Site Infection Research Articles

Unravelling Virulence Activities of Hospital Isolated Acinetobacter baumannii: Exploring The Prospective Application of Aspirin as an Antivirulence Agent

Acinetobacter baumannii infections pose a global public health threat due to the increasing resistance to various antimicrobial agents. This study reports the virulence characteristics of A. baumannii strains isolated from patients at Hospital Canselor Tuanku Muhriz UKM (HCTM) and explores the potential of aspirin as an antivirulence agent. Fourteen A. baumannii isolates from various infection sites exhibited resistance to at least two antibiotics. Among them, 43% (n=6) displayed high motility, correlating with the site of isolation. Additionally, 58% (n=7) formed strong biofilms, 36% (n=5) secreted proteases and 36% (n=5) resisted oxidative stress. Notably, isolates Ab_H4 and Ab_H10 displayed the highest virulence, warranting further investigation. Molecular analysis using polymerase chain reaction (PCR) showed that both Ab_H4 and Ab_H10 possessed the bap and katG genes. Although both strains were capable of secreting proteases, only Ab_H4 possessed the cpaA gene, suggesting the involvement of other genes in protease secretion in Ab_H10. Despite high motility, no pilT gene was detected in any isolates. Treatment with sub-inhibitory concentrations of aspirin (3.25 mg/ml) restored susceptibility to previously resistant antibiotics, disrupted biofilm formation and reduced proteases and catalases secretion. However, no significant impact on bacterial motility was observed. Interestingly, sub-inhibitory concentrations of aspirin induced biofilm formation in the environmental strain control (Ab_UKMCC), which was significantly reduced upon exposure to the MIC. These findings highlight the high virulence capabilities of several strains isolated from HCTM and show the potential of aspirin as an antivirulence agent, offering valuable insights for combating A. baumannii infections.

Phytophthora zoospores display klinokinetic behaviour in response to a chemoattractant.

Microswimmers are single-celled bodies powered by flagella. Typical examples are zoospores, dispersal agents of oomycete plant pathogens that are used to track down hosts and infect. Being motile, zoospores presumably identify infection sites using chemical cues such as sugars, alcohols and amino acids. With high-speed cameras we traced swimming trajectories of Phytophthora zoospores over time and quantified key trajectory parameters to investigate chemotactic responses. Zoospores adapt their native run-and-tumble swimming patterns in response to the amino acid glutamic acid by increasing the rate at which they turn. Simulations predict that tuneable tumble frequencies are sufficient to explain zoospore aggregation, implying positive klinokinesis. Zoospores thus exploit a retention strategy to remain at the plant surface once arriving there. Interference of G-protein mediated signalling affects swimming behaviour. Zoospores of a Phytophthora infestans G⍺-deficient mutant show higher tumbling frequencies but still respond and adapt to glutamic acid, suggesting chemoreception to be intact.

A Case of Lautropia mirabilis Infection in a Lung Transplant Patient and a Review of the Literature

Lautropia mirabilis is an opportunistic pathogen that typically causes intestinal and oral infections when the body’s immune system is compromised or the microbial flora is imbalanced. Respiratory infections caused by Lautropia mirabilis are extremely rare. The symptoms and severity of Lautropia mirabilis infection may vary depending on individual differences and the site of infection. Through a review of relevant literature and this case study, it has been observed that Lautropia mirabilis may also cause pulmonary infectious diseases, and in immunocompromised patients, it can lead to severe infections, potentially resulting in death.

The Relationship Between Obesity and Lateral Condyle Fracture Healing: A Pilot Study.

Childhood obesity is a growing public health concern in the United States. Obesity has been shown to lead to increased complications with regards to orthopaedic injuries, such as more severe fracture patterns, notably observed in injuries like lateral condyle fractures of the humerus. However, there is currently a gap in the literature regarding the relationship between obesity and the healing potential of these fractures. This study aims to determine whether obesity is associated with increased surgical time, wound/pin site infections, delayed union/nonunion, and time to union in pediatric patients with lateral condyle fractures of the humerus. A retrospective chart review was conducted at a level 1 trauma center on all patients 18 years or younger who sustained a lateral condyle fracture of the humerus. Patients were stratified into groups based on their body mass index-for-age percentile as defined by the Centers for Disease Control and Prevention; normal weight (<85%), overweight (85 to <95%), and obese (≥95%). Demographic data, Weiss classification, postoperative complications (infection, delayed union or nonunion, malunion, and need for repeat surgery), length of surgery, and time to union were recorded. Comparisons of categorical data were analyzed using χ2 tests. Analysis of variance was used to compare the means between weight cohorts for continuous data. A total of 123 patients were analyzed. Sixty-six were categorized as normal weight, 20 were overweight, and 37 were obese. There were no significant differences between weight classes for any complications, including infection, delayed/nonunion, malunion, or repeat surgery. There was no correlation with fracture severity as defined by the Weiss classification of lateral condyle fractures in regards to weight cohort (P = 0.098). There was no significant difference in length of surgery (P = 0.393) or average time to union (P = 0.236) between the weight cohorts. In this study, population with higher pediatric obesity rates than the population average, there was no significant correlation between body mass index-for-age and each of the surgical complications reviewed, length of surgery, or time to union, indicating the healing potential of lateral condyle fractures in obese pediatric patients is no more compromised than that of their normal weight peers. Level III-a retrospective study.

Effect of the Sho1 gene on the pathogenicity of Candida albicans and immune function in vivo

ObjectivesSho1, a ubiquitous membrane protein in fungi, plays a pivotal role in various physiological processes, such as osmotic stress, oxidative stress, temperature response, and virulence regulation across different fungal species. This study aimed to investigate the effect of the Sho1 gene on the pathogenicity of Candida albicans and its immune function in vivo. Materials and methodsNinety-nine clinical strains from various infection sites were collected to investigate the expression levels of the Sho1 gene compared to its levels in the standard strain (SC5314). Sho1-knockout strains (Sho1Δ/Δ) were constructed to investigate the impact of the Sho1 gene deletion on the biofilm formation, adhesion, and flocculation abilities of C. albicans. A mouse model of systemic infection was established to evaluate the impact of Sho1 deletion on survival, organ pathology, and immune cell function, as assessed by flow cytometry. ResultsThe expression level of the Sho1 gene was found to be higher in clinical strains derived from sterile fluids, sputum, and secretions compared to that in the standard strains. Deletion of the Sho1 gene diminished the biofilm-formation capacity of C. albicans, leading to a sparse structure and reduced thickness, as well as diminished adhesion and flocculation abilities. Deletion of the Sho1 gene prolonged mouse survival; decreased the fungal load in the liver, kidney, and spleen; and reduced inflammatory cell infiltration into the kidney. In the spleens of mice injected with the Sho1Δ/Δ strain, a decrease was observed in the percentage of M1-type macrophages and an increase in M2-type macrophages, resulting in a decreased M1/M2 macrophage ratio. Additionally, an increase was observed in the number of Th1 cells and a decrease in the number of Th2 and Th17 cells, leading to an increased Th1/Th2 ratio. ConclusionThe Sho1 gene significantly contributes to the pathogenesis of C. albicans by influencing its biological behaviour and immune response in vivo.

Pseudomonas aeruginosa LasR-deficient mutants have increased methylglyoxal and hydrogen peroxide sensitivity due to low intracellular glutathione.

Methylglyoxal is a highly reactive metabolite that is detected in various disease states, including those where Pseudomonas aeruginosa is present and MG resistance requires the glutathione-dependent glyoxalase enzyme GloA3 enzyme. This study reveals that P . aeruginosa strains with LasR mutations, which are commonly found in clinical isolates, are more sensitive to methylglyoxal (MG) and hydrogen peroxide due to lower intracellular glutathione levels and high activity of the CbrAB-Crc regulatory pathway. This could be significant for understanding the selective pressures that drive P. aeruginosa evolution in infection sites, as well as a better understanding of LasR-strain metabolism in infections such as those associated with cystic fibrosis.

Exploring diflunisal as a synergistic agent against Staphylococcus aureus biofilm formation.

Staphylococcus aureus is a bacterial pathogen of considerable significance in public health, capable of inducing a diverse range of infectious diseases. One of the most notorious mechanisms used by S. aureus to survive and colonize the site of infection is its ability to form biofilms. Diflunisal, a non-steroidal anti-inflammatory drug (NSAID), is a known inhibitor of the Agr system in S. aureus, which is key in regulating biofilm formation. This study evaluated the effect of broad-spectrum antibiotics in combination with diflunisal on S. aureus biofilm density. Eight antibiotics were tested independently at different concentrations and in combination with diflunisal to assess their effect on S. aureus biofilm formation. When using the antibiotics alone and with diflunisal, a significant control effect on biofilm formation was observed (p < 0.05), irrespective of diflunisal presence, but did not achieve a complete biofilm growth inhibition. Over time, diflunisal influenced biofilm formation; however, such an effect was correlated with antibiotic concentration and exposure time. With amikacin treatments, biofilm density increased with extended exposure time. In the case of imipenem, doripenem, levofloxacin, and ciprofloxacin, lower doses and absence of diflunisal showed higher control over biofilm growth with longer exposure. However, in all cases, diflunisal did not significantly affect the treatment effect on biofilm formation. In the absence of antibiotics, diflunisal significantly reduced biofilm formation by 53.12% (p < 0.05). This study suggests that diflunisal could be a potential treatment to control S. aureus biofilms, but it does not enhance biofilm inhibition when combined with antibiotics.

An aerosol nanocomposite microparticle formulation using rifampicin-cyclodextrin inclusion complexes for the treatment of pulmonary diseases

Rifampicin (RIF) is commonly used in the treatment of tuberculosis (TB), a bacterium that currently infects one fourth of the world’s population. Despite the effectiveness of RIF in treating TB, current RIF treatment regimens require frequent and prolonged dosing, leading to decreased patient compliance and, ultimately, increased mortality rates. This project aims to provide an alternative to oral RIF by means of an inhalable spray-dried formulation. TB uses alveolar macrophages to hide and replicate until the cells rupture, further spreading the bacteria. Therefore, delivering RIF directly to the lungs can increase the drug concentration at the site of infection while reducing off-site side effects. Cyclodextrin (CD) was used to create a RIF-CD inclusion complex to increase RIF solubility and biodegradable RIF-loaded NP (RIF NP) were developed to provide sustained release of RIF. RIF NP and RIF-CD inclusion complex were spray dried to form a dry powder nanocomposite microparticles (nCmP) formulation (RIF-CD nCmP). RIF-CD nCmP displayed appropriate aerosol dispersion characteristics for effective deposition in the alveolar region of the lungs (4.0 µm) with a fine particle fraction of 89 %. The nCmP provided both a burst release of RIF due to the RIF-CD complex and pH-sensitive release of RIF due to the RIF NP incorporated into the formulation. RIF-CD nCmP did not adversely affect lung epithelial cell viability and RIF NP were able to effectively redisperse from the nCmP after spray drying. These results suggest that RIF-CD nCmP can successfully deliver RIF to the site of TB infection while providing both immediate and sustained release of RIF. Overall, the RIF-CD nCmP formulation has the potential to improve the efficacy for the treatment of TB.

Development of ultrasensitive genosensor targeting pathogenic Leptospira DNA detection in artificial urine

In the last decades, to access the stages of leptospirosis pathogenicity, site of infection, progression, monitor disease, and after-treatment were required especially non-invasive techniques. This becomes one of the significant goals for researchers. In this study, we developed a highly sensitive DNA-based electrochemical sensor to detect pathogenic leptospires in urine samples using a gold screen-printed electrode. The gold working electrode was electrodeposited with diazonium salt (CMA) with external carboxylic acid from the surface, and the specific Loa22 single-stranded DNA (ssDNA) probe to Leptospira interrogans was immobilized through a carbodiimide chemical reaction. The modified working electrode was characterized by contact angle measurement, cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). After that, targeted DNA testing showed the EIS change in the range of 5 ag mL-1 - 16 fg mL-1 with a correlation R2 of 0.9638. The high sensitivity electrochemical sensor indicated a lower limit of detection to the attomolar level specifically 5 ag mL-1. Additionally, the developed genosensor exhibited high specificity without crossing other bacteria present in urine such as Escherichia coli, Staphylococcus aureus, and S. typhi as well as non-pathogenic leptospires L. biflexa serovar Patoc. Leptospires DNA was analyzed in both buffer solution and diluted artificial urine and detection in diluted artificial urine 1:1,000 was possible despite salt interferences. This study provides a highly sensitive lower detection platform for leptospirosis, offering potential for further development as a portable and point-of-care testing tool.

The Antifungal Activity of Chitosan Nanoparticle-Incorporated Probiotics Against Oral Candidiasis.

Candida species, especially Candida albicans, cause oral candidiasis, also known as oral thrush. It affects the elderly, newborns, patients under antibiotics, chemotherapeutic agents, and patients with weaker immune systems. Although successful, traditional antifungal medications are available, they may have negative effects and do not prevent recurrence. Conventional antifungal medications have a restricted range of effectiveness; hence, the need for a novel antifungal agent arises. Chitosan, a natural polymer made from chitin found in crustaceans, kills fungal cells by damaging membranes. Excellent biocompatibility and biodegradability make it a promising medical material. Probiotics, live bacteria, compete with pathogenic microbes for adhesion sites and nutrients, produce antimicrobials such as lactic acid, hydrogen peroxide, and bacteriocins, and modulate the host's immunological response. Adding probiotics to chitosan nanoparticles (CSNPs) boosts their antifungal activity against Candida species and increases their stability and transport to the infection site. The antifungal activity was evaluated through in vitro experiments utilizing Candida strains that are significant to oral candidiasis. Different concentrations of CSNPs and formulations loaded with probiotics were examined to assess their effectiveness. The antifungal properties were assessed using microbiological assays, specifically agar diffusion and minimum inhibitory concentration (MIC). The study demonstrated a notable fungicidal impact of CSNPs combined with probiotics against oral candidiasis. Furthermore, the MICvalues were lower for the probiotic-loaded CSNPs than for chitosan alone or probiotics alone. The combination of CSNPs and probiotics shows potential in effectively combating oral candidiasis by inhibiting fungal growth. This novel method offers a promising strategy for creating therapeutic treatments for oral candidiasis by utilizing the combined benefits of chitosan and probiotics to combat fungal infections effectively.

EspH utilizes phosphoinositide and Rab binding domains to interact with plasma membrane infection sites and Rab GTPases*

ABSTRACT Enteropathogenic E. coli (EPEC) is a Gram-negative bacterial pathogen that causes persistent diarrhea. Upon attachment to the apical plasma membrane of the intestinal epithelium, the pathogen translocates virulence proteins called effectors into the infected cells. These effectors hijack numerous host processes for the pathogen’s benefit. Therefore, studying the mechanisms underlying their action is crucial for a better understanding of the disease. We show that translocated EspH interacts with multiple host Rab GTPases. AlphaFold predictions and site-directed mutagenesis identified glutamic acid and lysine at positions 37 and 41 as Rab interacting residues in EspH. Mutating these sites abolished the ability of EspH to inhibit Akt and mTORC1 signaling, lysosomal exocytosis, and bacterial invasion. Knocking out the endogenous Rab8a gene expression highlighted the involvement of Rab8a in Akt/mTORC1 signaling and lysosomal exocytosis. A phosphoinositide binding domain with a critical tyrosine was identified in EspH. Mutating the tyrosine abolished the localization of EspH at infection sites and its capacity to interact with the Rabs. Our data suggest novel EspH-dependent mechanisms that elicit immune signaling and membrane trafficking during EPEC infection.

Nuclear factor kappa-B: The El Dorado of inflammatory immune response

For more than a decade, the nuclear factor kappa-B (NFκB) family and their signaling pathways have proved crucial to the immune system's functioning. According to research, this factor is implicated in almost every immune system event, including immune cell development and function, activation, and pathogen-activated cell death. A considerable body of evidence suggests the idea that, in addition to being a possible transcription factor, it plays a very significant role in the establishment of inflammation-associated immunological responses in host cells. Inflammation is a cascade of events that involve vasodilation and immune cell migration to the site of infection in order to defend the host. However, if dysregulation occurs, it may lead to the emergence of chronic inflammatory illnesses. When immune cells migrate to an inflamed area NFκB activation occurs, which causes release of pro-inflammatory cytokines and development of inflammatory response. Furthermore, this complex transcription factor activation takes part in several innate and adaptive immunity-related cellular processes, including immune cell proliferation and differentiation. Grasp the relationship between the immune system and inflammation requires a thorough understanding of NFκB's capabilities. This review explores the role of NFκB activity as a key inflammatory mediator in various malignancies and auto-inflammatory diseases. We have shed light on how NFκB regulates inflammatory responses by producing cytokines and chemokines and directing the transcription of inflammatory molecules involved in both innate as well as adaptive immunity.

Ambiguity of the influence of cytokines IL-8, IL-17A, TNFα, AND IFNγ on the antigen presenting CD66b+CD16+CD33+HLA-DR+ subpopulation of neutrophil granulocytes in children with acute hematogenic osteomyelitis

Dysfunctions of the immune system, in turn, of neutrophil granulocytes (NG), are the cause of the emergence and progression of the focus of infection in bone tissue and bone marrow in acute hematogenous osteomyelitis (AHO). When colonizing bones, S. aureus, osteoblasts, osteocytes and macrophages secrete chemoattractants and cytokines, which initiate the influx of large amounts of NG into the site of infection, which, in turn, secrete cytokines and form an inflammatory microenvironment that promotes the formation of osteoclasts that resorb bone. It is known that NG activated by cytokines undergo functional and phenotypic changes. In this regard, detecting the cytokines that lead to the transformation of the NC phenotype into an antigen-presenting cell (APC) in AHO is of interest. Goal, to determine the levels of neutrophil-associated serum cytokines IL-8, IL-17A, TNFα, IFNγ and their relationship with numerous and phenotypic characteristics of subpopulations CD66b+CD16+CD33+HLA-DR-, CD66b+CD16+CD33+HLA-DR+NG in localized and septicopyemic forms of CSO in children.Children (N = 28) aged 8-15 years with AHO were studied: group 1 – 20 children with a localized form; group 2 – 8 children with septicopyemic form; and a comparison group of 13 conditionally healthy children. The number of NG subpopulations CD66b+CD16+CD33+HLA-DR+, CD66b+CD16+CD33+HLA-DR-, receptors mean expression intensity (MFI) (FC 500, mAb Beckman Coulter, USA); serum cytokines IL-8, IL-17A, TNFα, IFNγ ELISA (ASCENT, Finland), test systems Cloud-Clone Corp. (USA).The appearance of two activated subpopulations in the peripheral blood (PB) of children with various forms of AHO severity were found: CD66b+CD16+CD33+HLA-DR+ with the APC phenotype, capable of presenting the S. aureus superantigen for T lymphocytes and a subpopulation with high cytotoxic activity CD66b+CD16+CD33+HLA-DR- while concentrations of serum cytokines IFNγ, IL-17 are high and levels of TNFα are increased. Due to the fact that the NG activation range correlates with the range of inflammatory tissue damage, including bone tissue, determination of the level of IFNγ, IL-17 can be useful for assessing the severity of AHO, and also possibly for monitoring infectious and inflammatory processes occurring in the bone tissue.Taking into account the leading role of NG in various inflammatory reactions, determining the expression of HLA-DR, in order to identify the manifestation of the APC-NG subpopulation in peripheral blood, may have diagnostic value not only for AHO, but also for other manifestations of infectious and inflammatory diseases.

Surgical management for the case of scrotal myiasis in a 7-day-old neonate: a case report

IntroductionNeonatal myiasis is a rare condition, with few reports available on the subject. Surgical management is recommended in some cases. In this study, we present the case of a 7-day-old male neonate with larvae in his scrotum who underwent surgery.Case presentationA full-term 7-day-old male infant (Aryan race) was referred to a children’s hospital. On the sixth day after birth, three 3–4 mm long larvae crawled out from his scrotum, with the number increasing over time. He was given intravenous antibiotics and topical mupirocin to combat secondary infections. The surgical treatment involved two steps: first, the larvae were extracted, and then the infection site was washed with betadine and hydrogen peroxide to help remove any possible remaining larvae.ConclusionScrotal myiasis is a rare disease that occurs in infants and requires immediate treatment. Surgical treatment is effective in removing dead or decaying larvae from a deep-seated location and washing the infection site to prevent secondary infection.

Febrile neutropenia induced by adjuvant radiotherapy for a patient with breast cancer accompanied with reversible splenial lesion syndrome (RESLES, TypeI): a case report

BackgroundReversible splenial lesion syndrome (RESLES) is known as a neuro-imaging syndrome with recurrent but reversible lesion of the corpus callosum, characterized by nonspecific but usually mild encephalopathies and specific imaging manifestations.There are few published reports in the field of oncology.Case presentationA 33-year-old female with right breast cancer and with no particular family history was admitted to hospital with high fever and severe headache, after receiving adjuvant radiotherapy. Blood routine test upon admission suggested neutropenia, considering myelosuppression associated with radiotherapy. There were no definite findings of common pathogenic microorganism, and no imaging indication of certain infectious sites other than a likely reversible corpus callosum syndrome suggested by brain MRI, which was relieved after systemic antibiotic therapy and granulocyte colony-stimulating factor injection.ConclusionsReversible splenial lesion syndrome is a kind of clinical-imaging syndrome with multiple clinical manifestations and etiologies. This breast cancer patient after postoperative adjuvant radiotherapy develops a complication of RESLES that rings an alarm bell to the oncologists not to easily recognize the corpus callosum lesion as infarction or metastasis. Meanwhile, the potential pathogenic mechanisms need to be explored further.

The role of infection in signalling root resorption: Anarrative review.

Root resorption consists of complex, multistep processes that involve cell signalling caused by inflammation and stromal cells, which promotes the secretion of receptor activator of nuclear factor κB ligand/ macrophage-colony stimulating factor (RANKL/M-CSF) resulting in a resorptive process. The aim of this narrative review was to analyse the literature related to root resorption resulting from microbial infection and to comparing it with non-microbial infection. An electronic literature search was performed using the PubMed database and applying keywords of articles published in English. Eligible papers were reviewed to reveal the descriptions of bone and root resorption processes. The abstracts were searched manually to identify articles about infection-stimulating bone and root resorption. Three main types of root resorption were identified, two associated with primary bacterial infection and one secondary to bacterial infection. These include external inflammatory resorption, internal inflammatory resorption and external cervical (invasive) resorption. The magnitude of cytokine involvement that promotes resorption and M-CSF/RANKL production depends on multiple factors, including pathogen virulence, site of infection and host genetic factors that activate the inflammation at the infection site. Two mechanisms activate the resorption mechanisms-the canonical and non-canonical pathways that can activate clastic cells independently of the RANKL/RANK canonical pathways. Two pathways of root resorption co-exist in the body. When resorption is caused by infection, chronic inflammation due to bacterial infection prolongs the secretions of pro-inflammatory cytokines that intensify root and bone resorption. The second pathway is bacterial independent of the non-infection root resorption that is part of the wound healing process, which is limited in time due to its innate ability.

Surface charge switchable fluorinated small molecular micelles for enhanced photodynamic therapy for bacterial infections

Photodynamic therapy (PDT) employs reactive oxygen species (ROS) from a photosensitizer (PS) under light, inhibiting multi-drug resistance in bacteria. However, hypoxic conditions in infection sites and biofilms challenge PDT efficiency. We developed fluorinated small molecular micelles (PF-CBMs) as PS carriers to address this, relieving hypoxia and enhancing PS penetration into biofilms. Perfluorocarbons in PF-CBMs transport more oxygen due to their excellent oxygen-dissolving capability. Fluorination enhances loading capacity and serum stability, reduces premature release, and improves cellular uptake, to improve PDT efficacy. PF-CBMs, with acid-induced surface charge transformation, exhibit superior biofilm penetration, resulting in increased antibiofilm activity of PDT. Compared to fluorine-free micelles (PC-CBMs), PF-CBMs demonstrate better serum stability, higher drug loading, and reduced premature release, leading to significantly improved antibacterial efficacy in vitro and in vivo. In conclusion, fluorinated micelles with surface charge reversal enhance PDT for antibacterial and antibiofilm applications.

Optimizing Dermal Delivery of Linezolid for Treating Skin and Soft Tissue Infections: NLC-Based Gel Formulation Using Taguchi Design

Background: Uncomplicated skin and soft tissue infections account for approximately 200 million visits to ambulatory care settings annually. Linezolid (LNZ) is an oxazolidinone that has proven its effectiveness in combating skin and soft tissue infections caused by gram-positive pathogens. LNZ is administered via oral suspension, tablets, or an intravenous route in most in-stances. However, its extended therapy leads to undesirable side effects like diarrhoea, thrombo-cytopenia, myelosuppression, lactic acidosis, etc. and even life-threatening complications. The dermal administration of LNZ offers an alternative route, ensuring localized and sustained release at the site of infection. This approach may reduce systemic exposure and allow for lower doses compared to oral ingestion, which can decrease the risk of adverse effects. Objective: This research aimed to develop a nanostructured lipid carrier (NLC)-based gel for de-livering LNZ via the dermal route to treat uncomplicated skin and soft tissue infections. Methods: NLC were developed by high-shear homogenisation and sonication method using glyc-eryl trimyristate as a solid lipid and neem oil as a liquid lipid. The Taguchi design was employed to optimize NLCs using surfactant concentration (mg), drug-to-lipid ratio, and sonication time (sec) as independent variables. Their effect on particle size, zeta potential, and entrapment effi-ciency was studied. The optimized nanocarriers were developed into a gel product and evaluated for drug release, permeation, and antibacterial activity. Results: The optimised process parameters to attain outcomes were 2% surfactant, 1:1 drug-to-lipid ratio and 300 seconds of sonication. The resulting NLC had an average size of 191.2 ± 2.76 nm, a zeta potential of -30.7 ± 4.50 mV, and 84.89 ± 2.76% drug entrapment. NLC-based gel dis-played anomalous transport with a 90.16 % drug release. The gel showed a strong antibacterial effect against Staphylococcus aureus with a 7.57 ± 0.12 cm mean zone of inhibition. Ex-vivo skin permeation studies revealed 24.19 ± 0.19 % drug permeation and 64.46 ± 0.58% cutaneous depo-sition. NLC-based gel demonstrated a significant decrease in colony-forming units in infected an-imal models. Conclusion: The ex-vivo investigations demonstrated the presence of LNZ at the infection site, enhancing therapeutic effectiveness. In vitro and in-vivo findings illustrated the substantial anti-bacterial efficacy of LNZ NLC-based gel. The adoption of NLC-based gel exhibits promising po-tential as a carrier for dermal delivery of LNZ.

Electrospun patches to deliver combination drug therapy for fungal infections

Fungal infections, though affecting healthcare globally, receive insufficient attention in clinical and academic settings. Invasive fungal infections, particularly caused by combat wounds, have been identified as a critical threat by the US Department of Defense. Monotherapy with traditional antifungals is often insufficient, and so combination therapies are explored to enhance treatment efficacy. However, systemic combination treatments can result in severe adverse effects, suggesting the need for localised delivery systems, such as drug-loaded electrospun patches, to administer antifungals directly to the infection site. This proof-of-concept study hypothesised that dual amorolfine and terbinafine therapy slowly releasing from electrospun patches would be an effective way of eradicating Candida albicans when the patch was applied directly to the fungal colony. The feasibility of creating electrospun materials loaded with amorolfine and terbinafine for combination antifungal therapy was investigated. Electrospinning was used to fabricate polycaprolactone (PCL) patches with varying drug loadings (2.5%, 5%, and 10% w/w) of amorolfine and terbinafine either individually or in combination. The incorporation of both drugs in the fibres was confirmed, with the drugs predominantly in an amorphous state. Results showed that combination therapy patches had a significantly greater and prolonged antifungal effect compared to monotherapy patches, with larger zones of inhibition and sustained efficacy over at least 7 days. This study therefore demonstrates that PCL-based electrospun patches containing amorolfine and terbinafine provide superior antifungal activity against C. albicans compared to monotherapy patches. This approach could lower required drug doses, reducing adverse effects, and enhance patient compliance due to prolonged drug release, leading to more effective antifungal therapy.

Algorithms for topical therapy of mycoses at the daily appointment of a dermatologist

This article discusses the immediacy of the problem of rising incidence of common mycoses that dermatovenerologists deal with at outpatient visits, the reasons for their occurrence, conversion from one course of the disease to another and the use of etiological effective treatments. The author described the mechanisms of development of different mycoses according to their etiology, comorbid disorders accompanying mycoses and the features of the clinical picture based on etiological factors and sites of infection. The article places special emphasis on the reasons for infection with fungal invasions in humans, conditions and numerous contact routes. Modern features of the course of fungal skin diseases include formation of biofilms in the sites of infection, multicentricity, extension of the pathological process, frequent formation of granulomas, follicles, occurrence of numerous mycoides, as well as the low virulence of dermatophytes. The publication also presents various clinical cases of somatically healthy patients suffering from various mycoses caused by variant factors, which have pathological processes located in different sites. According to the doctor’s prescription, patients used conventional treatment regimens that included external/ topical treatment and general therapy, strictly in accordance with clinical guidelines – the use of highly active broad-spectrum antifungal drugs with fungicidal, fungistatic, antibacterial, anti-inflammatory and antipruritic action. These properties ensure a low probability resistance of microorganisms or relapses during treatment with topical dosage forms of antifungal drugs for cutaneous application. Upon completion of the course of treatment, patients reported a significant improvement in their skin condition resulting in minimization of disease symptoms, disappearance of skin rashes, skin itching, and elimination of exfoliation.