Publications by authors named "Francesco Menichetti"

126 Publications

The relationship between cardiac injury, inflammation and coagulation in predicting COVID-19 outcome.

Sci Rep 2021 03 22;11(1):6515. Epub 2021 Mar 22.

Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

High sensitivity troponin T (hsTnT) is a strong predictor of adverse outcome during SARS-CoV-2 infection. However, its determinants remain partially unknown. We aimed to assess the relationship between severity of inflammatory response/coagulation abnormalities and hsTnT in Coronavirus Disease 2019 (COVID-19). We then explored the relevance of these pathways in defining mortality and complications risk and the potential effects of the treatments to attenuate such risk. In this single-center, prospective, observational study we enrolled 266 consecutive patients hospitalized for SARS-CoV-2 pneumonia. Primary endpoint was in-hospital COVID-19 mortality. hsTnT, even after adjustment for confounders, was associated with mortality. D-dimer and CRP presented stronger associations with hsTnT than PaO. Changes of hsTnT, D-dimer and CRP were related; but only D-dimer was associated with mortality. Moreover, low molecular weight heparin showed attenuation of the mortality in the whole population, particularly in subjects with higher hsTnT. D-dimer possessed a strong relationship with hsTnT and mortality. Anticoagulation treatment showed greater benefits with regard to mortality. These findings suggest a major role of SARS-CoV-2 coagulopathy in hsTnT elevation and its related mortality in COVID-19. A better understanding of the mechanisms related to COVID-19 might pave the way to therapy tailoring in these high-risk individuals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-85646-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985490PMC
March 2021

Diabetes and acute bacterial skin and skin structure infections.

Diabetes Res Clin Pract 2021 Mar 5;174:108732. Epub 2021 Mar 5.

Department of Clinical and Experimental Medicine, Infectious Diseases Unit, University of Pisa, Pisa, Italy.

Acute bacterial skin and skin structures infections (ABSSSIs) are associated with high morbidity, costs and mortality in patients with diabetes mellitus. Their appropriate management should include several figures and a well-organized approach. This review aims to highlight the interplay between diabetes and ABSSSIs and bring out the unmet clinical needs in this area. Pathogenetic mechanisms underlying the increased risk of ABSSSIs in diabetes mellitus are multifactorial: high glucose levels play a crucial pathogenetic role in the tissue damage and delayed clinical cure. Moreover, the presence of diabetes complications (neuropathy, vasculopathy) further complicates the management of ABSSSIs in patients with diabetes. Multidrug resistance organisms should be considered in this population based on patient risk factors and local epidemiology and etiological diagnosis should be obtained whenever possible. Moreover, drug-drug interactions and drug-related adverse events (such as nephrotoxicity) should be considered in the choice of antibiotic therapy. Reducing unnecessary hospitalizations and prolonged length of hospital stay is of primary importance now, more than ever. To achieve these objectives, a better knowledge of the interplay between acute and chronic hyperglycemia, multidrug resistant etiology, and short and long-term outcome is needed. Of importance, a multidisciplinary approach is crucial to achieve full recovery of these patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.diabres.2021.108732DOI Listing
March 2021

Incidence and Prognosis of Ventilator-Associated Pneumonia in Critically Ill Patients with COVID-19: A Multicenter Study.

J Clin Med 2021 Feb 3;10(4). Epub 2021 Feb 3.

Infectious Diseases Unit, San Martino Polyclinic Hospital-IRCCS for Oncology and Neurosciences, 16132 Genoa, Italy.

The primary objective of this multicenter, observational, retrospective study was to assess the incidence rate of ventilator-associated pneumonia (VAP) in coronavirus disease 2019 (COVID-19) patients in intensive care units (ICU). The secondary objective was to assess predictors of 30-day case-fatality of VAP. From 15 February to 15 May 2020, 586 COVID-19 patients were admitted to the participating ICU. Of them, 171 developed VAP (29%) and were included in the study. The incidence rate of VAP was of 18 events per 1000 ventilator days (95% confidence intervals [CI] 16-21). Deep respiratory cultures were available and positive in 77/171 patients (45%). The most frequent organisms were (27/77, 35%) and (18/77, 23%). The 30-day case-fatality of VAP was 46% (78/171). In multivariable analysis, septic shock at VAP onset (odds ratio [OR] 3.30, 95% CI 1.43-7.61, = 0.005) and acute respiratory distress syndrome at VAP onset (OR 13.21, 95% CI 3.05-57.26, < 0.001) were associated with fatality. In conclusion, VAP is frequent in critically ill COVID-19 patients. The related high fatality is likely the sum of the unfavorable prognostic impacts of the underlying viral and the superimposed bacterial diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm10040555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913191PMC
February 2021

Community-acquired Pneumonia Owing to Multidrug-Resistant Pathogens: A Step toward an Early Identification.

Ann Am Thorac Soc 2021 02;18(2):211-213

Infectious Diseases Unit, Department of Clinical and Experimental Medicine, Azienda Ospedaliera Universitaria Pisana, University of Pisa, Pisa, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1513/AnnalsATS.202009-1207EDDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869783PMC
February 2021

Autoimmune limbic encephalitis related to SARS-CoV-2 infection: Case-report and review of the literature.

Brain Behav Immun Health 2021 Mar 24;12:100210. Epub 2021 Jan 24.

Neurology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

Background: SARS-CoV-2 infection is associated with a wide spectrum of neurological complications, including encephalitis. Most cases showed features consistent with a central nervous system (CNS) cytokine-mediated damage. However, few cases arguing for an autoimmune mechanism have been described, mainly as single reports or sparse in large case series involving other CNS manifestations. In this paper, we described a case of definite autoimmune limbic encephalitis (LE) COVID-19 related and reviewed the existing literature on other reported cases.

Case Report: Two weeks after the onset of COVID-19 infection, a 74-year-old woman presented with subacute confusion and focal motor seizures with impaired awareness, starting from left temporal region. Cerebrospinal fluid analysis revealed hyperproteinorrachia. Brain MRI showed bilateral T2/FLAIR hyperintensities in both hippocampi and total body PET/TC scan revealed hypermetabolism in basal ganglia bilaterally. A diagnosis of autoimmune LE was made. Thus, high dose corticosteroids and antiseizure medications were started, with a marked improvement of neurological conditions.

Literature Review: We systematically reviewed the literature to identify all well-documented cases of definite autoimmune LE (according to Graus criteria) in patients with COVID-19 infection, identifying other five cases exhibiting a good response to immunomodulating therapy.

Conclusion: A very limited number of autoimmune LE have been described until now. It is important to monitor neurological symptoms in COVID-19 patients and to consider the possibility of an autoimmune LE, in particular when altered mental status and seizures appear late in the disease course. This allows to promptly start the appropriate treatments and avoid unnecessary delays.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbih.2021.100210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830195PMC
March 2021

Heparin in COVID-19 Patients Is Associated with Reduced In-Hospital Mortality: the Multicenter Italian CORIST Study.

Authors:
Augusto Di Castelnuovo Simona Costanzo Andrea Antinori Nausicaa Berselli Lorenzo Blandi Marialaura Bonaccio Roberto Cauda Giovanni Guaraldi Lorenzo Menicanti Marco Mennuni Giustino Parruti Giuseppe Patti Francesca Santilli Carlo Signorelli Alessandra Vergori Pasquale Abete Walter Ageno Antonella Agodi Piergiuseppe Agostoni Luca Aiello Samir Al Moghazi Rosa Arboretti Marinella Astuto Filippo Aucella Greta Barbieri Alessandro Bartoloni Paolo Bonfanti Francesco Cacciatore Lucia Caiano Laura Carrozzi Antonio Cascio Arturo Ciccullo Antonella Cingolani Francesco Cipollone Claudia Colomba Crizia Colombo Francesca Crosta Gian Battista Danzi Damiano D'Ardes Katleen de Gaetano Donati Francesco Di Gennaro Giuseppe Di Tano Gianpiero D'Offizi Massimo Fantoni Francesco Maria Fusco Ivan Gentile Francesco Gianfagna Elvira Grandone Emauele Graziani Leonardo Grisafi Gabriella Guarnieri Giovanni Larizza Armando Leone Gloria Maccagni Ferruccio Madaro Stefano Maitan Sandro Mancarella Massimo Mapelli Riccardo Maragna Rossella Marcucci Giulio Maresca Silvia Marongiu Claudia Marotta Lorenzo Marra Franco Mastroianni Maria Mazzitelli Alessandro Mengozzi Francesco Menichetti Marianna Meschiari Jovana Milic Filippo Minutolo Beatrice Molena Arturo Montineri Cristina Mussini Maria Musso Daniela Niola Anna Odone Marco Olivieri Antonella Palimodde Roberta Parisi Emanuela Pasi Raffaele Pesavento Francesco Petri Biagio Pinchera Venerino Poletti Claudia Ravaglia Andrea Rognoni Marco Rossato Marianna Rossi Vincenzo Sangiovanni Carlo Sanrocco Laura Scorzolini Raffaella Sgariglia Paola Giustina Simeone Eleonora Taddei Carlo Torti Roberto Vettor Andrea Vianello Marco Vinceti Alexandra Virano Laura Vocciante Raffaele De Caterina Licia Iacoviello

Thromb Haemost 2021 Jan 7. Epub 2021 Jan 7.

Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Isernia, Italy.

Introduction:  A hypercoagulable condition was described in patients with coronavirus disease 2019 (COVID-19) and proposed as a possible pathogenic mechanism contributing to disease progression and lethality.

Aim:  We evaluated if in-hospital administration of heparin improved survival in a large cohort of Italian COVID-19 patients.

Methods:  In a retrospective observational study, 2,574 unselected patients hospitalized in 30 clinical centers in Italy from February 19, 2020 to June 5, 2020 with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection were analyzed. The primary endpoint in a time-to event analysis was in-hospital death, comparing patients who received heparin (low-molecular-weight heparin [LMWH] or unfractionated heparin [UFH]) with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores.

Results:  Out of 2,574 COVID-19 patients, 70.1% received heparin. LMWH was largely the most used formulation (99.5%). Death rates for patients receiving heparin or not were 7.4 and 14.0 per 1,000 person-days, respectively. After adjustment for propensity scores, we found a 40% lower risk of death in patients receiving heparin (hazard ratio = 0.60; 95% confidence interval: 0.49-0.74; E-value = 2.04). This association was particularly evident in patients with a higher severity of disease or strong coagulation activation.

Conclusion:  In-hospital heparin treatment was associated with a lower mortality, particularly in severely ill COVID-19 patients and in those with strong coagulation activation. The results from randomized clinical trials are eagerly awaited to provide clear-cut recommendations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/a-1347-6070DOI Listing
January 2021

Pragmatic options for dose optimization of ceftazidime/avibactam with aztreonam in complex patients.

J Antimicrob Chemother 2021 Mar;76(4):1025-1031

Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, MI, USA.

Background: Avibactam is a β-lactamase inhibitor that is combined with aztreonam against Enterobacterales co-expressing serine- and metallo-β-lactamases (MBL). Optimal dosing of aztreonam with avibactam is not well-defined in critically ill patients and contingent on ceftazidime/avibactam product labelling.

Objectives: To identify a pragmatic dosing strategy for aztreonam with avibactam to maximize the probability of target attainment (PTA).

Methods: We conducted a prospective observational pharmacokinetic study. Five blood samples were collected around the fourth dose of aztreonam or ceftazidime/avibactam and assayed for all three drugs. Population pharmacokinetic (PK) analysis coupled with Monte Carlo simulations were used to create a dosing nomogram for aztreonam and ceftazidime/avibactam based on drug-specific pharmacodynamic (PD) targets.

Results: A total of 41 participants (59% male) median age of 75 years (IQR 63-79 years) were enrolled. They were critically ill (46%) with multiple comorbidities and complications including burns (20%). Population PK analysis identified higher volume of distribution and lower clearance (CL) compared with typical value expectations for aztreonam and ceftazidime/avibactam. Estimated glomerular filtration (eGFR) rate using the CKD-EPI equation predicted CL for all three drugs. The need for high doses of aztreonam and ceftazidime/avibactam above those in the existing product labels are not predicted by this analysis with the exception of ceftazidime/avibactam for patients with eGFR of 6-15 mL/min, in whom suboptimal PTA of ≤71% is predicted.

Conclusions: Pragmatic and lower daily-dose options are predicted for aztreonam and ceftazidime/avibactam when the eGFR is <90 mL/min. These options should be tested prospectively.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jac/dkaa549DOI Listing
March 2021

Predictors of hospital-acquired bacterial and fungal superinfections in COVID-19: a prospective observational study.

J Antimicrob Chemother 2021 03;76(4):1078-1084

Infectious Disease Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

Background: Bacterial and fungal superinfections may complicate the course of hospitalized patients with COVID-19.

Objectives: To identify predictors of superinfections in COVID-19.

Methods: Prospective, observational study including patients with COVID-19 consecutively admitted to the University Hospital of Pisa, Italy, between 4 March and 30 April 2020. Clinical data and outcomes were registered. Superinfection was defined as a bacterial or fungal infection that occurred ≥48 h after hospital admission. A multivariate analysis was performed to identify factors independently associated with superinfections.

Results: Overall, 315 patients with COVID-19 were hospitalized and 109 episodes of superinfections were documented in 69 (21.9%) patients. The median time from admission to superinfection was 19 days (range 11-29.75). Superinfections were caused by Enterobacterales (44.9%), non-fermenting Gram-negative bacilli (15.6%), Gram-positive bacteria (15.6%) and fungi (5.5%). Polymicrobial infections accounted for 18.3%. Predictors of superinfections were: intestinal colonization by carbapenem-resistant Enterobacterales (OR 16.03, 95% CI 6.5-39.5, P < 0.001); invasive mechanical ventilation (OR 5.6, 95% CI 2.4-13.1, P < 0.001); immunomodulatory agents (tocilizumab/baricitinib) (OR 5.09, 95% CI 2.2-11.8, P < 0.001); C-reactive protein on admission >7 mg/dl (OR 3.59, 95% CI 1.7-7.7, P = 0.001); and previous treatment with piperacillin/tazobactam (OR 2.85, 95% CI 1.1-7.2, P = 0.028). Length of hospital stay was longer in patients who developed superinfections ompared with those who did not (30 versus 11 days, P < 0.001), while mortality rates were similar (18.8% versus 23.2%, P = 0.445).

Conclusions: The risk of bacterial and fungal superinfections in COVID-19 is consistent. Patients who need empiric broad-spectrum antibiotics and immunomodulant drugs should be carefully selected. Infection control rules must be reinforced.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jac/dkaa530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7799007PMC
March 2021

Role of Low-Molecular-Weight Heparin in Hospitalized Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Pneumonia: A Prospective Observational Study.

Open Forum Infect Dis 2020 Dec 19;7(12):ofaa563. Epub 2020 Nov 19.

Infectious Disease Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

Background: This study was conducted to evaluate the impact of low-molecular-weight heparin (LMWH) on the outcome of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia.

Methods: This is a prospective observational study including consecutive patients with laboratory-confirmed SARS-CoV-2 pneumonia admitted to the University Hospital of Pisa (March 4-April 30, 2020). Demographic, clinical, and outcome data were collected. The primary endpoint was 30-day mortality. The secondary endpoint was a composite of death or severe acute respiratory distress syndrome (ARDS). Low-molecular-weight heparin, hydroxychloroquine, doxycycline, macrolides, antiretrovirals, remdesivir, baricitinib, tocilizumab, and steroids were evaluated as treatment exposures of interest. First, a Cox regression analysis, in which treatments were introduced as time-dependent variables, was performed to evaluate the association of exposures and outcomes. Then, a time-dependent propensity score (PS) was calculated and a PS matching was performed for each treatment variable.

Results: Among 315 patients with SARS-CoV-2 pneumonia, 70 (22.2%) died during hospital stay. The composite endpoint was achieved by 114 (36.2%) patients. Overall, 244 (77.5%) patients received LMWH, 238 (75.5%) received hydroxychloroquine, 201 (63.8%) received proteases inhibitors, 150 (47.6%) received doxycycline, 141 (44.8%) received steroids, 42 (13.3%) received macrolides, 40 (12.7%) received baricitinib, 13 (4.1%) received tocilizumab, and 13 (4.1%) received remdesivir. At multivariate analysis, LMWH was associated with a reduced risk of 30-day mortality (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.21-0.6;  < .001) and composite endpoint (HR, 0.61; 95% CI, 0.39-0.95;  = .029). The PS-matched cohort of 55 couples confirmed the same results for both primary and secondary endpoint.

Conclusions: This study suggests that LMWH might reduce the risk of in-hospital mortality and severe ARDS in coronavirus disease 2019. Randomized controlled trials are warranted to confirm these preliminary findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ofid/ofaa563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717381PMC
December 2020

Predictors of intensive care unit admission in patients with Legionella pneumonia: role of the time to appropriate antibiotic therapy.

Infection 2021 Apr 14;49(2):321-325. Epub 2020 Dec 14.

Division of Infectious Diseases, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

Purpose: Legionella spp. pneumonia (LP) is a cause of community-acquired pneumonia (CAP) that requires early intervention. The median mortality rate varies from 4 to 11%, but it is higher in patients admitted to intensive care unit (ICU). The objective of this study is to identify predictors of ICU admission in patients with LP.

Methods: A single-center, retrospective, observational study conducted in an academic tertiary-care hospital in Pisa, Italy. Adult patients with LP consecutively admitted to study center from October 2012 to October 2019.

Results: During the study period, 116 cases of LP were observed. The rate of ICU admission was 20.7% and the overall 30-day mortality rate was 12.1%. Mortality was 4.3% in patients hospitalized in medical wards versus 41.7% in patients transferred to ICU (p < 0.001). The majority of patients (74.1%) received levofloxacin as definitive therapy, followed by macrolides (16.4%), and combination of levofloxacin plus a macrolide (9.5%). In the multivariate analysis, diabetes (OR 8.28, CI 95% 2.11-35.52, p = 0.002), bilateral pneumonia (OR 10.1, CI 95% 2.74-37.27, p = 0.001), and cardiovascular events (OR 10.91, CI 95% 2.83-42.01, p = 0.001), were independently associated with ICU admission, while the receipt of macrolides/levofloxacin therapy within 24 h from admission was protective (OR 0.20, CI 95% 0.05-0.73, p = 0.01). Patients who received a late anti-Legionella antibiotic (> 24 h from admission) underwent urinary antigen test later compared to those who received early active antibiotic therapy (2 [2-4] vs. 1 [1-2] days, p < 0.001).

Conclusions: Admission to ICU carries significantly increased mortality in patients with diagnosis of LP. Initial therapy with an antibiotic active against Legionella (levofloxacin or macrolides) reduces the probability to be transferred to ICU and should be provided in all cases until Legionella etiology is excluded.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s15010-020-01565-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734452PMC
April 2021

Extremely drug-resistant NDM-9-producing ST147 causing infections in Italy, May 2020.

Euro Surveill 2020 12;25(48)

Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.

A large outbreak of New Delhi metallo-beta-lactamase (NDM)-1-producing sequence type (ST) 147 occurred in Tuscany, Italy in 2018-2019. In 2020, ST147 NDM-9-producing were detected at the University Hospital of Pisa, Tuscany, in two critically ill patients; one developed bacteraemia. Genomic and phylogenetic analyses suggest relatedness of 2018-2019 and 2020 strains, with a change from NDM-1 to NDM-9 in the latter and evolution by colistin, tigecycline and fosfomycin resistance acquisition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2807/1560-7917.ES.2020.25.48.2001779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716400PMC
December 2020

Interplay between Nox2 Activity and Platelet Activation in Patients with Sepsis and Septic Shock: A Prospective Study.

Oxid Med Cell Longev 2020 27;2020:4165358. Epub 2020 Oct 27.

Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

Background: Although preclinical studies highlighted the potential role of NADPH oxidase (NOX) in sepsis, only few studies evaluated the oxidative stress in patients with sepsis and septic shock. The objective of the study is to appraise the oxidative stress status and platelet function in patients with sepsis and septic shock compared to healthy controls.

Methods And Results: Patients with sepsis or septic shock admitted to the hospital Policlinico Umberto I (Sapienza University, Rome) underwent a blood sample collection within 1 hour from admission. Platelet aggregation, serum thromboxane B2 (TxB2), soluble NOX2-derived peptides (sNox2-dp), and hydrogen peroxide breakdown activity (HBA) were measured and compared to those of healthy volunteers. Overall, 33 patients were enrolled; of these, 20 (60.6%) had sepsis and 13 (39.4%) septic shock. Compared to healthy controls ( = 10, age 67.8 ± 3.2, male 50%), patients with sepsis and septic shock had higher platelet aggregation (49% (IQR 45-55), 60% (55.75-67.25), and 73% (IQR 69-80), respectively, < 0.001), higher serum TxB2 (77.5 (56.5-86.25), 122.5 (114-131.5), and 210 (195-230) pmol/L, respectively, < 0.001), higher sNox2-dp (10 (7.75-12), 19.5 (17.25-21), and 33 (29.5-39) pg/mL, respectively, < 0.001), and lower HBA (75% (67.25-81.5), 50% (45-54.75), and 27% (21.5-32.5), respectively, < 0.001). Although not statistically significant, a trend in higher levels of serum TxB2 and sNox2-dp in patients who died was observed.

Conclusions: Patients with septic shock exhibit higher Nox2 activity and platelet activation than patients with sepsis. These insights joined to better knowledge of these mechanisms could guide the identification of future prognostic biomarkers and new therapeutic strategies in the scenario of septic shock.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/4165358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641261PMC
October 2020

JAK inhibition reduces SARS-CoV-2 liver infectivity and modulates inflammatory responses to reduce morbidity and mortality.

Sci Adv 2021 01 1;7(1). Epub 2021 Jan 1.

Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.

Using AI, we identified baricitinib as having antiviral and anticytokine efficacy. We now show a 71% (95% CI 0.15 to 0.58) mortality benefit in 83 patients with moderate-severe SARS-CoV-2 pneumonia with few drug-induced adverse events, including a large elderly cohort (median age, 81 years). An additional 48 cases with mild-moderate pneumonia recovered uneventfully. Using organotypic 3D cultures of primary human liver cells, we demonstrate that interferon-α2 increases ACE2 expression and SARS-CoV-2 infectivity in parenchymal cells by greater than fivefold. RNA-seq reveals gene response signatures associated with platelet activation, fully inhibited by baricitinib. Using viral load quantifications and superresolution microscopy, we found that baricitinib exerts activity rapidly through the inhibition of host proteins (numb-associated kinases), uniquely among antivirals. This reveals mechanistic actions of a Janus kinase-1/2 inhibitor targeting viral entry, replication, and the cytokine storm and is associated with beneficial outcomes including in severely ill elderly patients, data that incentivize further randomized controlled trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/sciadv.abe4724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775747PMC
January 2021

Cefiderocol as rescue therapy for Acinetobacter baumannii and other carbapenem-resistant Gram-Negative infections in ICU patients.

Clin Infect Dis 2020 Sep 17. Epub 2020 Sep 17.

Infectious Diseases Unit, Department of Clinical and Experimental Medicine, University of Pisa.

Ten critically-ill patients with either bacteremia or ventilator-associated pneumonia caused by carbapenem-resistant A. baumannii, S. maltophilia or NDM-producing K. pneumoniae received cefiderocol. All strains had MIC ≤2 μg/mL. Thirty-day clinical success and survival rates were 70% and 90%, respectively. Two patients had a microbiological failure. Future prospective studies are warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciaa1410DOI Listing
September 2020

Common cardiovascular risk factors and in-hospital mortality in 3,894 patients with COVID-19: survival analysis and machine learning-based findings from the multicentre Italian CORIST Study.

Authors:
Augusto Di Castelnuovo Marialaura Bonaccio Simona Costanzo Alessandro Gialluisi Andrea Antinori Nausicaa Berselli Lorenzo Blandi Raffaele Bruno Roberto Cauda Giovanni Guaraldi Ilaria My Lorenzo Menicanti Giustino Parruti Giuseppe Patti Stefano Perlini Francesca Santilli Carlo Signorelli Giulio G Stefanini Alessandra Vergori Amina Abdeddaim Walter Ageno Antonella Agodi Piergiuseppe Agostoni Luca Aiello Samir Al Moghazi Filippo Aucella Greta Barbieri Alessandro Bartoloni Carolina Bologna Paolo Bonfanti Serena Brancati Francesco Cacciatore Lucia Caiano Francesco Cannata Laura Carrozzi Antonio Cascio Antonella Cingolani Francesco Cipollone Claudia Colomba Annalisa Crisetti Francesca Crosta Gian B Danzi Damiano D'Ardes Katleen de Gaetano Donati Francesco Di Gennaro Gisella Di Palma Giuseppe Di Tano Massimo Fantoni Tommaso Filippini Paola Fioretto Francesco M Fusco Ivan Gentile Leonardo Grisafi Gabriella Guarnieri Francesco Landi Giovanni Larizza Armando Leone Gloria Maccagni Sandro Maccarella Massimo Mapelli Riccardo Maragna Rossella Marcucci Giulio Maresca Claudia Marotta Lorenzo Marra Franco Mastroianni Alessandro Mengozzi Francesco Menichetti Jovana Milic Rita Murri Arturo Montineri Roberta Mussinelli Cristina Mussini Maria Musso Anna Odone Marco Olivieri Emanuela Pasi Francesco Petri Biagio Pinchera Carlo A Pivato Roberto Pizzi Venerino Poletti Francesca Raffaelli Claudia Ravaglia Giulia Righetti Andrea Rognoni Marco Rossato Marianna Rossi Anna Sabena Francesco Salinaro Vincenzo Sangiovanni Carlo Sanrocco Antonio Scarafino Laura Scorzolini Raffaella Sgariglia Paola G Simeone Enrico Spinoni Carlo Torti Enrico M Trecarichi Francesca Vezzani Giovanni Veronesi Roberto Vettor Andrea Vianello Marco Vinceti Raffaele De Caterina Licia Iacoviello

Nutr Metab Cardiovasc Dis 2020 10 31;30(11):1899-1913. Epub 2020 Jul 31.

Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, IS, Italy; Department of Medicine and Surgery, University of Insubria, Varese, Italy. Electronic address:

Background And Aims: There is poor knowledge on characteristics, comorbidities and laboratory measures associated with risk for adverse outcomes and in-hospital mortality in European Countries. We aimed at identifying baseline characteristics predisposing COVID-19 patients to in-hospital death.

Methods And Results: Retrospective observational study on 3894 patients with SARS-CoV-2 infection hospitalized from February 19th to May 23rd, 2020 and recruited in 30 clinical centres distributed throughout Italy. Machine learning (random forest)-based and Cox survival analysis. 61.7% of participants were men (median age 67 years), followed up for a median of 13 days. In-hospital mortality exhibited a geographical gradient, Northern Italian regions featuring more than twofold higher death rates as compared to Central/Southern areas (15.6% vs 6.4%, respectively). Machine learning analysis revealed that the most important features in death classification were impaired renal function, elevated C reactive protein and advanced age. These findings were confirmed by multivariable Cox survival analysis (hazard ratio (HR): 8.2; 95% confidence interval (CI) 4.6-14.7 for age ≥85 vs 18-44 y); HR = 4.7; 2.9-7.7 for estimated glomerular filtration rate levels <15 vs ≥ 90 mL/min/1.73 m; HR = 2.3; 1.5-3.6 for C-reactive protein levels ≥10 vs ≤ 3 mg/L). No relation was found with obesity, tobacco use, cardiovascular disease and related-comorbidities. The associations between these variables and mortality were substantially homogenous across all sub-groups analyses.

Conclusions: Impaired renal function, elevated C-reactive protein and advanced age were major predictors of in-hospital death in a large cohort of unselected patients with COVID-19, admitted to 30 different clinical centres all over Italy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.numecd.2020.07.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833278PMC
October 2020

Hyperglycemia at Hospital Admission Is Associated With Severity of the Prognosis in Patients Hospitalized for COVID-19: The Pisa COVID-19 Study.

Diabetes Care 2020 10 11;43(10):2345-2348. Epub 2020 Aug 11.

Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

Objective: To explore whether at-admission hyperglycemia is associated with worse outcomes in patients hospitalized for coronavirus disease 2019 (COVID-19).

Research Design And Methods: Hospitalized COVID-19 patients ( = 271) were subdivided based on at-admission glycemic status: ) glucose levels <7.78 mmol/L (NG) ( = 149 [55.0%]; median glucose 5.99 mmol/L [range 5.38-6.72]), ) known diabetes mellitus (DM) ( = 56 [20.7%]; 9.18 mmol/L [7.67-12.71]), and ) no diabetes and glucose levels ≥7.78 mmol/L (HG) ( = 66 [24.3%]; 8.57 mmol/L [8.18-10.47]).

Results: Neutrophils were higher and lymphocytes and PaO/FiO lower in HG than in DM and NG patients. DM and HG patients had higher D-dimer and worse inflammatory profile. Mortality was greater in HG (39.4% vs. 16.8%; unadjusted hazard ratio [HR] 2.20, 95% CI 1.27-3.81, = 0.005) than in NG (16.8%) and marginally so in DM (28.6%; 1.73, 0.92-3.25, = 0.086) patients. Upon multiple adjustments, only HG remained an independent predictor (HR 1.80, 95% CI 1.03-3.15, = 0.04). After stratification by quintile of glucose levels, mortality was higher in quintile 4 (Q4) (3.57, 1.46-8.76, = 0.005) and marginally in Q5 (29.6%) (2.32, 0.91-5.96, = 0.079) vs. Q1.

Conclusions: Hyperglycemia is an independent factor associated with severe prognosis in people hospitalized for COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2337/dc20-1380DOI Listing
October 2020

Pulmonary Aspergillosis: An Evolving Challenge for Diagnosis and Treatment.

Infect Dis Ther 2020 Sep 7;9(3):511-524. Epub 2020 Jul 7.

Division of Infectious Diseases, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

Aspergillus is a mold that may lead to different clinical pictures, from allergic to invasive disease, depending on the patient's immune status and structural lung diseases. Chronic pulmonary aspergillosis is an infection with a locally invasive presentation, reported especially in patients with chronic pulmonary disease, while aspergilloma is typically found in patients with previously formed cavities in the lungs. Allergic bronchopulmonary aspergillosis is due to a hypersensitivity reaction to Aspergillus antigens and is more frequently described in patients with moderate-severe asthma or cystic fibrosis. Invasive pulmonary aspergillosis mainly occurs in patients with neutropenia or immunodeficiency, but has increasingly been recognized as an emerging disease of non-neutropenic patients. The significance of this infection has dramatically increased in recent years, considering the high number of patients with an impaired immune state associated with the management and treatment of neoplasm, solid or hematological transplantation, autoimmune diseases, and inflammatory conditions. Moreover, prolonged steroid treatment is recognized as an important risk factor, especially for invasive disease. In this setting, critically ill patients admitted to intensive care units and/or with chronic obstructive pulmonary disease could be at higher risk for invasive infection. This review provides an update on the clinical features and risk factors of pulmonary aspergillosis. Current approaches for the diagnosis, management, and treatment of these different forms of pulmonary aspergillosis are discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40121-020-00315-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339098PMC
September 2020

COVID-19 and kidney transplantation: an Italian Survey and Consensus.

J Nephrol 2020 08 3;33(4):667-680. Epub 2020 Jun 3.

Division of General and Transplant Surgery, University of Pisa, Pisa, Italy.

Italy was the first Western country to face the COVID-19 pandemic. Here we report the results of a national survey on kidney transplantation activity in February and March 2020, and the results of a three-round Delphi consensus promoted by four scientific societies: the Italian Society of Organ Transplantation, the Italian Society of Nephrology, the Italian Society of Anesthesia and Intensive Care, and the Italian Group on Antimicrobial Stewardship. All 41 Italian transplant centers were invited to express their opinion in the Delphi rounds along with a group of seven experts. The survey revealed that, starting from March 2020, there was a decline in kidney transplantation activity in Italy, especially for living-related transplants. Overall, 60 recipients tested positive for SARS-CoV2 infection, 57 required hospitalization, 17 were admitted to the ICU, and 11 died. The online consensus had high response rates at each round (95.8%, 95.8%, and 89.5%, respectively). Eventually, 27 of 31 proposed statements were approved (87.1%), 12 at the first or second round (38.7%), and 3 at the third (9.7%). Based on the Italian experience, we discuss the reasons for the changes in kidney transplantation activity during the COVID-19 pandemic in Western countries. We also provide working recommendations for the organization and management of kidney transplantation under these conditions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40620-020-00755-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7268183PMC
August 2020

Severe respiratory failure in an immunocompetent host with invasive pulmonary aspergillosis and H1N1 influenza.

Infez Med 2020 Jun;28(2):263-267

Infectious Diseases Unit, Azienda Ospedaliera Universitaria Pisana, University of Pisa, Pisa, Italy.

Invasive pulmonary aspergillosis (IPA) is a life-threatening condition that usually occurs in immunocompromised hosts. However, according to recent reports it can affect immunocompetent hosts with severe influenza infection due to viral-dependent disruption of respiratory immune defenses. We present the case of a 61-year-old Caucasian man admitted to the Emergency Department with respiratory failure and fever, who was diagnosed with H1N1 influenza and IPA. Because of his poor general conditions, he was treated with a double antifungal scheme, although this lies outside the suggested treatment guidelines. This choice turned out to be extremely effective. He was discharged after one month and his clinical conditions showed rapid improvement, with nearly complete normalization of the radiological pattern in three months. IPA remains a life-threatening condition, even in immunocompetent hosts, and should therefore always be suspected; if necessary, a combined treatment should rapidly be started. We report this case as the interest in influenza-associated IPA is high, both due to the clinical severity of this condition, which is treatable if identified early, and the emerging importance of respiratory infections caused by viruses belonging to the SARS family, such as SARS-CoV-2.
View Article and Find Full Text PDF

Download full-text PDF

Source
June 2020

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

Open Forum Infect Dis 2020 May 21;7(5):ofaa139. Epub 2020 Apr 21.

Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

Background: Few data are reported in the literature about the outcome of patients with severe extended-spectrum β-lactamase-producing (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; = .02), septic shock (OR, 6.2; 95% CI, 3.8-7.9; < .001), and continuous renal replacement therapy (OR, 3.1; 95% CI, 1.9-5.3; = .001) were independently associated with clinical failure, whereas empiric therapy displaying in vitro activity (OR, 0.12; 95% CI, 0.01-0.34; < .001) and adequate source control of infection (OR, 0.42; 95% CI, 0.14-0.55; < .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 . Clinicians should be aware of the risk of clinical failure with standard-dose C/T therapy in septic patients receiving CRRT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ofid/ofaa139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237821PMC
May 2020

Efficacy of ceftazidime-avibactam plus aztreonam in patients with bloodstream infections caused by MBL- producing Enterobacterales.

Clin Infect Dis 2020 May 19. Epub 2020 May 19.

Infectious Diseases Unit, Azienda Ospedaliera Universitaria Pisana. University of Pisa, Italy.

Background: In vitro data support the use of combination of aztreonam (ATM) with ceftazidime-avibactam (CAZ-AVI), but clinical studies are lacking. The aim of our study was to compare the outcome of patients with bloodstream infections (BSIs) due to MBLs-producing Enterobacterales treated either with CAZ-AVI plus ATM or other active antibiotics (OAAs).

Methods: Prospective observational study including patients admitted to three hospitals in Italy and Greece. The primary outcome measure was the 30-day all-cause mortality. Secondary outcomes were clinical failure at day 14 and length of stay (LOS) after BSI diagnosis. Cox regression analysis including a propensity score (PS) for receiving CAZ-AVI plus ATM was performed to evaluate primary and secondary outcomes. A PS-based matched analysis was also performed.

Results: We enrolled 102 pts with BSI, 82 had infections caused by NDM-producing (79 K.pneumoniae and 3 E.coli) and 20 by VIM-producing (14 K.pneumoniae, 5 Enterobacter spp, 1 M.morganii) strains. The 30-day mortality rate was 19.2% in CAZ-AVI/ATM group vs 44% in OAAs group (p=0.007). The PS-adjusted analysis showed that the use of CAZ-AVI/ATM was associated with lower 30-day mortality (HR 0.37, 95% CI 0.13-0.74, p=0.01), lower clinical failure at day 14 (HR 0.30, 95% CI 0.14-0.65, p=0.002) and shorter LOS (sHR 0.49, 95% CI 0.30-0.82, p=0.007). The PS-matched analysis confirmed these findings.

Conclusions: CAZ-AVI/ATM combination offers therapeutic advantage compared to OAAs for patients with BSI due to MBL-producing Enterobacterales. Further studies are warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciaa586DOI Listing
May 2020

Interpreting procalcitonin in patients undergoing hemodialysis: a reliable or a misleading marker?

Intern Emerg Med 2021 01 2;16(1):11-13. Epub 2020 May 2.

Infectious Disease Unit, Department of Clinical and Experimental Medicine, Azienda Ospedaliera Universitaria Pisana, University of Pisa, Via Paradisa, 2, 56124, Pisa, PI, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11739-020-02341-zDOI Listing
January 2021

Comparison of the Safety and Tolerance Profile of Micafungin with that of Other Echinocandins and Azoles in Patients with Pre-existing Child-Pugh B or C Liver Disease: A Case-Control Retrospective Study.

Infect Dis Ther 2020 Mar 21;9(1):151-163. Epub 2020 Feb 21.

Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain.

Introduction: To assess the association between exposure to micafungin, other echinocandins, or azoles and the development of short-term liver injury (STLI) or long-term liver injury (LTLI) in patients with Child-Pugh B or C liver disease.

Methods: Multicenter case-control study of patients with Child-Pugh B or C liver disease who received antifungals (AF) for ≥ 72 h (May 2009-May 2015) in six Spanish and Italian hospitals. All micafungin patients were randomly matched with one patient who received another echinocandin and with one patient who received azole treatment. Primary outcome was development of STLI or LTLI (development of any type of liver tumor during the follow-up period).

Results: Of 2335 patients with chronic liver disease admitted to the six centers, 20 (0.85%) were found to have Child-Pugh B or C liver disease and received micafungin for ≥ 72 h. During AF treatment, the frequency of STLI was 10% in each group. Most cases of STLI were asymptomatic, and AFs had to be switched to another class of AF in only two patients (one micafungin and one azole). No patients developed acute liver insufficiency, were admitted to the ICU, or had to undergo transplantation. Follow-up data (median of 1.3 years) were available for 30 patients. LTLI was observed in only one patient, who had previously received treatment with azoles.

Conclusions: Our study suggests that the administration of micafungin to patients with end-stage liver disease does not imply a higher risk of developing STLI or LTLI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40121-020-00282-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054556PMC
March 2020

Prolonged outbreak of New Delhi metallo-beta-lactamase-producing carbapenem-resistant Enterobacterales (NDM-CRE), Tuscany, Italy, 2018 to 2019.

Euro Surveill 2020 02;25(6)

The members of the network are acknowledged at the end of the article.

In Tuscany, Italy, New Delhi metallo-beta-lactamase-producing carbapenem-resistant Enterobacterales (NDM-CRE) have increased since November 2018. Between November 2018 and October 2019, 1,645 samples were NDM-CRE-positive: 1,270 (77.2%) cases of intestinal carriage, 129 (7.8%) bloodstream infections and 246 (14.9%) infections/colonisations at other sites. were prevalent (1,495; 90.9%), with ST147/NDM-1 the dominant clone. Delayed outbreak identification and response resulted in sustained NDM-CRE transmission in the North-West area of Tuscany, but successfully contained spread within the region.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2807/1560-7917.ES.2020.25.6.2000085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029447PMC
February 2020

Antimicrobial stewardship in patients with acute bacterial skin and skin-structure infections: An international Delphi consensus.

J Glob Antimicrob Resist 2020 09 14;22:296-301. Epub 2020 Feb 14.

Infectious Diseases Unit, Cisanello Hospital, AOUP, Department of Clinical and Experimental Medicine, University of Pisa, 56100 Pisa, Italy. Electronic address:

Objectives: The aim of this survey was to identify a set of actions aimed to improve the diagnosis and management of acute bacterial skin and skin-structure infections (ABSSSIs) and the implementation of some principles of antimicrobial stewardship (AMS) in this setting.

Methods: A list of 76 statements for which there was a lack of clarity were generated by an expert panel and were validated by a group of experts. The questionnaire was administered to 112 experts in infectious diseases or microbiology. Participants were asked to vote on a list of statements. An agreement threshold of 66% was required to reach consensus.

Results: Overall, 57 responders participated in the survey. Positive consensus was reached on the fact that ABSSSIs represent a significant cause of infection in the emergency department, are frequently associated with increased hospital stay and are mainly caused by Staphylococcus aureus. The panellists strongly supported collection of samples from purulent infections by needle aspiration as well as collection of blood cultures in the presence of signs/symptoms of systemic infection. The importance of source control and prompt adequate microbiological documentation, the objective to reduce the length of hospital stay, the choice of a narrow-spectrum antibiotic and the role of new therapeutic options (e.g. long-acting drugs) in improving compliance also reached a positive consensus.

Conclusion: This Delphi survey provides useful indicators for the implementation of AMS principles in the clinical management of ABSSSI and offers interesting elements of discussion about the barriers existing in Europe for optimal implementation of AMS programmes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jgar.2020.02.002DOI Listing
September 2020

Clinical Features and Outcomes of Bloodstream Infections Caused by New Delhi Metallo-β-Lactamase-Producing During a Regional Outbreak.

Open Forum Infect Dis 2020 Feb 21;7(2):ofaa011. Epub 2020 Jan 21.

Infectious Disease Unit, Azienda Ospedaliera Universitaria Pisana, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

Limited data about New Delhi metallo-β-lactamase (NDM) bacteremia are available. Blood isolates from 40 patients with NDM bacteremia were studied for antibiotic susceptibility and whole-genomic sequencing. NDM bacteremia has high 30-day mortality. In most cases, aztreonam-avibactam is active in vitro. Ceftazidime-avibactam plus aztreonam may represent a feasible therapeutic option.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ofid/ofaa011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003035PMC
February 2020

Acute wound infections management: the 'Don'ts' from a multidisciplinary expert panel.

Expert Rev Anti Infect Ther 2020 03 17;18(3):231-240. Epub 2020 Feb 17.

Infectious Diseases Unit, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy.

: The management of acute wounds may be affected by malpractices leading to poor outcome, prolonged hospital stay and inappropriate use of antibiotic therapy.: Acute wound infections are represented by surgical site and post-traumatic infections. The aim of this expert opinion is to identify a list of inadvisable actions and to provide a guide for an optimal management of acute wound infections. A literature search using Pubmed/MEDLINE database was performed. Articles pertaining to areas covered published until December 2019 were selected. We identified the most common malpractices in this setting and, using the Choosing Wisely methodology, we proposed a list of "Don'ts" for an easy use in clinical practice.: Malpractices may occur from the surgical prophylaxis to the discharge of patient. A prolonged surgical prophylaxis, the underestimation of signs and symptoms, the omission of source control, the inappropriate collection of wound swab, the improper use of clinical microbiology and pharmacology, the lack of hygiene measures and the delay of discharge are all factors that may lead to unfavorable outcome. A multidisciplinary approach is needed to optimally manage these patients. The "Don'ts" refer to all professional figures involved in the management of patients with acute wound infections.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14787210.2020.1726740DOI Listing
March 2020

Time to appropriate antibiotic therapy is a predictor of outcome in patients with bloodstream infection caused by KPC-producing Klebsiella pneumoniae.

Crit Care 2020 01 30;24(1):29. Epub 2020 Jan 30.

Infectious Diseases Unit, Azienda Ospedaliera Universitaria Pisana, University of Pisa, Via Paradisa, 2, 56124, Pisa, PI, Italy.

Background: Bloodstream infections (BSIs) by Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (Kp) are associated with high mortality. The aim of this study is to assess the relationship between time to administration of appropriate antibiotic therapy and the outcome of patients with BSI due to KPC-Kp hospitalized in intensive care unit (ICU).

Methods: An observational study was conducted in the ICUs of two academic centers in Italy. Patients with KPC-Kp bacteremia hospitalized between January 2015 to December 2018 were included. The primary outcome was the relationship between time from blood cultures (BC) collection to appropriate antibiotic therapy and 30-day mortality. The secondary outcome was to evaluate the association of different treatment regimens with 30-day mortality and a composite endpoint (30-day mortality or nephrotoxicity). A Cox regression analysis to identify factors independently associated with 30-day mortality was performed. Hazard ratio (HR) and 95% confidence interval (CI) were calculated.

Results: A total of 102 patients with KPC-Kp BSI were included. The most common sources of infection were intra-abdominal (23.5%), urinary tract (20.6%), and skin and skin structure (17.6%). The 30-day mortality was 45%. Median time to appropriate antibiotic therapy was shorter in patients who survived (8.5 h [IQR 1-36]) versus those who died (48 h [IQR 5-108], p = 0.014). A propensity score matching showed that receipt of an in vitro active therapy within 24 h from BC collection was associated with lower 30-day mortality (HR = 0.36, 95% CI: 0.188-0.690, p = 0.0021). At Cox regression analysis, factors associated with 30-day mortality were primary bacteremia (HR 2.662 [95% CI 1.118-6.336], p = 0.027), cardiovascular disease (HR 2.196 [95% CI 1.082-4.457], p = 0.029), time (24-h increments) from BC collection to appropriate therapy (HR 1.382 [95% CI 1.132-1.687], p = 0.001), SOFA score (HR 1.122 [95% CI 1.036-1.216], p = 0.005), and age (HR 1.030 [95% CI 1.006-1.054], p = 0.012). Ceftazidime-avibactam-containing regimens were associated with reduced risk of composite endpoint (30-day mortality OR nephrotoxicity) (HR 0.231 [95% CI 0.071-0.745], p = 0.014) compared to colistin-containing regimens.

Conclusions: Time to appropriate antibiotic therapy is an independent predictor of 30-day mortality in patients with KPC-Kp BSI. Appropriate antibiotic therapy should begin within 24 h from the collection of BC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13054-020-2742-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6993311PMC
January 2020

Impact of Initial Antifungal Therapy on the Outcome of Patients With Candidemia and Septic Shock Admitted to Medical Wards: A Propensity Score-Adjusted Analysis.

Open Forum Infect Dis 2019 Jul 16;6(7):ofz251. Epub 2019 Jul 16.

Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

Background: Echinocandins are recommended as firstline therapy in patients with candidemia. However, there is debate on their efficacy in survival outcomes. The aim of this study is to evaluate whether the choice of initial antifungal therapy improves mortality in patients with candidemia in relation to the presence of septic shock.

Methods: Patients with candidemia hospitalized in internal medicine wards of 5 tertiary care centers were included in the study (December 2012-December 2014). Patient characteristics, therapeutic interventions, and outcome were reviewed. Propensity score (PS) was used as a covariate of the multivariate analysis to perform a stratified analysis according to PS quartiles and to match patients receiving "echinocandins" or "azoles."

Results: Overall, 439 patients with candidemia were included in the study. A total of 172 (39.2%) patients had septic shock. Thirty-day mortality was significantly higher in patients with septic shock (45.3%) compared with those without septic shock (31.5%; = .003). Among patients with septic shock, the use of echinocandins in the first 48 hours, compared with azoles, did not affect 30-day mortality in the PS-adjusted Cox regression analysis (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.37-1.59; = .48), the PS-stratified analysis, or the logistic regression model in matched cohorts (adjusted HR, 0.92; 95% CI, 0.51-1.63; = .77).

Conclusions: Echinocandin therapy seems not to improve the outcome of non-intensive care unit patients with septic shock due to candidemia. These findings support the urgent need of further studies in this patient population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ofid/ofz251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6634434PMC
July 2019