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West Nile Virus (WNV) poses a significant global public health threat as a mosquito-borne pathogen. While laboratory mouse models have historically played a crucial role in understanding virus biology, recent research has focused on utilizing immunocompromised models to study arboviruses like dengue and Zika viruses, particularly their interactions with Aedes aegypti mosquitoes. However, there has been a shortage of suitable mouse models for investigating WNV and St. Louis encephalitis virus interactions with their primary vectors, Culex spp. mosquitoes. Here, we establish the AG129 mouse (IFN α/β/γ R−/−) as an effective vertebrate model for examining mosquito–WNV interactions. Following intraperitoneal injection, AG129 mice exhibited transient viremia lasting several days, peaking on the second or third day post-infection, which is sufficient to infect Culex quinquefasciatus mosquitoes during a blood meal. We also observed WNV replication in the midgut and dissemination to other tissues, including the fat body, in infected mosquitoes. Notably, infectious virions were present in the saliva of a viremic AG129 mouse 16 days post-exposure, indicating successful transmission capacity. These findings highlight the utility of AG129 mice for studying vector competence and WNV–mosquito interactions.

The incidence of chikungunya has dramatically surged worldwide in recent decades, imposing an expanding burden on public health. In recent years, South America, particularly Brazil, has experienced outbreaks that have ravaged populations following the rapid dissemination of the chikungunya virus (CHIKV), which was first detected in 2014. The primary vector for CHIKV transmission is the urban mosquito species Aedes aegypti, which is highly prevalent throughout Brazil. However, the impact of the locally circulating CHIKV genotypes and specific combinations of local mosquito populations on vector competence remains unexplored. Here, we experimentally analyzed and compared the infectivity and transmissibility of the CHIKV-ECSA lineage recently isolated in Brazil among four Ae. aegypti populations collected from different regions of the country. When exposed to CHIKV-infected AG129 mice for blood feeding, all the mosquito populations displayed high infection rates and dissemination efficiency. Furthermore, we observed that all the populations were highly efficient in transmitting CHIKV to a vertebrate host (naïve AG129 mice) as early as eight days post-infection. These results demonstrate the high capacity of Brazilian Ae. aegypti populations to transmit the locally circulating CHIKV-ECSA lineage. This observation could help to explain the high prevalence of the CHIKV-ECSA lineage over the Asian lineage, which was also detected in Brazil in 2014. However, further studies comparing both lineages are necessary to gain a better understanding of the vector’s importance in the epidemiology of CHIKV in the Americas.

Respiratory syncytial virus (RSV) is increasingly recognized as being implicated in acute illness in older adults, with a significant weight in hospitalizations for respiratory illness and death. By means of a best-evidence review, this paper aims to investigate whether RSV can be considered a forgotten pathogen in older patients, looking at trends in the literature volume and exploring possible epidemiological and clinical features underlying the focus given to it. We then present an assessment of its disease burden and present and future strategies for its reduction, particularly in light of the recent availability of new vaccines.

(1) Background: The widespread use of MALDI-TOF coupled to mass spectrometry has improved diagnostic accuracy by identifying uncommon bacteria. Among Enterobacterales, Pantoea species have been seen to be implicated in several human infections, but their clinical and microbiological framework is currently based on a few anecdotal reports. (2) Methods: We conducted this five-year (2018–2023) single-center study aimed at investigating the prevalence and clinical and microbiological findings of Pantoea species bloodstream infections. (3) Results: Among the 4996 bloodstream infection Gram-negative isolates collected during the study period, Pantoea species accounted for 0.4% (n = 19) of isolates from 19 different patients, 5 of them being pediatric cases. Among Pantoea species isolates, P. agglomerans was the most frequently detected (45%; n = 9) followed by P. eucrina (30%; n = 6) and P. septica (15%; n = 3). Malignancy (35.7%) in adults and malignancy (40%) and cerebrovascular disease following meconium aspiration (40%) in pediatric patients as comorbidities and shivering and/or fever following parenteral infusion (36.8%) as a symptom/sign of Pantoea species bloodstream infection onset were the most frequently observed clinical features. Among adults, primary bloodstream infection was the most frequent (50%), whereas among pediatric patients, the most commonly identified sources of infection were catheter-related (40%) and the respiratory tract (40%). Overall, Pantoea species bloodstream infection isolates displayed high susceptibility to all the antibiotics except for ampicillin (63.2%), fosfomycin (73.7%), and piperacillin/tazobactam (84.2%). Targeted antibiotic treatment was prescribed as monotherapy for adults (71.4%) and combination therapy for pediatric patients (60%). The most prescribed antibiotic regimens were piperacillin/tazobactam (21.4%) in adults and meropenem- (40%) and aminoglycoside-containing (40%) antibiotics in pediatric patients. The overall 28-day all-cause mortality rate was 5.3% (n = 1). (4) Conclusions: The prevalence and 28-day mortality rate of Pantoea species bloodstream infections were low. The prescription of targeted therapy including broad-spectrum antibiotics could indicate an underestimation of the specific involvement of the Pantoea species in the onset of the disease, warranting further studies defining their pathogenic potential.

Background: The relationship between superinfection by multidrug-resistant Gram-negative bacteria and mortality among SARS-CoV-2 hospitalized patients is still unclear. Carbapenem-resistant Acinetobacter baumannii and carbapenemase-producing Enterobacterales are among the most frequently isolated species when it comes to hospital-acquired superinfections among SARS-CoV-2 patients. Methods: Herein, a retrospective study was carried out using data from adult patients hospitalized for COVID-19. The interaction between in-hospital mortality and rectal carriage and superinfection by carbapenemase-producing Enterobacterales and/or carbapenem-resistant Acinetobacter baumannii was assessed. Results: The incidence of KPC-producing Klebsiella pneumoniae and/or carbapenem-resistant Acinetobacter baumannii rectal carriage was 30%. Bloodstream infection and/or pneumonia due to KPC-producing Klebsiella pneumoniae and/or carbapenem-resistant Acinetobacter baumannii occurred in 20% of patients. A higher Charlson comorbidity index (OR 1.41, 95% CI 1.24–1.59), being submitted to invasive mechanical ventilation/ECMO ≥ 96 h (OR 6.34, 95% CI 3.18–12.62), being treated with systemic corticosteroids (OR 4.67, 95% CI 2.43–9.05) and having lymphopenia at the time of admission (OR 0.54, 95% CI 0.40–0.72) were the features most strongly associated with in-hospital mortality. Conclusions: Although KPC-producing Klebsiella pneumoniae and/or carbapenem-resistant Acinetobacter baumannii rectal carriage, and/or bloodstream infection/pneumonia were diagnosed in a remarkable percentage of COVID-19 patients, their impact on in-hospital mortality was not significant. Further studies are needed to assess the burden of antimicrobial resistance as a legacy of COVID-19 in order to identify future prevention opportunities.

There is a growing interest in tissue engineering, in which biomaterials play a pivotal role in promoting bone regeneration. Furthermore, smart functionalization can provide biomaterials with the additional role of preventing orthopedic infections. Due to the growing microbial resistance to antimicrobials used to treat those infections, metal ions, such as silver, thanks to their known wide range of bactericidal properties, are believed to be promising additives in developing antibacterial biomaterials. In this work, novel poly(ε-caprolactone) (PCL)-based 3D scaffolds have been designed and developed, where the polymer matrix was modified with both silver (Ag), to supply antibacterial behavior, and calcium phosphates (biphasic calcium phosphate, BCP) particles to impart bioactive/bioresorbable properties. The microstructural analysis showed that constructs were characterized by square-shaped macropores, in line with the morphology and size of the templating salts used as pore formers. Degradation tests demonstrated the important role of calcium phosphates in improving PCL hydrophilicity, leading to a higher degradation degree for BCP/PCL composites compared to the neat polymer after 18 days of soaking. The appearance of an inhibition halo around the silver-functionalized PCL scaffolds for assayed microorganisms and a significant (p < 0.05) decrease in both adherent and planktonic bacteria demonstrate the Ag+ release from the 3D constructs. Furthermore, the PCL scaffolds enriched with the lowest silver percentages did not hamper the viability and proliferation of Saos-2 cells. A synergic combination of antimicrobial, osteoproliferative and biodegradable features provided to 3D scaffolds the required potential for bone tissue engineering, beside anti-microbial properties for reduction in prosthetic joints infections.

Cefiderocol susceptibility testing represents a major challenge for clinical microbiology. Although disc diffusion showed robustness to test cefiderocol susceptibility, large areas of technical uncertainty (ATU) are reported by current EUCAST breakpoints. Herein, we evaluated the in vitro activity of cefiderocol on a collection of 286 difficult-to-treat Gram-negative isolates using disc diffusion and ComASP® cefiderocol microdilution panel. Broth microdilution (BMD) in iron-depleted Mueller–Hinton broth was used as reference method. Following the EUCAST guidelines, disc diffusion allowed to determine cefiderocol susceptibility (susceptible or resistant) in 78.6%, 88.1%, 85.4% and 100% of Enterobacterales, P. aeruginosa, A. baumannii and S. maltophilia isolates tested, respectively. ComASP® cefiderocol panel showed 94% and 84% of overall categorical agreement and essential agreement. Only one very major error and two major errors were observed, for MIC values nearly close to the resistance breakpoint (2 mg/L). Overall, 20.5% of the carbapenemase-producing Enterobacterales that achieved ATU results by the disc diffusion method tested resistant by both ComASP® panel and reference BMD. Conversely, all VIM-producing P. aeruginosa showed MIC values in the susceptible range (≤2 mg/L). Lastly, only six out of seven (85.7%) A. baumannii isolates showing inhibition zones ® panel and the reference BMD suggesting that inhibition zone ® cefiderocol microdilution panel could be a viable solution to overcome the challenge of cefiderocol susceptibility testing in routine microbiology laboratories.

Introduction: Surveillance of Candida species isolates from blood cultures (BCs) in Europe is considered fragmented, unable to allow the definition of targets of antifungal stewardship recommendations especially during the SARS-CoV-2 pandemic. Methods: We performed a multicentric retrospective study including all consecutive BC Candida isolates from six Southern European tertiary hospitals (1st January 2020 to 31st December 2021). Etiology, antifungal susceptibility patterns, and clinical setting were analyzed and compared. Results: C. albicans was the dominant species (45.1%), while C. auris was undetected. Candida species positive BC events increased significantly in COVID-19 ICUs in 2021 but decreased in other ICUs. Resistance to azole increased significantly and remained very high in C. albicans (fluconazole from 0.7% to 4.5%, p = 0.03) and C. parapsilosis complex (fluconazole up to 24.5% and voriconazole up to 8.9%), respectively. Resistance to caspofungin was remarkable in C. tropicalis (10%) and C. krusei (20%), while resistance to at least one echinocandin increased in 2021, especially in C. parapsilosis complex (from 0.8% to 5.1%, p = 0.05). Although no significant differences were observed over the study period, fluconazole and echinocandin resistance increased in COVID-19 ICUs by up to 14% and 5.8%, respectively, but remained undetected in non-intensive COVID-19 wards. Conclusions: Antifungal stewardship activities aimed at monitoring resistance to echinocandin in C. tropicalis and C. krusei, and against the spread of fluconazole resistant C. parapsilosis complex isolates are highly desirable. In COVID-19 patients, antifungal resistance was mostly present when the illness had a critical course.

Rapid detection of extended-spectrum-β-lactamase (ESBL) is of paramount importance to accelerate clinical decision-making, optimize antibiotic treatment, and implement adequate infection control measures. This study was aimed at assessing the impact of direct detection of CTX-M ESBL-producers on antimicrobial management of Escherichia coli bloodstream infections over a 2-year period. This study included all E. coli bloodstream infection (BSI) events that were serially processed through a rapid workflow with communication to the clinicians of direct detection of CTX-M ESBL-producers and conventional culture-based workflow. Antimicrobial management was retrospectively analyzed to assess the contribution of the rapid test result. A total of 199 E. coli BSI events with a report of direct detection of CTX-M ESBL production results were included. Of these, 33.7% (n = 67) and 66.3% (n = 132) were reported as positive and negative CTX-M producers, respectively. Detection of CTX-M positive results induced more antibiotic therapy modifications (mainly towards carbapenem-containing regimens, p < 0.01), and antimicrobial susceptibility testing results of CTX-M ESBL-producing E. coli isolates induced more antibiotic escalations towards carbapenem-containing regimens (p < 0.01). Direct detection of CTX-M ESBL-producing E. coli resulted in a remarkable rate of antibiotic optimizations on the same day of blood culture processing. Observing antibiotic management following the availability of antimicrobial susceptibility testing results, additional early optimizations in escalation could probably have been made if the rapid test data had been used. Detection of CTX-M negative results resulted in few therapeutic changes, which could have probably been higher, integrating epidemiological and clinical data.

Polymorphonuclear leukocytes (PMNs) are the most important cell type involved in the early nonspecific host response to bacterial pathogens. Staphylococcus aureus has evolved mechanisms to evade immune responses that contribute to its persistence in PMNs, and acquired resistance to several antimicrobials. Additionally, methicillin-resistant S. aureus (MRSA) is one of the most common causes of acute bacterial skin and skin-structure infections (ABSSSIs). Dalbavancin (DBV), a lipoglycopeptide, is indicated for the treatment of ABSSSIs, and has a broad spectrum of action against most microorganisms. Here, we sought to determine the effect of DBV on the neutrophil killing of MRSA and its potential immunomodulating activity. Our results revealed that DBV boosts MRSA killing by acting on both bacteria and PMNs. DBV pre-treatment of PMNs did not change the respiratory burst or degranulation, while an increased trend in neutrophil extracellular traps-associated elastase and in the production of TNFα and CXCL8 was revealed. In parallel, DBV caused a delay in the apoptosis of MRSA-infected neutrophils. In conclusion, we demonstrated a cooperative effect between the antimicrobial properties of PMNs and DBV, thus owing to their immunomodulatory activity. In the choice of the treatment management of serious S. aureus infections, DBV should be considered as an outstanding option since it reinforces PMNs pathogen clearance capability by exerting its effect directly, not only on MRSA but also on neutrophils.

ABSTRACT Positive and negative ions (PAIs and NAIs, respectively) generated by air ionizers curb indoor spread of airborne pathogens through cellular oxidative damage. Thus, here, we asked whether ion exposure of Staphylococcus aureus and Escherichia coli bacteria—either plated on agar or trapped in air filters—would affect their viability and whether this effect would be influenced by variations in bacterial type and load, action area, distance from the ion generator, exposure time, or filter type. We selected these two vegetative bacterium species because, besides being representative of Gram-positive and Gram-negative strains, respectively, they are widely recognized as the two most common airborne pathogens. We observed a robust ion inhibitory effect on the viability of free bacteria regardless of the experimental condition employed. Specifically, 12-h ion exposure of plated S. aureus and E. coli, at either 5 cm or 10 cm from the ion source, reduced bacterial viability by ∼95% and 70%, respectively. Furthermore, 3-h ion exposure was sufficient to reduce the viability of both bacterial species trapped in filters. Our results showing a strong antibacterial activity of PAI and NAI under all experimental conditions tested further support the use of air ionizers for preventing and/or containing airborne infection in domestic and nondomestic settings. IMPORTANCE Indoor air is a well-established vehicle for direct and indirect spread of a wide variety of human pathogens—as bioaerosols are composed of bacteria, viruses, fungi, and other types of organisms—that may trigger some pathologies. Plasmacluster ionizers are known for their ability to generate positively or negatively charged air ions (PAIs and NAIs, respectively) that can kill/inactivate indoor airborne pathogens, through oxidative stress-induced damage, in various environments. Given these premises, the aim of this study was to evaluate the viability of Gram-positive and Gram-negative bacteria exposed to PAI and NAI under different experimental variables such as bacterial type and load, action area, distance from the ion generator, ion exposure time, and filter type. Altogether, our findings, demonstrating a remarkable PAI and NAI antibacterial activity, stress the importance of using air ionizers to prevent indoor airborne infection.

The rapid identification of pathogens of bloodstream infections (BSIs) and the detection of antibiotic resistance markers are critically important for optimizing antibiotic therapy and infection control. The purpose of this study was to evaluate two approaches based on MALDI-TOF MS technology for direct identification of Gram-negative bacteria and automatic detection of Klebsiella pneumoniae carbapenemase (KPC) producers using the Bruker MBT Subtyping IVD Module in a large routine laboratory over a three-year period. MALDI-TOF MS analysis was performed directly from blood culture (BC) bottles following bacterial pellet recovery by Rapid MBT Sepsityper® Kit and on blood agar 4-h subcultures. Automated detection of blaKPC-carrying pKpQIL-plasmid by Bruker MBT Subtyping Module was evaluated in BCs tested positive to K. pneumoniae or E. coli. The results were compared with those obtained with conventional reference methods. Among the 2858 (93.4%) monomicrobial BCs, the overall species identification rates of the Rapid Sepsityper and the short-term subculture protocols were 84.5% (n = 2416) and 90.8% (n = 2595), respectively (p < 0.01). Excellent specificity for KPC-producers identification were observed for both MALDI-TOF MS protocols. The pKpQIL plasmid-related peak was detected in overall 91 of the 120 (75.8%) KPC-producing isolates. Notably, 14 out of the 17 (82.3%) K. pneumoniae isolates carrying blaKPC variants associated with ceftazidime/avibactam resistance and tested negative by the immunocromatography assay, were correctly identified as KPC-producers by MALDI-TOF MS. In conclusion, combination of both Rapid Sepsityper and short-term subculture protocols may represent an optimal solution to promptly identify more than 95% of Gram-negative bacteria causing BSIs. MALDI Biotyper® platform enabled a reliable and robust automated detection of KPC producers in parallel with species identification. However, integration of molecular or immunocromatographic assays are recommended according to local epidemiology.

Infections triggered by filamentous fungi placed in the order Mucorales, phylum Zygomycota, can cause serious harm to immunocompromised patients. Since there is lack of a standardized PCR (polymerase chain reaction) assay for early diagnosis of this fungal infection, this work was aimed to develop a new PCR assay able to detect the presence of Mucorales genera in clinical specimens. Here, we describe a novel diagnostic TaqMan MGB probe assay for precise and rapid detection of the most common clinical species of Mucorales. Zygomycete-specific oligonucleotides were designed to specifically amplify and bind highly conserved sequences of fungal 28S rRNA gene. Additionally, we succeeded in differentiating Mucorales species (i.e., Rhizopus, Lichtheimia, Mucor, and Rhizomucor) in artificially infected serum samples, suggesting that the quantitative capability of this real-time PCR assay could potentially optimize the diagnosis of mucormycosis.

The role of β-lactamases in reduced susceptibility or resistance to cefiderocol has been supported by recent reports. The purpose of this study was to investigate the in vitro impact of clinically available β-lactamase inhibitors on cefiderocol activity against characterized carbapenemase-producing Gram-negative isolates. A collection of 39 well-characterized Gram-negative isolates obtained from various clinical sources and countries were included. Cefiderocol antimicrobial susceptibility was evaluated via reference broth microdilution. The chequerboard microdilution method and time–kill assays were used to determine the synergy of tazobactam, avibactam, vaborbactam and relebactam in combination with cefiderocol. MICs of cefiderocol presented a 4- to 256-fold reduction against Klebsiella pneumoniae carbapenemase (KPC)-producing Gram-negative isolates (predominantly K. pneumoniae) when avibactam, vaborbactam and relebactam were combined individually. Notably, the KPC-inhibitors led to a 4- to 32-fold reduction in cefiderocol MICs in the four cefiderocol-resistant KPC-producing K. pneumoniae isolates, showing restoration of cefiderocol susceptibility (MIC ≤ 2 mg/L) in ten out of twelve cases. Tazobactam led to a 4- to 64-fold decrease in cefiderocol MICs only in K. pneumoniae strains harbouring blaKPC-41, blaKPC-31, blaKPC-53 and blaKPC-66. The synergistic effect of all serine-β-lactamase inhibitors on cefiderocol activity was also shown in OXA-48-like-producing Enterobacterales strains. Conversely, a combination of β-lactamases inhibitors with cefiderocol was not synergistic with all OXA-23-like-producing strains and most metallo-β-lactamases producers. In conclusion, the addition of clinically available serine β-lactamase inhibitors to cefiderocol might represent an important development in the formulation to increase its spectrum and therapeutic efficacy, and to limit in vivo resistance emergence.

The aim of the study was to evaluate the EUCAST RAST method by extending analysis to 16–20 h reading time and performance with new β-lactam/β-lactamase inhibitor combinations. A total of 676 positive blood cultures (BCs) were enrolled. Results at 4 h, 6 h, 8 h and 16–20 h were interpreted according to bacterial species using EUCAST RAST breakpoints (version 5.1). For species for which no breakpoints were available, tentative breakpoints were used. Categorical agreement with the Microscan microdilution system was analysed. Among the 676 BCs enrolled, 641 were monomicrobial and were included in the analysis. Categorical agreement ranged from 98.9% at 4 h to 99.4% at 16–20 h. The rates of very major errors were 3.3%, 3.7% and 3.4% at 4 h, 6 h and 8 h, respectively, and decreased to 1% at 16–20 h (p < 0.001). The number of major errors was low for each reading time (0.2% and 0.4% at 4 h and 6 h, respectively, and 0.3% at both 8 h and 16–20 h). The proportions of results in the area of technical uncertainty were 9.9%, 5.9%, 5% and 5.2% for readings at 4 h, 6 h, 8 h and 16–20 h, respectively. Tentative breakpoints proposed for Enterobacterales other than E.coli/K.pneumoniae and coagulase-negative staphylococci showed overall performances comparable to those observed for E. coli/K. pneumoniae and S. aureus. In conclusion, EUCAST RAST has been shown to be reliable to determine microbial susceptibility to main antimicrobials, including ceftazidime/avibactam and ceftolozane/tazobactam. A poorer performance was observed for certain species/antimicrobial agent combinations. The better performance observed at 16–20 h compared to the early readings may confer to the method greater potential for antimicrobial de-escalation interventions.

Biomedical implants, an essential part of the medical treatments, still suffer from bacterial infections that hamper patients’ recovery and lives. Antibiotics are widely used to cure those infections but brought antibiotic resistance. Essential oils (EOs) demonstrate excellent antimicrobial activity and low resistance development risk. However, EO application in medicine is still quite scarce and almost no research work considers its use in combination with bioresorbable biomaterials, such as the poly(ε-caprolactone) (PCL) polymer. This work aimed to combine the antibacterial properties of EOs and their components, particularly eugenol and cinnamon oil, against Staphylococcus aureus, S. epidermidis and Escherichia coli, with those of PCL for medical applications in which good tissue regeneration and antimicrobial effects are required. The PCL porous scaffolds, added with increasing (from 30% to 50%) concentrations of eugenol and cinnamon oil, were characterized by square-shaped macropores. Saos-2 cells’ cell viability/proliferation was hampered by 40 and 50% EO-enriched PCL, whereas no cytotoxic effect was recorded for both 30% EO-added PCL and pure-PCL. The antibacterial tests revealed the presence of a small inhibition halo around the 30% eugenol and cinnamon oil-functionalized PCL scaffolds only for staphylococci, whereas a significant decrease on both adherent and planktonic bacteria was recorded for all the three microorganisms, thus proving that, even if the EOs are only in part released by the EO-added PCL scaffolds, an anti-adhesive feature is anyway achieved. The scaffold will have the ability to support new tissue formation and simultaneously will be able to prevent post-surgical infection. This research shows the great potential in the use of EOs or their single components, at low concentrations, for biomaterial functionalization with enhanced anti-bacterial and biointegration properties.

A significant challenge in orthopedics is the design of biomaterial devices that are able to perform biological functions by substituting or repairing various tissues and controlling bone repair when required. This review presents an overview of the current state of our recent research into biomaterial modifications to reduce bacterial adhesive ability, compared with previous reviews and excellent research papers, but it is not intended to be exhaustive. In particular, we investigated biomaterials for replacement, such as metallic materials (titanium and titanium alloys) and polymers (ultra-high-molecular-weight polyethylene), and biomaterials for regeneration, such as poly(ε-caprolactone) and calcium phosphates as composites. Biomaterials have been designed, developed, and characterized to define surface/bulk features; they have also been subjected to bacterial adhesion assays to verify their potential capability to counteract infections. The addition of metal ions (e.g., silver), natural antimicrobial compounds (e.g., essential oils), or antioxidant agents (e.g., vitamin E) to different biomaterials conferred strong antibacterial properties and anti-adhesive features, improving their capability to counteract prosthetic joint infections and biofilm formation, which are important issues in orthopedic surgery. The complexity of biological materials is still far from being reached by materials science through the development of sophisticated biomaterials. However, close interdisciplinary work by materials scientists, engineers, microbiologists, chemists, physicists, and orthopedic surgeons is indeed necessary to modify the structures of biomaterials in order to achieve implant integration and tissue regeneration while avoiding microbial contamination.

In this study, we designed and developed novel poly(ε-caprolactone) (PCL)-based biomaterials, for use as bone scaffolds, through modification with both biphasic calcium phosphate (BCP), to impart bioactive/bioresorbable properties, and with silver nitrate, to provide antibacterial protection against Staphylococcus aureus, a microorganism involved in prosthetic joint infections (PJIs). Field emission scanning electron microscopy (FESEM) showed that the samples were characterized by square-shaped macropores, and energy dispersive X-ray spectroscopy analysis confirmed the presence of PCL and BCP phases, while inductively coupled plasma–mass spectrometry (ICP–MS) established the release of Ag+ in the medium (~0.15–0.8 wt% of initial Ag content). Adhesion assays revealed a significant (p < 0.0001) reduction in both adherent and planktonic staphylococci on the Ag-functionalized biomaterials, and the presence of an inhibition halo confirmed Ag release from enriched samples. To assess the potential outcome in promoting bone integration, preliminary tests on sarcoma osteogenic-2 (Saos-2) cells indicated PCL and BCP/PCL biocompatibility, but a reduction in viability was observed for Ag-added biomaterials. Due to their combined biodegrading and antimicrobial properties, the silver-enriched BCP/PCL-based scaffolds showed good potential for engineering of bone tissue and for reducing PJIs as a microbial anti-adhesive tool used in the delivery of targeted antimicrobial molecules, even if the amount of silver needs to be tuned to improve osteointegration.