Carbapenemase-producing Enterobacterales (CPE) represent an important threat to global health, resulting in an urgent issue in clinical settings. CPE often exhibit a multidrug-resistant (MDR) phenotype, thus reducing the antimicrobial armamentarium, with few antibiotics retaining residual antimicrobial activity against these pathogens. Carbapenemases are divided into three classes (A, B, and D) according to the Ambler classification system. Among these, KPC (class A), NDM, VIM, IMP (class B), and OXA-48-like (class D) represent the most important carbapenemases in terms of diffusion and clinical impact. CPE diffusion has been observed worldwide, with current endemicity in multiple territories around the world. In this context, the clonal spread and plasmid-mediated transmission of carbapenemases have contributed to the global spread of CPE worldwide and to the diffusion of carbapenemases among different Enterobacterales species. In recent years, novel molecules showing excellent in vitro and in vivo activity have been developed against CPE. However, the recent emergence of novel traits of resistance to these molecules has already been reported in several cases, mitigating the initial promising results. This review aims to provide an updated description of the major classes of carbapenemases, their global distribution, and future perspectives to limit the diffusion of CPEs.

The oral microbiota can be influenced by multiple factors, but only a few studies have focused on the role of glycemic control in determining early alterations of oral microbiota and their association with pathogenesis of both periodontitis and caries. The aim of this study is to evaluate the interplay between bacteria composition, oral hygiene, and glycemic control in a cohort of children with T1D. A total of 89 T1D children were enrolled (62% males, mean age: 12.6 ± 2.2 years). Physical and clinical characteristics, glucometabolic parameters, insulin treatment, and oral hygiene habits data were collected. Microbiological analysis was performed from saliva samples. A high prevalence of cariogenic and periodontopathogens bacteria in our cohort was detected. In particular, in all subjects Actinomyces spp., Aggregatibacter actinomycetemcomitans, Prevotella intermedia, and Lactobacillus spp. were isolated. S. mutans was found in about half of the analyzed sample (49.4%), in particular in patients with imbalance values of glycemic control. Moreover, a higher presence of both S. mutans and Veillonella spp. was detected in subjects with poorer glycemic control, in terms of HbA1c, %TIR and %TAR, even adjusting for age, sex, and hygiene habits as covariates. Virtuous oral hygiene habits, such as frequency of toothbrush changes and professional oral hygiene, negatively correlated with the simultaneous presence of Tannerella forsythia, Treponema denticola, and Porphyromonas gingivalis, red complex bacteria. Our study shows it is crucial to pay attention to glycemic control and regular oral hygiene to prevent the establishment of an oral microbiota predisposing to dental and periodontal pathology in subjects with T1D since childhood.

In recent years, novel antimicrobials have been developed to counter the emergence of antimicrobial resistance and provide effective therapeutic options against multidrug-resistant (MDR) Gram-negative bacilli (GNB). Cefiderocol, a siderophore cephalosporin, represents a novel valuable antimicrobial drug for the treatment of infections caused by MDR-GNB. The mechanism of cefiderocol to penetrate through the outer membrane of bacterial cells, termed “Trojan horse”, makes this antimicrobial drug unique and immune to the various resistance strategies adopted by GNB. Its broad spectrum of action, potent antibacterial activity, pharmacokinetics properties, safety, and tolerability make cefiderocol a key drug for the treatment of infections due to MDR strains. Although this novel antimicrobial molecule contributed to revolutionizing the therapeutic armamentarium against MDR-GNB, the recent emergence of cefiderocol-resistant strains has redefined its role in clinical practice and required new strategies to preserve its antibacterial activity. In this review, we provide an updated discussion regarding the mechanism of action, emerging mechanisms of resistance, pharmacokinetic/pharmacodynamic (PK/PD) properties, and efficacy data of cefiderocol against the major Gram-negative bacteria and future prospects.

The present study investigated the compounds present in the low molecular mass fraction of Lentinus edodes mushroom (shiitake) extract and their anti-virulence activity against oral pathogens (reference and clinical Streptococcus mutans, Actinomyces naeslundii, and Prevotella intermedia strains). Oxalic, succinic, and quinic acids, and adenine, inosine, and uridine were identified by HPLC-DAD-ESI-MS/MS. Their anti-biofilm production and preformed biofilm disaggregation activities were studied using commercial standard compounds at different concentrations. As regards S. mutans, the highest activity was shown by adenine at 5 mg mL⁻¹ both in the biofilm inhibition (BI 50%) and biofilm disaggregation tests (BD 20%). Considering A. naeslundii, BI values close to 80% were registered for oxalic acid at 1 mg mL⁻¹ and 2 mg mL⁻¹ and BD 50% for quinic acid at 3 mg mL⁻¹. A weaker activity was found against P. intermedia. Furthermore, different mixtures of the commercial standards were tested showing that the activity of a compound can be strongly and sometimes negatively affected by the presence of the other compounds.

This observational study aimed to: (i) assess the presence of periodontal disease among patients requiring aortic valve replacement; (ii) investigate the presence of oral pathogens in aortic valve specimens and compare them with the microorganisms detected in the oral cavity. Twenty-six patients (15 men and 11 women) were scheduled to be visited the day before the cardiac surgery: periodontal conditions were accurately registered through clinical and radiographic examinations; dental plaque or salivary samples were collected. Valve specimens were collected during surgical aortic valve replacement and analyzed for pathogens detection through microbiological 16SrRna gene sequencing. Bacteria found in plaque samples and valve specimens were assessed according to oral and periodontal conditions. A qualitative comparison between oral and cardiac profiles of the microorganisms detected was performed. The overall number of patients examined for soft tissues conditions was 19, as 7 patients were edentulous. Twelve and three individuals, respectively, presented moderate and severe periodontitis. Nine valves were found to be positive for the presence of oral and periodontopathic bacterial DNA. The microbial species found in valve samples of patients with periodontitis suggest that the presence of these microorganisms in valvular tissue seems to be not coincidental.

In the lungs of patients with cystic fibrosis (CF), the main pathogen Pseudomonas aeruginosa is often co-isolated with other microbes, likely engaging in inter-species interactions. In the case of chronic co-infections, this cohabitation can last for a long time and evolve over time, potentially contributing to the clinical outcome. Interactions involving the emerging pathogens Achromobacter spp. have only rarely been studied, reporting inhibition of P. aeruginosa biofilm formation. To evaluate the possible evolution of such interplay, we assessed the ability of Achromobacter spp. isolates to affect the biofilm formation of co-isolated P. aeruginosa strains during long-term chronic co-infections. We observed both competition and cohabitation. An Achromobacter sp. isolate secreted exoproducts interfering with the adhesion ability of a co-isolated P. aeruginosa strain and affected its biofilm formation. Conversely, a clonal Achromobacter sp. strain later isolated from the same patient, as well as two longitudinal strains from another patient, did not show similar competitive behavior against its P. aeruginosa co-isolates. Genetic variants supporting the higher virulence of the competitive Achromobacter sp. isolate were found in its genome. Our results confirm that both inter-species competition and cohabitation are represented during chronic co-infections in CF airways, and evolution of these interplays can happen even at the late stages of chronic infection.