# Antimicrobial Peptides--Mechanisms of Action, Antimicrobial Effects and Clinical Applications
## 4 Clinical Application of AMPs  
### The Use of AMPs against Infectious Agents: A Current State of Evidence  
Considering their mechanism of action, AMPs can successfully surpass many drawbacks linked to the use of conventional antimicrobials, such as increased rate of multidrug resistance (which is becoming a public health hazard in recent years), as well as certain issues with potential systemic toxicity and their overall activity [121]. The broad spectrum of action and swift antimicrobial effects, with a lower propensity for resistance development, is what makes AMPs emerging and very promising candidates for more pervasive use in the treatment of infectious diseases [22]. Having more than one specific mechanism of antimicrobial activity of certain AMPs (such as thanatin and a synthetic lipoprotein F365) is an advantage in comparison to several cationic AMPs, which opens the door for achieving a true clinical potential against infections caused by multidrug-resistant pathogens [122; 123; 124]. This is supported by recent studies that concentrated on in vivo characterization and structure-activity relationships of such compounds [122]. However, thus far, only a handful of AMPs (from more than three thousand discovered) have been approved for frank clinical usage by the Food and Drug Administration (FDA), and the best-studied ones are gramicidins, polymyxins, and nisins [125; 126] (Figure 7). Gramicidins were in restricted use for applications such as infections of surface wounds and the upper respiratory system [127]; conversely, polymyxins can be used not only for treating ocular infections but also for gastrointestinal infections and systemic infections caused by antibiotic-resistant Gram-negative bacterial agents [128]. Another effective cyclic AMP that has its role in treating complicated skin and skin-structure infections as a result of _Staphylococcus aureus_ infection is daptomycin, which is often used in combination therapy to improve treatment success rates [129; 130]. Dental care, stomach ulcer therapy, and the treatment of colonic infections are known applications of nisins in humans [130; 131; 132]. Clinical trials appraising the use of linear AMPs (such as pexiganan, omiganan, and DPK060) against different bacterial and fungal infections are currently underway. As an analog of peptide magainin (extracted from the skin of _Xenopus laevis_) with 22 amino-acid residues, pexiganan demonstrates robust antimicrobial activity against bacterial and fungal pathogens, including multiple-resistant ones [125]. Its use as a topical agent in the treatment of foot ulcers that develop in patients with diabetes has been assessed in two phase III clinical trials (CT identifier: NCT01590758, NCT01594762) and also in comparison with the oral formulation (NCT00563433, NCT00563394)--but its spectrum of usage also entails decubital ulcers, as well as infected burns and surgical wounds [133]. Omiganan is a topical cationic 12 amino acid peptide assessed for the treatment of catheter infections, genital warts, rosacea, acne vulgaris, and atopic dermatitis (NCT00321153, NCT03091426, NCT01784133) [125,133]. Kininogen-derived compound DPK060 shows strong and diverse antibacterial activity. Its efficacy as a local emollient in treating acute external otitis and atopic dermatitis has been investigated in phase II clinical trials (NCT01447017, NCT01522391) [134]. A cationic fraction of human lactoferricin, known as hLF1-11, is proposed for intravenous usage in immunocompromised recipients of stem cell transplants for treating both bacterial and fungal infections (NCT00509938) [126,135]. Many other AMPs are in development specifically for fungal diseases; one notable example is a cationic peptide novexatin (generated from defensins) for treating fungal toe infections, while a dimeric peptide CZEN-002 derived from melanocyte-stimulating hormone is another addition to the treatment armamentarium against vaginal candidiasis, an important clinical entity within the vaginitis syndrome [126].