Objective: The objective of this review is to describe the outcomes of patients treated with ceftaroline in the non-Food and Drug Administration (FDA) approved indication of methicillin-resistant Staphylococcus aureus (MRSA) infections in both pediatric and adult populations. Data sources: A systematic overview was conducted by searching PubMed, Medline, and The Cochrane Library up to January 2019. Study selection and data extraction: All English-language clinical trials and case reports related to the efficacy of ceftaroline in new, not-yet-approved FDA indications in MRSA infections in pediatric or adult populations. Data synthesis: In the case of MRSA bacteremia (MRSAB) infections, three different randomized studies in pediatric patients showed effectiveness of ceftaroline. When used in the case of adult populations with MRSA bacteremia, a small trial of 16 patients showed 50% clinical success in patients with acute bacterial skin and skin structure infections versus 63% clinical success in patients with community-acquired bacterial pneumonia. Another case series of six refractory case reports showed 50% clinical success of ceftaroline in patients with MRSA. Conclusions: Although there are few case reports and limited data to date, ceftaroline fosamil should continue to be studied as an alternative therapy in MRSA infections in both pediatric and adult populations. Clinical success rates of ceftaroline were, in most cases, considered high when treating patients with MRSA infection. More clinical trials need to be studied. In the specific case of MRSA bacteremia, the treatment options remain few and ceftaroline should be extensively studied for the salvage treatment of MRSAB.

Sexually transmitted diseases (STDs) are a major global health issue. Approximately 250 million new cases of STDs occur each year globally. Currently, only three STDs (human papillomavirus (HPV), hepatitis A, and hepatitis B) are preventable by vaccines. Vaccines for other STDs, including gonorrhea, chlamydia, and syphilis, await successful development. Currently, all of these STDs are treated with antibiotics. However, the efficacy of antibiotics is facing growing challenge due to the emergence of bacterial resistance. Therefore, alternative therapeutic approaches, including the development of vaccines against these STDs, should be explored to tackle this important global public health issue. Mass vaccination could be more efficient in reducing the spread of these highly contagious diseases. Bacterial outer membrane vesicle (OMV) is a potential antigen used to prevent STDs. OMVs are released spontaneously during growth by many Gram-negative bacteria. They present a wide range of surface antigens in native conformation that possess interesting properties such as immunogenicity, adjuvant potential, and the ability to be taken up by immune cells, all of which make them an attractive target for application as vaccines against pathogenic bacteria. The major challenge associated with the use of OMVs is its fragile structure and stability. However, a particulate form of the vaccine could be a suitable delivery system that can protect the antigen from degradation by a harsh acidic or enzymatic environment. The particulate form of the vaccine can also act as an adjuvant by itself. This review will highlight some practical methods for formulating microparticulate OMV-based vaccines for STDs.

Autoinducers AI-1 and AI-2 play an important role in bacterial quorum sensing (QS), a form of chemical communication between bacteria. The autoinducer N-octanoyl-L-Homoserinehomoserine lactone (C8-HSL) serves as a major inter- and intraspecies communicator or ‘signal’, mainly for Gram-negative bacteria. C8-HSL is proposed to have immunogenic properties. The aim of this project is to evaluate C8-HSL as a potential vaccine adjuvant. For this purpose, a microparticulate formulation was developed. The C8-HSL microparticles (MPs) were formulated by a water/oil/water (W/O/W) double-emulsion solvent evaporation method using PLGA (poly (lactic-co-glycolic acid)) polymer. We tested C8-HSL MPs with two spray-dried bovine serum albumin (BSA)-encapsulated bacterial antigens: colonization factor antigen I (CFA/I) from Escherichia coli (E. coli.) and the inactive protective antigen (PA) from Bacillus anthracis (B. anthracis). We formulated and tested C8-HSL MP to determine its immunogenicity potential and its ability to serve as an adjuvant with particulate vaccine formulations. An in vitro immunogenicity assessment was performed using Griess’s assay, which indirectly measures the nitric oxide radical (NOˑ) released by dendritic cells (DCs). The C8-HSL MP adjuvant was compared with FDA-approved adjuvants to determine its immunogenicity potential. C8-HSL MP was combined with particulate vaccines for measles, Zika and the marketed influenza vaccine. The cytotoxicity study showed that MPs were non-cytotoxic toward DCs. Griess’s assay showed a comparable release of NOˑ from DCs when exposed to CFA and PA bacterial antigens. Nitric oxide radical (NOˑ) release was significantly higher when C8-HSL MPs were combined with particulate vaccines for measles and Zika. C8-HSL MPs showed immunostimulatory potential when combined with the influenza vaccine. The results showed that C8-HSL MPs were as immunogenic as FDA-approved adjuvants such as alum, MF59, and CpG. This proof-of-concept study showed that C8-HSL MP displayed adjuvant potential when combined with several particulate vaccines, indicating that C8-HSL MPs can increase the immunogenicity of both bacterial and viral vaccines.

Background: Our study aims at assessing the pre-clinical impact of the synergistic mechanism of Daptomycin (DAP) and Ceftaroline (CFT) in patients with Methicillin-resistant Staphylococcus aureus bacteremia infections (MRSAB). Methods: A systematic overview was conducted by searching PubMed, Oxford academic, and Cochrane library up to June 2020. Study selection and data extraction: All English- language clinical trials, in vitro studies, and case reports related to the synergistic drug therapy for MRSAB. Results: In the case of MRSAB infections, we examined two different in vitro studies that showed effective synergism with DAP and CFT. The minimum inhibitory concentration (MIC) range observed for each is as follow: DAP 0.125-1 mg/L, CFT 0.38-1 mg/L, DAP + CFT 0.094-0.5 mg/L, vancomycin (VAN) 0.75-2 mg/L, VAN + CFT 0.25-2 mg/L. DAP + CFT combination displayed the most efficacy with the lowest MIC. The statistical analysis performed showed that DAP + CFT obtained significantly lower fractional inhibitory concentration (FIC) values (0.941 ± 0.328) compared with VAN + CFT. In vitro activities of regimens tested on DAP non-susceptibility and VAN intermediate after 96 hours showed DAP 8.29 ± 0.03a log10 CFU/mL, VAN 6.82 ± 0.04a log10 Colony Forming Unit (CFU)/mL, CFT 4.63 ± 0.19a log10 CFU/mL, DAP + CFT 1.15 ± 0.20b log10 CFU/mL, VAN + CFT 3.18 ± 0.49a log10 CFU/mL. ( a meaning significantly different than DAP plus CFT, P< equal to 0.001b meaning therapeutic enhancement combination was defined as ≥ 2 log10 CFU/ml reduction over the most active single agent). Based on these results, although DAP was not susceptible, the colony forming unit (CFU) for DAP and CFT had the best therapeutic results. Conclusion: In vitro studies have shown that combination DAP and CFT is more efficacious than the combination on VAN and CFT in MRSA bacteremia infections. The synergic effects of DAP (bactericidal) and CFT (bactericidal) is statistically significant, in recent trials, warranting promising evidence for its use in complicated bacteremia infection.