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Candida spp. are emerging pathogens of hospital-acquired infections that causes invasive candidiasis, leading to human mortality and morbidity. Evolution of resistance to different groups of antifungal drugs is a major concern nowadays. Resistance mechanism in some of the antifungal drugs are formation of biofilms, alterations in drug target and lowered intracellular drug levels caused by efflux pumps. Introduction of novel strategies are necessitous to eliminate the phenomenon of drug resistance.  Drug repurposing is a promising therapeutic strategy that can improve the efficacy of antifungal therapy for invasive candidiasis. Antibiotics and antifungal drugs were combined against resistant Candida spp. and the in vitro antifungal synergy were analyzed by disk diffusion methods, checkerboard microbroth dilution method and time-kill curves. Synergistic effects were seen against drug-resistant strains, but drug-susceptible strains show indifferent effects in experimental studies. Profiting from the synergistic effects of combination therapy, alternative therapeutic approaches for drug resistance could be designed. This review will discuss different antifungal drugs and their mechanism, drug-resistance mechanisms and some of the antibiotic and antifungal combinations that provide novel insights in treating invasive fungal infections.

Non-responder refers to an individual did not develop their anti HBs, even after administration of a 2 complete series of the HBV vaccine. Due to mutant variants, vaccine failure occurred in numerous reports but the incidence of these mutants were unknown. Primary HBV vaccine series failed for nearly 5% of immunocompetent people. There is no clear vision on nonresponse but certain individuals are at major risk, those with persistent diseases, immunosuppressant medication and genetic predisposition. CD-4 T-helper cells that was obtained from viral peptides played an important role in Human Leukocyte antigen (HLA) along with Major Histocompatibility Complex (MHC) and individuals who failed to respond had defect in T helper cells stimulation or antigen presentation. After administration of a course of vaccine, antibody will be produced against major hydrophilic domain of HBsAg in determinant epitope cluster. As upcoming approaches, antigen dose were increased, alternative vaccination, new adjuvants such as immunostimulatory DNA sequences and accelerating vaccination schedules are followed in practice. Increased dosage vaccines, upgraded immunogenicity, adjuvants, surrogate mechanism, combined vaccines and administration of intradermal vaccines are the relevant approaches for a non-responder. Further studies has to be conducted on HLA alleles that can overcome the obstacles in HBV therapeutics.

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