiologic outcome in 2 treatment arms of a clinical study can be obtained with this new method. The findings indicate that this method can be used as a tool to decrease the variability in radiographic findings during antibiotic treatment for CAP.

Background Haemophilus influenzae is one of the main aetiological agents of community-acquired respiratory tract infections. The primary aim of this study was to evaluate the antibacterial activity of telithromycin against H. influenzae clinical isolates showing different pattern of resistance in comparison with azithromycin and clarithromycin at 1/4 ×, 1/2 ×, 1 ×, 2 ×, 4 × minimum inhibitory concentration (MIC) and to peak concentrations in epithelial lining fluid (ELF). The secondary aim was to determine the influence of CO2 enriched atmosphere on bacterial susceptibility. Results Telithromycin showed high activity against H. influenzae, including strains susceptible to β-lactams (n = 200), β-lactamase producer (n = 50) and β-lactamase negative ampicillin resistant (BLNAR) (n = 10), with MIC from ≤0.03 to 4 mg/L, and MIC50/MIC90 of 1/2 mg/L with susceptibility rate of 100%, and minimum bactericidal concentrations (MBC) from 2 to 4-fold higher than the MIC. Azithromycin was the most active tested macrolide (range: 0.25 – 4 mg/L; MIC50/MIC90: 1/2 mg/L), comparable to telithromycin, while clarithromycin showed the highest MICs and MBCs (range: 0.25 – 8 mg/L; MIC50/MIC90: 2/8 mg/L). In time-kill studies, telithromycin showed a bactericidal activity at the higher concentrations (4 – 2 × MIC and ELF) against all the strains, being complete after 12 – 24 hours from drug exposition. At MIC concentrations, at ambient air, bactericidal activity of telithromycin and azithromycin was quite similar at 12 hours, and better than that of clarithromycin. Besides, telithromycin and clarithromycin at ELF concentrations were bactericidal after 12 hours of incubation for most strains, while 24 hours were needed to azithromycin to be bactericidal. Incubation in CO2 significantly influenced the MICs and MBCs, and only slightly the in vitro killing curves. Conclusion Telithromycin showed an in-vitro potency against H. influenzae comparable to azithromycin, with an in-vitro killing rate more rapid and superior to clarithromycin at 2X-MIC against β-lactamase producers and BLNAR strains, and to azithromycin at ELF concentrations against β-lactamase negative strains. Against all strains, MICs and MBCs were lower in the absence of CO2 for the tested antibiotics, showing an adverse effect of incubation in a CO2 environment. The in-vitro potency together with the tissue concentrations of the antimicrobial, should be considered in predicting efficacy.

1047 cases. Pulsed-field gel electrophoresis of ApaI-digested genomic DNA was performed and banding patterns were compared visually. Nine distinct clones were defined, each containing 3–21 isolates. It is of interest that all but three of the 15 isolates that exhibited an MIC of imipenem of 8 mg/L were indistinguishable, indicating a clonal spread of these acinetobacters. This particular clone was not defined among the remaining low-level carbapenem-resistant isolates or among those that were fully susceptible. Carbapenem-resistant acinetobacters have been reported sporadically from clinical infections after prolonged exposure to carbapenems.2 However, the emergence of strains that exhibit low-level resistance to carbapenems is limited. In a UK burns unit, acinetobacters that exhibit MICs of 2 and 0.5 mg/L of meropenem and imipenem, respectively, have been reported.3 In addition, a USA electronic surveillance programme has recorded a yearly increase in A. baumanni strains with reduced susceptibility to imipenem.4 In our region, acinetobacters are one of the most frequent nosocomial pathogens, and the majority of them are multidrug-resistant, leading to an extensive use of carbapenems.5 The detection in one of the largest Greek hospitals that the vast majority of A. baumannii exhibit low-level resistance to carbapenems is a novel observation, suggesting a potential for wider dissemination. Since the disc diffusion method is not always sensitive in the detection of strains with lowlevel resistance to carbapenems,3 it is important that our diagnostic laboratories use a reference susceptibility method to screen periodically for the presence of such acinetobacters. The continuing spread of low-level carbapenem-resistant A. baumannii clones in our hospital demands more prudent use of antimicrobials and more strict infection control measures. Further studies, to determine if similar clones exist in other hospitals, are important in continuing to monitor this situation.