METHODS: TEM, SEM and ATP efflux assay were used to evaluate the effect of hybrid peptides on the integrity of the pneumococcal cell wall/membrane. DNA retardation assay was assessed to measure the impact of hybrid peptides on the migration of genomic DNA through the agarose gel. In vitro synergistic effect was checked using the chequerboard assay. ICR male mice were used to evaluate the in vivo toxicity and antibacterial activity of the hybrid peptides in a standalone form and in combination with ceftriaxone.
RESULTS: The results obtained from TEM and SEM indicated that the hybrid peptides caused significant morphological alterations in Streptococcus pneumoniae and disrupting the integrity of the cell wall/membrane. The rapid release of ATP from pneumococcal cells after one hour of incubation proposing that the antibacterial action for the hybrid peptides is based on membrane permeabilization and damage. The DNA retardation assay revealed that at 62.5 µg/ml all the hybrid peptides were capable of binding and preventing the pneumococcal genomic DNA from migrating through the agarose gel. In vitro synergy was observed when pneumococcal cells treated with combinations of hybrid peptides with each other and with conventional drugs erythromycin and ceftriaxone. The in vivo therapeutic efficacy results revealed that the hybrid peptide RN7-IN8 at 20 mg/kg could improve the survival rate of pneumococcal bacteremia infected mice, as 50% of the infected mice survived up to seven days post-infection. In vivo antibacterial efficacy of the hybrid peptide RN7-IN8 was signficantly improved when combined with the standard antibiotic ceftriaxone at (20 mg/kg + 20 mg/kg) as 100% of the infected mice survived up to seven days post-infection.
DISCUSSION: Our results suggest that attacking and breaching the cell wall/membrane is most probably the principal mechanism for the hybrid peptides. In addition, the hybrid peptides could possess another mechanism of action by inhibiting intracellular functions such as DNA synthesis. AMPs could play a great role in combating antibiotic resistance as they can reduce the therapeutic concentrations of standard drugs.
METHODS: A systematic literature search was performed using electronic databases, such as EMBASE, PubMed/Medline, CINAHL, NHS and CEA Registry from 2000 until 2017. The quality of each included study was assessed using Joanna Briggs Institute Critical Appraisal Checklist for Economic Evaluations and Consolidated Health Economic Evaluation Reporting Standards Statement checklist.
RESULTS: Of the 313 papers retrieved, five papers were included in this review after assessment for eligibility. The majority of the studies were cost-effectiveness studies, comparing ASP to standard care. Four included economic studies were conducted from the provider (hospital) perspective while the other study was from payer (National Health System) perspective. The cost included for economic analysis were as following: personnel costs, warded cost, medical costs, procedure costs and other costs.
CONCLUSIONS: All studies were generally well-conducted with relatively good quality of reporting. Implementing ASP in the hospital setting may be cost-effective. However, comprehensive cost-effectiveness data for ASP remain relatively scant, underlining the need for more prospective clinical and epidemiological studies to incorporate robust economic analyses into clinical decisions. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.