Skin Infections Research Articles

NIR‐II emissive biohybrid nanovesicles as mild‐temperature photothermal antibiofilm agents against acute bacterial skin and skin‐structure infections

AbstractThe emergence of antibiotic‐resistant bacteria poses a significant challenge to the prompt and appropriate treatment of pathogenic bacteria infections, such as acute bacterial skin and skin‐structure infections (ABSSSI), especially in the presence of biofilms. Bacterial biofilms are naturally resistant to antibiotics and the human immune system, making biofilm‐based infections extremely difficult to treat. Therefore, developing new antibacterial therapies targeting biofilms is crucial. Aggregation‐induced emission luminogens with fluorescence in the second near‐infrared window (NIR‐II AIEgens), which can be activated by a near‐infrared laser to generate heat, offer an effective and precise photothermal therapy (PTT) approach for treating deep‐tissue bacterial infections. However, the presence of biofilms impedes the entry of photosensitizers into the infected area, requiring higher drug doses and increasing the risk of PTT. Herein, we developed a biocompatible AIEgen‐based biohybrid nano formulation that incorporates the BPBBT (NIR‐II AIEgen) and antibiofilm α‐amylase into a red blood cell (RBC) membrane‐derived nanovesicle carrier for a PTT/biofilm degradation combination therapy. The synergistic effect of this new formulation enhances both the photothermal capability of BPBBT and the biofilm degradation compared to traditional individual treatments. The new combination therapy demonstrated significant improvement in treating severe Staphylococcus aureus infections caused by biofilms in vitro and in vivo, presenting a promising alternative to traditional antibiotic therapy.

Smile incision and reverse shotgun approach in distal interphalangeal joint arthrodesis

BackgroundArthrodesis serves as the traditional therapeutic approach for advanced distal interphalangeal joint (DIPJ) arthritis. However, the conventional technique may prove insufficient when the excision of pronounced volar and lateral spurs is required. To address this, we innovated the 'smile incision with reverse shotgun approach'. This method enhances joint exposure and yields superior cosmetic results by extending the transverse skin incision over the DIPJ and cleaving the accessory collateral ligament, thereby improving access to the volar and lateral joint margins. This article meticulously elucidates the surgical procedure and presents preliminary results of its implementation.MethodThe clinical data of 22 consecutive patients (36 fingers) who received DIPJ arthrodesis by this procedure during March 2018 to October 2022, with a mean follow-up period of 9.8 months, were reviewed. Patients’ demographics, union rate, complications, radiographic findings, as well as visual analogue scale (VAS) for pain and satisfaction, were collected and analyzed.ResultsThirty-five of 36 fingers achieved uneventful bony union (97.2%). The average VAS for pain and satisfaction as well as he coronal plane deviation of DIPJ significantly improved after the operation (all, P < 0.05). No skin necrosis, nail deformity, or infection were observed during the follow-up period.ConclusionThe smile incision and reverse shotgun approach provided excellent DIPJ exposure, high union rate, and cosmetic appearance for DIPJ arthrodesis surgery. This technique may be a good surgical option for DIPJ arthrodesis when more volar part joint preparation and more volar implant insertion sites are necessary.

Subcutaneous furosemide in heart failure: a systematic review

Abstract Background and aim Intravenous loop diuretics are the primary treatment for congestion in patients with decompensated heart failure (HF). Furosemide is the most commonly used loop diuretic and is licensed for administration either orally, intramuscularly or intravenously but not subcutaneously. Recently developed, pH-neutral, concentrated, ‘skin-friendly’ preparations of furosemide have been developed which allow subcutaneous administration. In this systematic review, we summarize and critically appraise the current evidence for subcutaneous furosemide in patients with HF. Methods and results The electronic databases MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.gov registry were searched up to 31 December 2023. Of the 17 studies identified, 5 were randomised controlled trials (RCTs), 2 were non-randomised controlled studies, 3 were prospective observational cohort studies, and 7 were retrospective observational studies. All RCTs utilised novel pH-neutral, subcutaneous preparations of furosemide. Bioavailability of novel subcutaneous preparations were similar to intravenous furosemide 10 mg/ml: 99.7% for an 8 mg/ml preparation and 112% for a 30 mg/ml preparation. Natriuresis and diuresis were also similar with novel subcutaneous and conventional intravenous furosemide. Adverse events of novel preparations included infusion site pain or discomfort, localised skin erythema and minimal swelling. All studies of conventional subcutaneous furosemide were non-randomised with very limited data re bioavailability or diuretic and natriuretic effect. Conventional subcutaneous furosemide was associated with substantial skin irritation (affecting 3–23% of patients), and skin infections requiring treatment with antibiotics (3–17%). Conclusions Novel, pH-neutral preparations of subcutaneous furosemide achieved similar diuresis, natriuresis, and bioavailability to intravenous furosemide, and were well tolerated. Novel preparations may be a treatment option for patients with HF.

Chemical analysis, antibacterial and anti-inflammatory effect of Achillea fragrantissima essential oil growing wild in Egypt

BackgroundAchillea fragrantissima (F. Asteraceae) is traditionally used to treat skin infections and inflammation. The present work intended to prepare essential oils (EOs) from A. fragrantissima aerial parts growing widely in Egypt and investigate its antibacterial activity against skin-related pathogens and in vitro cell-based anti-inflammatory activity.MethodsEOs of the fresh aerial parts were extracted by hydrodistillation (HD), microwave-assisted hydrodistillation (MAHD), and head-space (HS), while those of the dried ones were prepared by supercritical fluid (SF). The result EOs were analyzed using GC/MS. The antibacterial activity was evaluated alongside Pseudomonas aeruginosa ATCC 9027, Escherichia coli ATCC 8739, Staphylococcus aureus ATCC 25923, Streptococcus pyogenes ATCC 12344, Clostridium perfringens ATCC 13124 by agar diffusion, microwell dilution, and biofilm formation tests. The anti-inflammatory activity was evaluated by measuring tumor necrosis factor-alpha (TNF-α), interleukin 2 (IL-2), and 6 (IL-6) in lipopolysaccharides (LPS)- stimulated RAW 264.7 cells using ELISA assays in addition, expression of nitric oxide synthase (iNOS) was measured via western blot.ResultsThe SF method gave the highest EO yield (1.50 mL v/w). Oxygenated components constituted the highest percentage in the four methods, 84.14, 79.21, 73.29 and 33.57% in the HS, HD, MAHD, and SF, respectively. Moreover, variation in the amount of identified compounds was apparent; in HS EO α-thujone (29.37%), artemisia ketone (19.59%), and santolina alcohol (14.66%) are major components, while α-thujone (20.38%) and piperatone (12.09%) were significant in HD. Moreover, ( +)-spathulenol (12.22%) and piperatone (10.48%) were significant in MAHD, while piperatone (14.83%) and β-sitosterol (11.07%) were significant in SF EO. HD, MAHD, and SF EOs exhibited susceptibility against P. aeruginosa (IZ = 9–14 mm), E. coli (11–13 mm), and C. perfringens (IZ = 10–14 mm) in agar diffusion assay. MAHD EOs demonstrated potent growth inhibition (MICs = 0.25–2 mg/mL), followed by HD EOs (MICs = 13–52 mg/mL) to all tested microorganisms in well microdilution assay. Also, they exert MBC values equal to or higher than the MICs. Furthermore, SF EOs inhibited the biofilm formation of all tested microorganisms by 65.12—80.84%. Specifically, MAHD and HD EOs efficiently suppress the biofilm of S. pyogenes (77.87%) and P. aeruginosa (60. 29%), respectively. Ultimately, HD and SF EOs showed anti-inflammatory activity by suppressing the TNF-α, IL-2, and IL-6 release and iNOS expression in LPS-stimulated RAW 264.7 macrophages.ConclusionA. fragrantissima EO is rich in oxygenated volatile compounds with antibacterial and anti-inflammatory activities. It is encouraged as a bioactive agent for adjusting skin infections, though additional studies are essential for their safety in clinical settings.

ECRG4 mediates host response to cutaneous infection by regulating neutrophil recruitment and adhesion receptor expression

ECRG4 mediates host response to cutaneous infection by regulating neutrophil recruitment and adhesion receptor expression

Crystal structure of N-terminally hexahistidine-tagged Onchocerca volvulus macrophage migration inhibitory factor-1.

Onchocerca volvulus causes blindness, onchocerciasis, skin infections and devastating neurological diseases such as nodding syndrome. New treatments are needed because the currently used drug, ivermectin, is contraindicated in pregnant women and those co-infected with Loa loa. The Seattle Structural Genomics Center for Infectious Disease (SSGCID) produced, crystallized and determined the apo structure of N-terminally hexahistidine-tagged O. volvulus macrophage migration inhibitory factor-1 (His-OvMIF-1). OvMIF-1 is a possible drug target. His-OvMIF-1 has a unique jellyfish-like structure with a prototypical macrophage migration inhibitory factor (MIF) trimer as the `head' and a unique C-terminal `tail'. Deleting the N-terminal tag reveals an OvMIF-1 structure with a larger cavity than that observed in human MIF that can be targeted for drug repurposing and discovery. Removal of the tag will be necessary to determine the actual biological oligomer of OvMIF-1 because size-exclusion chomatographic analysis of His-OvMIF-1 suggests a monomer, while PISA analysis suggests a hexamer stabilized by the unique C-terminal tails.

Evaluation of biofilm formation and antimicrobial susceptibility (drug resistance) of Candida albicans isolates.

Candida albicans comprises over 80% of isolates from all forms of human candidiasis. Biofilm formation enhances their capacity to withstand therapeutic treatments. In addition to providing protection, biofilm formation by C. albicans enhances its pathogenicity. Understanding the fundamental mechanisms underlying biofilm formation is crucial to advance our understanding and treatment of invasive Candida infections. An initial screening of 57 Candida spp. isolates using CHROMagar Candida (CHROMagar) media revealed that 46 were C. albicans. Of these, 12 isolates (33.3%) had the capacity to form biofilms. These 12 isolates were subjected to multiple biochemical and physiological tests, as well as 18S rRNA sequencing, to confirm the presence of C. albicans. Upon analysis of their sensitivity to conventional antifungal agents, the isolates showed varying resistance to terbinafine (91.6%), voriconazole (50%), and fluconazole (42%). Among these, only CD50 showed resistance to all antifungal agents. Isolate CD50 also showed the presence of major biofilm-specific genes such as ALS3, EFG1, and BCR1, as confirmed by PCR. Exposure of CD50 to gentamicin-miconazole, a commonly prescribed drug combination to treat skin infections, resulted in elevated levels of gene expression, with ALS3 showing the highest fold increase. These observations highlight the necessity of understanding the proteins involved in biofilm formation and designing ligands with potential antifungal efficacy.

A peptide targeting outer membrane protein A of Acinetobacter baumannii exhibits antibacterial activity by reducing bacterial pathogenicity.

The World Health Organization has classified multidrug-resistant (MDR) Acinetobacter baumannii as a significant threat to human health, necessitating the urgent discovery of new antibacterial drugs to combat bacterial resistance. Outer membrane protein A of A. baumannii (AbOmpA) is an outer membrane-anchored β-barrel-shaped pore protein that plays a critical role in bacterial adhesion, invasion, and biofilm formation. Therefore, AbOmpA is considered a key virulence factor of A. baumannii. Herein, we screened three phage display peptide libraries targeting AbOmpA and identified several peptides. Among them, P92 (amino acid sequence: QMGFMTSPKHSV) exhibited the highest binding affinity with AbOmpA, with a KD value of 7.84 nM. In vitro studies demonstrated that although P92 did not directly inhibit bacterial growth, it significantly reduced the invasion and adhesion capabilities of multiple clinical isolates of MDR A. baumannii and concentration-dependently inhibited biofilm formation by acting on OmpA. Furthermore, the polymerase chain reaction results confirmed a significant positive correlation between the antibacterial effect of P92 and OmpA expression levels. Encouragingly, P92 also displayed remarkable therapeutic efficacy against A. baumannii infection in various models, including an in vitro cell infection model, a mouse skin infection model, and a mouse sepsis model. These results highlight P92 as a novel and highly effective antimicrobial molecule specifically targeting the virulence factor AbOmpA.

A large cohort from an immunology reference center and an algorithm for the follow-up of chronic neutropenia.

Chronic neutropenia causes involve nutritional deficiencies and inborn errors of immunity(IEI), such as severe congenital neutropenia. To classify common chronic neutropenia causes in a pediatric immunology unit. We enrolled 109 chronic neutropenia patients admitted to a pediatric immunology department between 2002-2022. We recorded clinical/laboratory features and genetic characteristics. The male/female ratio was 63/46. Fifty-eight patients had parental consanguinity(57.4%). 26.6% (n = 29) patients had at least one individual in their family with neutropenia. Common symtpoms at presentation were upper respiratory tract infections(URTI)(31.1%), oral aphthae(23.6%), skin infections(23.6%), pneumonia(20.8%), and recurrent abscesses(12.3%). Common infections during follow-up were URTI(56.8%), pneumonia(33%), skin infections(25.6%), gastroenteritis(18.3%), and recurrent abscesses(14,6%). Common long-term complications were dental problems(n = 51), osteoporosis(n = 22), growth retardation(n = 14), malignancy(n = 16)[myelodysplastic syndrome(n = 10), large granulocytic leukemia(n = 1), acute lymphoblastic leukemia(n = 1), Hodgkin lymphoma(n = 1), EBV-related lymphoma(n = 1), leiomyosarcoma(n = 1), and thyroid neoplasm(n = 1)]. We performed a genetic study in 86 patients, and 69(71%) got a genetic diagnosis. Common gene defects were HAX-1(n = 26), ELA-2 (ELANE)(n = 10), AP3B1(n = 4), and ADA-2(n = 4) gene defects. The IEI ratio(70.6%) was high. GCSF treatment(93.4%), immunoglobulin replacement therapy(18.7%), and HSCT(15.9%) were the treatment options. The mortality rate was 12.9%(n = 14). The most common long term complications were dental problems that is three times more common in patients with known genetic mutations. We prepared an algorithm for chronic neutropenia depending on the present cohort. An important rate of inborn errors of immunity, especially combined immunodeficiency(11.9%) was presented in addition to congenital phagocytic cell defects. Early diagnosis will allow us tailor the disease-specific treatment options sooner, preventing irreversible consequences.

A Prospective Observational Study on Hand, Foot, and Mouth Disease: Incidence of Secondary Bacterial Skin Infections

A Prospective Observational Study on Hand, Foot, and Mouth Disease: Incidence of Secondary Bacterial Skin Infections

Primary cutaneous infections with non-tuberculous mycobacteria: a report of 6 cases

BackgroundThe incidence of non-tuberculous mycobacterium infection has shown a gradual increasing trend in recent years, among which cutaneous manifestations as an important aspect. This study aimed to describe the clinical features and microbiological findings in 6 cases of primary cutaneous nontuberculous mycobacterium infection.MethodsIn this retrospective study from June 2021 to June 2022, the clinical data and microbiological results of six cases diagnosed with primary cutaneous non-tuberculous mycobacterium infection in department of dermatology, Hangzhou Third People’s Hospital were analyzed.ResultsAll six cases were primary cutaneous non-tuberculous mycobacterium infections, four of which had a history of trauma or exposure, and two had an underlying disease that could lead to compromised immunity. All patients presented with erythema nodular skin lesions, four on the upper or lower extremities, one on the face, and one on the right hip. The histopathological findings of five patients who underwent biopsy were granulomatous inflammatory changes with mixed infiltration. Laboratory cultures using tissue or tissue fluid were all successful, including four Mycobacterium marinum, one Mycobacterium abscessus, and one Mycobacterium avium. Metagenomics next-generation sequencing detected results consistent with culture colonies in only two cases. With the exception of case 4, all patients responded well to oral medication, with a course of treatment ranging from 4 months to 1 year, and the prognosis was good.ConclusionsThe clinical features of primary cutaneous non-tuberculous mycobacterium infection are often lacking in specificity, and the identification of related strains is difficult for a variety of reasons. Although the results of metagenomics next-generation sequencing are useful for pathogen spectrum identification, its diagnostic value should be carefully reevaluated under certain circumstances. Patients with suspected triggers who do not respond well to conventional treatments should be suspected as atypical infection and potential immunosuppression. If diagnosed and treated promptly, the prognosis of primary cutaneous non-tuberculous mycobacterium infection is generally good.

Photogallery. Fungal lesions of skin and nails infections in HIV-associated immunodeficiency

Against the background of any immunodeficiency, including that caused by HIV infection, the risk of developing superficial and invasive fungal diseases increases. Among people living with HIV, the most common fungal skin lesions are candidiasis, rubromycosis, and pityriasis versicolor. As immunosuppression worsens in HIV-positive patients not on antiretroviral therapy, the frequency and severity of mycoses increases. Thus, rubromycosis can spread beyond the feet, covering large areas of skin; sometimes the smooth skin of the hands, large folds, and areas of long hair growth are affected. In this case, the peripheral inflammatory ridge along the edge of the lesions, characteristic of rubromycosis, is sometimes absent. According to some reports, over half of patients in the secondary disease stage of HIV infection suffer from onychomycosis. The progression of the disease often occurs in a short time. In addition to the nail plates of the feet, the nails on the hands are often affected. In patients with HIV infection who do not receive antiretroviral therapy, difficult-to-treat onychomycosis occurs. Cryptococcosis is an opportunistic mycosis caused by yeast-like fungi Cryptococcus spp. It usually develops in HIV-positive individuals with a CD4+ T-lymphocyte level of less than 100 cells/μl. Skin lesions are usually secondary and indicate cryptococcal dissemination. Dermatological manifestations of cryptococcosis are varied. These may include papules and nodules surrounded by erythema and prone to ulceration, vesicular, pustular, herpetiform, acne-like rashes, ulcerative-necrotic lesions. We present to your attention a photogallery of cases of fungal skin lesions that developed against the background of HIV-associated immunosuppression.

Biochemical analysis of soft tissue infectious fluids and its diagnostic value in necrotizing soft tissue infections: a 5-year cohort study

BackgroundNecrotizing soft tissue infections (NSTI) are rapidly progressing and life-threatening conditions that require prompt diagnosis. However, differentiating NSTI from other non-necrotizing skin and soft tissue infections (SSTIs) remains challenging. We aimed to evaluate the diagnostic value of the biochemical analysis of soft tissue infectious fluid in distinguishing NSTIs from non-necrotizing SSTIs.MethodsThis cohort study prospectively enrolled adult patients between May 2023 and April 2024, and retrospectively included patients from April 2019 to April 2023. Patients with a clinical suspicion of NSTI in the limbs who underwent successful ultrasound-guided aspiration to obtain soft tissue infectious fluid for biochemical analysis were evaluated and classified into the NSTI and non-necrotizing SSTI groups based on their final discharge diagnosis. Common extravascular body fluid (EBF) criteria were applied.ResultsOf the 72 patients who met the inclusion criteria, 10 patients with abscesses identified via ultrasound-guided aspiration were excluded. Based on discharge diagnoses, 39 and 23 patients were classified into the NSTI and non-necrotizing SSTI groups, respectively. Biochemical analysis revealed significantly higher albumin, lactate, lactate dehydrogenase (LDH), and total protein levels in the NSTI group than in the non-necrotizing SSTI group, and the NSTI group had significantly lower glucose levels and pH in soft tissue fluids.In the biochemical analysis, LDH demonstrated outstanding discrimination (area under the curve (AUC) = 0.955; p < 0.001) among the biochemical markers. Albumin (AUC = 0.884; p < 0.001), lactate (AUC = 0.891; p < 0.001), and total protein (AUC = 0.883; p < 0.001) levels also showed excellent discrimination. Glucose level (AUC = 0.774; p < 0.001) and pH (AUC = 0.780; p < 0.001) showed acceptable discrimination. When the EBF criteria were evaluated, the total scores of Light’s criteria (AUC = 0.925; p < 0.001), fluid-to-serum LDH ratio (AUC = 0.929; p < 0.001), and fluid-to-serum total protein ratio (AUC = 0.927; p < 0.001) demonstrated outstanding discrimination.ConclusionBiochemical analysis and EBF criteria demonstrated diagnostic performances ranging from acceptable to outstanding for NSTI when analyzing soft tissue infectious fluid. These findings provide valuable diagnostic insights into the recognition of NSTI. Further research is required to validate these findings.

Evaluating omadacycline dosing regimens against drug-resistant pathogens including Staphylococcus aureus, Streptococcus pneumoniae and Haemophilus influenzae in adults: a pharmacokinetic/pharmacodynamic analysis using Monte Carlo simulation.

The objective of this study was to evaluate the efficacy of various dosing regimens of omadacycline against main drug-resistant pathogens in the treatment of acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). Monte Carlo simulations were conducted using pharmacokinetic parameters and pharmacodynamic data to calculate cumulative fractions of response (CFRs) in terms of drug area under the concentration curve/minimum inhibition concentration targets.CFR ≥ 90% was considered optimal for a dosage regimen. CFR of any approved oral/intravenous regimen with loading-dose was ≥ 90% against methicillin-resistant Staphylococcus aureus (MRSA) for ABSSSI and penicillin-resistant Streptococcus pneumonia, tetracycline-resistant Streptococcus pneumonia, MRSA and β-lactamase positive Haemophilus influenzae for CABP. In conclusion, approved oral/intravenous loading and maintenance doses of omadacycline showed enough efficacy in the treatment of ABSSI and CABP caused by the main drug-resistant pathogens.

Formulation and Optimization of Solid Lipid Nanoparticle-based Gel for Dermal Delivery of Linezolid Using Taguchi Design.

Linezolid (LNZ) is a synthetic oxazolidinone antibiotic approved for the treatment of uncomplicated and complicated skin and soft tissue infections caused by gram-positive bacteria. Typically, LNZ is administered orally or intravenously in most cases. However, prolonged therapy is associated with various side effects and life threatening complications. Cutaneous application of LNZ will assist in reducing the dose, hence minimizing the unwanted side/adverse effects associated with oral administration. Dermal delivery provides an alternative route of administration, facilitating a local and sustained concentration of the antimicrobial at the site of infection. The current research work aimed to formulate solid lipid nanoparticles (SLNs) based gel for dermal delivery of LNZ in the management of uncomplicated skin and soft tissue infections to maximise its benefits and minimise the side effects. SLNs were prepared by high-shear homogenisation and ultrasound method using Dynasan 114 as solid lipid and Pluronic F-68 as surfactant. The effect of surfactant concentration, drug-to-lipid ratio, and sonication time was investigated on particle size, zeta potential, and entrapment efficiency using the Taguchi design. The main effect plot of means and signal-to-noise ratio were generated to determine the optimized formulation. The optimized batch was formulated into a gel, and ex-vivo permeation study, in-vitro and in-vivo antibacterial activity were conducted. The optimised process parameters to achieve results were 2% surfactant concentration, a drug-to-lipid ratio of 1:2, and 360 s of sonication time. The optimized batch was 206.3± 0.17nm in size with a surface charge of -24.4± 4.67mV and entrapment efficiency of 80.90 ± 0.45%. SLN-based gel demonstrated anomalous transport with an 85.43% in vitro drug release. The gel showed a 5 cm zone of inhibition while evaluated for in vitro antibacterial activity against Staphylococcus aureus. Ex-vivo skin permeation studies demonstrated 20.308% drug permeation and 54.96% cutaneous deposition. In-vivo results showed a significant reduction in colony-forming units in the group treated with LNZ SLN-based gel. Ex-vivo studies ascertain the presence of the drug at the desired site and improve therapy. In-vivo results demonstrated the ability of SLN-based gel to significantly reduce the number of bacteria in the stripped infection model. The utilization of SLN as an LNZ carrier holds significant promise in dermal delivery.

A multivariable model of clinical features for distinguishing sporotrichosis and Mycobacterium marinum cutaneous infection

To investigate differences in the clinical features of patients with sporotrichosis and cutaneous Mycobacterium marinum infection, and develop a prediction model for the initial identification. A total of 121 patients were selected based on the results from etiological culture. Logistic regression analyses were employed to identify the most valuable variables. In the multivariate logistic regression analysis, the following were finally considered independent predictors (OR = 3.650∼14.024, P<0.05) of cutaneous M. marinum infection: age<60 years (P = 0.031); female (P = 0.001); only the extremities involved (P = 0.031); clear triggers (P = 0.022); and presence of swelling (P = 0.024). A nomogram was developed based on these factors, and the area under the curve was 0.860. The model presented is based on clinical features and can help identify patients with sporotrichosis and cutaneous M. marinum infection. This may help increase the accuracy of doctors’ initial examination and diagnostic outcomes.

Nanoformulations Insights: A Novel Paradigm for Antifungal Therapies and Future Perspectives.

Currently, fungal infections are becoming more prevalent worldwide. Subsequently, many antifungal agents are available to cure diseases like pemphigus, athlete's foot, acne, psoriasis, hyperpigmentation, albinism, and skin cancer. Still, they fall short due to pitfalls in physiochemical properties. Conventional medications like lotion, creams, ointments, poultices, and gels are available for antifungal therapy but present many shortcomings. They are associated with drug retention and poor penetration problems, resulting in drug resistance, hypersensitivity, and diminished efficacy. On the contrary, nanoformulations have gained tremendous potential in overcoming the drawbacks of conventional delivery. Furthermore, the potential breakthroughs of nanoformulations are site-specific targeting. It has improved bioavailability, patient-tailored approach, reduced drug retention and hypersensitivity, and improved skin penetration. Nowadays, nanoformulations are gaining popularity for antifungal therapy against superficial skin infections. Nanoformulations-based liposomes, niosomes, nanosponges, solid lipid nanoparticles, and potential applications have been explored for antifungal therapy due to enhanced activity and reduced toxicity. Researchers are now more focused on developing patient-oriented target-based nano delivery to cover the lacunas of conventional treatment with higher immune stimulatory effects. Future direction involves the construction of novel nanotherapeutic devices, nanorobotics, and robust methods. In addition, for the preparations of nanoformulations for clinical studies, animal modeling solves the problems of antifungal therapy. This review describes insights into various superficial fungal skin infections and their potential applications, nanocarrier-based drug delivery, and mechanism of action. In addition, it focuses on regulatory considerations, pharmacokinetic and pharmacodynamic studies, clinical trials, patents, challenges, and future inputs for researchers to improve antifungal therapy.

Construction and evaluation of transdermal delivery system of terbinafine-loaded plant exosomes for the treatment of cutaneous fungal infections

Local transdermal of antifungal agents is a problem that limits the effectiveness of clinical treatment of dermatomycosis. In this study, cucumber-derived plant extracellular vesicles (PEV) were extracted and loaded with the antifungal drug terbinafine (TBF) to form TBF-PEV, which was applied locally to the site of skin fungal infection to improve the transdermal transport capacity of TBF and the antifungal effect in vitro and in vivo. Chemical enhancer and physical enhancer methods were replaced by low immunogenicity and non-irritating PEV. TBF-PEV caused obvious curling and wrinkling in the skin, induced changes in the distribution of skin lipids, and changed the structure and content of skin lipids and proteins, thereby increasing the transdermal efficiency of TBF. The local drug concentration was increased, and the antifungal effect was improved in vitro and in vivo. It was first found that PEV inhibited the growth of Candida albicans with high efflux pump expression. In general, this paper has certain significance in local transdermal treatment of fungal skin infections and reversal of fungal resistance.

Extrapulmonary Mycobacterium abscessus Infections, France, 2012-20201.

Mycobacterium abscessus infection is challenging to treat. Extrapulmonary M. abscessus infections (EP-MAB) are less common than pulmonary M. abscessus infections. To evaluate treatment regimens, we retrospectively analyzed consecutive microbiologically confirmed EP-MAB cases diagnosed in France during 2012-2020. We studied 45 patients with EP-MAB, including 14 bone and joint infections, 10 skin and soft tissue infections, and 8 lymph node infections. Most (62%) patients had no reported immunodeficiency. In 27 patients, EP-MAB followed healthcare-associated (44%) or environmental (16%) injuries. Of the 45 isolates, 25 were subspecies abscessus, 10 bolletii, and 9 massiliense; 1 was unidentified. Cure was achieved for 36 (80%) patients who received a median antimicrobial regimen of 6 months; 22 (55%) also underwent surgery. Four patients died, and 5 were unavailable for follow-up. EP-MAB predominantly affects immunocompetent patients after an injury; outcomes are favorable. We propose a >6-month regimen of antimicrobial therapy with consideration for surgery and regular patient reassessment.

Pulmonary manifestations in hyper IgE syndrome: A case series and review of Indian literature.

Recurrent pulmonary infections starting from childhood often prompt evaluation for primary immunodeficiency disorders (PIDs). Hyper IgE syndrome (HIES) is a less common PID characterised by recurrent skin and pulmonary infections associated with elevated IgE levels. Staphylococcal infections are more commonly seen in these individuals, resulting in structural lung abnormalities such as pneumatoceles and bronchiectasis. The associated non-immunologic features (characteristic facies, retained primary dentition, scoliosis, osteopenia, and hyperextensible joints) should raise suspicion of this syndrome. We present four cases of HIES and review the pulmonary manifestations in this disease as reported in the Indian literature.