(1) Background: The advantage of using carbapenems over beta-lactam/beta-lactamase inhibitor combinations in critically ill septic patients still remains a debated issue. We aimed to assess the comparative impact of an optimized pharmacokinetic/pharmacodynamic (PK/PD) target attainment of piperacillin-tazobactam vs. meropenem on the trend over time of both Sequential Organ Failure Assessment (SOFA) score and inflammatory biomarkers in critically ill patients receiving continuous infusion (CI) monotherapy with piperacillin-tazobactam or meropenem for treating documented Gram-negative bloodstream infections (BSI) and/or ventilator-associated pneumonia (VAP). (2) Methods: We performed a retrospective observational study comparing critically ill patients receiving targeted treatment with CI meropenem monotherapy for documented Gram-negative BSIs or VAP with a historical cohort of critical patients receiving CI piperacillin-tazobactam monotherapy. Patients included in the two groups were admitted to the general and post-transplant intensive care unit in the period July 2021–September 2023 and fulfilled the same inclusion criteria. The delta values of the SOFA score between the baseline of meropenem or piperacillin-tazobactam treatment and those at 48-h (delta 48-h SOFA score) or at 7-days (delta 7-days SOFA) were selected as primary outcomes. Delta 48-h and 7-days C-reactive protein (CRP) and procalcitonin (PCT), microbiological eradication, resistance occurrence, clinical cure, multi-drug resistant colonization at 90-day, ICU, and 30-day mortality rate were selected as secondary outcomes. Univariate analysis comparing primary and secondary outcomes between critically ill patients receiving CI monotherapy with piperacillin-tazobactam vs. meropenem was carried out. (3) Results: Overall, 32 critically ill patients receiving CI meropenem monotherapy were compared with a historical cohort of 43 cases receiving CI piperacillin-tazobactam monotherapy. No significant differences in terms of demographics and clinical features emerged at baseline between the two groups. Optimal PK/PD target was attained in 83.7% and 100.0% of patients receiving piperacillin-tazobactam and meropenem, respectively. No significant differences were observed between groups in terms of median values of delta 48-h SOFA (0 points vs. 1 point; p = 0.89) and median delta 7-days SOFA (2 points vs. 1 point; p = 0.43). Similarly, no significant differences were found between patients receiving piperacillin-tazobactam vs. meropenem for any of the secondary outcomes. (4) Conclusion: Our findings may support the contention that in critically ill patients with documented Gram-negative BSIs and/or VAP, the decreases in the SOFA score and in the inflammatory biomarkers serum levels achievable with CI piperacillin-tazobactam monotherapy at 48-h and at 7-days may be of similar extent and as effective as to those achievable with CI meropenem monotherapy provided that optimization on real-time by means of a TDM-based expert clinical pharmacological advice program is granted. Full article

Sepsis poses a significant global health challenge due to immune system dysregulation. This narrative review explores the complex relationship between antibiotics and the immune system, aiming to clarify the involved mechanisms and their clinical impacts. From pre-clinical studies, antibiotics exhibit various immunomodulatory effects, including the regulation of pro-inflammatory cytokine production, interaction with Toll-Like Receptors, modulation of the P38/Pmk-1 Pathway, inhibition of Matrix Metalloproteinases, blockade of nitric oxide synthase, and regulation of caspase-induced apoptosis. Additionally, antibiotic-induced alterations to the microbiome are associated with changes in systemic immunity, affecting cellular and humoral responses. The adjunctive use of antibiotics in sepsis patients, particularly macrolides, has attracted attention due to their immune-regulatory effects. However, there are limited data comparing different types of macrolides. More robust evidence comes from studies on community-acquired pneumonia, especially in severe cases with a hyper-inflammatory response. While studies on septic shock have shown mixed results regarding mortality rates and immune response modulation, conflicting findings are also observed with macrolides in acute respiratory distress syndrome. In conclusion, there is a pressing need to tailor antibiotic therapy based on the patient’s immune profile to optimize outcomes in sepsis management. Full article

Antimicrobial de-escalation (ADE) is defined as the discontinuation of one or more antimicrobials in empirical therapy, or the replacement of a broad-spectrum antimicrobial with a narrower-spectrum antimicrobial. The aim of this review is to provide an overview of the available literature on the effectiveness and safety of ADE in critically ill patients, with a focus on special conditions such as anti-fungal therapy and high-risk categories. Although it is widely considered a safe strategy for antimicrobial stewardship (AMS), to date, there has been no assessment of the effect of de-escalation on the development of resistance. Conversely, some authors suggest that prolonged antibiotic treatment may be a side effect of de-escalation, especially in high-risk categories such as neutropenic critically ill patients and intra-abdominal infections (IAIs). Moreover, microbiological documentation is crucial for increasing ADE rates in critically ill patients with infections, and efforts should be focused on exploring new diagnostic tools to accelerate pathogen identification. For these reasons, ADE can be safely used in patients with infections, as confirmed by high-quality and reliable microbiological samplings, although further studies are warranted to clarify its applicability in selected populations. Full article

Over the past century, antibiotic usage has skyrocketed in the treatment of critically ill patients. There have been increasing calls to establish guidelines for appropriate treatment and durations of antibiosis. Antibiotic treatment, even when appropriately tailored to the patient and infection, is not without cost. Short term risks—hepatic/renal dysfunction, intermediate effects—concomitant superinfections, and long-term risks—potentiating antimicrobial resistance (AMR), are all possible consequences of antimicrobial administration. These risks are increased by longer periods of treatment and unnecessarily broad treatment courses. Recently, the literature has focused on multiple strategies to determine the appropriate duration of antimicrobial therapy. Further, there is a clinical shift to multi-modal approaches to determine the most suitable timepoint at which to end an antibiotic course. An approach utilising biomarker assays and an inter-disciplinary team of pharmacists, nurses, physicians, and microbiologists appears to be the way forward to develop sound clinical decision-making surrounding antibiotic treatment. Full article

Intensive care units constitute a critical setting for the management of infections. The patients’ fragilities and spread of multidrug-resistant microorganisms lead to relevant difficulties in the patients’ care. Recent epidemiological surveys documented the Gram-negative bacteria supremacy among intensive care unit (ICU) infection aetiologies, accounting for numerous multidrug-resistant isolates. Regarding this specific setting, clinical microbiology support holds a crucial role in the definition of diagnostic algorithms. Eventually, the complete patient evaluation requires integrating local epidemiological knowledge into the best practice and the standardization of antimicrobial stewardship programs. Clinical laboratories usually receive respiratory tract and blood samples from ICU patients, which express a significant predisposition to severe infections. Therefore, conventional or rapid diagnostic workflows should be modified depending on patients’ urgency and preliminary colonization data. Additionally, it is essential to complete each microbiological report with rapid phenotypic minimum inhibitory concentration (MIC) values and information about resistance markers. Microbiologists also help in the eventual integration of ultimate genome analysis techniques into complicated diagnostic workflows. Herein, we want to emphasize the role of the microbiologist in the decisional process of critical patient management. Full article

Healthcare-associated infections (HAIs) pose significant challenges in healthcare systems, with preventable surveillance playing a crucial role. Traditional surveillance, although effective, is resource-intensive. The development of new technologies, such as artificial intelligence (AI), can support traditional surveillance in analysing an increasing amount of health data or meeting patient needs. We conducted a scoping review, following the PRISMA-ScR guideline, searching for studies of new digital technologies applied to the surveillance, control, and prevention of HAIs in hospitals and LTCFs published from 2018 to 4 November 2023. The literature search yielded 1292 articles. After title/abstract screening and full-text screening, 43 articles were included. The mean study duration was 43.7 months. Surgical site infections (SSIs) were the most-investigated HAI and machine learning was the most-applied technology. Three main themes emerged from the thematic analysis: patient empowerment, workload reduction and cost reduction, and improved sensitivity and personalization. Comparative analysis between new technologies and traditional methods showed different population types, with machine learning methods examining larger populations for AI algorithm training. While digital tools show promise in HAI surveillance, especially for SSIs, challenges persist in resource distribution and interdisciplinary integration in healthcare settings, highlighting the need for ongoing development and implementation strategies. Full article