Prognostic Significance of NLR and PLR in COVID-19: A Multi-Cohort Validation Study.

INTRODUCTION: Recent studies have highlighted the prognostic value of easily accessible inflammatory markers, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) for predicting severe outcomes in patients affected by Coronavirus disease 2019 (COVID-19). Our study validates NLR and PLR cut-off values from a prior cohort at IRCCS Policlinico San Matteo (OSM) of Pavia, Italy, across two new cohorts from different hospitals. This aims to enhance the generalizability of these prognostic indicators. METHODS: In this retrospective cohort study, conducted at Milan's Ospedale Luigi Sacco (OLS) and IRCCS Ospedale Maggiore Policlinico (OMP) hospitals, we assess the predictive capacity of NLR and PLR for three main outcomes-non-invasive ventilation (NIV) or continuous positive airway pressure (CPAP) usage, invasive ventilation (IV), and death-in patients with COVID-19 at admission. For each outcome, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were computed separately for male and female cohorts. Distinct NLR and PLR cut-off values were used for men (7.00, 7.29, 7.00 for NLR; 239.22, 248.00, 250.39 for PLR) and women (6.36, 7.00, 6.28 for NLR; 233.00, 246.45, 241.54 for PLR), retrieved from the first cohort at OSM. RESULTS: A total of 3599 patients were included in our study, 1842 from OLS and 1757 from OMP. OLS and OMP sensitivity values for both NLR and PLR (NLR: 24-67%, PLR: 40-64%) were inferior to specificity values (NLR: 64-76%, PLR: 55-72%). Additionally, PPVs generally remained lower (< 63%), while NPVs consistently surpassed 68% for PLR and 72% for NLR. Finally, both PLR and NLR exhibited consistently higher NPVs for more severe outcomes (> 82%) compared to NPVs for CPAP/NIV. CONCLUSIONS: Consistent findings across diverse patient populations validate the reliability and applicability of NLR and PLR cut-off values. High NPVs emphasize their role in identifying individuals less likely to experience severe outcomes. These markers not only aid in risk stratification but also guide resource allocation in emergencies or limited-resource situations.

Carbapenem or new ß-lactam-ß-lactamase inhibitors? An Italian survey supported by SITA, SIMIT and SIAARTI to identify the factors affecting empiric antimicrobial therapy choice in real-life clinical practice.

While a tailored antibiotic treatment plan is often straightforward, what we often observe in daily clinical practice is a highly variable approach when defining empirical therapy. Specifically, a debate exists on preference to spare the new ß-lactams and ß-lactamase inhibitors (BL-BLIs) or to apply a carbapenem-sparing strategy first. To investigate, we designed a web survey aimed at investigating the variables considered relevant to empirically choosing one antibiotic over the other. Submitted to Italian infectious diseases and intensive care physicians through the support of Società Italiana di Malattie Infettive e Tropicali (SIMIT), Società Italiana di Terapia Antinfettiva (SITA) and Società Italiana Anestesia, Analgesia, Rianimazione e Terapia Intensiva (SIAARTI). We found that demographic characteristics were irrelevant when deciding for empirical therapy. Clinical and anamnestic data were most meaningful. Significantly considered were underlying comorbidities and previous exposure to antimicrobial treatments. History of third-generation cephalosporin-resistant, carbapenem-resistant and/or metallo-ß-lactamase-producing Enterobacterales rectal colonisation and/or infection were considered the most relevant by most physicians. Unexpectedly, clinicians considered less the source of infection. These results prompt the need of straightforward methods to retrieve medical histories and the magnitude of rectal colonisation data, often not routinely obtained.

Optimizing Antibiotic Therapy for Intravenous Drug Users: A Narrative Review Unraveling Pharmacokinetics/Pharmacodynamics Challenges.

Intravenous drug users (IVDUs) face heightened susceptibility to life-threatening gram-positive bacterial infections, particularly methicillin-resistant Staphylococcus aureus (MRSA). While the standard antibiotic dosing strategies for special patients, such as obese or critically ill individuals, are known to be inadequate, raising concerns about treatment efficacy, a similar sort of understanding has not been assessed for IVDUs yet. With this in mind, this review examines the pharmacokinetic/pharmacodynamic characteristics of antibiotics commonly used against gram-positive bacteria in IVDUs. Focusing on daptomycin, vancomycin, teicoplanin, aminoglycosides, and the novel lipoglycopeptide dalbavancin, the study reveals significant pharmacokinetic variations in IVDUs, suggesting the need for personalized dosing. Concomitant opioid substitution therapy and other factors, such as malnutrition, contribute to altered pharmacokinetics/pharmacodynamics, emphasizing the importance of targeted therapeutic drug monitoring. Overall, our study calls for increased awareness among clinicians regarding the unique pharmacokinetic/pharmacodynamic challenges in IVDUs and advocates for tailored antibiotic dosing strategies to enhance treatment outcomes in this marginalized population.

Proactive therapeutic monitoring of dalbavancin concentrations in the long-term management of chronic osteoarticular/periprosthetic joint infections.

Here, we describe the use of proactive therapeutic drug monitoring (TDM) to individualize the optimal timing of drug injections in 16 adult patients with chronic osteoarticular infections receiving a median of 7 injections of dalbavancin (up to 12 injections in 15 months). Dalbavancin injections were repeated at medians of 39-47 days, with infusion intervals ranging from 26 to 69 days. TDM can facilitates a precise, targeted use of dalbavancin for infections requiring prolonged treatments.

Mortality of Patients With Candidemia and COVID-19: A Systematic Review With Meta-analysis.

Mortality of candidemia in coronavirus disease 2019 (COVID-19) patients has not been deeply studied despite evidence suggesting an increased occurrence. We performed a systematic review and meta-analysis to summarize the available evidence about these patients' mortality and length of stay. Data about the in-hospital, all-cause and 30-day mortality, and length of stay were pooled. Subgroup analyses were performed to assess sources of heterogeneity. Twenty-six articles out of the 1915 records retrieved during the search were included in this review. The pooled in-hospital mortality was 62.62% (95% CI, 54.77% to 69.86%), while the mortality in intensive care unit (ICU) was 66.77% (95% CI, 57.70% to 74.75%). The pooled median in-hospital length of stay was 30.41 (95% CI, 12.28 to 48.55) days, while the pooled median length of stay in the ICU was 28.28 (95% CI, 20.84 to 35.73) days. The subgroup analyses did not identify the sources of heterogeneity in any of the analyses. Our results showed high mortality in patients with candidemia and COVID-19, suggesting the need to consider screening measures to prevent this life-threatening condition.

Preliminary Evidence of Good Safety Profile and Outcomes of Early Treatment with Tixagevimab/Cilgavimab Compared to Previously Employed Monoclonal Antibodies for COVID-19 in Immunocompromised Patients.

OBJECTIVES: Monoclonal antibodies (mAbs) have proven to be a valuable tool against COVID-19, mostly among subjects with risk factors for progression to severe illness. Tixagevimab/cilgavimab (TIX/CIL), a combination of two Fc-modified human monoclonal antibodies, has been recently approved to be employed as early treatment. METHODS: Two groups of immunocompromised patients exposed to different early treatments (i.e., TIX/CIL vs. other mAbs [casirivimab/imdevimab, bamlanivimab/etesevimab, sotrovimab]) were compared in terms of clinical outcomes (hospitalisation and mortality within 14 days from administration) and time to the negativity of nasal swabs. We used either Pearson's chi-square or Fisher's exact test for categorical variables, whereas the Wilcoxon rank-sum test was employed for continuous ones. Kaplan-Meier curves were produced to compare the time to nasopharyngeal swab negativity. RESULTS: Early treatment with TIX/CIL was administered to 19 immunocompromised patients, while 89 patients received other mAbs. Most of them were solid organ transplant recipients or suffering from hematologic or solid malignancies. Overall, no significant difference was observed between the two groups regarding clinical outcomes. In the TIX/CIL group, one patient (1/19, 5.3%), who was admitted to the emergency room within the first 14 days from treatment and was hospitalised due to COVID-19 progression, died. Regarding the time to nasal swab negativity, no significant difference (p = 0.088) emerged. CONCLUSIONS: Early treatment of SARS-CoV-2 infection with TIX/CIL showed favourable outcomes in a small group of immunocompromised patients, reporting no significant difference compared to similar patients treated with other mAbs.

Drug resistant tuberculosis in Italy through a global health lens.

Drug-resistant tuberculosis (DR-TB) is a major global health challenge. In 2021, about one third of DR-TB patients worldwide were enrolled in treatment. In order to reach the targets set during by the 2018 UN General Assembly (UNGA) Political Declaration on Tuberculosis, a global effort must be made by both high- and low-incidence countries. Data concerning high-incidence countries are vast in the literature, but insufficient political attention has been paid in low-incidence countries to face this infectious threat. This review aims at providing an overview of DR-TB focused on different facets of DR-TB management. First, global and Italian data on the main at-risk populations for TB and DR-TB were gathered, together with the latest studies on the correlation between TB risk factors and the onset of drug resistance. Second, this review provides an analysis of obsolete Italian guidelines on the diagnosis and management of TB and DR-TB, highlighting the challenges that our country is currently facing to properly implement the latest international recommendations. Finally, some key suggestions are provided to design public health (PH) policies that can effectively tackle the DR-TB issue from a "global health" perspective.

Therapeutic Drug Monitoring of Dalbavancin in Real Life: A Two-Year Experience.

Dalbavancin is a long-acting lipoglycopeptide that is registered for the treatment of acute bacterial skin and skin structure infections, and it is also increasingly used for infections that require prolonged antibiotic treatment. Here, we present the results from the first 2 years of a service set up in December 2021 for the therapeutic drug monitoring (TDM) of dalbavancin in clinical settings. In particular, we compared the trough concentration (Cmin) to maximum concentration (Cmax) in patients with osteoarticular infections receiving prolonged treatment with dalbavancin. Log-linear regression models were used to estimate the timing of dalbavancin administration with the goal of maintaining Cmin concentrations of >8 mg/L in the two TDM-based strategies. From December 2021 to November 2023, 366 TDMs of dalbavancin from 81 patients were performed. The Cmin and Cmax concentrations of dalbavancin ranged from 4.1 to 70.5 mg/L and from 74.9 to 995.6 mg/L, respectively. With log-linear regression models, we estimated that each injection should be administered every 42-48 days to maintain the Cmin concentrations. Out of the 81 patients, 37 received at least three doses of dalbavancin for the treatment of osteoarticular infections. Despite there being no significant differences in the days of dalbavancin treatment (130 ± 97 versus 106 ± 102 days), the patients in the Cmax-based TDM group received a significantly lower number of dalbavancin injections (5.2 ± 1.8 versus 7.3 ± 2.6 injections, p = 0.005), and they were administered over a longer period of time (40 ± 10 versus 29 ± 14 days, p = 0.013) than in the Cmin-based TDM group. In conclusion, Cmax-based TDM was associated with a significant reduction in the inter-individual variability of dalbavancin concentrations and lower drug dosing frequency than those of Cmin-based TDM. This approach could, therefore, favor a more rational and targeted use of dalbavancin in patients requiring prolonged treatment.

What is the impact of SARS-CoV-2 pandemic on antimicrobial stewardship programs (ASPs)? The results of a survey among a regional network of infectious disease centres.

Discontinuation of antimicrobial stewardship programs (ASPs) and increased antibiotic use were described during SARS-CoV-2 pandemic. In order to measure COVID-19 impact on ASPs in a setting of high multidrug resistance organisms (MDRO) prevalence, a qualitative survey was designed. In July 2021, eighteen ID Units were asked to answer a questionnaire about their hospital characteristics, ASPs implementation status before the pandemic and impact of SARS-CoV-2 pandemic on ASPs after the 1st and 2nd pandemic waves in Italy. Nine ID centres (50%) reported a reduction of ASPs and in 7 cases (38.9%) these were suspended. After the early pandemic waves, the proportion of centres that restarted their ASPs was higher among the ID centres where antimicrobial stewardship was formally identified as a priority objective (9/11, 82%, vs 2/7, 28%). SARS-CoV-2 pandemic had a severe impact in ASPs in a region highly affected by COVID-19 and antimicrobial resistance but weaknesses related to the pre-existent ASPs might have played a role.

Safety Profile and Outcomes of Early COVID-19 Treatments in Immunocompromised Patients: A Single-Centre Cohort Study.

BACKGROUND: Early treatment with remdesivir (RMD) or monoclonal antibodies (mAbs) could be a valuable tool in patients at risk of severe COVID-19 with unsatisfactory responses to vaccination. We aim to assess the safety and clinical outcomes of these treatments among immunocompromised subjects. METHODS: We retrospectively reviewed all nonhospitalized patients who received an early treatment with RMD or mAbs for COVID-19, from 25 November 2021 to 25 January 2022, in a large tertiary hospital. Outcomes included frequency of adverse drug reaction (ADR), duration of symptoms and molecular swab positivity, emergency department access, hospital or intensive care unit admission, and mortality in the 14 days following treatment administration. RESULTS: Early treatments were administered to 143 patients, 106/143 (74.1%) immunocompromised, including 41 solid organ and 6 hematopoietic stem cell transplant recipients. Overall, 23/143 (16.1%) subjects reported ADRs. Median time from treatment start to SARS-CoV-2 nasopharyngeal swab negativity and symptom resolution was 10 (IQR 6-16) and 2.5 days (IQR 1.0-6.0), respectively, without differences between immunocompromised and nonimmunocompromised patients. In the 14 days after treatment administration, 5/143 patients (3.5%) were hospitalized and one died as a result of causes related to COVID-19, all of them were immunocompromised. CONCLUSIONS: RMD and mAbs have minimal ADRs and favourable outcomes in immunocompromised patients.