Aim: The aim of the study was to evaluate the in vitro activity of N-acetylcysteine (NAC), alone or in combination with beta-lactams, against carbapenem-resistant Klebsiella pneumoniae (CR-Kp) and Acinetobacter baumannii (CR-Ab). Methods: The antibacterial activity of each compound was tested by broth microdilution and the synergism was evaluated by the checkerboard method. Killing studies of NAC alone and in combination with beta-lactams were performed. Bacterial morphological changes were investigated with scanning electron microscopy (SEM). Results: Overall, 30 strains were included (15 CR-Kp and 15 CR-Ab). The NAC Minimal Inhibitory Concentrations (MIC)50/90 were 5/5 and 2.5/5 mg/mL for CR-Kp and CR-Ab, respectively. For both microorganisms, NAC, in addition to beta-lactams (meropenem for CR-Kp, meropenem and ampicillin/sulbactam for CR-Ab, respectively), was able to enhance their activity. The killing studies showed a rapid and concentration-dependent activity of NAC alone; the addition of NAC to meropenem or ampicillin/sulbactam at subinhibitory concentrations induced a fast and lasting bactericidal activity that persisted over time. The SEM analyses showed evident morphological alterations of the bacterial cells following incubation with NAC, alone and in combination with meropenem. Conclusions: NAC demonstrated a high in vitro activity against CR-Kp and CR-Ab and was able to enhance beta-lactams’ susceptibility in the tested strains. The preliminary data on the SEM analyses confirmed the in vitro results.

Introduction: E-selectin is a recognized marker of endothelial activation; however, its place in Coronavirus Disease 2019 (COVID-19) has not been fully explored. Aims of the study are to compare sE-selectin values among the Intensive Care Unit (ICU)-admitted and non-admitted, survived and non-survived patients and those with or without thrombosis. Methods: A single-center study of patients with COVID-19 hospitalized at Policlinico Umberto I (Rome) from March to May 2020 was performed. Simple and multiple logistic regression models were developed. Results: One hundred patients were included, with a median age (IQR) of 65 years (58–78). Twenty-nine (29%) were admitted to ICU, twenty-eight (28%) died and nineteen (19%) had a thrombotic event. The median value (IQR) of sE-selectin was 26.1 ng/mL (18.1–35). sE-selectin values did not differ between deceased and survivors (p = 0.06) and among patients with or without a thrombotic event (p = 0.22). Compared with patients who did not receive ICU treatments, patients requiring ICU care had higher levels of sE-selectin (36.6 vs. 24.1 ng/mL; p < 0.001). In the multiple logistic regression model, sE-selectin levels > 33 ng/mL, PaO₂/FiO₂ < 200 and PaO₂/FiO₂ 200–300 were significantly associated with an increased risk of ICU admission. sE-selectin values significantly correlated with a neutrophil count (R = 0.32 (p = 0.001)) and the number of days from the symptoms onset to hospitalization (R = 0.28 (p = 0.004)). Conclusions: sE-selectin levels are predictive of ICU admission in COVID-19 patients. Since data on the relation between sE-selectin and COVID-19 are scarce, this study aims to contribute toward the comprehension of the pathogenic aspects of COVID-19 disease, giving a possible clinical marker able to predict its severity.

Little is known regarding outcomes and optimal therapeutic regimens of infections caused by KPC-producing Klebsiella pneumoniae (KPC-Kp) resistant to ceftazidime/avibactam (CZA) and susceptible to meropenem (MEM). Although in-vitro susceptible to MEM, the possibility of developing MEM resistance overtime is a concern. We described the clinical characteristics of patients with colonization/infection due to KPC-variant with a focus on the in-vitro activity of fosfomycin (FOS)-containing combinations. Patients with colonization/infection due to KPC-variant were included. FOS susceptibility was performed by agar dilution method. Synergistic activity of FOS-based combinations was evaluated by gradient strip-agar diffusion method. The emergence of in-vitro MEM resistance was also tested. Eleven patients were included, 8 with infection [4 ventilator-associated pneumonia, 4 bloodstream infections], 3 with colonization. A previous therapy with CZA was administered to all the patients (mean cumulative duration 23 days). All subjects with infection received meropenem, in monotherapy (n=4) or with amikacin (n=2) or fosfomycin (n=2) and achieved clinical cure. A new CZA-susceptible and MEM-resistant KPC-Kp strain was subsequently isolated in 3 patients (27.3%). Meropenem/vaborbactam (MVB) showed high in-vitro activity, while FOS+MEM combination was synergistic in 40% of cases. In-vitro resistance to MEM was observed, with maintenance of CZA resistance. Detection of KPC-variant may occur within the same patient, especially if CZA has been previously administered. Although clinical success has been obtained with carbapenems, the emergence of MEM resistance is a concern. Fosfomycin plus meropenem is synergistic and may represent a valuable combination option for KPC-variant, while MVB may be considered in monotherapy. The detection of KPC-variants in an endemic setting for KPC-Kp represents a worryingly emerging condition. The optimal therapeutic approach is still unknown and the development of meropenem resistance is a concern, which may finally lead to a therapeutic failure in the clinical practice. In these cases, the addition of fosfomycin to meropenem or a more potent antibiotic such as meropenem/vaborbactam may represent valuable therapeutic options.

A case of post-neurosurgical ventriculitis caused by a KPC-producing Klebsiella pneumoniae (KPC-Kp) with a ceftazidime/avibactam-resistant, meropenem-susceptible phenotype is reported. The patient had a concomitant bloodstream infection with a wild-type KPC-Kp with a ceftazidime/avibactam-susceptible, meropenem-resistant phenotype. Prolonged treatment with intravenous fosfomycin and meropenem/vaborbactam achieved clinical success. Therapeutic drug monitoring performed during the first days of treatment showed for the first time that vaborbactam efficiently penetrates cerebrospinal fluid. In contrast, meropenem was undetectable in cerebrospinal fluid at each sampling, suggesting that additional doses of meropenem may be required to appropriately prescribe meropenem/vaborbactam for central nervous system infections. Plasma and cerebrospinal fluid levels of fosfomycin were adequate, confirming the potential of this agent possibly even in the fight against multidrug-resistant organisms. This case highlights the need for therapeutic drug monitoring as a crucial tool for optimizing treatment in complicated cases where the pharmacokinetic behaviour of antibiotics is difficult to predict.

The rise of antimicrobial resistance and the global burden of cancer demand innovative therapeutic strategies. Frog skin secretions offer a rich source of bioactive peptides, some of which exhibit remarkable dual functionality—potent antimicrobial activity coupled with selective anticancer effects. This review highlights frog skin-derived peptides that bridge the gap between antimicrobial and anticancer therapeutics, emphasizing their structural diversity, mechanisms of action, and translational potential. A comprehensive literature search was conducted to identify peptides isolated from diverse anuran species, with emphasis on studies reporting structural features, activity against Gram-positive and Gram-negative bacteria, including multidrug resistant clinical isolates, anticancer effects, and underlying molecular mechanisms of cytotoxicity. Peptides such as dermaseptins, temporins, and brevinins disrupt microbial membranes while triggering apoptosis or necrosis in cancer cells. Key physicochemical characteristics, including net positive charge, amphipathicity, and α-helical conformation, contribute to their dual functionality. Recent advances in peptide engineering and delivery have improved stability, selectivity, and therapeutic efficacy, enhancing the clinical prospects of these naturally occurring bioactive molecules. Frog skin peptides represent promising candidates for the development of next-generation antimicrobial and anticancer therapeutics.