Cefiderocol is a new molecule effective against multidrug-resistant (MDR) Gram-negative pathogens. Currently, there is limited evidence regarding the use of cefiderocol in central nervous system (CNS) infections. Data on the cerebrospinal fluid penetration rate of cefiderocol are limited and heterogeneous, and there is no consensus on the dosing scheme of cefiderocol to penetrate the blood–brain barrier. We present a case series and a literature review of CNS infections caused by MDR pathogens that were treated with cefiderocol: some of these patients were treated with different dose schemes of cefiderocol and underwent therapeutic drug monitoring both on plasma and cerebrospinal fluid (CSF). The CSF penetration rates and the clinical outcomes were evaluated.

Trichosporon spp. endocarditis is a severe and hard-to-treat infection. Immunosuppressed subjects and carriers of prosthetic valves or intracardiac devices are at risk. This article presents the case of an immunocompetent 74-year-old man affected by endocarditis of the prosthetic aortic valve. After Bentall surgery, cultures of the removed valve demonstrated Trichosporon ashaii as the etiological agent. The patient was treated with amphotericin B at first and subsequently with fluconazole. Given the fragility of the patient and the aggressiveness of the pathogen, life-long prophylactic therapy with fluconazole was prescribed. After 5 years follow-up, no drug-related toxicities were reported and the patient never showed any signs of recurrence. The review of the literature illustrates that Trichosporon spp. endocarditis may present even many years after heart surgery, and it is often associated with massive valve vegetations, severe embolic complications, and unfavorable outcome. Due to the absence of international guidelines, there is no unanimous therapeutic approach, but amphotericin B and azoles are usually prescribed. Additionally, a prompt surgical intervention seems to be of paramount importance. When dealing with a life-threatening disease, such as mycotic endocarditis of prosthetic valves, it is essential to consider and treat even rare etiological agents such as Trichosporon spp.

Central nervous system infections are among the most severe infectious conditions in the neonatal period and are still burdened by significant mortality, especially in preterm infants and those with a low birth weight or other comorbidities. In this study, we examined the role of fosfomycin-containing antibiotic regimens in neonates with central nervous system infections. We included six neonates over a period of five years: four with meningitis and two with cerebral abscesses. All patients underwent fosfomycin therapy after failing first-line antibiotic regimens. Of the six neonates, two died; two developed neurological and psychomotor deficits and two recovered uneventfully. None of the neonates experienced adverse reactions to fosfomycin, confirming the safety of the molecule in this population. In conclusion, the deep penetration in the central nervous system, the unique mechanism of action, the synergy with other antibiotic therapies, and the excellent safety profile all make fosfomycin an attractive drug for the treatment of neonatal central nervous system infections.

Background: Dalbavancin (DBV) is a long-acting lipoglycopeptide with activity against Gram-positive pathogens approved for the treatment of acute bacterial skin and skin structure infections (ABSSSI). Its pharmacological profile supports use in infections requiring prolonged therapy, yet its role in osteomyelitis without implantable devices (OM-WoID) remains off-label. This study aims to describe real-world DBV use in a large tertiary care hospital, focusing on its effectiveness in OM-WoID. Methods: This is a monocentric, retrospective analysis including all patients receiving DBV at ASST Spedali Civili di Brescia, Italy, from April 2017 to July 2023. The statistical analysis focused on patients who received DBV for either ABSSSI or OM-WoID, with the latter transitioning to DBV after traditional daily intravenous therapy. Clinical, microbiological, and treatment data were extracted from electronic records and stored in REDCap. Effectiveness was defined as infection resolution or improvement; treatment failure encompassed clinical worsening, recurrence or suppressive therapy. Predictors of failure were identified through univariate and stepwise multivariate logistic regression. Results: During the study period, 157 patients (63.0% male; mean age 62.5 ± 20 years) received at least one dose of DBV, predominantly for off-label indications (66.2%). Early discharge was the most common reason for switching to DBV (66.3%). Focusing specifically on patients treated for ABSSSI (53) and OM-WoID (43), treatment success was achieved in 81.1% of ABSSSI and 90.7% of OM-WoID cases. In the stepwise multivariate logistic regression, older age was independently associated with an increased risk of treatment failure (OR 1.07, 95% CI 1.01–1.13; p = 0.028), while the presence of multimorbidity significantly reduced the risk (OR 0.07, 95% CI 0.01–0.77; p = 0.029). Discussion: Our study offers a comprehensive real-world analysis of DBV use in both approved and off-label indications. Although current clinical experience with DBV remains limited, DBV emerges as a valuable step-down option for the management of invasive Gram-positive infections in our setting. Consistent with previous evidence, older age independently increased the risk of treatment failure, whereas multimorbidity appeared protective, likely due to selection bias and the more intensive monitoring, earlier interventions, and tailored management such patients often receive. Our results support a broader range of approved indications for DBV to allow earlier discharge and more efficient use of healthcare resources.

Background: Carbapenem-resistant Enterobacterales and difficult-to-treat resistance (DTR) Pseudomonas aeruginosa are a growing public health issue. Cefiderocol demonstrated activity against β-lactamase-producing Gram-negative bacteria (GNB). However, bone PharmacoKinetics (PK) data is lacking. Here, we report a case of post-traumatic chronic osteomyelitis caused by extensively drug-resistant (XDR) Pseudomonas aeruginosa which was successfully treated with cefiderocol. Moreover, we conducted a non-systematic review of the available literature. Case Report: We described the case of a 64-year-old man who was admitted to a traumatology ward after a work accident caused crushing of his left foot. Microbiological tests on intraoperative biopsies demonstrated XDR P. aeruginosa and K. oxytoca. Despite the administrations of different antibiotics regimens and multiple surgical revisions, the patient developed chronic osteomyelitis. To prevent amputation, cefiderocol was prescribed for six weeks, resulting in a complete clinical resolution of osteomyelitis. Review of the Literature: We performed a non-systematic review of the literature searching the public databases PubMed and Google Scholar. We identified nine case reports. In most patients (60%) the cause of osteomyelitis was post-surgical, and all the reported cases were healthcare associated. Osteomyelitis treatment required both antimicrobial therapy and surgery in all the cases described. Cefiderocol was often prescribed in association with other antibiotics (70%). Clinical cure was described in all the reported cases. Conclusions: This study highlights that cefiderocol is safe and efficacious to treat osteomyelitis caused by carbapenem-resistant GNB. However, evidence is limited to a few case reports.