Significant healthcare resource utilisation in the management of skin and soft tissue infections in the Torres Strait, Australia.

INTRODUCTION: Aboriginal and Torres Strait Islander Peoples (First Nations Australians) living in remote communities are hospitalised with skin and soft tissue infections (SSTIs) at three times the rate of non-First Nations Australians. The Torres Strait in tropical northern Australia has a highly dispersed population mainly comprising First Nations Australians. This study aimed to define the health service utilisation and health system costs associated with SSTIs in the Torres Strait and to improve the quality of regional healthcare delivery. METHODS: The research team conducted a retrospective, de-identified audit of health records for a 2-year period, 2018-2019. The aim was to define health service utilisation, episodes of outpatient care, emergency department care, inpatient care and aeromedical retrieval services for SSTIs. RESULTS: Across 2018 - 2019, there were 3509 outpatient episodes of care for SSTIs as well as 507 emergency department visits and 100 hospitalisations. For individuals with an SSTI, the mean outpatient clinic episode cost $240; the mean emergency department episode cost $400.85, the mean inpatient episode cost $8403.05 while an aeromedical retrieval service cost $18,670. The total costs to the health system for all services accessed for SSTI management was $6,169,881 per year, 3% of the total annual health service budget. CONCLUSION: Healthcare costs associated with SSTIs in the Torres Strait are substantial. The implementation of effective preventative and primary care interventions may enable resources to be reallocated to address other health priorities in the Torres Strait.

Vaccination with staphylococcal protein A protects mice against systemic complications of skin infection recurrences.

Skin and soft tissue infections (SSTIs) are the most common diseases caused by Staphylococcus aureus (S. aureus), which can progress to threatening conditions due to recurrences and systemic complications. Staphylococcal protein A (SpA) is an immunomodulator antigen of S. aureus, which allows bacterial evasion from the immune system by interfering with different types of immune responses to pathogen antigens. Immunization with SpA could potentially unmask the pathogen to the immune system, leading to the production of antibodies that can protect from a second encounter with S. aureus, as it occurs in skin infection recurrences. Here, we describe a study in which mice are immunized with a mutated form of SpA mixed with the Adjuvant System 01 (SpAmut/AS01) before a primary S. aureus skin infection. Although mice are not protected from the infection under these conditions, they are able to mount a broader pathogen-specific functional immune response that results in protection against systemic dissemination of bacteria following an S. aureus second infection (recurrence). We show that this "hidden effect" of SpA can be partially explained by higher functionality of induced anti-SpA antibodies, which promotes better phagocytic activity. Moreover, a broader and stronger humoral response is elicited against several S. aureus antigens that during an infection are masked by SpA activity, which could prevent S. aureus spreading from the skin through the blood.

Successful treatment of cutaneous protothecosis with fluconazole: A case report and epidemiology study of Prototheca infection in China.

BACKGROUND: Protothecosis is an infection of humans and animals caused by a rare conditionally pathogenic fungus (prototheca). It can occur in immunocompromised or normal patients. AIMS: To describe the epidemiology of prototheca infection in China. METHODS: We report a case of successful treatment of cutaneous protothecosis with fluconazole and analyzed the epidemiological characteristics, risk factors, clinical manifestations, diagnosis, treatment and prognosis of prototheca infections in China. RESULTS: We describe this case and 29 cases of prototheca infections in China. At present, Prototheca wickerhamii (Pw) infection is the most common infection in China, and single or combined itraconazole is the preferred treatment. CONCLUSIONS: These results provide detailed information and relevant clinical treatment strategies for the diagnosis and treatment of protothecosis in China.

Applications of nitric oxide-releasing nanomaterials in dermatology: Skin infections and wound healing.

Nitric oxide (NO) is produced in most cells in the skin and is an important regulator of essential cutaneous functions, including responses to UV irradiation, microbial defense, wound healing, melanogenesis and epidermal permeability barrier homeostasis. Harnessing the physiological activities of NO for therapeutic use is difficult because the molecule is highly reactive and unstable. A variety of exogenous NO delivery platforms have been developed and evaluated; however, they have limited clinical applications in dermatology due to instability and poor cutaneous penetration. NO-releasing nanomaterials overcome these limitations, providing targeted tissue delivery, and sustained and controlled NO release. This review provides a comprehensive and up-to-date evaluation of the use of NO-releasing nanomaterials in dermatology for the treatment of skin and soft tissue infections and wound healing.

Effects of photodynamic therapy in patients with infected skin ulcers: A meta-analysis.

The purpose of the meta-analysis was to evaluate and compare the photodynamic therapy's effectiveness in treating infected skin wounds. The results of this meta-analysis were analysed, and the odds ratio (OR) and mean difference (MD) with 95% confidence intervals (CIs) were calculated using dichotomous or contentious random- or fixed-effect models. For the current meta-analysis, 6 examinations spanning from 2013 to 2021 were included, encompassing 154 patients with infected skin wounds were the used studies' starting point. Photodynamic therapy had a significantly lower wound ulcer size (MD, -4.42; 95% CI, -7.56--1.28, p = 0.006), better tissue repair (MD, -8.62; 95% CI, -16.76--0.48, p = 0.04) and lower microbial cell viability (OR, 0.13; 95% CI, 0.04-0.42, p < 0.001) compared with red light exposure in subjects with infected skin wounds. The examined data revealed that photodynamic therapy had a significantly lower wound ulcer size, better tissue repair and lower microbial cell viability compared with red light exposure in subjects with infected skin wounds. However, given that all examinations had a small sample size, consideration should be given to their values.

Frequency of skin diseases in renal transplant recipients and patients with chronic kidney disease in a tertiary center: a cross-sectional study.

BACKGROUND: The prevalence of chronic kidney disease (CKD) has increased in the recent decades, along with the number of patients in the terminal stages of this disease, requiring transplantation. Some skin disorders are more frequent in patients with CKD and in renal transplant recipients (RTR). OBJECTIVES: To evaluate the frequency of skin diseases in RTR and patients with CKD receiving conservative treatment. DESIGN AND SETTING: This observational cross-sectional study recruited consecutive patients with CKD and RTR from a nephrology clinic at a teaching hospital in Brazil between 2015 and 2020. METHODS: Quantitative, descriptive, and analytical approaches were used. The sample was selected based on convenience sampling. Data were collected from dermatological visits and participants' medical records. RESULTS: Overall, 308 participants were included: 206 RTR (66.9%, median age: 48 years, interquartile range [IQR] 38.0-56.0, 63.6% men) and 102 patients with CKD (33.1%, median age: 61.0 years, IQR 50.0-71.2, 48% men). The frequency of infectious skin diseases (39.3% vs. 21.6% P = 0.002) were higher in RTR than in patients with CKD. Neoplastic skin lesions were present in nine (4.4%) RTR and in only one (1.0%) patient with CKD. Among the RTR, the ratio of basal cell carcinoma to squamous cell carcinoma was 2:1. CONCLUSIONS: This study revealed that an increased frequency of infectious skin diseases may be expected in patients who have undergone kidney transplantation. Among skin cancers, BCC is more frequently observed in RTR, especially in those using azathioprine.

Experience with dalbavancin use in various gram-positive infections within Aberdeen Royal Infirmary OPAT service.

PURPOSE: Dalbavancin, approved in 2014 for Gram-positive acute bacterial skin and skin structure infections (ABSSSI), has pharmacokinetics enabling treatment with one or two doses. Dalbavancin might be useful in outpatient parenteral antibiotic therapy (OPAT) of deep-seated infections, otherwise requiring inpatient admission. We documented our experience with pragmatic dalbavancin use to assess its effectiveness for varied indications, on- and off-label, as primary or sequential consolidation therapy. METHODS: Patients prescribed dalbavancin between 1 December 2021 and 1 October 2022 were screened for demographics of age, sex, Charlson comorbidity index (CCI), allergies, pathogens, doses of dalbavancin, other antibiotics administered and surgery. Where available, infection markers were recorded. The primary outcome was a cure at the end of treatment. Secondary outcomes included any adverse events and for those with treatment failures, response to salvage antibiotics. RESULTS: Sixty-seven per cent of patients were cured. Cure rates by indication were 93% for ABSSSI, 100% for bacteraemia, 90% for acute osteomyelitis, 0% for chronic osteomyelitis, 75% for native joint septic arthritis and 33% for prosthetic joint infection. Most bone and joint infections that were not cured did not have source control, and the goal of treatment was suppressive. Successful suppression rates were greater at 48% for chronic osteomyelitis and 66% for prosthetic joint infections. Adverse events occurred in 14 of 102 patients. CONCLUSION: This report adds to clinical experience with dalbavancin for off-label indications whilst further validating its role in ABSSSI. Dalbavancin as primary therapy in deep-seated infections merits investigation in formal clinical trials.

Target attainment of intravenous lefamulin for treatment of acute bacterial skin and skin structure infections.

OBJECTIVES: Lefamulin is a pleuromutilin antibiotic approved for the treatment of community-acquired bacterial pneumonia (CABP). Its spectrum of activity, good penetration into soft tissues and low rates of cross-resistance also make lefamulin a potentially valuable option for treatment of acute bacterial skin and skin structure infections (ABSSSIs). A Phase 2 trial of lefamulin for ABSSSI indicated similar efficacy of 100 and 150 mg q12h IV dosing regimens. In the present study, the potential of lefamulin for this indication was further evaluated from a translational pharmacokinetic/pharmacodynamic perspective. METHODS: PTA was determined for various dosages using Monte Carlo simulations of a population pharmacokinetic model of lefamulin in ABSSSI patients and preclinical exposure targets associated with bacteriostasis and a 1-log reduction in bacterial count. Overall target attainment against MSSA and MRSA was calculated using lefamulin MIC distributions. RESULTS: Overall attainment of the bacteriostasis target was 94% against MSSA and 84% against MRSA for the IV dosage approved for CABP (150 mg q12h). Using the same target, for the 100 mg q12h regimen, overall target attainment dropped to 68% against MSSA and 50% against MRSA. Using the 1-log reduction target, overall target attainment for both regimens was <40%. CONCLUSIONS: Lefamulin at the currently approved IV dosage covers most Staphylococcus aureus isolates when targeting drug exposure associated with bacteriostasis, suggesting potential of lefamulin for the treatment of ABSSSIs. Lefamulin may not be appropriate in ABSSSI when rapid bactericidal activity is warranted.

Left ventricular assist device-associated driveline infections as a specific form of complicated skin and soft tissue infection/acute bacterial skin and skin structure infection - issues and therapeutic options.

PURPOSE OF REVIEW: This review comments on the current guidelines for the treatment of wound infections under definition of acute bacterial skin and skin structure infections (ABSSSI). However, wound infections around a catheter, such as driveline infections of a left ventricular assist device (LVAD) are not specifically listed under this definition in any of the existing guidelines. RECENT FINDINGS: Definitions and classification of LVAD infections may vary across countries, and the existing guidelines and recommendations may not be equally interpreted among physicians, making it unclear if these infections can be considered as ABSSSI. Consequently, the use of certain antibiotics that are approved for ABSSSI may be considered as 'off-label' for LVAD infections, leading to rejection of reimbursement applications in some countries, affecting treatment strategies, and hence, patients' outcomes. However, we believe driveline exit site infections related to LVAD can be included within the ABSSSI definition. SUMMARY: We argue that driveline infections meet the criteria for ABSSSI which would enlarge the 'on-label' antibiotic armamentarium for treating these severe infections, thereby improving the patients' quality of life.

HIV and skin infections.

HIV infection alters the skin microbiome and predisposes to a wide range of cutaneous infections, from atypical presentations of common skin infections to severe disseminated infections involving the skin that are AIDS-defining illnesses. Bacterial infection of the skin, most commonly caused by Staphylococcus aureus, occurs frequently and can result in bacteremia. Nontuberculous mycobacterial infections that are usually localized to the skin may disseminate, and guidance on the treatment of these infections is limited. Herpes simplex can be severe, and less common presentations such as herpetic sycosis and herpes vegetans have been reported. Severe herpes zoster, including disseminated infection, requires intravenous antiviral treatment. Viral warts can be particularly difficult to treat, and in atypical or treatment-resistant cases a biopsy should be considered. Superficial candidosis occurs very commonly in people living with HIV, and antifungal resistance is an increasing problem in non-albicans Candida species. Systemic infections carry a poor prognosis. In tropical settings the endemic mycoses including histoplasmosis are a problem for people living with HIV, and opportunistic infections can affect those with advanced HIV in all parts of the world. Most cutaneous infections can develop or worsen as a result of immune reconstitution in the weeks to months after starting antiretroviral therapy. Direct microscopic examination of clinical material can facilitate rapid diagnosis and treatment initiation, although culture is important to provide microbiological confirmation and guide treatment.

Unusual herpetic reactivation in a young female following botox injection: a case report study.

BACKGROUND: Botox injections are commonly used for cosmetic and therapeutic purposes because they temporarily paralyze muscles, reduce wrinkles, and alleviate certain medical conditions. Although generally considered safe and effective, Botox injections may cause potential complications. While herpes reactivation is more commonly associated with immunosuppressive therapies, such as chemotherapy or corticosteroid use, its association with Botox injection is poorly documented. CASE PRESENTATION: A 33-year-old woman presented with progressive painful rashes and vesicles on her forehead, scalp, and right upper eyelid, accompanied by fever and malaise following a Botox injection to treat wrinkles. A positive Tzanck smear test result confirmed the diagnosis of herpes infection. The patient was treated with antiviral medication, and her symptoms gradually regressed over several days. CONCLUSIONS: Although herpes reactivation is more commonly associated with immunosuppressive therapies, few cases of herpes zoster and herpes simplex following Botox injection have been reported. The pathogenesis of herpes reactivation following Botox injection is unclear; however, it has been hypothesized that the Botox protein is a potent antigen that may activate the cellular immune system, making it easier for the virus to reactivate. Healthcare providers should be aware of this potential complication and consider it when evaluating patients who present with painful rashes following Botox injections. In addition, individuals who want to receive Botox injections should be informed of this complication. The diagnosis of herpetic infection should be made promptly, and antiviral therapy should be initiated to minimize the risk of complications. Further research is needed to better understand the pathogenesis and risk factors for herpes following Botox injection and to develop strategies for preventing and managing this complication.

Part 2: Understanding the role of Malassezia spp. in skin disorders: pathogenesis of Malassezia associated skin infections.

INTRODUCTION: Malassezia is a major component of the skin microbiome, a lipophilic symbiotic organism of the mammalian skin, which can switch to opportunistic pathogens triggering multiple dermatological disorders in humans and animals. This phenomenon is favored by endogenous and exogenous host predisposing factors, which may switch Malassezia from a commensal to a pathogenic phenotype. AREA COVERED: This review summarizes and discusses the most recent literature on the pathogenesis of Malassezia yeasts, which ultimately results in skin disorders with different clinical presentation. A literature search of Malassezia pathogenesis was performed via PubMed and Google scholar (up to May 2023), using the following keywords: Pathogenesis and Malassezia;host risk factors and Malassezia, Malassezia and skin disorders; Malassezia and virulence factors: Malassezia and metabolite production; Immunology and Malassezia. EXPERT OPINION: Malassezia yeasts can maintain skin homeostasis being part of the cutaneous mycobiota; however, when the environmental or host conditions change, these yeasts are endowed with a remarkable plasticity and adaptation by modifying their metabolism and thus contributing to the appearance or aggravation of human and animal skin disorders.

Imported Toxigenic Corynebacterium Diphtheriae in Refugees with Polymicrobial Skin Infections, Germany, 2022.

During August-December 2022, toxigenic Corynebacterium diphtheriae was isolated from 25 refugees with skin infections and 2 refugees with asymptomatic throat colonization at a refugee reception center in Germany. None had systemic toxin-mediated illness. Of erosive/ulcerative skin infections, 96% were polymicrobial. Erosive/ulcerative wounds in refugees should undergo testing to rule out cutaneous diphtheria.

Endemic infectious cutaneous ulcers syndrome in the Oti Region of Ghana: Study of cutaneous leishmaniasis, yaws and Haemophilus ducreyi cutaneous ulcers.

BACKGROUND: A recent study detected cutaneous leishmaniasis (CL) in 31.9% of persons with skin ulcers in the Oti Region of Ghana, resulting in a need to investigate other potential causes of the unexplained skin ulcers. METHODOLOGY/PRINCIPAL FINDINGS: A community based cross-sectional study was conducted in the Oti region to investigate skin ulcers of undetermined aetiologies. To confirm a diagnosis of cutaneous leishmaniasis, Buruli ulcer, Haemophilus ducreyi ulcers, or yaws, DNA obtained from each patient skin ulcer sample was systematically subjected to polymerase chain reaction (PCR) for Leishmania spp., Mycobacterium ulcerans, Haemophilus ducreyi, and Treponema pallidum sub species pertenue. A total of 101 skin ulcer samples were obtained from 101 persons. Co-infection of more than one organism was observed in 68.3% of the samples. Forty (39.6%) participants had a positive result for Leishmania spp., 68 (67.3%) for Treponema pallidum sub. Sp. pertenue, and 74 (73.3%) for H. ducreyi. Twenty (19.8%) of the patient ulcers were simultaneously infected with Leishmania spp., Treponema pallidum sub. Sp. pertenue, and H. ducreyi. None of the patients' lesions yielded a positive result for Mycobacterium ulcerans. CONCLUSIONS/SIGNIFICANCE: This study detected single and mixed occurrence of the causative organisms of CL, yaws, and H. ducreyi cutaneous ulcers in CL endemic communities of the Oti Region in Ghana. These findings emphasize the importance of integrating multiple skin diseases on a common research platform and calls for the development of a comprehensive guideline for diagnosing and treating tropical ulcers in the study areas.