Pragmatic overview on acute bacterial and fungal infections of the central nervous system: a holistic update from diagnosis to treatment.

Although progress has led to a drop in infections, meningitis still represents a threat worldwide, affecting some areas more than others. As a medical emergency, it requires prompt recognition and treatment. Moreover, diagnosis relies on invasive methods, while representing a tug-of-war with timely therapeutic interventions, since delays are burdened by mortality and life-long sequalae. While counterbalancing the overuse of antimicrobials, it is imperative to assess correct interventions in order to optimize treatments and reduce negative outcomes. Because the drop in mortality and consequences has been consistent, although not as impactful as with other vaccine-preventable diseases, the WHO has traced a roadmap detailing actions to reduce the meningitis burden by 2030. There are currently no updated guidelines, whereas novel diagnostic methods as well as pharmacological interventions are increasing, along with the shifting epidemiology. In light of the above, this paper wishes to summarize existing data and evidences and suggest potential novel solutions to a complex problem.

Cerebrospinal fluid drain infection caused by pandrug-resistant Staphylococcus epidermidis successfully treated with ceftaroline in combination with fosfomycin and vancomycin.

External ventricular drain-related cerebrospinal fluid infection represents a fearsome complication of neurosurgical interventions. Although vancomycin represents the standard of care for methicillin-resistant CoNS healthcare-associated ventriculitis, resistance phenomena have been described. We reported a case of a persistent external ventricular fluid drain infection after device removal by pandrug-resistant Staphylococcus epidermidis successfully treated with intravenous ceftaroline in combination with fosfomycin and vancomycin. No evidence regarding pandrug-resistant S. epidermidis therapy currently exists to our knowledge. In this case, the S. epidermidis phenotype emerged during the therapy course, possibly due to initial device retention, biofilm formation and the host immune impaired response. Despite being poorly studied in vivo, ceftaroline may be considered an option when other alternatives are unavailable, thanks to its described activity against CoNS in vitro. This case extends the experience with ceftaroline for central nervous system infections suggesting it could also be used in high antimicrobial resistance settings for immunocompromised people.

The Subcutaneous Administration of Beta-Lactams: A Case Report and Literary Review-To Do Small Things in a Great Way.

The subcutaneous (s.c.) route is a commonly used method for delivering various drugs, although its application in the administration of antibiotics is relatively uncommon. In this case, we report a successful treatment of nosocomial pneumonia using piperacillin/tazobactam via continuous subcutaneous administration. Furthermore, this article provides an overview of the current literature regarding the s.c. administration of beta-lactam antibiotics. Based on our analysis, we identified only 15 studies that described the s.c. use of beta-lactam antibiotics in human subjects. Among these studies, cephalosporins were the most extensively investigated antibiotic class, with 10 available studies. According to the study findings, all three antibiotic classes (cephalosporins, penicillins, and carbapenems) demonstrated a similar pharmacokinetic profile when administered via the subcutaneous route. The subcutaneous route appears to be associated with a lower peak serum concentration (Cmax) but a comparable minimum blood concentration (Cmin) and an extended half-life (t1/2) when compared to conventional routes of antibiotic administration. Further research is necessary to determine whether subcutaneously administered beta-lactam antibiotics in human subjects achieve pharmacodynamic targets and demonstrate clinical efficacy.

A 67-Year-Old Man with Chronic Lymphocytic Leukemia (CLL) on Maintenance Therapy with Ibrutinib with Persistent SARS-CoV-2 Infection Unresponsive to Antiviral Treatments.

BACKGROUND SARS-CoV-2 infection can persist in immunocompromised patients with hematological malignancies, despite antiviral treatment. This report is of a 67-year-old man with chronic lymphocytic leukemia (CLL), secondary hypogammaglobulinemia, and thrombocytopenia on maintenance therapy with ibrutinib, with persistent SARS-CoV-2 infection unresponsive to antiviral treatment, including remdesivir, nirmatrelvir/ritonavir (Paxlovid), and tixagevimab/cilgavimab (Evusheld). CASE REPORT The patient was admitted to our hospital 3 times. During his first hospitalization, he was treated with 5-day course of remdesivir and intravenous steroids; however, antigen and molecular nasopharyngeal swabs were persistently positive, and he was discharged home. Due to respiratory worsening, he was rehospitalized, and despite being treated initially with tixagevimab/cilgavimab, and subsequently with a remdesivir course of 5 days, SARS-CoV-2 tests remained persistently positive. During his third hospital stay, our patient was subjected to combined therapy with remdesivir and nirmatrelvir/ritonavir for 5 days, obtaining a significant reduction of viral load at both antigen and molecular testing. As an ultimate attempt to achieve a negative status before discharge, a 10-day course of combined remdesivir and nirmatrelvir/ritonavir was administered, with a temporary reduction of viral load, followed by a sudden increase immediately after the discontinuation of Paxlovid. Due to worsening hematological disease and bacterial over-infections, the patient gradually worsened until death. CONCLUSIONS This is an emblematic case of correlation between persistent SARS-CoV-2 infection and immunosuppression status in hematological hosts. In these patients, the viral load remains high, favoring the evolution of the virus, and the immunodeficiency makes it difficult to identify the appropriate therapeutic approach.

Difficult-to-Treat Pathogens: A Review on the Management of Multidrug-Resistant Staphylococcus epidermidis.

Multidrug-resistant Staphylococcus epidermidis (MDRSE) is responsible for difficult-to-treat infections in humans and hospital-acquired-infections. This review discusses the epidemiology, microbiology, diagnosis, and treatment of MDRSE infection and identifies knowledge gaps. By using the search term "pan resistant Staphylococcus epidermidis" OR "multi-drug resistant Staphylococcus epidermidis" OR "multidrug-resistant lineages of Staphylococcus epidermidis", a total of 64 records have been identified from various previously published studies. The proportion of methicillin resistance in S. epidermidis has been reported to be as high as 92%. Several studies across the world have aimed to detect the main phylogenetic lineages and antibiotically resistant genes through culture, mass spectrometry, and genomic analysis. Molecular biology tools are now available for the identification of S. epidermidis and its drug resistance mechanisms, especially in blood cultures. However, understanding the distinction between a simple colonization and a bloodstream infection (BSI) caused by S. epidermidis is still a challenge for clinicians. Some important parameters to keep in mind are the number of positive samples, the symptoms and signs of the patient, the comorbidities of the patient, the presence of central venous catheter (CVC) or other medical device, and the resistance phenotype of the organism. The agent of choice for empiric parenteral therapy is vancomycin. Other treatment options, depending on different clinical settings, may include teicoplanin, daptomycin, oxazolidinones, long-acting lipoglycopeptides, and ceftaroline. For patients with S. epidermidis infections associated with the presence of an indwelling device, assessment regarding whether the device warrants removal is an important component of management. This study provides an overview of the MDRSE infection. Further studies are needed to explore and establish the most correct form of management of this infection.

Safety and Efficacy of a Single Procedure of Extraction and Reimplantation of Infected Cardiovascular Implantable Electronic Device (CIED) in Comparison with Deferral Timing: An Observational Retrospective Multicentric Study.

(1) Background: Infections are among the most frequent and life-threatening complications of cardiovascular implantable electronic device (CIED) implantation. The aim of this study is to compare the outcome and safety of a single-procedure device extraction and contralateral implantation versus the standard-of-care (SoC) two-stage replacement for infected CIEDs. (2) Methods: We retrospectively included 66 patients with CIED infections who were treated at two Italian hospitals. Of the 66 patients enrolled in the study, 27 underwent a single procedure, whereas 39 received SoC treatment. All patients were followed up for 12 months after the procedure. (3) Results: Considering those lost to follow-up, there were no differences in the mortality rates between the two cohorts, with survival rates of 81.5% in the single-procedure group and 84.6% in the SoC group (p = 0.075). (4) Conclusions: Single-procedure reimplantation associated with an active antibiofilm therapy may be a feasible and effective therapeutic option in CIED-dependent and frail patients. Further studies are warranted to define the best treatment regimen and strategies to select patients suitable for the single-procedure reimplantation.