Therapeutic Approaches for Combating Aspergillus Associated Infection.

Now-a-days fungal infection emerges as a significant problem to healthcare management systems due to high frequency of associated morbidity, mortality toxicity, drug-drug interactions, and resistance of the antifungal agents. Aspergillus is the most common mold that cause infection in immunocompromised hosts. It's a hyaline mold that is cosmopolitan and ubiquitous in nature. Aspergillus infects around 10 million population each year with a mortality rate of 30-90%. Clinically available antifungal formulations are restricted to four classes (i.e., polyene, triazole, echinocandin, and allylamine), and each of them have their own limitations associated with the activity spectrum, the emergence of resistance, and toxicity. Consequently, novel antifungal agents with modified and altered chemical structures are required to combat these invasive fungal infections. To overcome these limitations, there is an urgent need for new antifungal agents that can act as potent drugs in near future. Currently, some compounds have shown effective antifungal activity. In this review article, we have discussed all potential antifungal therapies that contain old antifungal drugs, combination therapies, and recent novel antifungal formulations, with a focus on the Aspergillus associated infections.

Chemotherapeutic Strategies for Combating Staphylococcus aureus Infections.

Staphylococcus aureus is a prominent human pathogen that causes nosocomial and community acquired infections. The accelerating emergence and prevalence of staphylococcal infections have grotesque health consequences which are mostly due to its anomalous capability to acquire drug resistance and scarcity of novel classes of antibacterials. Many combating therapies are centered on primary targets of S. aureus which are cell envelope, ribosomes and nucleic acids. This review describes various chemotherapeutic strategies for combating S. aureus infections including monotherapy, combination drug therapy, phage endolysin therapy, lysostaphins and antibacterial drones. Monotherapy has dwindled in due course of time, but combination therapy, endolysin therapy, lysostaphin and antibacterial drones are emerging alternatives which efficiently conquer the shortcomings of monotherapy. Combinations of more than one antibiotic agents or combination of adjuvant with antibiotics provide a synergistic approach to combat infections causing pathogenic strains. Phage endolysin therapy and lysostaphin are also presented as possible alternatives to conventional antibiotic therapies. Antibacterial Drones go a step further by specifically targeting the virulence genes in bacteria, giving them a certain advantage over existing antibacterial strategies. But the challenge remains on the better understanding of these strategies for executing and implementing them in the health sector. In this day and age, most of the S. aureus strains are resistant to an ample number of antibiotics, so there is an urgent need to overcome such multidrug-resistant strains for the welfare of our community.

Antimycotic Drugs and their Mechanisms of Resistance to Candida Species.

Fungal infections have shown an upsurge in recent decades, which is mainly because of the increasing number of immunocompromised patients and the occurrence of invasive candidiasis has been found to be 7-15 fold greater than that of invasive aspergillosis. The genus Candida comprises more than 150 distinct species, however, only a few of them are found to be pathogenic to humans. Mortality rates of Candida species are found to be around 45% and the reasons for this intensified mortality are inefficient diagnostic techniques and unfitting initial treatment strategies. There are only a few antifungal drug classes that are employed for the remedy of invasive fungal infections. which include azoles, polyenes, echinocandins, and pyrimidine analogs. During the last 2-3 decades, the usage of antifungal drugs has increased several folds due to which the reports of escalating antifungal drug resistance have also been recorded. The resistance is mostly to the triazole- based compounds. Due to the occurrence of antifungal drug resistance, the success rates of treatment have been reduced as well as major changes have been observed in the frequency of fungal infections. In this review, we have summarized the major molecular mechanisms for the development of antifungal drug resistance.

Antibiotic Adjuvants: A Promising Approach to Combat Multidrug Resistant Bacteria.

The escalating emergence and prevalence of infections caused by multi-drug resistant (MDR) pathogenic bacteria accentuate the crucial need to develop novel and effectual therapeutic strategies to control this threat. The recent past surprisingly indicates a staggering decline in effective strategies against MDR. Different approaches have been employed to minimize the effect of resistance, but the question still lingers over the astounding number of drugs already tried and tested. Furthermore, the detection of new drug targets and the action of new antibacterial agents against already existing drug targets also complicate the condition. Antibiotic adjuvants are considered as one such promising approach for overcoming bacterial resistance. Adjuvants can potentiate the action of generally adopted antibacterial drugs against MDR bacterial pathogens either by minimizing the impact and emergence of resistance or improving the action of antibacterial drugs. This review provides an overview of the mechanism of antibiotic resistance, the main types of adjuvants and their mode of action, achievements and progression.

Candida auris and Nosocomial Infection.

The existence of the multi-drug resistant (MDR) pathogenic fungus, Candida auris came to light in 2009. This particular organism is capable of causing nosocomial infections in immunecompromised persons. This pathogen is associated with consistent candidemia with high mortality rate and presents a serious global health threat. Whole genome sequence (WGS) investigation detected powerful phylogeographic Candida auris genotypes which are specialized to particular geological areas indicating dissemination of particular genotype among provinces. Furthermore, this organism frequently exhibits multidrug-resistance and displays an unusual sensitivity profile. Identification techniques that are commercialized to test Candida auris often show inconsistent results and this misidentification leads to treatment failure which complicates the management of candidiasis. Till date, Candida auris has been progressively recorded from several countries and therefore its preventive control measures are paramount to interrupt its transmission. In this review, we discussed prevalence, biology, drug-resistance phenomena, virulence factors and management of Candida auris infections.