Ceftolozane/Tazobactam for Treatment of Severe ESBL-Producing Enterobacterales Infections: A Multicenter Nationwide Clinical Experience (CEFTABUSE II Study)

Background. Few data are reported in the literature about the outcome of patients with severe extended-spectrum beta-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

Preparation of metalated azine complexes of iridium(III)

Arylaldazine and acetoneazine complexes [IrCl(eta(5)-C5Me5){kappa(1)-[N=C(H)(R2C(6)H(4))]-N=C(H)(R2C(6)H(4))}{P(OR1)(3)}]-BPh4 (1, 2) and [IrCl(eta(5)-C5Me5){kappa(1)-[N=C(CH3)(2)]-N=C(CH3)(2)}{P(OR1)(3)}]BPh4 (3, 4) [R1 = Me (1, 3), Et (2, 4); R2 = H (a), 4-CH3 (b), 2,6-(CH3)(2) (f)] were prepared by allowing chloro complexes IrCl2(eta(5)-C5Me5)[P(OR1)(3)] to react first with AgOTf and then with the appropriate azine. In solution, kappa(1)-complexes 1-4 undergo a metalation reaction, affording chelate kappa(2)-azine derivatives [Ir{kappa(2)-R2C6H3(H) C=N-N=C(H)(R2C(6)H(4))}(eta(5)-C5Me5){P(OR1)(3)}] BPh4 (5, 6) and [Ir{kappa(2)-CH2(CH3)C=N-N=C(CH3)(2)}(eta(5)-C5Me5){P(OR1)(3)}]BPh4 (7, 8) [R1 = Me (5, 7), Et (6, 8); R2 = H (a), 4-CH3 (b), 4-CH3O (c); 4-F (d), 4-NO2 (e)]. The complexes were characterised spectroscopically and by X-ray crystal structure determination of [Ir{kappa(2)-C6H4(H)C=N-N=C(H)(C6H5)}(eta(5)-C5Me5){P(OEt)(3)}]BPh4 (6a). Most of the kappa(2)-arylazine derivatives showed photoluminescence properties upon excitation with near-UV and violet light, with emission peaks at around 650 nm. The photoluminescence features were rationalised according to DFT calculations

Candidemia in the elderly: What does it change?

BACKGROUND: Candidemia is a life-threatening fungal infection and it can affect patients of all ages. Characterization of candidemia in the elderly is lacking. METHODS: We performed a retrospective study of adults (≥ 18 years) with candidemia diagnosed in our center in 2010-2015. Demographics, comorbidities, clinical and microbiologic characteristics, antifungal treatment and outcome were compared between older (≤65 years) and younger (>65 years) patients. RESULTS: Among 302 patients with candidemia identified during the study period, 188 (62%) belonged to the elderly group. Comorbidities were significantly more frequent in older patients and included chronic pulmonary diseases, cardiovascular diseases, diabetes mellitus, and chronic renal failure (p ranging from <0.0001 to 0.017). A significantly higher proportion of older patients had septic shock (p = 0.040) at the time of candidemia. Candida albicans accounted for 53% of isolates and there were no significant differences between patients' age and Candida species. Thirty-day mortality was significantly higher in older (45%) than in younger (28%) patients (p = 0.003). Factors associated with a significant higher proportion of death in the elderly included older age (i.e.: old-old), being hospitalized in ICU rather than in other wards, suffering from chronic pulmonary diseases, the presence of septic shock, multiple organ failure, dialysis and being infected with C. glabrata (p ranging from <0.0001 to 0.034). On multivariate analysis septic shock (HR 1.744 [CI95% 1.049-2.898], p = 0.032) and multiple organ failure (HR 2.242 [CI95% 1.070-4.698], p = 0.032) were independently associated with a higher risk of death. The probability of 30-days survival of older patients was significantly reduced when compared to that of younger patients (p = 0.005) who did not receive any treatment. In the elderly, there was a trend toward higher MICs for fluconazole/C. albicans, fluconazole/C. glabrata, amphotericin B/C. albicans, and caspofungin/C. glabrata. CONCLUSIONS: In our study, we found that elderly patients with Candida bloodstream infections are characterized by a high mortality rate. In particular, the lack of any antifungal therapy as well as the occurrence of septic shock increased significantly the overall mortality. Additionally, we found that there was a trend of higher MIC for specific drug/Candida combination

Candidemia in the elderly: What does it change?

Candidemia is a life-threatening fungal infection and it can affect patients of all ages. Characterization of candidemia in the elderly is lacking.We performed a retrospective study of adults (≥ 18 years) with candidemia diagnosed in our center in 2010-2015. Demographics, comorbidities, clinical and microbiologic characteristics, antifungal treatment and outcome were compared between older (≤65 years) and younger (>65 years) patients.Among 302 patients with candidemia identified during the study period, 188 (62%) belonged to the elderly group. Comorbidities were significantly more frequent in older patients and included chronic pulmonary diseases, cardiovascular diseases, diabetes mellitus, and chronic renal failure (p ranging from <0.0001 to 0.017). A significantly higher proportion of older patients had septic shock (p = 0.040) at the time of candidemia. Candida albicans accounted for 53% of isolates and there were no significant differences between patients' age and Candida species. Thirty-day mortality was significantly higher in older (45%) than in younger (28%) patients (p = 0.003). Factors associated with a significant higher proportion of death in the elderly included older age (i.e.: old-old), being hospitalized in ICU rather than in other wards, suffering from chronic pulmonary diseases, the presence of septic shock, multiple organ failure, dialysis and being infected with C. glabrata (p ranging from <0.0001 to 0.034). On multivariate analysis septic shock (HR 1.744 [CI95% 1.049-2.898], p = 0.032) and multiple organ failure (HR 2.242 [CI95% 1.070-4.698], p = 0.032) were independently associated with a higher risk of death. The probability of 30-days survival of older patients was significantly reduced when compared to that of younger patients (p = 0.005) who did not receive any treatment. In the elderly, there was a trend toward higher MICs for fluconazole/C. albicans, fluconazole/C. glabrata, amphotericin B/C. albicans, and caspofungin/C. glabrata.In our study, we found that elderly patients with Candida bloodstream infections are characterized by a high mortality rate. In particular, the lack of any antifungal therapy as well as the occurrence of septic shock increased significantly the overall mortality. Additionally, we found that there was a trend of higher MIC for specific drug/Candida combination

Central venous catheter unrelated candidemia influences the outcome of infection in patients with solid tumors

Systemic infections due to Candida spp. is common among immunocompromised patients, including those with solid tumors (ST). Clinical characteristics of candidemia in 114 patients with ST were compared with those of 249 candidemic patients without ST (non-ST). Patients with ST were more likely to be hospitalized in medical departments, to have a significantly higher Charlson's score and to undergo a significantly later central venous catheter (CVC) removal (P < 0.001). Similarly, the use of total parenteral nutrition was more common in ST patients (P = 0.026). Although there was a trend toward a more appropriate use of antifungal therapy in ST (60%) than in non-ST patients (49%), the difference was not statistically significant (P = 0.059). Thirty-day mortality was significantly higher in ST (49%) than in non-ST patients (36%, P = 0.016). Multivariate analysis showed that either higher age or septic shock was an independent risk factor for mortality in both groups of patients. Conversely, a CVC-unrelated candidemia represented an independent risk factor for mortality in ST patients (HR 3.581 [CI 95% 1.412-9.087, P = 0.007]). Overall, these data show that candidemia in ST patients is characterized by an extremely high mortality rate

Outcome of 188 elderly patients with BSIs due to <i>Candida</i> species considered in this study.

<p>Outcome of 188 elderly patients with BSIs due to <i>Candida</i> species considered in this study.</p

Outcome of 114 younger patients with BSIs due to <i>Candida</i> species considered in this study.

<p>Outcome of 114 younger patients with BSIs due to <i>Candida</i> species considered in this study.</p

Demographics and clinical characteristics of 302 patients with BSIs due to <i>Candida</i> species considered in this study.

<p>Demographics and clinical characteristics of 302 patients with BSIs due to <i>Candida</i> species considered in this study.</p

May some HCV genotype 1 patients still benefit from dual therapy? The role of very early HCV kinetics

When treating HCV patients with conventional dual therapy in the current context of rapidly evolving HCV therapy, outcome prediction is crucial and HCV kinetics, as early as 48 hours after the start of treatment, may play a major role. We aimed at clarifying the role of HCV very early kinetics. We consecutively enrolled mono-infected HCV patients at 7 treatment sites in Central Italy and evaluated the predictive value of logarithmic decay of HCV RNA 48 hours after the start of dual therapy (Delta48). Among the 171 enrolled patients, 144 were evaluable for early and sustained virological response (EVR, SVR) prediction; 108 (75.0%) reached EVR and 84 (58.3%) reached SVR. Mean Delta48 was 1.68±1.22 log10 IU/ml, being higher in patients with SVR and EVR. Those genotype-1 patients experiencing a Delta48 >2 logs showed a very high chance of success (100% positive predictive value), even in the absence of rapid virological response (RVR). Evaluation of very early HCV kinetics helped identify a small but significant proportion of genotype-1 patients (close to 10%) in addition to those identified with RVR, who could be treated with dual therapy in spite of not reaching RVR. In the current European context, whereby sustainability of HCV therapy is a crucial issue, conventional dual therapy may still play a reasonable role in patients with good tolerance and early prediction of success

Candidemia in the elderly: What does it change? - Fig 2

<p>Fluconazole (A), amphotericin B (B), and caspofungin (C) MICs for clinical isolates of <i>Candida</i> spp. recovered from younger (gray bars) and older (black bars) patients.</p