Towards the development of an epitope-focused vaccine for SARS-CoV-2.

The rapid spread of COVID-19 on all continents and the mortality induced by SARS-CoV-2 virus, the cause of the pandemic coronavirus disease 2019 (COVID-19) has motivated an unprecedented effort for vaccine development. Inactivated viruses as well as vaccines focused on the partial or total sequence of the Spike protein using different novel platforms such us RNA, DNA, proteins, and non-replicating viral vectors have been developed. The high global need for vaccines, now and in the future, and the emergence of new variants of concern still requires development of accessible vaccines that can be adapted according to the most prevalent variants in the respective regions. Here, we describe the immunogenic properties of a group of theoretically predicted RBD peptides to be used as the first step towards the development of an effective, safe and low-cost epitope-focused vaccine. One of the tested peptides named P5, proved to be safe and immunogenic. Subcutaneous administration of the peptide, formulated with alumina, induced high levels of specific IgG antibodies in mice and hamsters, as well as an increase of IFN-γ expression by CD8+ T cells in C57 and BALB/c mice upon in vitro stimulation with P5. Neutralizing titers of anti-P5 antibodies, however, were disappointingly low, a deficiency that we will attempt to resolve by the inclusion of additional immunogenic epitopes to P5. The safety and immunogenicity data reported in this study support the use of this peptide as a starting point for the design of an epitope restricted vaccine.

Multidrug-resistant Klebsiella oxytoca ventriculitis, successfully treated with intraventricular tigecycline: A case report.

A 38-year-old male presented to the hospital with headache, fever, and meningeal signs. He had undergone a surgical review of a ventriculoperitoneal shunt system one month earlier. A head computed tomography scan showed hydrocephalus. His medical history included a human immunodeficiency virus infection identified four years before and resolved cryptococcal meningitis, which had necessitated the implantation of the shunt system. Ventricular cerebrospinal fluid (CSF) was obtained, which showed inflammation and, in culture, grew a Gram-negative bacillus identified as multidrug-resistant Klebsiella oxytoca. The shunt was removed and a ventricular drain was installed. Treatment with meropenem and amikacin was established without a response; the CSF white blood cell count continued to increase, with cultures remaining positive. The patient's clinical condition deteriorated to stupor. With informed consent, intraventricular (ITV) treatment with tigecycline was initiated at a dose of 5 mg every 24 h and, three days later, the CSF cultures were negativized. Tigecycline levels in the CSF were quantified by liquid chromatography with ultraviolet detection and showed peak concentrations achieved at two hours after the dose of between 178 and 310 µg/mL. After 11 days of treatment with ITV tigecycline and eight negative CSF cultures, a new CSF shunt was installed. During follow-up review 10 months later, the patient reported he was working. The dose of tigecycline used in this study produced levels 15 to 20 times the minimum inhibitory concentration of the bacteria for up to six hours with adequate tolerance.

Clinical and electroencephalographic assessment of cefepime during treatment of nosocomial infections in neurological patients.

OBJECTIVE: Cefepime neurotoxicity usually occurs in patients with renal impairment. The aim of this study was to evaluate the neurotoxicity of cefepime administered by continuous intravenous infusion during treatment of nosocomial infections in neurological patients with normal renal function. METHODS: This was an open pilot study of neurological patients with infections caused by cefepime sensitive bacteria. Patients had baseline neurological assessment and electroencephalogram (EEG). Cefepime plasma concentrations were determined 48 hours after infusion was initiated and at end of treatment (EOT). RESULTS: Eleven patients were included. These were diagnosed with a brain tumor (9), cerebrovascular disease (1) and polyneuropathy (1). Infections were surgical site infection in 5, clinically defined nosocomial pneumonia in 4, and bacterial meningitis associated to postoperative CSF fistula in 2. Gram-negative organisms were isolated in 10 patients. Cefepime dose was 2 g/day in 9 patients and 4 g/day in 2. Mean cefepime plasma concentration at 48h was 13.6 ± 2.0 µg/mL (range 4.6 to 24.5 µg/mL), at EOT was 11.9 ± 1.8 µg/mL (range 3.0 to18.9 µg/mL ). EEG interpreted by two experts showed at baseline alpha background rhythm in 5 and theta-alpha rhythm in 6 patients. On EEG at EOT background rhythm was alpha in 4 and theta-alpha in 7, one patient presented isolated sharp and slow wave activity. No mental status changes or seizures occurred and all infections resolved. CONCLUSION: Significant EEG change was observed in 1of 11 patients. A preserved mental status may correlate with cefepime safety in neurological patients with normal renal function during cefepime treatment.