Recent Patents on Anti-Infective Drug Discovery - Volume 13, Issue 1, 2018

Background: In 2014, an estimated 1.8 million people died from Mycobacterium tuberculosis (MTB); moreover, 680,000 people developed multidrug-resistant TB (MDRTB). Methods: Currently available anti-MDR and XDR regimens are long-lasting and expensive, need high adherence and are undermined by a high frequency of adverse drug events, thus leading to a low success rate; furthermore, in the last 50 years only two new molecules, bedaquiline (BDQ) and delamanid, have been approved and released for the treatment of MDR-TB. Results: BDQ, patent number US 7,498,343B2, is a diarylquinoline anti-mycobacterial drug, active regardless of the state of MTB; in fact, its efficacy is conserved against replicating and non-replicating bacilli, despite extracellular or intracellular location. BDQ has been approved by the Food and Drug Administration (FDA) only for combination treatment of pulmonary multidrug-resistant tuberculosis (MDR-TB), in adult patients, when an effective treatment cannot be provided otherwise due to resistance or poor tolerability; however, due to high bactericidal activity, BDQ may be used in future to treat extrapulmonary tuberculosis and Mycobacterium other than tuberculosis (MOTT) infection. Conclusion: BDQ may play a major role to get closer to TB eradication and to ensure higher retention in care, even in fully susceptible MTB strains and against non-replicating mycobacteria in latent-TB, providing an alternative to standard regimen.

Background: After the era of serendipitous discovery of penicillin and outburst in the discovery and development of highly efficient antibiotics, a surge in resistance against the target specific drugs was observed, primarily due to a combination of selective pressure of antibiotics use and spontaneous mutations. As per the World Health Organization, antibiotic resistance is one of the greatest threats to the mankind. Objective: Short antimicrobial peptides (SAMPs) can be considered as a viable therapeutic alternative to conventional antibiotics in tackling resistant microbes. The ubiquitous nature of SAMPs combined with their ability to act via non-specific modes of action, high activity against a wide spectrum of drug-sensitive and drug-resistant microbes, and relative insusceptibility against the development of resistance adds to their desirability as new generation antibiotics. Results: Due to the natural tendency of peptides to get metabolized by proteolytic enzymes, modification of naturally occurring SAMPs is desirable. The modifications can be done either by incorporating unnatural or modified amino acids into the peptide chain or by protecting C and N termini. The characteristic feature of SAMPs is their hydrophobicity and cationicity, which aid in the effective killing of microbes by selectively binding target and lysing the microbial cells with less deleterious effects on the host cells as compared to AMPs and other conventional antibiotics. Conclusion: Herein, we discussed the arsenal of short peptides and peptidomimetics starting from the smallest unit possible – a dipeptide to a decapeptide along with their activity profiles as antimicrobials. Recently, various SAMPs have paved their ways from in vitro studies to clinical trials, as evident from the most recent patent (EP1951194) on oral hygiene. This step by step growth of SAMPs has restored the hope in peptide-based therapeutics, which may prove an essential tool in eradicating antimicrobial resistance and tackling various microbial infections.

Background: Silver nanoparticles (AgNPs), are amongst the utmost striking nanosized materials that are extensively applied in a variety of biomedical applications which includes diagnostic use, disease management, medical device coating, drug delivery and for personal health care. Discussion: With the growing interest and its application in the health care sector, it is becoming necessary for a better understanding and exploration of AgNPs mechanism of action like biological interaction, their possible toxicity, and safety concern to human exposure. AgNPs have been the subject of researchers attention and interest due to the unique properties and quality such as shape and size depending optical, electrical, and antimicrobial potentials (antibacterial, antifungal, antiviral etc.). In recent times, several studies have been conducted on AgNPs antimicrobial potential and also a number of patents related to its synthesis, clinical role and importance have also been registered. In this review, a short overview of AgNPs synthesis approach is presented (physical, chemical, and biological or green synthesis) and it also delivers a historical outlook of AgNPs application as an antimicrobial agent which includes combined evidence of microbial resistance and safety issues with human exposure.

Background: Antibiotic resistance is one of the most serious health threats to modern medicine. The lack of potent antibiotics puts us at a disadvantage in the fight against infectious diseases, especially those caused by antibiotic-resistant microbial strains. To this end, an urgent need to search for alternative antimicrobial approaches has arisen. In the last decade, light-based anti-infective therapy has made significant strides in this fight to combat antibiotic resistance among various microbial strains. This method includes utilizing antimicrobial blue light, antimicrobial photodynamic therapy, and germicidal ultraviolet irradiation, among others. Light-based therapy is advantageous over traditional antibiotics in that it eradicates microbial cells rapidly and the likelihood of light-resistance development by microbes is low. Methods: This review highlights the patents on light-based therapy that were filed approximately within the last decade and are dedicated to eradicating pathogenic microorganisms. The primary database that was used for the search was Google Patents. The searches were performed using the keywords including blue light, antimicrobial photodynamic therapy, ultraviolet irradiation, antibiotic resistance, disinfection, bacterium, fungus, and virus. Results: Forty-five patents were obtained in our search: 9 patents for the antimicrobial blue light approach, 21 for antimicrobial photodynamic therapy, 11 for UV irradiation, and lastly 4 for other light-based anti-infective approaches. The treatments and devices discussed in this review are interestingly enough able to be used in various different functions and settings, such as dental applications, certain eye diseases, skin and hard surface cleansing, decontamination of internal organs (e.g., the stomach), decontamination of apparel and equipment, eradication of pathogenic microorganisms from buildings and rooms, etc. Most of the devices and inventions introduce methods of destroying pathogenic bacteria and fungi without harming human cells and tissues. Conclusions: Light-based antimicrobial approaches hold great promise for the future in regards to treating antibiotic-resistant infections and related diseases.

Background: Multi-drug resistance among Pseudomonas aeruginosa (P. aeruginosa) clinical isolates is increasing and becoming a serious problem for public health authorities worldwide. Objective: The aim of the current study is to introduce a potent antibacterial compound against the resistant P. aeruginosa. Methods: In this study, we evaluated the antibacterial effects of extracts and essential oils of Ferula gummosa Boiss (F. gummosa) on 33 P. aeruginosa clinical isolates by microdilution method and assessed the association of antimicrobial activity with the extended spectrum β-lactamase (ESBL) producing, biofilm forming and aliginate production of the strains. In addition, the presence of some genes involved in these properties, including blaGES- 1, blaRER-1, blaCTX-M, blaVEB-1, blaOXA-1, blaOXA-4, blaOXA-10, ppyR, pslA, pelA, algU, algL, algD, fliC and oxaA was determined using PCR. Results: We revealed that all of our extracts and essential oils had significant antibacterial effects (p<0.001), but the aqueous extracts showed a relatively lower antibacterial activity compared with the methanolic ones. Furthermore, the minimum inhibitory concentration required for the ESBL producing strains was significantly higher than the non-ESBL producing ones (p<0.001). Loss of some genes such as blaPER-1, blaGES-1, blaOXA-1 and blaOXA-4 caused sensitivity to F. gummosa derivatives (p<0.05). Conclusion: The findings of this study indicate that the antibacterial effects of the extract and essential oils of F. gummosa may be a potential novel treatment against drug-resistant P. aeruginosa clinical isolates.