Skin Infections Research Articles

Phytochemical Analysis and Evaluation of the Antifungal Activity of Five Plants against Four Dermatophytes Responsible for Superficial Infections

This study is of great interest due to the rise in superficial infections caused by dermatophytes and the need to find natural alternatives to synthetic antifungals. The objective of this research was to determine the phytochemical composition and antifungal activity of total extracts from five plants: Zanthoxylum gilletii, Distemonanthus benthamianus, Gmelina arborea, Justicia secunda, and Anacardium occidentale against four dermatophytes, namely Microsporum canis, Trichophyton mentagrophytes, Trichophyton rubrum, and Trichophyton soudanense. To achieve this, aqueous and hydroethanolic extracts were prepared and subjected to phytochemical analysis, followed by evaluations of antifungal activity using the slant double-tube method. Antifungal parameters (IC50 and MFC) were determined. The results revealed the presence of various bioactive compounds, such as flavonoids, tannins, and alkaloids, in most of the extracts. Z. gilletii and D. benthamianus showed strong efficacy, with IC50 values of 0.004 to 0.00609 mg/mL and 0.018 to 0.155 mg/mL, and MFC values of 0.0975 to 0.39 mg/mL and 0.39 to 12.5 mg/mL respectively, particularly against M. canis and T. soudanense. In contrast, A. occidentale showed no significant antifungal activity. This study thus highlights the potential of plant extracts in the treatment of skin infections and justifies further research to explore their clinical application.

Trichophyton indotineae Erg1Ala448Thr Strain Expressed Constitutively High Levels of Sterol 14-α Demethylase Erg11B mRNA, While Transporter MDR3 and Erg11A mRNA Expression Was Induced After Addition of Short Chain Azoles

Trichophyton indotineae is an emerging pathogen causing recalcitrant skin infections and exhibiting multiple resistances to azoles and allylamines. Squalene epoxidase erg1Ala448Thr mutants often show association with azole resistance. RT-PCR gene expression analysis helps to elucidate the connection between ergosterol biosynthesis regulation and efflux control through the activation of multidrug resistance (MDR) and major facilitator superfamily (MFS1) transporters as well as heat shock proteins (HSP). Several T. indotineae isolates demonstrated a heat-dependent increase of Erg11B transcripts combined with downregulation of Erg1, suggesting a protective role for Erg11B. They also showed persistent upregulation of MFS1. The addition of fluconazole or voriconazole induced the expression of Erg11A, MDR3 and, to a lesser extent, Erg11B and Erg1. The azole-resistant erg1Ala448Thr mutant UKJ 476/21 exhibited exceptionally high transcript levels of sterol 14-αdemethylase Erg11B, combined with the inability of HSP60 and HSP90 to respond to increasing growth temperatures. Itraconazole demonstrated similar effects in a few T. indotineae isolates, but terbinafine did not enhance Erg1 transcription at all. Overexpression of Erg11B may explain the multiple azole resistance phenotype, whereas Erg11B point mutations are not associated with resistance to azoles used for medical treatment.

Biochemical and biological studies of irradiated and non-irradiated extracts of Solanum aculeastrum Dunal fruit

This study explores the impact of γ-irradiation on ethanolic extracts of Solanum aculeastrum Dunal. The anti-cancer and antimicrobial properties were investigated. The obtained results revealed that total phenol (TP) and total flavonoid (TF) of total ethanol extract (100%) (FTE) were higher than 70% ethanol extract (SE), and these contents increased after gamma radiation with 5 kGy. The results of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the Solanum aculeastrum extracts suggested that FTE and 5 kGy-irradiated FTE can be used to control and prevent skin infections caused by MRSA and endocarditis, urinary tract infections, and prostatitis caused by Enterococcus faecalis. The FTE sample irradiated at 5 kGy showed cytotoxicity for A431 and Hct-116 cell lines similar to the control sample and higher than the toxicity revealed by the samples irradiated at 10 kGy. In normal cells (Bj-1), the toxicity was decreased after irradiation (IC50 = 31 μg/ml) compared to the non-irradiated extract (IC50 = 26.1 μg/ml). Molecular docking suggested Sortase A to play a role in chlorogenic acid antibacterial activity towards Staphylococcus aureus. In conclusion, γ-irradiation can be used to enhance the phytoconstituents of Solanum aculeastrum fruit extracts and, consequently, its biological properties.

A triple-mode strategy combining low-temperature photothermal, photodynamic, and chemodynamic therapies for treating infectious skin wounds.

The skin is the first natural barrier of the human body. Bacterial infections severely hinder the healing process of skin wounds and pose a great threat to human health. Therefore, it is particularly urgent to develop new antimicrobial strategies for bacterial pathogen clearance and wound healing. In this study, a metal-organic framework (MOF), Fe-MIL88B-NH2, was incorporated with the photosensitizer indocyanine green (ICG) to construct composite nanoparticles (MOF@ICG NPs) with multiple antibacterial activities. Under mild near-infrared (NIR) irradiation, the photosensitizer ICG in the MOF@ICG NPs undergoes photothermal conversion (∼45 °C) and photodynamic reactions to generate heat and singlet oxygen (1O2). In addition, the Fenton reaction of the NPs with hydrogen peroxide (H2O2) in the bacterial infection microenvironment resulted in the generation of hydroxyl radicals (˙OH), thus achieving the three-mode combination of low-temperature photothermal therapy (PTT)/photodynamic therapy (PDT)/chemodynamic therapy (CDT). The in vitro experimental results showed that MOF@ICG MPs had excellent antibacterial properties and good cytocompatibility, with some ability to promote the migration of L-929 fibroblasts. Furthermore, under NIR irradiation, MOF@ICG NPs could significantly kill bacteria and promote skin wound healing according to the results of animal experiments. The wound healing rate reached 87.1% after 7 days of treatment. The research results break through the limitations of single-mode antibacterial technology and provide certain theoretical guidance and technical support for the research and development of new antibacterial materials.

Infectious complications of Stevens-Johnson syndrome and toxic epidermal necrolysis: A systematic review and meta-analysis.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare severe cutaneous adverse reactions to medications characterized by keratinocyte necrosis leading to loss of protective barrier function and increased susceptibility to infection. Infection is a major cause of morbidity, and septicemia is the leading cause of mortality in this population. This systematic review and meta-analysis aimed to determine infectious complications' prevalence and risk factors in adults with SJS and TEN. This review was registered with the International Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY) and conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. Thirty-six articles describing results from 1446 cases were included. Skin infection was the most commonly diagnosed infection. The pooled prevalence of sepsis, respiratory tract infection, skin infection, and urinary tract infection was 27.3%, 21.5%, 37.5%, and 21.8%, respectively. Staphylococcus aureus was the most commonly identified organism. The overall quality of the studies was suboptimal, and the level of heterogeneity was high. The skin, bloodstream, respiratory, and urinary tracts are most commonly infected in the course of adult SJS and TEN. During hospitalization, clinicians should closely monitor and promptly investigate for these as well as several other infectious complications. More research is needed, with greater attention to the risk factors and causative organisms that cause these infections.

Radical-Scavenging Violet Phosphorus Nanosheets for Attenuating Hyperinflammation and Promoting Infected Wound Healing.

Antibacterial therapy targeting the regulation of macrophage polarization may be a useful approach for normalizing the immune environment and accelerating wound healing. Inspired by black phosphorus-based nanoplatforms, more stable yet less-explored violet phosphorus nanosheets (VPNSs) are expected to provide a superior solution for effectively combating bacterial infections. In this study, an average thickness of 5-7nm VPNSs arefabricated through the liquid-phase exfoliation method to serve as an immunoregulatory dressing for the treatment of infected wounds. VPNSs attenuated excessive reactive oxygen species (ROS) and reduced the accumulation of proinflammatory M1 macrophages, showing notable antioxidant and anti-inflammatory properties. Comprehensive RNA sequencing further elucidated the potential immunoregulatory mechanisms of VPNSs, including modulation of the inflammatory response and enzyme regulator activity. Additionally, the inherent photothermal properties of the VPNSs contributed significantly to their antibacterial efficacy. When combined with near-infrared laser irradiation, VPNSs showed remarkable effectiveness in reducing infection-related complications and expediting wound healing in infected skin wound models. The rapid promotion of wound healing through ROS clearance, the regulation of macrophage polarization, and hyperthermia generation underscores the potential of the violet-phosphorus-based nanoplatforms as clinically viable agents for treating infected wounds. This study suggests that VPNSs are promising candidates for clinical anti-infective and anti-inflammatory applications.

Investigation of Bacterial Outer Membrane Proteins and Suggesting Antiadhesive Agents from Guava Plant in Skin Infections

Klebsiella pneumoniae is an opportunistic pathogenic bacterium belonging to Enterobacteriaceae family that owns outer membrane proteins called omp35 and omp36 which are responsible for colonization and adhesion to host tissues such as skin. Twenty pre-diagnosed bacterial isolates of K. pneumoniae of wounds and burn swabs were selected in this study, and the diagnosis was confirmed by VITEK-2 automated system. Whole DNA was isolated then amplified by PCR then gel electrophoresis was performed to detect the prevalence of the genes that encode both of omp35 and omp36 in bacterial isolates. Phylogenetic tree of both studied genes was conducted to investigate the precursor of tested isolates in relation to NCBI data. Virtually, the affinity of two medicinal components of fruit Guava (Psidium guajava L.), which are Quercetin and L-arabinopyranoside, were tested as antiadhesive materials against omp35 and omp35 proteins by molecular docking tools. Results showed that 15 out of 20 skin-infecting K. pneumoniae isolates owned both omp35 and omp36 genes as detected by gel electrophoresis and the phylogenetic trees of both genes illustrated that they were related to surgical and nosocomial swab infection precursors in their origin in NCBI. High affinity of Quercetin was recorded towards omp35 protein and omp36 protein which were (-8.1 and -7.8) respectively, in the same time the affinity of L-arabinopyranoside was (-5.2 and -5.3) towards omp35 and omp36 proteins; resulting in suggesting medicinal ingredients of Guava fruit to prevent adhesion and colonization of K. pneumoniae and other Enterobacteriaceae members which might invade wounded skin by bacterial outer membrane proteins.

Otomycosis Caused by Trichophyton mentagrophytes: About Two Cases

Otomycosis is a common superficial fungal infection that affects the external auditory canal. The infection may present as acute, subacute, or chronic, and is typically unilateral, the species causing fungal infection in the ear include molds, yeasts. Members of the dermatophytes, normally seen from infected skin and nails, have seldom been implicated in otomycosis. Both patients had presented with unilateral ear pain and reduced hearing. on examination of a swab, secretions bearing fungal filaments of dermatophyte elements. Culture yielded Trichophyton mentagrophytes. The dermatophytic infection of the ear is a rare condition whose symptoms are not specific and their diagnosis requiring a careful sampling and mycological examination.

Prediction of lumpy skin disease virus using customized CBAM-DenseNet-attention model

Lumpy skin disease virus (LSDV) is an extremely infectious, viral, and chronic skin disease that is caused by the Capripox virus. This viral disease is predominantly found in cows. Mosquitoes and ticks are the primary transmitters for the spread of this virus. Recently, LSDV has been rapidly spreading all over the world, especially in several areas of Pakistan, India, and Iran. Thousands of cows have died due to this infectious virus in Pakistan and early detection of LSDV is needed to avoid further loss. The prediction and classification of LSDV are hindered by the lack of publicly available datasets. Despite a few studies using LSDV datasets, such datasets are often small, which may lead to model overfitting. In this regard, we collect the dataset from several online sources, as well as, collecting images from veterinary farms in different areas of Pakistan. Deep learning has been widely used in the medical field for disease detection and classification. Therefore, this study leverages DenseNet deep learning models for LSDV detection and classification. Experiments are performed using VGG-16, ResNet-50, MobileNet-V2, custom-designed convolutional neural network, and Inception-V3. The DenseNet architecture presents a Convolutional Block Attention Module (CBAM) and Spatial Attention (SA) for the prediction and classification of LSD. Results demonstrate that a 99.11% accuracy can be obtained on the augmented dataset while a 94.23% accuracy can be achieved with the original dataset for chicken pox, monkey pox, and LSDV. Comparison with state-of-the-art studies corroborates the superior performance of the proposed model.

Negative outcome in cutaneous Mycobacterium marinum infection treated with surgical intervention: Two-case report.

Mycobacterium marinum (M marinum), a slow-growing nontuberculous mycobacterium (NTM), is widely distributed in aquatic environments. It is a well-known cutaneous pathogen, which causes sporotrichosis-like lesions. In this report, we describe 2 cases of subcutaneous M marinum infection. Both patients underwent several surgical procedures at local hospitals, and despite optimal surgical site healing, new lesions appeared in adjacent sites. Based on NTM culture, identification by gene sequencing, and matrix-assisted laser desorption ionization time-of-flight mass spectrometry, the diagnosis of subcutaneous NTM infection was confirmed. The patients were treated with oral rifampicin 0.45 g/day and clarithromycin 1 g/day and oral doxycycline hydrochloride capsules (200 mg/day), respectively. Both patients were treated for 8 and 5 weeks, respectively, and the lesions healed. Surgical debridement cannot compete with or impede NTM lymphatic spread; antimicrobial therapy is the first choice for the treatment of M marinum infections.

Preventing Possible Parasitic Skin Infections After an Earthquake: A Practical Recommendation

Preventing Possible Parasitic Skin Infections After an Earthquake: A Practical Recommendation

A hand-washing community-based educational intervention to reduce abscess incidence among people who inject drugs: a cluster randomised controlled clinical trial protocol (the HAWA study protocol)

BackgroundBesides the high prevalence of HIV and HCV infections, people who inject drugs (PWID) have a cumulative risk of acquiring skin and soft tissue infections (SSTI) from, among other things, social precariousness, homelessness/unstable housing, and unhygienic injecting practices. We propose to evaluate whether a two-component educational hand hygiene intervention which combines training in hand-washing with the supply of a single-use alcohol-based hand rub, called MONO-RUB, is effective in reducing injection-related abscesses in the PWID population. Specifically, we shall implement a nationwide, two-arm, multi-centre, cluster randomised controlled trial to evaluate the effectiveness and cost-effectiveness of this intervention in PWID.MethodsHAWA is a community-based participatory research study to be conducted in 22 harm reduction centres (HR) in France (not yet recruiting); the latter will be randomised into two clusters: centres providing standard HR services and the intervention (i.e., intervention group) and those providing standard HR services only (i.e., control group). After randomization, each cluster will include 220 PWID, with an inclusion period of 12 months and an individual follow-up period of 6 months. For each participant, we will collect data at M0, M3 and M6 from photos of injection sites on the participant’s body, a face-to-face injection-related SSTI questionnaire, and a CATI questionnaire. The primary outcome is the reduction in abscess prevalence between M0 and M6, which will be compared between the control and intervention arms, and measured from observed (photographs) and self-declared (SSTI questionnaire) data. We will also assess the cost-effectiveness of the intervention.DiscussionThe HAWA trial will be the first cluster randomized controlled trial to improve hand hygiene among PWID with a view to reducing SSTI. If effective and cost-effective, the intervention combined with the distribution of MONO-RUBs (or a similar cleaning product) may prove to be an important HR tool, helping to reduce the enormous burden of infection-related deaths and diseases in PWID.Trial RegistrationNCT06131788, received on 2 January 2024.

Monocyte-regulated interleukin 12 production drives clearance of Staphylococcus aureus.

Staphylococcus aureus is a versatile bacterium responsible for conditions ranging from mild skin and soft-tissue infections to serious disorders such as pneumonia and sepsis. Monocytes play a role in protection against pathogens by migrating to inflamed tissues and differentiating into macrophages but their specific role in the context of S. aureus pulmonary infection has not been fully elucidated. Using a CCR2-DTR transgenic mouse model we demonstrate that over the course of infection monocyte depletion resulted in worse airway clearance of S. aureus. The bronchoalveolar lavage fluid (BALF) of CCR2-DTR mice after S. aureus infection displayed significant decreases in interleukin-12 (IL-12), IFN-γ, IP-10, MIG and RANTES, all IFN-γ regulated, compared to wild-type (WT) infected controls. NK cells were identified as the main producers of IFN-γ, but both NK cells and IFN-γ were dispensable for clearance. We demonstrated through cytokine production and RNA-seq analysis that IL-12 and IL-12 regulated genes are strongly induced in monocytes upon S. aureus infection. Administration of IL-12 during infection restored the bacterial burdens in the BALF and lungs of monocyte-depleted CCR2-DTR mice to the levels of WT mice, independent of IFN-γ. In the absence of monocytes, alveolar macrophages are the primary phagocytic cells, and IL-12 influences their capacity to produce reactive oxygen species and clear S. aureus. These results show that production of IL-12 contributes to the control of S. aureus via its influence on alveolar macrophage function.

Expert opinion on candidacy for bone conduction hearing implants Osia System and Baha Connect System.

<b>Introduction:</b> Bone conduction hearing implants (BCHI) are a widely used rehabilitation solution for patients with conductive hearing loss (CHL), mixed hearing loss (MHL), or single-sided deafness (SSD).<b>Aim:</b> This expert review presents candidacy criteria considerations when choosing between active transcutaneous bone-conduction hearing devices (Osia<sup></sup> System) and passive percutaneous bone-conduction hearing devices (Baha<sup></sup> Connect System) to help streamline the decision-making process in those contexts where economics have a major impact on professionals' and patients' choice.<b>Methods:</b> Eight experts participated in two online surveys and two virtual meetings to discuss real-world clinical experience to highlight treatment approaches and factors considered when counseling the patients and selecting an optimal BCHI solution. Key considerations for decision-making were recorded following consensus from all experts.<b>Conclusions:</b> Aspects in decision making include the requirement to use local <i>versus</i> general anesthesia for the implantation procedure, bone thickness, considerations for future magnetic resonance imaging (MRI) procedures, and patient preference. Increased risk of skin infections, requirements for cleaning and managing the implant site, particularly for those with limited dexterity, as well as esthetic concerns could make the Baha<sup></sup> Connect System unsuitable for some patients. In these cases, the Osia<sup></sup> System may provide clear advantages, particularly in patients for whom good hearing performance is a priority, and this would need to be discussed individually with the patient in a multidisciplinary setting. Conversely, for patients requiring minimally invasive surgery, who have contraindications for general anesthesia or require frequent head MRI scans in the future, the Baha Connect System may be more suitable.

Pathological and Fungal Isolation study of dog skin disease in Iraq Governorates

Dogs are susceptible to several types of infectious diseases can be worrisome for their owner because some of them are fatal if not treated soon enough. Fungal infection can be contracted through different parts of body furthermore many of them are zoonotic infection among human and dogs the signs of any disease typical depend on location of infection either local or system infection. Local infection usually involves skin surface that look like wound the objective of this study was to briefly about the most common pathogenic fungal infection in dogs by describing information about the causative agent, clinical signs and grossly appearance with histopathological change skin examination current study were done on 200 dogs collected in Iraq governorates (Baghdad, Erbil, Anbar, Sulaymaniyah) during a period 6 months (January – June) 2023. 200 examined dogs with different age, breed and sex ( k9, ornamental and stray dogs ) were observed fungal isolation and pathological examination with clinical signs by using diagnostic tools for skin biopsies (biopsy punch) from suspected infected skin dogs. Results showed pathogenic fungi after collected on fungal culture for detection pathogenic fungal (Dermatophyte Test Agar) D.T.M Agar Base. Fungal isolation constitutes the following pathogenic fungi (100 infected samples from 200 suspected samples). 60% Aspergillus niger, 30% Trichophyton Verrucosum, 10% Alternaria spp. Clinical signs and grossly lesion showed complete skin ulcer, allopecia, odema, abscessation while microscopic appearance revealed skin ulcer, hyperkeratosis, folliculitis, necrosis, apoptosis, pyogranuloma and granulation tissue with septate hyphae in skin dermis and epidermis which infected with Aspergillus niger.

Protective effect of Tecoma stans (L.) Juss.ex Kunth in CFA-induced arthritic rats

Ethnopharmacological relevanceTecoma stans (L.) Juss.ex Kunth (Bignoniaceae) is mainly found in tropical and subtropical regions of Africa and Asia. The leaves, flowers, roots, and bark are used to treat various aliments includes, skin infections, kidney problems, intestinal disorders, jaundice, toothaches, joint pain and repair cracked bones, antidotes for snake, scorpion, and rat bites. Aim of the studyThe objective of the study is to assess the anti-arthritic properties of T. stans leaf using Complete Freund's adjuvant (CFA)-induced rat. Materials and methodThe ethanol extract of T. stans leaf (ETSL) was subjected toGas Chromatography-Mass Spectrometry (GC-MS) and Liquid Chromatography-Mass Spectrometry (LC-MS) analysis for the identification of potential bioactive. The anti-arthritic activity was carried out by administering CFA (0.1 ml) into the sub-plantar surface of the right hind paw. The experimental animals were treated with indomethacin (10 mg/kg) and ETSL (250, 500 mg/kg) once a day orally for fourteen days. The arthritic parameters and hematological and biochemical parameters were evaluated using standard kit reagents. The levels of pro-inflammatory cytokines and inflammatory mediators were measured in blood serum. Antioxidant parameters were assessed in homogenized liver and joint tissues. Radiological and histopathological analysis of joint was performed. A computational molecular docking investigation of the phytoconstituents was conducted against COX-2, IL-1β, IL-6, and TNF-α receptors. ResultsThe ETSL at 500 mg/kg demonstrated significant (p < 0.01) restoration of arthritic parameters, hematological and biochemical indices and oxidative stress in CFA-induced rats which was further supported by radiological histological examination. In addition, there was significant (p < 0.05) reduction observed in pro-inflammatory cytokines, inflammatory mediators and up-regulation of anti-inflammatory cytokines in the treated group. Verbascoside was found to exhibit better biding affinities −10.4, −7.4, −7 and −6.2 kcal/mol against COX-2, IL-1β, TNF-α, and IL-6 respectively, confirmed through in silico study. ConclusionsThe observed outcome suggests that ETSL at a dosage of 500 mg/kg demonstrated notable anti-arthritic effects by suppressing pro-inflammatory cytokines and oxidative stress biomarkers. This effect could potentially be attributed to the presence of bioactive verbascoside identified in the LC-MS analysis.

New therapeutic approaches for S.aureus infections treatment

Staphylococcus aureus (S. aureus) is an opportunistic pathogen that causes a range of diseases, from mild skin and soft tissue infections and food poisoning to serious conditions such as pneumonia, endocarditis, sepsis, and hospital-acquired infections. Due to the aggressive nature of the disease, limitations of existing treatments, and the spread of antibiotic-resistant strains, the development of alternative strategies to combat bacterial infections has progressed faster than the development of new antibiotics. In this review, we analyze the epidemiological situation of morbidity and mortality associated with S. aureus infection, as well as antimicrobial resistance of this organism on a global scale. We reviewed the pathogenesis and virulent factors of S. aureus, their mechanisms of antibiotic resistance, and the importance of diagnosing staphylococcal infections to ensure timely intervention. This review also discusses the latest approaches to combating antibiotic resistance in Staphylococcus aureus, including preventive and therapeutic antimicrobial strategies. Such methods as the use of bacteriophages in treatment, antimicrobial peptides, probiotic microorganisms and their metabolites, and the use of inhibitors to suppress bacterial communication are considered.

Validation of MEWS, NEWS, NEWS-2 and qSOFA for different infection foci at the emergency department, the acutelines cohort.

Sepsis is a leading cause of morbidity and mortality globally. The lack of specific prognostic markers necessitates tools for early risk identification in patients with suspected infections in emergency department (ED). This study evaluates the prognostic accuracy of various Early Warning Scores (EWS)-MEWS, NEWS, NEWS-2, and qSOFA-for in-hospital mortality, 30-day mortality, and ICU admission, considering the site of infection. A retrospective analysis was conducted using data from the Acutelines cohort, which included data collected from patients admitted to the University Medical Centre Groningen ED between September 2020 and July 2023. Patients were included if they had an ICD-10 code for infection. EWS were calculated using clinical data within 8h post-admission. Predictive performance was assessed using AUC-ROC, calibration by the Hosmer-Lemeshow test and calibration curves, and operative characteristics like sensitivity and specificity. A total of 1661 patients were analyzed, with infections distributed as follows: lower respiratory tract (32.9%), urinary tract (30.7%), abdominal (12.5%), skin and soft tissue (9.5%), and others (8.2%). The overall in-hospital mortality was 6.7%, and ICU admission was 7.1%. The highest AUC-ROC for in-hospital mortality prediction was observed with NEWS and NEWS-2 in abdominal infections (0.86), while the lowest was for qSOFA in skin and soft tissue infections (0.57). Predictive performance varied by infection site. The study highlights the variability in EWS performance based on infection site, emphasizing the need to consider the source of infection in EWS development for sepsis prognosis. Tailored or hybrid models may enhance predictive accuracy, balancing simplicity and specificity.

Population pharmacokinetics/pharmacodynamics of minocycline plus rifampicin in patients with complicated skin and skin structure infections caused by MRSA.

The population pharmacokinetics/pharmacodynamics (PK/PD) of minocycline, rifampicin and linezolid in patients with complicated skin and soft tissue infections (cSSTIs) caused by MRSA are described. Samples were collected in a Phase 4 study of oral minocycline plus rifampicin versus linezolid showing minocycline plus rifampicin to be non-inferior to linezolid. Antibiotics were assayed by HPLC or LC-MS, and a population PK model was developed using Pmetrics. The association between PK/PD indices and patient outcomes was explored. A three-compartment model (with an absorption compartment) with first-order input and elimination best described the data for the three drugs. No covariates were included in the final model. The population median values (95% credibility limits) of the clearance and volume of distribution were 7.412 L/h (5.121-8.361) and 14.155 L (6.799-33.901) for minocycline, 5.683 L/h (3.703-7.726) and 7.736 L (6.031-8.948) for rifampicin, and 1.970 L/h (1.326-2.499) and 20.169 L (12.857-32.629) for linezolid, respectively. Maximum a posteriori probability-Bayesian estimation plots of observed versus predicted had a slope of 0.999 r20.967 for minocycline, slope 0.998 r20.769 for rifampicin and slope 0.998 r20.895 for linezolid. PK/PD indices were not related to clinical outcome. Taking a translational minocycline fAUC24h/MIC target of >0.5 for minocycline in the presence of rifampicin, 96% (49/51) of patients reached the target. Population PK models of minocycline, rifampicin and linezolid were developed in patients with MRSA cSSTI and almost all patients reached the predefined PD index targets. As a result, neither AUC, MIC nor the AUC/MIC ratio could be related to clinical outcome.

Effects of aminolevulinic acid photodynamic therapy combined with antibiotics on Mycobacterium abscessus skin infections: an in vitro and in vivo study

BackgroundMycobacterium abscessus skin infections have emerged as a major medical issue. Traditional antibiotic treatments are challenging, prolonged, and often lead to recurrence, creating an urgent need for new therapies. This study investigates the effectiveness of aminolevulinic acid photodynamic therapy (ALA-PDT) combined with antibiotics in treatmenting M. abscessus, using both in vitro and in vivo methods. MethodsWe treated eight patients with M. abscessus skin infections following cosmetic surgery, using ALA-PDT (ALA concentration: 20%; red light: 80J/cm2) combined with oral or intravenous antibiotics,including clarithromycin, moxifloxacin and amikacin, to treat 8 patients with M. abscessus skin infection after medical cosmetic surgery, and assessed the treatment outcomes. Additionally, four bacterial strains (MAB-A1, MAB-A2, MAB-B1, and MAB-B2) isolated from patients were tested in vitro for ALA-PDT efficacy to determine the optimal ALA-PDT dosage. Furthermore, the strains’ single colony morphology, biofilm formation, and genome characteristics of were analyzed to explore the factors influencing ALA-PDT's bactericidal effects. Finally, a combined ALA-PDT and antibiotics sterilization experiment was conducted in vitro. ResultsClinically, ALA-PDT combined with antibiotics showed strong efficacy in treating M. abscessus skin infections, with no recurrence observed during follow-up. In vitro, ALA-PDT effectively killed M. abscessus, although MAB-B1 and MAB-B2 required a higher ALA-PDT dose compared with MAB-A1 and MAB-A2. Compared to MAB-A1 and MAB-A2, MAB-B1 and MAB-B2 exhibited stronger biofilm formation capabilities and bacterial virulence as well as genome mutations primarily affecting fatty acid synthesis and metabolism, potentially explaining their increased ALA-PDT dosage requirement. Notably, the combination of ALA-PDT and antibiotics exerted markedly higher bactericidal effects in vitro compared with antibiotics alone. ConclusionsALA-PDT combined with antibiotics emerged as an effective treatment for M. abscessus skin infections. However, optimal dosage and antibiotic combinations should be tailored to the characteristics of specific clinical strains.