Antimicrobial Stewardship in the Covid-19 Pandemic.

During COVID-19 pandemic, implementing and maintaining an antimicrobial stewardship protocol obtained both low rates of MDR microorganisms and low antimicrobial use in an 800-bed hospital network in northern Italy. Infectious diseases specialist consulting was crucial to maintain this protocol active.

Classification and analysis of outcome predictors in non-critically ill COVID-19 patients.

BACKGROUND: Early detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients who could develop a severe form of COVID-19 must be considered of great importance to carry out adequate care and optimise the use of limited resources. AIMS: To use several machine learning classification models to analyse a series of non-critically ill COVID-19 patients admitted to a general medicine ward to verify if any clinical variables recorded could predict the clinical outcome. METHODS: We retrospectively analysed non-critically ill patients with COVID-19 admitted to the general ward of the hospital in Pordenone from 1 March 2020 to 30 April 2020. Patients' characteristics were compared based on clinical outcomes. Through several machine learning classification models, some predictors for clinical outcome were detected. RESULTS: In the considered period, we analysed 176 consecutive patients admitted: 119 (67.6%) were discharged, 35 (19.9%) dead and 22 (12.5%) were transferred to intensive care unit. The most accurate models were a random forest model (M2) and a conditional inference tree model (M5) (accuracy = 0.79; 95% confidence interval 0.64-0.90, for both). For M2, glomerular filtration rate and creatinine were the most accurate predictors for the outcome, followed by age and fraction-inspired oxygen. For M5, serum sodium, body temperature and arterial pressure of oxygen and inspiratory fraction of oxygen ratio were the most reliable predictors. CONCLUSIONS: In non-critically ill COVID-19 patients admitted to a medical ward, glomerular filtration rate, creatinine and serum sodium were promising predictors for the clinical outcome. Some factors not determined by COVID-19, such as age or dementia, influence clinical outcomes.

Endocrine treatment versus chemotherapy in postmenopausal women with hormone receptor-positive, HER2-negative, metastatic breast cancer: a systematic review and network meta-analysis.

BACKGROUND: Although international guidelines support the administration of hormone therapies with or without targeted therapies in postmenopausal women with hormone-receptor-positive, HER2-negative metastatic breast cancer, upfront use of chemotherapy remains common even in the absence of visceral crisis. Because first-line or second-line treatments, or both, based on chemotherapy and on hormone therapy have been scarcely investigated in head-to-head randomised controlled trials, we aimed to compare these two different approaches. METHODS: We did a systematic review and network meta-analysis with a systematic literature search on PubMed, Embase, Cochrane Central Register of Clinical Trials, Web of Science, and online archives of the most relevant international oncology conferences. We included all phase 2 and 3 randomised controlled trials investigating chemotherapy with or without targeted therapies and hormone therapies with or without targeted therapies as first-line or second-line treatments, or both, in postmenopausal women with hormone-receptor-positive, HER2-negative metastatic breast cancer, published between Jan 1, 2000, and Dec 31, 2017. Additional recently published randomised controlled trials relevant to the topic were also subsequently added. No language restrictions were adopted for our search. A Bayesian network meta-analysis was done to compare hazard ratios (HRs) for progression-free survival (the primary outcome), and to compare odds ratios (ORs) for the proportion of patients achieving an overall response (the secondary outcome). All treatments were compared to anastrozole and to palbociclib plus letrozole. This study is registered in the Open Science Framework online public database, registration DOI 10.17605/OSF.IO/496VR. FINDINGS: We identified 2689 published results and 140 studies (comprising 50 029 patients) were included in the analysis. Palbociclib plus letrozole (HR 0·42; 95% credible interval [CrI] 0·25-0·70), ribociclib plus letrozole (0·43; 0·24-0·77), abemaciclib plus anastrozole or letrozole (0·42; 0·23-0·76), palbociclib plus fulvestrant (0·37; 0·23-0·59), ribociclib plus fulvestrant (0·48; 0·31-0·74), abemaciclib plus fulvestrant (0·44; 0·28-0·70), everolimus plus exemestane (0·42; 0·28-0·67), and, in patients with a PIK3CA mutation, alpelisib plus fulvestrant (0·39; 0·22-0·66), and several chemotherapy-based regimens, including anthracycline and taxane-containing regimens, were associated with better progression-free survival than was anastrozole alone. No chemotherapy or hormone therapy regimen was significantly better than palbociclib plus letrozole for progression-free survival. Paclitaxel plus bevacizumab was the only clinically relevant regimen that was significantly better than palbociclib plus letrozole in terms of the proportion of patients achieving an overall response (OR 8·95; 95% CrI 1·03-76·92). INTERPRETATION: In the first-line or second-line setting, CDK4/6 inhibitors plus hormone therapies are better than standard hormone therapies in terms of progression-free survival. Moreover, no chemotherapy regimen with or without targeted therapy is significantly better than CDK4/6 inhibitors plus hormone therapies in terms of progression-free survival. Our data support treatment guideline recommendations involving the new combinations of hormone therapies plus targeted therapies as first-line or second-line treatments, or in both settings, in women with hormone-receptor-positive, HER2-negative metastatic breast cancer. FUNDING: None.

Recurrent seizures during acute acquired toxoplasmosis in an immunocompetent traveller returning from Africa.

INTRODUCTION: We report an unusual case of acute acquired toxoplasmosis (AAT) presenting as lymphadenopathy and recurrent seizures in an immunocompetent 15-year-old boy. MATERIALS AND METHODS: The patient reported an 18-day vacation to Africa (Ethiopia), 39 days prior to the first seizure. Electroencephalogram (EEG) showed sporadic single-spike or sharp-wave paroxysms and the magnetic resonance imaging (RMI) of the brain was negative. The serology for T. gondii was compatible with an acute infection defined as positive for both toxoplasma-specific IgG and IgM and a low avidity (6 %), confirmed by a reference laboratory. The patient reported other two episodes of seizures, occurring 7 days apart. He was treated with pyrimethamine plus sulfadiazine and leucovorin for 4 weeks, with an improvement of lymphadenitis and normalization of EEG. After 5 months, new seizures were reported and a diagnosis of epilepsy was done. Toxoplasma polymerase chain reaction (PCR) of cerebrospinal fluid (CSF) and blood were negative. A treatment with valproic acid was started, obtaining control of the neurological disease. CONCLUSION: Awareness of this neurologic manifestation by clinicians is required, also in immunocompetent patients. The relationship between toxoplasmosis and recurrent seizure needs to be investigated by new studies.

A network meta-analysis of everolimus plus exemestane versus chemotherapy in the first- and second-line treatment of estrogen receptor-positive metastatic breast cancer.

The goal of this study was to compare the efficacy and toxicity of chemotherapy to exemestane plus everolimus (EXE/EVE) through a network meta-analysis (NMA) of randomized controlled trials. NMA methods extend standard pairwise meta-analysis to allow simultaneous comparison of multiple treatments while maintaining randomization of individual studies. The method enables "direct" evidence (i.e., evidence from studies directly comparing two interventions) and "indirect" evidence (i.e., evidence from studies that do not compare the two interventions directly) to be pooled under the assumption of evidence consistency. We used NMA to evaluate progression-free survival (PFS) and time to progression (TTP) curves in 34 studies, and response rate (RR) and the hazard ratios (HRs) of the PFS/TTP in 36 studies. A number needed to treat (NNT) analysis was also performed as well as descriptive comparison of reported toxicities. The NMA for PFS/TTP curves and for HR shows EXE/EVE is more efficacious than capecitabine plus sunitinib, CMF, megestrol acetate and tamoxifen, with an average of related-PFS/TTP difference ranging from about 10 months for capecitabine plus sunitinib to more than 6 months for tamoxifen. The NMA for overall RR shows that EXE/EVE provides a better RR than bevacizumab plus capecitabine, capecitabine, capecitabine plus sorafenib, capecitabine plus sunitinib, CMF, gemcitabine plus epirubicin plus paclitaxel, EVE plus tamoxifen, EXE, FEC, megestrol acetate, mitoxantrone, and tamoxifen. Finally, the NMA for NNT shows that EXE/EVE is more beneficial as compared to BMF, capecitabine, capecitabine plus sunitinib, CMF, FEC, megestrol acetate, mitoxantrone, and tamoxifen. The combination of EXE/EVE as first- or second-line therapy for ER+ve/HER2-ve metastatic breast cancer is more efficacious than several chemotherapy regimens that were reported in the literature. Toxicities also favored EXE/EVE in most instances.

Pure anti-tumor effect of zoledronic acid in naïve bone-only metastatic and locally advanced breast cancer: proof from the "biological window therapy".

The study investigated the anti-tumour effect of zoledronic acid (ZA) administered alone in a biological window therapy in naïve bone-only metastatic and locally advanced breast cancer (LABC) patients. 33 patients with LABC (Group 1) and 20 patients with a first diagnosis of bone metastasis only (Group 2) received 4 mg single dose of ZA, 14 days (biological window) before starting any treatment. In Group 1, Ki67, CD34, p53/bcl-2 and caspase 3 expression along with the adenosine triphosphate (ATP) levels and RNA disruption index were evaluated as markers of tumor growth in tumour specimens obtained before and after ZA administration (basal, day 14). In Group 2, the total enumeration of circulating tumour cells (CTCs), and of M30+ve CTCs along with the soluble marker of cell death (M30/M65) were carried-out as markers of tumor dissemination at baseline, at 48 h and day 14th. In Group 1, there was a significant reduction in Ki67, CD34, bcl-2 expression after 14 days ZA based-treatment (p = 0.0032; p = 0.0001, p < 0.00001 respectively). ZA showed a significant increase of RNA disruption (p < 0.0076). In Group 2, we observed a significant reduction of CTCs number after 48 h (p = 0.0012), followed by a significant rebound at 14 days (p = 0.012). The apoptotic CTCs/M30+ve and M65 levels significantly increased under treatment (p = 0.018 and p = 0.039 respectively) after drug administration when compared to the baseline. These results are the first prospective in vivo data showing the direct pure anti-tumour effect (either on the tumour cell or on CTCs) of ZA.

Time is running out. No excuses to delay implementation of antimicrobial stewardship programmes: impact, sustainability, resilience and efficiency through an interrupted time series analysis (2017-2022).

Introduction: The WHO declared antimicrobial resistance (AMR) a significant concern in 2014, sparking initiatives to ensure responsible antibiotic use. In human medicine, Antimicrobial Stewardship Programmes (ASPs) in hospitals play a pivotal role in combating AMR. Although evidence supports the effectiveness of ASPs in optimizing antimicrobial use, often the lack of resources becomes an excuse to limit their dissemination and use. This paper provides a comprehensive report on a 6-year analysis of an ASP implemented in a healthcare region in north-east Italy. Methods: A retrospective data collection was conducted to assess the programme's impact on antibiotic consumption expressed as DDDs/100 patient-days, its sustainability over time, resilience during the COVID-19 pandemic and the efficiency of the ASP (relationship between workload and human resources). Results: A substantial overall reduction in antibiotic consumption (-14%), particularly in fluoroquinolones (-64%) and carbapenems (-68%), was demonstrated, showcasing the programme's impact. Sustainability was confirmed through enduring trends in antibiotic consumption and ecological analysis over time. The ASP demonstrates resilience by maintaining positive trends even amid the challenging COVID-19 pandemic. Efficiency was underscored by an increase in on-site consultations despite consistent human resources until 2021. Conclusions: This study offers insights into the prolonged success of a resource-efficient ASP, emphasizing the crucial role of long-term commitment in fostering responsible antibiotic use in the context of global health challenges such as AMR.

The Management of Recurrent Urinary Tract Infection: Non-Antibiotic Bundle Treatment.

Recurrent urinary tract infections (rUTIs) are a common condition with high morbidity and negatively impact the quality of life. They account for approximately 25% of all antibiotic prescriptions and are a public health concern in an era of increasing multidrug-resistant organisms (MDROs). Several non-antibiotic treatment strategies have been tried to curb antimicrobial use, and many are effective to some degree, but no experience testing multimodal interventions. We created a "care bundle" consisting of behavioral interventions, vaginal and oral probiotics, D-mannose, and cranberry to be followed for six months. We enrolled women with rUTIs over three years. Changes in urinary tract infections, antibiotic use, chronic symptoms, and quality of life were compared in the six months before and after participation in the study. Forty-seven women were enrolled in the study, six of whom were excluded from the final analysis. We observed a 76% reduction in urinary tract infections (p < 0.001) and a reduction in total antibiotic exposure of more than 90% (p < 0.001); all chronic symptoms showed a trend toward reduction. Adherence to the bundle was high (87.2%). Overall, 80.5% of women experienced an improvement in their quality of life. In our experience, a bundle protocol is effective in reducing recurrences and antimicrobial use in a cohort of women with rUTIs and results in a subjective improvement in chronic symptoms and quality of life. Further research with larger sample size is needed to confirm these findings.

Dalbavancin in catheter-related bloodstream infections: a pilot study.

Background: Catheter-related bloodstream infections (CRBSI) represent a frequent complication of vascular catheterization, with high morbidity, mortality, and associated costs. Most infections are caused by Gram-positive bacteria; thus dalbavancin, a new long-acting lipoglicopeptide, may have a role in early patient discharge strategies optimizing treatment and reducing overall costs. Methods: In this small pilot feasibility study, we assessed the efficacy and safety of a "single step" treatment strategy combining dalbavancin administration (1500 mg IV single dose), catheter removal, and early discharge in adult patients admitted to medical wards in a three-year period. Results: We enrolled sixteen patients with confirmed Gram-positive CRBSI, with a mean age of 68 years and relevant comorbidities (median Charlson Comorbidity index=7). The most frequent causative agents were staphylococci, with 25% of methicillin-resistant strains, and the majority of infected devices were short term central venous catheter (CVC) and peripherally inserted central catheter (PICC). Ten out of sixteen patients had been treated empirically before dalbavancin administration. The mean time from dalbavancin administration to discharge was 2 days; none of the patients had adverse drug-related reactions; at 30- and 90-day follow-up, no patients have been readmitted to the hospital due to bacteraemia recurrence. Conclusions: Our results indicate that single-dose dalbavancin is highly effective, well-tolerated, and cost-saving for Gram-positive CRBSI.

Mortality predictors in hospitalised COVID-19 patients and the role of anti-SARS-CoV-2 IgG antibodies and remdesivir.

Background: In a pre-vaccination era serologic tests may be used to evaluate the seroprevalence and efficacy of containment strategies applied to the community. Subsequently, SARS-CoV-2 vaccination has successfully reduced hospitalization and admission to intensive care. The role of antiviral treatment for COVID-19 remains debated. Objective: We investigated the effect of SARS-CoV-2 IgG Spike (S) antibody responses in hospitalized patients on 30-day mortality. Finally, we assessed whether other predictive factors affected mortality after 30 days. Methods: Observational study on COVID-19 patients admitted from October 1, 2021, to January 30, 2022. Results: 520 patients were studied; 108 died at the 30-day follow-up (21%). A borderline significance for mortality was observed in favour of the high antibody titer group (24% vs 17%, p=0.05). From the univariate Cox regression analysis, a high IgG-S titer was significantly correlated to lower 30-day mortality (p=0.04, HR: 0.7; 95%CI: 0.44-0.98). The administration of remdesivir (p=0.01) and the age <65 years (p=2.3e-05) were found to be protective for the considered outcome (respectively, HR: 0.5, 95%CI: 0.34-0.86, and HR: 0.1, 95%CI: 0.04-0.30). Conclusions: S-antibodies and remdesivir could play a protecting role in increasing the survival of hospitalized COVID-19 patients who are not suffering from a critical disease. Advanced age is a risk factor for poor outcomes among infected people.

Epidemiology of respiratory virus before and during COVID-19 pandemic.

The COVID pandemic has forcefully turned the spotlight on the importance of the diagnosis of respiratory virus infections. Viruses have always been a frequent and common cause of respiratory tract infections. Rapid molecular diagnostics applied to the diagnostics of respiratory virus infections has revolutionized microbiology laboratories only a few years ago. Few studies illustrate the epidemiology of respiratory viruses, and fewer still those that have compared the pre-pandemic to the pandemic period. During the first year of the pandemic (2020-2021) it was clear to everyone to witness a sudden disappearance of the circulation of all the other respiratory viruses, especially those typically isolated during the winter time, such as RSV and Influenza virus. In our study we wanted to verify this phenomenon and to study the epidemiology of our local reality, analyzing three consecutive flu seasons (2018-2019, 2019-2020, 2020-2021). The results lead us to note that the prevalence of positivity to respiratory virus infections went from 49.8% (2018-2019) and 39% (2019-2020) to 13.4% (2020-2021). This decrease is at least partly attributable to the security measures adopted (social distancing and mask), but it certainly opens up new scenarios when the restriction measures will be terminated. We believe such studies can provide real-world evidence of the effectiveness of public health interventions implemented during current and future pandemics.

Rapidly progressive ischemic strokes and transient antiphospholipid syndrome during a mild SARS-CoV-2 infection.

SARS-CoV-2 infection is associated with an increased risk of thrombotic events, especially during severe forms of disease. Here we describe the clinical history of a patient with a mild form of Covid-19 infection presenting with multiple cerebral ischemic lesions that evolved in an atypical way.

Development and Validation of the Acute PNeumonia Early Assessment Score for Safely Discharging Low-Risk SARS-CoV-2-Infected Patients from the Emergency Department.

A continuous demand for assistance and an overcrowded emergency department (ED) require early and safe discharge of low-risk severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients. We developed (n = 128) and validated (n = 330) the acute PNeumonia early assessment (aPNea) score in a tertiary hospital and preliminarily tested the score on an external secondary hospital (n = 97). The score's performance was compared to that of the National Early Warning Score 2 (NEWS2). The composite outcome of either death or oral intubation within 30 days from admission occurred in 101 and 28 patients in the two hospitals, respectively. The area under the receiver operating characteristic (AUROC) curve of the aPNea model was 0.86 (95% confidence interval (CI), 0.78-0.93) and 0.79 (95% CI, 0.73-0.89) for the development and validation cohorts, respectively. The aPNea score discriminated low-risk patients better than NEWS2 at a 10% outcome probability, corresponding to five cut-off points and one cut-off point, respectively. aPNea's cut-off reduced the number of unnecessary hospitalizations without missing outcomes by 27% (95% CI, 9-41) in the validation cohort. NEWS2 was not significant. In the external cohort, aPNea's cut-off had 93% sensitivity (95% CI, 83-102) and a 94% negative predictive value (95% CI, 87-102). In conclusion, the aPNea score appears to be appropriate for discharging low-risk SARS-CoV-2-infected patients from the ED.

Home management of COVID-19 symptomatic patients: a safety study on COVID committed home medical teams.

To reduce the overburden in the hospital, during the COVID-19 pandemic, some "COVID Committed Home Medical Teams" (CCHTs) were created in Italy. These units consist of a small pool of general practitioners who aim to evaluate all patients with COVID-19 who require a medical examination directly at home. After the first visit (which can end with patient hospitalisation or home management), CCHTs periodically monitor the patients' clinical conditions and vital signs (usually a revaluation every 24-48 hours, except for a sudden worsening). However, this strategy - which reduces the pressure on hospitals - has never been evaluated for patient safety. Our study aims to determine whether a home-based monitoring and treatment strategy for non-severe COVID-19 patients was safe as direct hospital admission by the emergency department. We conducted a retrospective observational study about 1,182 patients admitted to the hospital for COVID-19 between September 2020 and April 2021, confronting in-hospital and 30-day mortality in both CCHT-referred (n=275) and directly admitted by emergency department (n=907). Patients assessed by the CCHT had lower in-hospital and 30-day mortality (18% vs 28%, p=0.001; and 20% vs 30%, p=0.002); but, in the propensity score matching comparison, there was no characteristic between the two groups turned out significantly different. CCHT did not correlate with in-hospital or 30-day mortality. CCHT is a safe strategy to reduce hospital overburden for COVID-19 during pandemic surges.

Multiple Bayesian network meta-analyses to establish therapeutic algorithms for metastatic triple negative breast cancer.

Metastatic triple-negative breast cancer (mTNBC) is a poor prognostic disease with limited treatments and uncertain therapeutic algorithms. We performed a systematic review and multiple Bayesian network meta-analyses according to treatment line to establish an optimal therapeutic sequencing strategy for this lethal disease. We included 125 first-line trials (37,812 patients) and 33 s/further-lines trials (11,321 patients). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall response rates (ORR), overall survival (OS) and safety, for first and further lines, separately. We also estimated separate treatment rankings for the first and subsequent lines according to each endpoint, based on (surface under the cumulative ranking curve) SUCRA values. No first-line treatment was associated with superior PFS and OS than paclitaxel ± bevacizumab. Platinum-based polychemotherapies were generally superior in terms of ORR, at the cost of higher toxicity.. PARP-inhibitors in germline-BRCA1/2-mutant patients, and immunotherapy + chemotherapy in PD-L1-positive mTNBC, performed similar to paclitaxel ± bevacizumab. In PD-L1-positive mTNBC, pembrolizumab + chemotherapy was better than atezolizumab + nab-paclitaxel in terms of OS according to SUCRA values. In second/further-lines, sacituzumab govitecan outperformed all other treatments on all endpoints, followed by PARP-inhibitors in germline-BRCA1/2-mutant tumors. Trastuzumab deruxtecan in HER2-low mTNBC performed similarly and was the best advanced-line treatment in terms of PFS and OS after sacituzumab govitecan, according to SUCRA values. Moreover, comparisons with sacituzumab govitecan, talazoparib and olaparib were not statistically significant. The most effective alternatives or candidates for subsequent lines were represented by nab-paclitaxel (in ORR), capecitabine (in PFS) and eribulin (in PFS and OS).

Testing Hardy-Weinberg equilibrium: an objective Bayesian analysis.

We analyze the general (multiallelic) Hardy-Weinberg equilibrium problem from an objective Bayesian testing standpoint. We argue that for small or moderate sample sizes the answer is rather sensitive to the prior chosen, and this suggests to carry out a sensitivity analysis with respect to the prior. This goal is achieved through the identification of a class of priors specifically designed for this testing problem. In this paper, we consider the class of intrinsic priors under the full model, indexed by a tuning quantity, the training sample size. These priors are objective, satisfy Savage's continuity condition and have proved to behave extremely well for many statistical testing problems. We compute the posterior probability of the Hardy-Weinberg equilibrium model for the class of intrinsic priors, assess robustness over the range of plausible answers, as well as stability of the decision in favor of either hypothesis.

Peritoneal Tuberculosis during Infliximab Treatment in a Patient with Ulcerative Colitis Despite a Negative Quantiferon Test.

Infliximab is an IgG1 antitumor necrosis factor monoclonal antibody that is commonly used to treat inflammatory bowel disease (IBD) and other autoimmune disorders. However, it is known to increase the risk of reactivation of latent tuberculosis (LTBI) due to its capability to disrupt TB granulomas. We describe a case of extrapulmonary TB in a patient with ulcerative colitis who was treated with Infliximab after a negative Quantiferon Test. In addition, we report briefly on the current controversy about the appropriateness, interval, and methods for the repeated screening of latent TB in IBD patients that are treated with antitumor necrosis factor alpha (TNF-α) antibodies.

Ceftobiprole and pneumonia in adults admitted to the emergency department is it time to assess a new therapeutic algorithm?

OBJECTIVE: Ceftobiprole is an advance generation cephalosporin which has broad-spectrum bacterial activity (both against Gram-positive and negative pathogens) and was approved for the treatment of community-acquired pneumonia (CAP) and non-ventilated hospital-acquired pneumonia (HAP) in most European countries. We aimed to evaluate the efficacy and safety of ceftobiprole in the treatment of pneumonia in a cohort of severely ill patients admitted to the emergency department (ED). METHODS: 1-year observational retrospective mono-centric study. Were defined two primary endpoints: first, to evaluate the clinical cure at the test-of-cure (TOC); the second, to evaluate the early improvement, defined as a reduction of symptoms and inflammatory parameters 72 hours after the start of treatment. The secondary endpoint is to evaluate the reduction of antibiotic "burden" using ceftobiprole despite standard of care in severe hospital-acquired pneumonia. RESULTS: During the study period, a total of 48 patients with severe pneumonia received ceftobiprole: twenty-two patients (45.8%) as empiric therapy, 9 (18.5%) as a de-escalation option from previous combination therapies, 13 patients (27.1%) as an escalation therapy from ceftriaxone or amoxicillin/clavulanate and four patients (8.3%) as a targeted therapy based on microbiological results. Ceftobiprole mean duration therapy was 10.2 days. Forty-six patients with severe pneumonia had an early clinical improvement 72 hours after the start of treatment (95.8%). In general, ceftobiprole was well tolerated; only one patient suspended the drug because of poor tolerability. The clinical cure at TOC was 85.4% and 30-days crude mortality was 10.4%. CONCLUSIONS: This study confirms that ceftobiprole is effective in severely ill patients with pneumonia at risk of poor outcomes.

Acute kidney injury and single-dose administration of aminoglycoside in the Emergency Department: a comparison through propensity score matching.

Purpose: According to the Surviving Sepsis Campaign, aminoglycosides (AG) can be administered together with a ß-lactam in patients with septic shock. Some authors propose administering a single dose of an AG combined with a ß-lactam antibiotic in septic patients to extend the spectrum of antibiotic therapy. The aim of this study has been to investigate whether a single shot of AG when septic patients present at the Emergency Department (ED) is associated with acute kidney injury (AKI). Methods: We retrospectively enrolled patients based on a 3-year internal registry of septic patients visited in the Emergency Department (ED) of Pordenone Hospital. We compared the patients treated with a single dose of gentamicin (in addition to the ß-lactam) and those who had not been treated to verify AKI incidence. Results: 355 patients were enrolled. The median age was 71 years (IQR 60-78). Less than 1% of the patients had a chronic renal disease. The most frequent infection source was the urinary tract (31%), followed by intra-abdominal and lower respiratory tract infections (15% for both). 131 patients received gentamicin. Unmatched data showed a significant difference between the two groups in AKI (79/131, 60.3% versus 102/224, 45.5%; p=0.010) and in infectious disease specialist's consultation (77/131, 59% versus 93/224, 41.5%; p=0.002). However, after propensity score matching, no significant difference was found. Conclusion: Our experience shows that a single-shot administration of gentamicin upon admission to the ED does not determine an increased incidence of AKI in septic patients.

Diagnostic performance of an automated chemiluminescence immunoassay for SARS-CoV-2 IgG and IgM antibodies detection: A real life experience.

BACKGROUND: Recently many serological assays for detection of antibodies to SARS-COV-2 virus were introduced on the market. Aim of this study was to assess the diagnostic performance of an automated CLIA for quantitative detection of anti-SARS-CoV-2 IgM and IgG antibodies. METHODS: A total of 354 sera, 89 from consecutive patients diagnosed with COVID-19 (43 mild, 32 severe and 13 critical) and 265 from asymptomatic and negative on rRT-PCR testing healthcare workers, were evaluated for IgM and IgG anti-SARS-CoV-2 antibodies with MAGLUMI immunoassay. RESULTS: The overall sensitivity and specificity were 86.5% (95%CI: 77.6-92.8) and 98.5% (95%CI:96.2-99.6), respectively. PPV, PPN, LR+, LR- and OR were 95.1 (95%CI: 87.8-98.6), 95.6 (95%CI: 92.4-97.7), 57.3 (95%CI: 21.6-152.1), 7.3 (95%CI: 4.31-12.4) and 418.6 (95%CI: 131.2-1335.2), respectively. The levels of SARS-CoV-2 IgM and IgG antibodies were 1.22 â€‹± â€‹1.2 AU/mL and 15.86 â€‹± â€‹24.83 AU/mL, 2.86 â€‹± â€‹2.4 AU/mL and 69.3 â€‹± â€‹55.5 AU/mL, 2.47 â€‹± â€‹1.33 AU/mL and 83.9 â€‹± â€‹83.9 AU/mL in mild, severe and critical COVID-19 groups, respectively. A significant difference in antibody levels between mild and severe/critical subjects has been shown. CONCLUSIONS: The CLIA assay showed good diagnostic performance and a significant association between antibody levels and severity of the disease was found.