Non-fermentative gram-negative bloodstream infection in northern Italy: a multicenter cohort study.

BACKGROUND: The management of non-fermentative gram-negative bloodstream infection (NFGN-BSI) offers numerous challenges. In this study the aim is to analyse a large cohort of patients with NFGN-BSI recruited in the northern Italy to describe epidemiology, etiological and susceptibility pattern, therapeutic management and outcome. METHODS: Multicentre retrospective cohort study of patients hospitalised at three large teaching hospitals in northern Italy in a fourth year period. RESULTS: 355 BSI episodes were analyzed, due to P. aeruginosa (72.7%), A. baumannii (16.6%), and Stenotrophomonas maltophilia (10.7%). Overall, 21.4% of isolates were defined as DTR, highest rate among A. baumannii (64.4%). All-cause 30-day mortality rate was 17.5%. Rates of XDR or DTR A. baumannii isolation were significantly higher in non-surviving patients. Independent risk factors for 30-day mortality were: age (HR 1.03, 95%CI 1.00-1.04, p = 0.003), septic shock (HR 2.84, 95%CI 1.67-4.82, p < 0.001) and BSI due to Acinetobacter baumannii (HR 2.23, 95%CI 1.27-3.94, p = 0.005). CONCLUSION: The overall prevalence of DTR was high in the NFGN BSI cohort analyzied, mainly among Acinetobacter baumannii episodes (64.4%). Acinetobacter baumannii is showed to be an independent predictor of mortality. These evidences marked the urgent need of new therapeutic options against this pathogen. TRIAL REGISTRATION NUMBER: 79/2017/O/OssN. Approved: March14th, 2017.

Quality of care indicators in the MAnageMent of BlOOdstream infections caused by Enterobacteriaceae (MAMBOO-E study): state of the art and research agenda.

OBJECTIVES: The impact on outcome of five interventions was reviewed in order to investigate the state of the art for management of Enterobacteriaceae bloodstream infection (E-BSI). METHODS: We searched for randomised controlled trials (RCTs) and observational studies published from January 2008 to March 2019 in PubMed, EMBASE and Cochrane Library. Populations consisted of patients with E-BSI. Interventions were as follows: (i) performance of imaging to assess BSI source and/or complications; (ii) follow-up blood cultures (FU-BCs); (iii) use of loading dose followed by extended/continuous infusion (E/CI) of ß-lactams; (iv) duration of treatment (short- versus long-term); and (v) infectious diseases (ID) consultation. Patients without intervention were considered as controls. The main outcome was 30-day mortality. RoB 2.0 and ROBINS-I tools were used for bias assessment. RESULTS: No study was eligible for interventions i, iii and v. For FU-BCs, one observational study including 901 patients with E-BSI was considered. Intervention consisted of repeating BCs within 2-7 days after index BCs. All-cause 30-day mortality was 14.2% (35/247) in the intervention group versus 14.7% (96/654) in the control group. For short treatment duration, two RCTs and six observational studies were included comprising 4473 patients with E-BSI. All-cause mortality was similar in the short and long treatment groups (OR = 1.10, 95% CI 0.83-1.44). CONCLUSION: Of the assessed interventions, only short treatment duration in non-immunocompromised patients with E-BSI is supported by current data. Studies investigating the use of systematic imaging, FU-BCs, E/CI ß-lactams and ID consultation in patients with E-BSI are needed.

COVID-19 in solid organ transplant recipients: No difference in survival compared to general population.

Coronavirus disease 2019 (COVID-19) may be associated with worse outcome in solid organ transplant (SOT) recipients. We performed a prospective cohort study of hospitalized patients with confirmed diagnosis of COVID-19, from March 15 to April 30, 2020, at two tertiary hospitals in Emilia-Romagna Region. SOT recipients were compared with non-SOT patients. Primary endpoint was all-cause 30-day mortality. Relationship between SOT status and mortality was investigated by univariable and multivariable Cox regression analysis. Patients were assessed from COVID-19 diagnosis to death or 30-day whichever occurred first. Study cohort consisted of 885 patients, of them 24 SOT recipients (n = 22, kidney, n = 2 liver). SOT recipients were younger, had lower BMI, but higher Charlson Index. At admission they presented less frequently with fever and respiratory failure. No difference in 30-day mortality between the two groups (19% vs 22.1%) was found; however, there was a trend toward higher rate of respiratory failure (50% vs 33.1%, P = .07) in SOT recipients. Superinfections were more represented in SOT recipients, (50% vs 15.5%, P < .001). At multivariate analysis adjusted for main covariates, there was no association between SOT and 30-day mortality HR 1.15 (95% CI 0.39-3.35) P = .79. Our data suggest that mortality among COVID-19 SOT recipients is similar to general population.

Efficacy of corticosteroid treatment for hospitalized patients with severe COVID-19: a multicentre study.

OBJECTIVE: To assess the efficacy of corticosteroids in patients with coronavirus disease 2019 (COVID-19). METHODS: A multicentre observational study was performed from 22 February through 30 June 2020. We included consecutive adult patients with severe COVID-19, defined as respiratory rate ≥30 breath per minute, oxygen saturation ≤93% on ambient air or arterial partial pressure of oxygen to fraction of inspired oxygen ≤300 mm Hg. We excluded patients being treated with other immunomodulant drugs, receiving low-dose corticosteroids and receiving corticosteroids 72 hours after admission. The primary endpoint was 30-day mortality from hospital admission. The main exposure variable was corticosteroid therapy at a dose of ≥0.5 mg/kg of prednisone equivalents. It was introduced as binomial covariate in a logistic regression model for the primary endpoint and inverse probability of treatment weighting using the propensity score. RESULTS: Of 1717 patients with COVID-19 evaluated, 513 were included in the study, and of these, 170 (33%) were treated with corticosteroids. During hospitalization, 166 patients (34%) met the criteria of the primary outcome (60/170, 35% in the corticosteroid group and 106/343, 31% in the noncorticosteroid group). At multivariable analysis corticosteroid treatment was not associated with lower 30-day mortality rate (adjusted odds ratio, 0.59; 95% confidence interval (CI), 0.20-1.74; p 0.33). After inverse probability of treatment weighting, corticosteroids were not associated with lower 30-day mortality (average treatment effect, 0.05; 95% CI, -0.02 to 0.09; p 0.12). However, subgroup analysis revealed that in patients with PO2/FiO2 < 200 mm Hg at admission (135 patients, 52 (38%) treated with corticosteroids), corticosteroid treatment was associated with a lower risk of 30-day mortality (23/52, 44% vs. 45/83, 54%; adjusted odds ratio, 0.20; 95% CI, 0.04-0.90; p 0.036). CONCLUSIONS: The effect of corticosteroid treatment on mortality might be limited to critically ill COVID-19 patients.

Development and validation of a prediction model for severe respiratory failure in hospitalized patients with SARS-CoV-2 infection: a multicentre cohort study (PREDI-CO study).

OBJECTIVES: We aimed to develop and validate a risk score to predict severe respiratory failure (SRF) among patients hospitalized with coronavirus disease-2019 (COVID-19). METHODS: We performed a multicentre cohort study among hospitalized (>24 hours) patients diagnosed with COVID-19 from 22 February to 3 April 2020, at 11 Italian hospitals. Patients were divided into derivation and validation cohorts according to random sorting of hospitals. SRF was assessed from admission to hospital discharge and was defined as: Spo2 <93% with 100% Fio2, respiratory rate >30 breaths/min or respiratory distress. Multivariable logistic regression models were built to identify predictors of SRF, ß-coefficients were used to develop a risk score. Trial Registration NCT04316949. RESULTS: We analysed 1113 patients (644 derivation, 469 validation cohort). Mean (±SD) age was 65.7 (±15) years, 704 (63.3%) were male. SRF occurred in 189/644 (29%) and 187/469 (40%) patients in the derivation and validation cohorts, respectively. At multivariate analysis, risk factors for SRF in the derivation cohort assessed at hospitalization were age ≥70 years (OR 2.74; 95% CI 1.66-4.50), obesity (OR 4.62; 95% CI 2.78-7.70), body temperature ≥38°C (OR 1.73; 95% CI 1.30-2.29), respiratory rate ≥22 breaths/min (OR 3.75; 95% CI 2.01-7.01), lymphocytes ≤900 cells/mm3 (OR 2.69; 95% CI 1.60-4.51), creatinine ≥1 mg/dL (OR 2.38; 95% CI 1.59-3.56), C-reactive protein ≥10 mg/dL (OR 5.91; 95% CI 4.88-7.17) and lactate dehydrogenase ≥350 IU/L (OR 2.39; 95% CI 1.11-5.11). Assigning points to each variable, an individual risk score (PREDI-CO score) was obtained. Area under the receiver-operator curve was 0.89 (0.86-0.92). At a score of >3, sensitivity, specificity, and positive and negative predictive values were 71.6% (65%-79%), 89.1% (86%-92%), 74% (67%-80%) and 89% (85%-91%), respectively. PREDI-CO score showed similar prognostic ability in the validation cohort: area under the receiver-operator curve 0.85 (0.81-0.88). At a score of >3, sensitivity, specificity, and positive and negative predictive values were 80% (73%-85%), 76% (70%-81%), 69% (60%-74%) and 85% (80%-89%), respectively. CONCLUSION: PREDI-CO score can be useful to allocate resources and prioritize treatments during the COVID-19 pandemic.

Prognostic Utility of the New Definition of Difficult-to-Treat Resistance Among Patients With Gram-Negative Bloodstream Infections.

BACKGROUND: To compare the prognostic utility of the new definition of difficult-to-treat resistance (DTR) vs established definitions in a cohort of patients with Gram-negative bloodstream infections (GNBSIs). METHODS: This was a retrospective single-center study of adult patients with monomicrobial GNBSI, hospitalized from 2013 to 2016. DTR was defined as isolate demonstrating intermediate or resistant phenotype to all reported agents in the carbapenem, beta-lactam, and fluoroquinolone classes. Carbapenem resistance (CR) was defined according to 2015 Centers for Disease Control and Prevention criteria. Each isolate was further classified according to the Magiorakos et al. criteria as non-multidrug-resistant (non-MDR), MDR, extensively drug-resistant (XDR), or pan-drug-resistant (PDR). The primary outcome was all-cause 30-day mortality. RESULTS: Overall, 1576 patients were analyzed. Enterobacteriaceae accounted for 88.7% of BSIs, with Escherichia coli (n = 941) and Klebsiella pneumoniae (n = 326) being the most common pathogens. Pseudomonas aeruginosa was the most common nonfermentative bacteria (n = 130, 8.2%). Overall, 11% of strains were defined as DTR and 13% as CR. Episodes were further classified as non-MDR (68.8%), MDR (21.9%), XDR (8.8%), and PDR (0.4%). The prevalence rates of DTR, CR, and XDR were similar among Enterobacteriaceae and Acinetobacter baumannii, whereas they differed in P. aeruginosa. All the analyzed resistance definitions significantly improved prediction of 30-day mortality when introduced into a baseline multivariate model, to a similar degree: 9%, 10%, and 11% for DTR, Magiorakos, and CR definitions, respectively. CONCLUSIONS: DTR seems a promising tool to identify challenging GNBSIs, mainly those due to P. aeruginosa. With the availability of new agents for CR infections, further multicenter assessments of DTR are needed.

Risk factors for treatment failure in patients receiving ß-lactam/ß-lactamase inhibitor combinations for Enterobacteriaceae bloodstream infection: A retrospective, single-centre, cohort study.

The aim of this study was to investigate risk factors for treatment failure in patients receiving in vitro-active therapy with ß-lactam/ß-lactamase inhibitor (BL/BLI) for Enterobacteriaceae bloodstream infection (E-BSI). This was a retrospective, single-centre study of patients diagnosed with E-BSI at an Italian centre over a 4-year period. Exclusion criteria were age <18 years, clinical data unavailable, polymicrobial BSI, failure to receive in vitro-active therapy and death within 72 h from drawing the index blood culture. Patients who received BL/BLI as appropriate empirical and/or definitive therapy for ≥50% of the total treatment duration were selected. The primary endpoint was all-cause 30-day mortality. The secondary endpoint was 90-day relapse. Of 1319 eligible patients, 835 were selected. A total of 714 received BL/BLI as appropriate empirical therapy, of whom 522 remained on BL/BLI as definitive therapy and 192 shifted to another antibiotic for <50% of the treatment duration; 121 received BL/BLI as definitive therapy only. Non-susceptibility to extended-spectrum cephalosporins (NS-ESCs) was detected in 207 episodes (24.8%). All-cause 30-day mortality was 6.8%. In multivariate analysis adjusted for NS-ESC, independent predictors of mortality were Charlson comorbidity index, septic shock, Proteus spp. and CVC-related BSI, whilst urinary source was a protective factor. The 90-day relapse rate was 4.2%. Immunosuppression was the main independent predictor for relapse. BL/BLI was the most common antibiotic administered to patients with E-BSI in this cohort. Among patients appropriately treated with BL/BLI, failure rates were low and were primarily associated with underlying diseases, clinical severity at BSI onset and infection source.

Vitamin D insufficiency is associated with subclinical atherosclerosis in HIV-1-infected patients on combination antiretroviral therapy.

Objectives: Vitamin D insufficiency has been associated with faster progression of atherosclerosis and increased cardiovascular disease risk, but limited data are available in HIV-infected people. So, we examined potential correlation between vitamin D status and atherosclerosis in people living with HIV.Methods: A cross-sectional study was performed including adult HIV-infected patients on stable antiretroviral therapy, aged 40-60 years, and with a recent carotid ultrasonography. Subclinical atherosclerosis was defined as a carotid intima-media thickness (IMT) ≥0.9 mm at any site. Patients with diabetes mellitus or atherosclerotic cardiovascular disease were excluded.Results: On the whole, 188 patients were enrolled: 86.2% were men and the mean age was 49.1 years. The mean CD4 T lymphocyte count was 567 cells/mm3, 176 (93.6%) had plasma HIV RNA <20 copies/mL, 51.1% were smoker, 29.2% had hypertension, 27.7% metabolic syndrome, and 44.7% LDL cholesterol >150 mg/dL. The mean serum concentration of vitamin D was 35.2 ng/mL, and 84 (44.6%) patients had a vitamin D insufficiency (<30 ng/mL). Subclinical atherosclerosis was reported in 105 (55.8%) and the mean vitamin D concentration was significantly lower among patients with subclinical atherosclerosis than among those without (18.2 vs 41.3 ng/mL, p < 0.001). Moreover, the multivariate linear regression analysis adjusted by confounding factors showed an independent association between subclinical atherosclerosis and vitamin D insufficiency, age >50 years, smoking, hypertension, metabolic syndrome, higher BMI, higher LDL cholesterol, longer duration of HIV infection, lower nadir CD4 cell count, and longer exposure to boosted protease inhibitors.Conclusion: In our study, vitamin D insufficiency is significantly associated with subclinical atherosclerosis, so its role in HIV-associated cardiovascular disease should be further evaluated as a possible target for intervention.