Class Of Antimicrobial Agents Research Articles

Structure, Function, and Physicochemical Properties of Pore-forming Antimicrobial Peptides.

Antimicrobial peptides (AMPs), a class of antimicrobial agents, possess considerable potential to treat various microbial ailments. The broad range of activity and rare complete bacterial resistance to AMPs make them ideal candidates for commercial development. These peptides with widely varying compositions and sources share recurrent structural and functional features in mechanisms of action. Studying the mechanisms of AMP activity against bacteria may lead to the development of new antimicrobial agents that are more potent. Generally, AMPs are effective against bacteria by forming pores or disrupting membrane barriers. The important structural aspects of cytoplasmic membranes of pathogens and host cells will also be outlined to understand the selective antimicrobial actions. The antimicrobial activities of AMPs are related to multiple physicochemical properties, such as length, sequence, helicity, charge, hydrophobicity, amphipathicity, polar angle, and also self-association. These parameters are interrelated and need to be considered in combination. So, gathering the most relevant available information will help to design and choose the most effective AMPs.

DESIGN, SYNTHESIS AND ANTIBACTERIAL ASSESSMENT OF ACTIVE (4-ARYLAZO-3-METHYL-2-THIENYL) 4-ANTIPYRINE KETONES.

The chemicals formed from antipyrines are flexible organic building blocks that are employed in the development of pharmaceuticals. By diazotizing (4-arylazo-3-hydroxy-2-thienyl) 4-antipyrine ketones 1a, 1b and 1c and (4-arylazo-3-methyl-2-thienyl) 4-antipyrine ketones (2a, 2b and 2c) further replaced with six other coupling components, a broad spectrum of hybrid molecules have been created. Mass spectra, NMR, FTIR, and elemental analyses have all been used to confirm the structures of the synthesised compounds. The antimicrobial screening was investigated by agar well diffusion and diluting the broth technique against both Gram-negative and positive-tested bacterial strains. (3-methyl-5-(phenylamino)-4-(4-tolylazo)-2-thienyl) 4-antipyrine ketone (2a) was found to be superior to Ciprofloxacin against test strains: Acinetobacter sp (34.33 ±1.15 mm), Listeria monocytogenes (29.33 ±1.15 mm) and Streptococcus sp. (19.33 ±1.15 mm). Also, good to moderate activities were expressed as minimum inhibitory concentration (MIC) and minimum bacterial concentration (MBC) which were recorded at 9±1 to 59.67±4.51 µg/mL and 16±4 to > 512 µg/mL, respectively, using compounds 2a, 2b, and 2c. MBC/MIC ratio showed, that only, 2a and 2b have a bactericidal effect but other antipyrines with bacteriostatic strength. It was suggested that the use of these novel synthesized (4-arylazo-3-methyl-2-thienyl) 4-antipyrine ketone derivatives molecules as a new chemical class of antimicrobial agents.

Efficacy of carbapenems and alternative antimicrobials for treating complicated urinary tract infections caused by caused by third-generation cephalosporin-resistant gram-negative bacteria: A systematic review and meta-analysis of randomised controlled trials

Specific data concerning the efficacy of alternative antibiotics for carbapenems against complicated urinary tract infections (cUTIs) attributed to antimicrobial-resistant (AMR) uropathogens are lacking. This study aimed to assess the efficacy of carbapenems and non-carbapenem antibiotics in the clinical outcomes of cUTIs caused by AMR uropathogens. In this systematic review and meta-analysis, databases, including MEDLINE/PubMed, the Cochrane Library, Embase and ClinicalTrials.gov, were searched. The study eligibility criteria were research articles conducted as randomised controlled trials that evaluated the composite outcomes of cUTIs. Participants were adult patients with cUTIs caused by gram-negative uropathogens resistant to third-generation cephalosporins. The intervention involved a non-carbapenem class of antimicrobial agents with in vitro activities against gram-negative uropathogens resistant to third-generation cephalosporins. Two independent researchers assessed the risk-of-bias using the second version of the Cochrane risk-of-bias tool for randomised trials. The treatment effects on each outcome were estimated as a risk ratio (RR) with a 95% confidence interval (CI) using the random-effects model. Heterogeneity was assessed using the Cochrane Q-test and I2 statistics. Through database searches, 955 articles were retrieved. After screening the titles and abstracts, 52 articles were screened in full text. Finally, 12 studies met the inclusion criteria. No significant differences in efficacy were observed between alternative antibiotics and carbapenems (composite outcome, RR, 0.96; 95% CI, 0.63-1.49; I2=21%; low certainty of evidence). Alternative antibiotics had clinical efficacy similar to that of carbapenems for treating patients with cUTI caused by gram-negative uropathogens resistant to third-generation cephalosporins.

Emergence and genomic characterization of Proteus mirabilis harboring blaNDM-1 in Korean companion dogs

Proteus mirabilis is a commensal bacterium dwelling in the gastrointestinal (GI) tract of humans and animals. Although New Delhi metallo-β-lactamase 1 (NDM-1) producing P. mirabilis is emerging as a threat, its epidemiology in our society remains largely unknown. LHPm1, the first P. mirabilis isolate harboring NDM-1, was detected from a companion dog that resides with a human owner. The whole-genome study revealed 20 different antimicrobial resistance (AMR) genes against various classes of antimicrobial agents, which corresponded to the MIC results. Genomic regions, including MDR genes, were identified with multiple variations and visualized in a comparative manner. In the whole-genome epidemiological analysis, multiple phylogroups were identified, revealing the genetic relationship of LHPm1 with other P. mirabilis strains carrying various AMR genes. These genetic findings offer comprehensive insights into NDM-1-producing P. mirabilis, underscoring the need for urgent control measures and surveillance programs using a “one health approach”.

Genetic diversity and antimicrobial susceptibility of Streptococcus suis from diseased Swiss pigs collected between 2019 – 2022

Streptococcus suis is an important pathogen causing severe disease in pigs and humans, giving rise to economic losses in the pig production industry. Out of 65 S. suis isolates collected from diseased pigs in Switzerland between 2019 and 2022, 57 isolates were thoroughly examined by phenotypic and whole genome sequence (WGS) based characterization. The isolates’ genomes were sequenced allowing for a comprehensive analysis of their distribution in terms of serovar, sequence type (ST), clonal complex (CC), and classical virulence markers. Antimicrobial resistance (AMR) genes were screened, and phenotypic susceptibility to eight classes of antimicrobial agents was examined. Serovar 6, devoid of any resistance genes, was found to be most prevalent, followed by serovars 1, 3, 1/2, and 9. Thirty STs were identified, with ST1104 being the most prevalent. Serovar 2 and serovar 1/2 were associated with CC1, potentially containing the most virulent variants. Based on single nucleotide polymorphism (SNP) analyses, fifteen isolates belonged to one of seven putative transmission clusters each consisting of two or three isolates. High phenotypic AMR rates were detected for tetracyclines (80%) and macrolides (35%) and associated with the resistance genes tet(O) and erm(B), respectively. In contrast, susceptibility to β-lactam antibiotics and phenicols was high. Determination of phenotypic AMR profiling, including the minimum inhibitory concentrations (MICs) of the tested antimicrobial agents, sets a baseline for future studies. The study provides valuable insights into the genetic diversity and antimicrobial susceptibility of Swiss S. suis isolates, facilitating the identification of emerging clones relevant to public health concerns.

Стратегия эффективного административного контроля антимикробной терапии в отделении реанимации и интенсивной терапии хирургического профиля: ретроспективное пилотное исследование.

Objective: To evaluate a strategy for effective administrative control of targeted antimicrobial therapy in surgical intensive care unit (ICU) patients. Materials and methods. The study included 3522 patients who were treated in ICU No. 1 in the period 2022 to 2023. The first group (control), treatment period 2022, included 1764 patients. The second group (research), treatment period 2023, included 1758 patients. In both groups, the use of antimicrobial drugs (AMP) was carried out in accordance with the antibacterial therapy control strategy (ASCT); in group 2, systemic administrative control was additionally carried out in the form of the use of the “Effective Hospital” program and a developed analytical system with monitoring the financial stability of the unit, aimed at daily monitoring of operating activities. A comparative analysis of the frequency of use of various classes of antimicrobial agents, the incidence of infectious complications, mortality rates and financial costs between groups was performed. Results. There was a significant decrease in the consumption of AMPs of the carbapenem group from 8194 vials in 2022 to 6577 vials in 2023, which was a decrease of 19.7%; a decrease in the consumption of tetracycline group AMPs in 2023 compared to 2022, from 2338 bottles to 1581 bottles, which amounted to 32.4%; reduction in the consumption of vancomycin and linezolid in 2023 compared to 2022 from 562 vials to 313 vials, which amounted to 44.3%. There was a decrease in the incidence of VAP from 59.3 (57.6; 62.9) in 2022 to 48.1 (38.65; 61.9) units in 2023, which amounted to 10.8% (p = 0.053). The increase in the frequency of deaths from 10.9% (9.1; 12.4) in 2022 to 11.5% (10.5; 12.7) in 2023 did not have significant differences (p = 0.67). The total expenditure on AMP in 2023 significantly decreased by 22.3%, which allowed saving 1,477,205.53 rubles (p = 0.012). Conclusion. The use of a daily strategy of administrative control of operational activities and the use of antimicrobial therapy in the ICU can reduce the costs of expensive antimicrobial agents, reduce the incidence of nosocomial infectious and inflammatory complications without changing overall mortality.

Molecular characterization of Escherichia coli isolates recovered from broilers with cellulitis

Avian cellulitis in broilers, caused by avian pathogenic Escherichia coli, is a major cause for carcass rejections during meat inspection, resulting in significant economic losses. In this study, we analysed E. coli isolates obtained from broiler chickens affected by cellulitis for their genetic relatedness and antimicrobial resistance phenotype and genotype. The objective was to determine whether there is a clonal spread or whether these clinical isolates differ. For this purpose, E. coli was isolated from swab samples collected from diseased broilers across 77 poultry farms in Germany, resulting in 107 isolates. These isolates were subjected to serotyping, PCR-based phylotyping and macrorestriction analysis with subsequent pulsed-field gel-electrophoresis for typing purposes. In addition, the presence of virulence genes associated with avian pathogenic E. coli (APEC) was investigated by PCR. Antimicrobial susceptibility of the isolates was examined by the disk diffusion method according to CLSI guidelines and subsequently, the presence of corresponding resistance genes was investigated by PCR. Typing results revealed that a significant proportion of the isolates belonged to serotype O78:K80, which is one of the major APEC serotypes. Phylogenetic grouping showed that phylogenetic group D was most commonly represented (n = 49). Macrorestriction analysis showed overall heterogenous results, however, some clustering of closely related isolates was observed. The level of antimicrobial resistance was high, with 83.8% of isolates non-susceptible to at least one class of antimicrobial agents and 40% of isolates showing resistance to at least three classes. The most frequently observed resistance was to ampicillin, mediated by blaTEM (n = 56). However, few isolates were non-susceptible to ciprofloxacin (n = 8) and none of the isolates was resistant to 3rd generation cephalosporins or carbapenems. Overall, the results show that genetically diverse APEC associated with avian cellulitis can be found among and within German poultry farms. While most isolates were antimicrobial resistant, resistance levels to high(est) priority critically important antimicrobials were low.

Potent Inhibition of E. coli DXP Synthase by a gem-Diaryl Bisubstrate Analog.

New antimicrobial strategies are needed to address pathogen resistance to currently used antibiotics. Bacterial central metabolism is a promising target space for the development of agents that selectively target bacterial pathogens. 1-Deoxy-d-xylulose 5-phosphate synthase (DXPS) converts pyruvate and d-glyceraldehyde 3-phosphate (d-GAP) to DXP, which is required for synthesis of essential vitamins and isoprenoids in bacterial pathogens. Thus, DXPS is a promising antimicrobial target. Toward this goal, our lab has demonstrated selective inhibition of Escherichia coli DXPS by alkyl acetylphosphonate (alkylAP)-based bisubstrate analogs that exploit the requirement for ternary complex formation in the DXPS mechanism. Here, we present the first DXPS structure with a bisubstrate analog bound in the active site. Insights gained from this cocrystal structure guided structure-activity relationship studies of the bisubstrate scaffold. A low nanomolar inhibitor (compound 8) bearing a gem-dibenzyl glycine moiety conjugated to the acetylphosphonate pyruvate mimic via a triazole-based linker emerged from this study. Compound 8 was found to exhibit slow, tight-binding inhibition, with contacts to E. coli DXPS residues R99 and R478 demonstrated to be important for this behavior. This work has discovered the most potent DXPS inhibitor to date and highlights a new role of R99 that can be exploited in future inhibitor designs toward the development of a novel class of antimicrobial agents.

Antifungal efficacy of scorpion derived peptide K1K8 against Candida albicans in vitro and in vivo

As an alternative class of antimicrobial agents, antimicrobial peptides (AMPs) have gained significant attention. In this study, K1K8, a scorpion AMP derivative, showed effective activity against Candida albicans including clinically resistant strains. K1K8 killed C. albicans cells mainly by damaging the cell membrane and inducing necrosis via an ROS-related pathway. K1K8 could also interact with DNA after damaging the nuclear envelope. Moreover, K1K8 inhibited hyphal development and biofilm formation of C. albicans in a dose-dependent manner. In the mouse skin infection model, K1K8 significantly decreased the counts of C. albicans cells in the infection area. Overall, K1K8 is a potential anti-infective agent against skin infections caused by C. albicans.

Predominance of multidrug-resistant bacteria causing urinary tract infections among symptomatic patients in East Africa: a call for action.

In low- and middle-income countries, antibiotics are often prescribed for patients with symptoms of urinary tract infections (UTIs) without microbiological confirmation. Inappropriate antibiotic use can contribute to antimicrobial resistance (AMR) and the selection of MDR bacteria. Data on antibiotic susceptibility of cultured bacteria are important in drafting empirical treatment guidelines and monitoring resistance trends, which can prevent the spread of AMR. In East Africa, antibiotic susceptibility data are sparse. To fill the gap, this study reports common microorganisms and their susceptibility patterns isolated from patients with UTI-like symptoms in Kenya, Tanzania and Uganda. Within each country, patients were recruited from three sites that were sociodemographically distinct and representative of different populations. UTI was defined by the presence of >104 cfu/mL of one or two uropathogens in mid-stream urine samples. Identification of microorganisms was done using biochemical methods. Antimicrobial susceptibility testing was performed by the Kirby-Bauer disc diffusion assay. MDR bacteria were defined as isolates resistant to at least one agent in three or more classes of antimicrobial agents. Microbiologically confirmed UTI was observed in 2653 (35.0%) of the 7583 patients studied. The predominant bacteria were Escherichia coli (37.0%), Staphylococcus spp. (26.3%), Klebsiella spp. (5.8%) and Enterococcus spp. (5.5%). E. coli contributed 982 of the isolates, with an MDR proportion of 52.2%. Staphylococcus spp. contributed 697 of the isolates, with an MDR rate of 60.3%. The overall proportion of MDR bacteria (n = 1153) was 50.9%. MDR bacteria are common causes of UTI in patients attending healthcare centres in East African countries, which emphasizes the need for investment in laboratory culture capacity and diagnostic algorithms to improve accuracy of diagnosis that will lead to appropriate antibiotic use to prevent and control AMR.

Resurrecting ancestral antibiotics: unveiling the origins of modern lipid II targeting glycopeptides

Antibiotics are central to modern medicine, and yet they are mainly the products of intra and inter-kingdom evolutionary warfare. To understand how nature evolves antibiotics around a common mechanism of action, we investigated the origins of an extremely valuable class of compounds, lipid II targeting glycopeptide antibiotics (GPAs, exemplified by teicoplanin and vancomycin), which are used as last resort for the treatment of antibiotic resistant bacterial infections. Using a molecule-centred approach and computational techniques, we first predicted the nonribosomal peptide synthetase assembly line of paleomycin, the ancestral parent of lipid II targeting GPAs. Subsequently, we employed synthetic biology techniques to produce the predicted peptide and validated its antibiotic activity. We revealed the structure of paleomycin, which enabled us to address how nature morphs a peptide antibiotic scaffold through evolution. In doing so, we obtained temporal snapshots of key selection domains in nonribosomal peptide synthesis during the biosynthetic journey from ancestral, teicoplanin-like GPAs to modern GPAs such as vancomycin. Our study demonstrates the synergy of computational techniques and synthetic biology approaches enabling us to journey back in time, trace the temporal evolution of antibiotics, and revive these ancestral molecules. It also reveals the optimisation strategies nature has applied to evolve modern GPAs, laying the foundation for future efforts to engineer this important class of antimicrobial agents.

Antimicrobial Activity of Ceragenins against Vancomycin-Susceptible and -Resistant Enterococcus spp.

Ceragenins (CSAs) are a new class of antimicrobial agents designed to mimic the activities of endogenous antimicrobial peptides. In this study, the antibacterial activities of various ceragenins (CSA-13, CSA-44, CSA-90, CSA-131, CSA-138, CSA-142, and CSA-192), linezolid, and daptomycin were assessed against 50 non-repeated Enterococcus spp. (17 of them vancomycin-resistant Enterococcus-VRE) isolated from various clinical specimens. Among the ceragenins evaluated, the MIC50 and MIC90 values of CSA-44 and CSA-192 were the lowest (2 and 4 μg/mL, respectively), and further studies were continued with these two ceragenins. Potential interactions between CSA-44 or CSA-192 and linezolid were tested and synergistic interactions were seen with the CSA-192-linezolid combination against three Enterococcus spp., one of them VRE. The effects of CSA-44 and CSA-192 on the MIC values of vancomycin were also investigated, and the largest MIC change was seen in the vancomycin-CSA-192 combination. The in vivo effects of CSA-44 and CSA-192 were evaluated in a Caenorhabditis elegans model system. Compared to no treatment, increased survival was observed with C. elegans when treated with ceragenins. In conclusion, CSA-44 and CSA-192 appear to be good candidates (alone or in combination) for the treatment of enterococcal infections, including those from VRE.

A rationally engineered small antimicrobial peptide with potent antibacterial activity.

Antimicrobial resistance (AMR)is a silent pandemic declared by the WHO that requires urgent attention in the post-COVID world. AMR is a critical public health concern worldwide, potentially affecting people at different stages of life, including the veterinary and agriculture industries. Notably, very few new-age antimicrobial agents are in the current developmental pipeline. Thus, the design, discovery, and development of new antimicrobial agents are required to address the menace of AMR. Antimicrobial peptides (AMPs)are an important class of antimicrobial agents for combating AMR due to their broad-spectrum activity and ability to evade AMR through a multimodal mechanism of action. However, molecular size, aggregability, proteolytic degradation, cytotoxicity, and hemolysis activity significantly limit the clinical application of natural AMPs. The de novo design and engineering of a short synthetic amphipathic AMP (≤16 aa, Mol. Wt. ≤ 2 kDa) with an unusual architecture comprised of coded and noncoded amino acids (NCAAs)is presented here, which demonstrates potent antibacterial activity against a few selected bacterial strains mentioned in the WHO priority list. The designer AMP is conformationally ordered in solution and effectively permeabilizes the outer and inner membranes, leading to bacterial growth inhibition and death. Additionally, the peptide is resistant to proteolysis and has negligible cytotoxicity and hemolysis activity up to 150 μM toward cultured human cell lines and erythrocytes. The designer AMP is unique and appears to be a potent therapeutic candidate, which can be subsequently subjected to preclinical studies to explicitly understand and address the menace of AMR.

An injectable and light curable hyaluronic acid composite gel with anti-biofilm, anti-inflammatory and pro-healing characteristics for accelerating infected wound healing

Bacterial biofilm formation and drug resistance are common issues associated with wound healing. Antimicrobial peptides (AMPs) are a new class of antimicrobial agents with the potential to solve these global health issues. New injectable adhesive antibacterial hydrogels have excellent prospects of becoming the next innovative wound-healing dressings. In this study, the hyaluronic acid was connected to the antibacterial peptide Plantaricin 149 (Pln149), obtaining HAD@AMP. HAD@AMP performed well in efficient antimicrobial activity, good histocompatibility, low drug resistance, low bacterial biofilm formation, and fast wound healing process which are essential for rapid healing of infected wound. During the hydrogel degradation process, Pln149 was released to inhibit bacterial communication and reduce bacterial biofilm formation. Meanwhile, HAD@AMP could up-regulate anti-inflammatory and pro-angiogenic factors, and down-regulate inflammatory factors to promote the healing of infected wounds, which provide a new idea for skin healing strategies.

Visualizing the membrane disruption action of antimicrobial peptides by cryo-electron tomography

The abuse of antibiotics has led to the emergence of multidrug-resistant microbial pathogens, presenting a pressing challenge in global healthcare. Membrane-disrupting antimicrobial peptides (AMPs) combat so-called superbugs via mechanisms different than conventional antibiotics and have good application prospects in medicine, agriculture, and the food industry. However, the mechanism-of-action of AMPs has not been fully characterized at the cellular level due to a lack of high-resolution imaging technologies that can capture cellular-membrane disruption events in the hydrated state. Previously, we reported PepD2M, a de novo-designed AMP with potent and wide-spectrum bactericidal and fungicidal activity. In this study, we use cryo-electron tomography (cryo-ET) and high-speed atomic force microscopy (HS-AFM) to directly visualize the pepD2M-induced disruption of the outer and inner membranes of the Gram-negative bacterium Escherichia coli, and compared with a well-known pore-forming peptide, melittin. Our high-resolution cryo-ET images reveal how pepD2M disrupts the E. coli membrane using a carpet/detergent-like mechanism. Our studies reveal the direct membrane-disrupting consequence of AMPs on the bacterial membrane by cryo-ET, and this information provides critical insights into the mechanisms of this class of antimicrobial agents.

Structural characterization, antioxidant and anti-uropathogenic potential of biogenic silver nanoparticles using brown seaweed Turbinaria ornata.

Alternative treatment strategies for urinary tract infections (UTIs) are becoming more necessary due to increasing drug resistance patterns in uropathogens. Nanoparticle-based therapeutics is emerging as a way to treat UTIs. In the present study, using Turbinaria ornata extract, silver nanoparticles (AgNPs) were synthesized, characterized, and their anti-uropathogenic activity was evaluated. The stability and formation of synthesized To-AgNPs were confirmed by UV-visible spectroscopy, FTIR, XRD, SEM, and DLS. An FTIR spectrum confirmed the presence of seaweed functional groups in To-AgNPs, a XRD analysis confirmed their crystalline nature, and SEM imaging confirmed their spherical nature with an average size of 73.98 nm with diameters ranging from 64.67 to 81.28 nm. This was confirmed by TEM results. DLS determined that the cumulant hydrodynamic diameter of To-AgNPs was 128.3 nm with a PdI of 0.313 and the zeta potential value were found to be -63.3 mV which indicates the To-AgNPs are negatively charged and more stable. DPPH assays were used to assess the antioxidant activity of biosynthesized To-AgNPs, while an agar well diffusion method was used to test the antibacterial activity against uropathogens, including Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis, and Klebsiella pneumoniae. The To-AgNPs showed the highest susceptibility to S. aureus (15.75 ± 0.35 mm) and E. coli (15 ± 0.7 mm) with MIC values of 0.0625 and 0.125 mg/ml, respectively in macro broth dilution method and observed considerable membrane damage under CLSM and SEM. To-AgNPs displayed stronger antioxidant and antimicrobial activity, suggesting they may be developed as a new class of antimicrobial agents for treating UTIs.

In vitro Studies of Antibacterial and Antifungal Activity of Novel Substituted Benzimidazole Derivatives

A series of 2-substituted amino-1-(1H-benzo[d]imidazol-1-yl)ethanone was prepared by reacting with benzimidazole and chloroacetyl chloride by stirring method. The resultant compound was dissolved in ethanol and refluxed with aryl/aralkyl amine in the presence of anhydrous potassium carbonate. The tested compounds were evaluated against bacterial agents such as E. coli, P. aeruginosa, K. pneumonia, S. typhi, and S. aureus, amoxicillin has been used as a control drug, and also screened for antifungal activity against C. albicans and A. niger at 50 and 100 mg/mL level, griseofulvin used as control drug. The structure-activity relationship led to the conclusion compound PS3 showed equipotent potent, PS4 showed moderate, and PS2 showed less moderate activity. The aromatic/aliphatic chain containing compounds PS1 and PS5 showed the least activity against all bacteria. Compound PS3, PS4 and PS1 showed better activity against C. albicans at 100 µg/mL concentration. The tested compounds PS1, PS3, PS2 and PS4 showed good activity at 100 µg/mL concentration. The compound PS3 can serve as a lead molecule for further development as a new class of antimicrobial agent. GRAPHICAL ABSTRACT

Prescription pattern of antimicrobial agents prescribed in outpatient department of dermatology in a tertiary care hospital in India

Background: Skin diseases contribute largely to global disease burden. Antimicrobial agents are used for treatment of various skin diseases of microbial aetiology caused by fungi, bacteria, viruses and ectoparasites. The primary objective of this study was to study the prescription pattern of antimicrobial agents in dermatology, to provide insights into the disease patterns, profile of the drugs used and their rationality. Methods: Cross-sectional observational study was conducted in dermatology outpatient department of T. N. M. C. and B. Y. L. Nair Charitable Hospital, Mumbai for period of 6 months. 372 prescriptions containing an antimicrobial agent (AMA) were analysed. Demographic data, disease pattern, associated comorbidities and prescription details were recorded after taking written informed consent. Results: Fungal infections were the most common (48%) followed by bacterial infections (31%). The most encountered condition was dermatophytosis. Average number of AMA per prescription was 2.33±0.73. Percentage of AMA prescribed by generic name was 48%. Percentage of AMA prescribed from National list of essential medicines 2015 (NLEM) was 32.60%. 87.9% of AMA were prescribed as combination therapy and 12.10% were prescribed as monotherapy. The commonest prescribed drugs were antifungals followed by antibiotics. Topical creams were the commonest prescribed dosage form. Conclusions: The most common class of antimicrobial agents prescribed was antifungal agents. Prescribing combination of oral antimicrobials with topical antimicrobials was found to be high. This study provides a framework for continuous prescription audit of antimicrobials in an outpatient setting and thus can help in rational use of antimicrobials in dermatological prescribing.

A pilot study on ultrashort peptide with fluconazole: A promising novel anticandidal combination.

Human infections caused by Candida albicans are common and range in severity from relatively treatable skin and mucosal conditions to systemic, fatal invasive candidiasis. The treatment of fungal infections is challenged by major obstacles, including the scarcity of effective therapeutic options, the toxicity of available medications, and the escalating antifungal resistance. Hence, there exists an urgent need to develop new classes of antimicrobial agents. This study was conducted to investigate the effect of KW-23 peptide against standard and resistant strains of C. albicans alone and in combination with fluconazole. A conjugated ultrashort antimicrobial peptide (KW-23) was designed and synthesized. KW-23 was challenged against standard and multidrug-resistant C. albicans alone and in combination with fluconazole using standard antimicrobial and checkerboard assays. The toxicity of the peptide was examined using hemolytic assays. KW-23 positively affected the standard and resistant Candidal strains (at 5 and 15 μg/mL respectively), exhibiting potent synergistic antimicrobial activity against the standard strain when combined with fluconazole. The effect of the combination was additive against the resistant strain (0.6 μg/mL). Furthermore, the peptide exhibited negligible toxicity on human erythrocytes. KW-23 and its combination with fluconazole could be a promising candidate for developing anticandidal agents.

Seed dressing with M451 promotes seedling growth in wheat and reduces root phytopathogenic fungi without affecting endophytes.

Fungal plant infections result in substantial losses to the agricultural sector. A range of fungicide seed dressings are available to control seed-borne fungal diseases; however, they lack sufficient efficacy because of intrinsic tolerance and acquired resistance. Moreover, many fungicide seed dressings can also penetrate plants, negatively affecting plant growth owing to their toxic effects on endophytes, as well as contributing to the spread of antibiotic resistance. Here, we evaluated the efficacy of M451, a member of a new class of antimicrobial agents that are not relevant to human healthcare. As a seed dressing for wheat seeds, M451 exhibited significant antifungal activity against one of the most devastating plant fungal pathogens, Fusarium spp. Furthermore, M451 was more active than the commercially used fungicide Maxim XL against both seed-borne and soil-borne F. oxysporum infection. Importantly, and unlike other antifungals, M451 seed dressing did not inhibit any of the major characteristics of wheat grains and seedlings, such as germination percentage, germination time, grain vigor, shoot- and root weight and length, but rather improved some of these parameters. The results also demonstrated that M451 had no negative impacts on endophytes and did not accumulate in grains. Thus, M451 may have potential applications as an antifungal agent in wheat cultivation.