37 research outputs found

    Outcomes and Predictors of Mortality in Patients With KPC-Kp Infections Treated With Meropenem Vaborbactam: An Observational Multicenter Study

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    Background Meropenem-vaborbactam is a recent and promising option for the treatment of KPC-producing Klebsiella pneumoniae (KPC-Kp) infections, including those resistant to ceftazidime-avibactam.Methods We conducted a retrospective analysis of observational data from 19 Italian hospitals on use and outcomes of patients treated with meropenem-vaborbactam for at least >= 24 hours for KPC-Kp infections. Crude and propensity-weighted multiple Cox regression models were performed to ascertain risk factors independently associated with 30-day mortality.Results The cohort included 342 adults with bloodstream infections (n = 172) and nonbacteremic infections (n = 170), of which 107 were lower respiratory tract infections, 30 were complicated urinary tract infections, and 33 were infections involving other sites. Most infections (62.3%) were managed with meropenem-vaborbactam monotherapy, or in combination with at least 1 other active drug (usually fosfomycin, tigecycline, or gentamicin) (37.7%). The 30-day mortality rate was 31.6% (108/342). In multiple Cox regression model, 30-day mortality was independently associated with septic shock at infection onset, Charlson comorbidity index >= 3, dialysis, concomitant COVID-19, and INCREMENT score >= 8. Administration of meropenem-vaborbactam within 48 hours from infection onset was a negative predictor of mortality. All predictors, except administration of meropenem-vaborbactam within 48 hours, remained significant when the multiple Cox regression model was repeated after adjustment for the propensity score for receipt of combination therapy.Conclusions Despite the limits of a retrospective study, the data derived from this multicenter cohort provide additional evidence on the efficacy of meropenem-vaborbactam in treating severe KPC-Kp infections, even when used as monotherapy

    Effect of Size and Heterogeneity of Samples on Biomarker Discovery: Synthetic and Real Data Assessment

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    MOTIVATION: The identification of robust lists of molecular biomarkers related to a disease is a fundamental step for early diagnosis and treatment. However, methodologies for the discovery of biomarkers using microarray data often provide results with limited overlap. These differences are imputable to 1) dataset size (few subjects with respect to the number of features); 2) heterogeneity of the disease; 3) heterogeneity of experimental protocols and computational pipelines employed in the analysis. In this paper, we focus on the first two issues and assess, both on simulated (through an in silico regulation network model) and real clinical datasets, the consistency of candidate biomarkers provided by a number of different methods. METHODS: We extensively simulated the effect of heterogeneity characteristic of complex diseases on different sets of microarray data. Heterogeneity was reproduced by simulating both intrinsic variability of the population and the alteration of regulatory mechanisms. Population variability was simulated by modeling evolution of a pool of subjects; then, a subset of them underwent alterations in regulatory mechanisms so as to mimic the disease state. RESULTS: The simulated data allowed us to outline advantages and drawbacks of different methods across multiple studies and varying number of samples and to evaluate precision of feature selection on a benchmark with known biomarkers. Although comparable classification accuracy was reached by different methods, the use of external cross-validation loops is helpful in finding features with a higher degree of precision and stability. Application to real data confirmed these results

    SARS Cov-2 infection in a renal-transplanted patient: A case report

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    The clinical manifestation of COVID-19 can vary from an asymptomatic course to ARDS requiring invasive mechanical ventilation and extracorporeal membrane oxygenation. A kidney transplanted patient infected with SARS CoV-2 infection showed a mild disease despite immune suppression. It is possible that Immunosuppression can "be protective" as the cytokine storm is an important factor in the disease story. Despite the good outcome reported in the present case report, is remains of vital importance the solid organ transplant patients use precautions in order to avoid the infection

    Drug Resistant Tuberculosis Among Foreigners and Natives in a City of Northern Italy. A Retrospective Study Period of Eight Years.

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    Background: Drug-resistant tuberculosis (TB) represents a threat in TB control, because of cumbersome clinical management, toxicity and prolonged treatment. Drug resistance trend in Emilia-Romagna, a region of Northern Italy, is not increasing and in 2016 is even decreased. The present study describes the TB epidemiological and anti-TB drug resistance trend among natives and foreign-born cases between 2009 and 2017, in a low TB burden and high immigrant receiving setting (Ferrara, a city of Northern Italy, Emilia-Romagna region). Methods: We retrospectively identified all bacteriologically confirmed TB cases (confirmed by NAAT or culture) diagnosed in Ferrara University-Hospital from 2009 to 2017. We recorded gender, age, country of birth, site of disease, smear positivity, sensitivity or resistance toward one (mono-resistant), two or more first-line anti-TB drug (poly-resistant), MDR, and XDR-TB. Results: 109 out of the 167 TB cases (65.3%) were foreign-born and 58 natives, 95 males and 72 females, 120 pulmonary (PTB) and 47 extra-pulmonary (EPTB) cases. Among PTB cases, a positive smear was recorded in 56.6 % of foreign-born subjects and 45.5 % of natives. Foreign-born cases were significantly younger than natives (33.9 vs 62.2 years, p<0.01). The proportion of foreign-born cases increased from 57.1% to 78.9% over the study period (2009-2017). Antibiotic resistance profile was available in 134 cases (80.2%). 32/96 foreign-born and 14/38 native subjects presented drug resistant TB (p > 0.05). All multidrug-resistant (MDR) (2/134) and extensively-resistant (XDR) (1/134) cases were East-European and smear negative cases. We did not observe any increasing or decreasing trend in drug resistance profile over the 8 year study period (Figure 1). However, even if not statistically significant, we found an association with the country of birth: East-Europeans presented the higher rate of drug resistant cases (44.1%), Asians, the lower (23.8%). Conclusions: In a low TB burden setting, TB cases cluster mostly among foreign-born subjects and are generally sensitive to first-line drugs. In our series, most of drug-resistant cases, all MDR and XDR cases were recorded among East-Europeans. Drug-resistance rate is not increasing and its profile reflects those of the country of birth and may vary with the variation of immigration flows
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