Dihydrothiazolo ring-fused 2-pyridone antimicrobial compounds treat Streptococcus pyogenes skin and soft tissue infection.

We have developed GmPcides from a peptidomimetic dihydrothiazolo ring-fused 2-pyridone scaffold that has antimicrobial activities against a broad spectrum of Gram-positive pathogens. Here, we examine the treatment efficacy of GmPcides using skin and soft tissue infection (SSTI) and biofilm formation models by Streptococcus pyogenes. Screening our compound library for minimal inhibitory (MIC) and minimal bactericidal (MBC) concentrations identified GmPcide PS757 as highly active against S. pyogenes. Treatment of S. pyogenes biofilm with PS757 revealed robust efficacy against all phases of biofilm formation by preventing initial biofilm development, ceasing biofilm maturation and eradicating mature biofilm. In a murine model of S. pyogenes SSTI, subcutaneous delivery of PS757 resulted in reduced levels of tissue damage, decreased bacterial burdens, and accelerated rates of wound healing, which were associated with down-regulation of key virulence factors, including M protein and the SpeB cysteine protease. These data demonstrate that GmPcides show considerable promise for treating S. pyogenes infections.

The bacterial profile and antibiotic susceptibility in skin and soft tissue infections at a tertiary care hospital of Quetta, Pakistan.

Objectives: To determine the bacterial profile and antibiotic susceptibility in skin and soft tissue infections among patients in a tertiary care setting. METHODS: The cross-sectional cohort study was conducted at the Centre for Advanced Studies in Vaccinology and Biotechnology, University of Balochistan, Quetta, Pakistan, from June 2021 to May 2022, and comprised bacteriainfected skin samples that were collected from the Bolan Medical Complex Hospital, Quetta, and the Sandeman Provincial Hospital, Quetta. The swab samples were immediately cultured, and positive samples were evaluated for biochemical tests, antibiotic susceptibility test and polymerase chain reaction. Data was analysed using SPSS 22. RESULTS: Of the 800 samples, 598(74.7%) tested positive for pathogenic bacteria. Staphylococcus aureus accounted for 316(39.5%) infections, followed by clostridium perfringens 18.96(2.37%), escherichia coli 120(15.12%), pseudomonas aeruginosa 98(12.25%) and klebsiella pneumoniae 44(5.5%). Among all the infected samples, 380(47.5%) belonged to males, 218(27.25%) to patients aged 5-20 years, 448(56%) to the uneducated subjects, and 462(57.87%) to patients having lower socioeconomic status. Pseudomonas aeruginosa showed the highest level of resistance against all antibiotics. Conclusion: Regular surveillance and proper use of antibiotics should be encouraged in hospitals to limit the spread of antibiotic resistance against pathogenic bacteria.

Common Skin Conditions in Children and Adolescents: Bacterial Infections.

Bacterial skin infections represent a significant health care burden. Cellulitis and erysipelas are rapidly spreading, painful, superficial skin infections, usually caused by streptococci or Staphylococcus aureus. Folliculitis is an infection of hair follicles mostly caused by S aureus. Simple folliculitis typically is self-limited. Topical benzoyl peroxide is a first-line nonantibiotic treatment. Mupirocin and clindamycin are topical antibiotic options. For treatment-resistant cases, oral cephalexin or dicloxacillin is an appropriate option. Impetigo is a common, self-limited infection in children. Bullous impetigo is caused by S aureus, and nonbullous impetigo is caused by beta-hemolytic streptococci, S aureus, or both. In most cases, topical mupirocin or retapamulin (Altabax) is effective. Oral antibiotics should be considered for household outbreaks or patients with multiple lesions. Abscesses are red, painful collections of purulence in the dermis and deeper tissues caused by S aureus or polymicrobial infections. Furuncles are abscesses of a hair follicle, whereas carbuncles involve several hair follicles. In recurrent cases of these lesions, culture of the exudate is recommended. Abscess, furuncle, and carbuncle management consists of incision and drainage. Oral antibiotics are not necessary in most cases but should be prescribed for patients with severe immunocompromise or systemic signs of infection. In bacterial skin infections, methicillin-resistant S aureus coverage should be considered for patients with infections that have not improved with treatment.

Three Cases of Non-Tuberculosis Mycobacterium Skin Infection Outbreak in Beauty Institutions.

BACKGROUND: From June 2021 to July 2021, our hospital confirmed 3 cases of Mycobacterium infection in skin abscesses. All 3 patients underwent thread embedding and weight loss surgery at the same informal beauty institution, with a history of silk protein injection. None of the patients had any other underlying diseases or surgical history. Symptoms and signs show that the disease is acute and the course of the disease is short. All patients have found subcutaneous masses in different parts of the body. In most cases, the masses show redness and swelling, and some of the masses are accompanied by tenderness, wave sensation, and rupture. After some of the masses rupture, purulent secretions can be seen. METHODS: The pus secreted by the skin lesions of the three patients were cultured to a single bacterium, which was identified by MALDI-TOF MS. Multiple locus sequence typing (MLST) was performed using three specific genes (hsp65, rpoB, and secA1) and seven housekeeping genes (argH, cya, glpK, gnd, murC, pta, and purH). The results were queried through the MLST database of Mycobacterium abscess. RESULTS: All three strains of bacteria were Mycobacterium abscess type ST279 massiliense subtype. Three antibacterial drugs including cefmetazole, amikacin, and clarithromycin were administered in combination with 5-aminolevulinic acid photodynamic therapy (ALA-PDT). After 3 - 6 months, there was no obvious redness or swelling in the surrounding tissues of the wound, and no obvious purulent secretions were observed. All patients were cured and discharged from the hospital. After a follow-up of six months, there was no recurrence of the lesions. CONCLUSIONS: Medical institutions must strictly follow infection control guidelines and take preventive measures to prevent such incidents from happening again. ALA-PDT as a combination therapy for nontuberculous Mycobacterium (NTM) skin infections can improve treatment efficacy and shorten antibiotic usage time.

Single Intravenous Dose Dalbavancin Pathway for the Treatment of Acute Bacterial Skin and Skin Structure Infections: Considerations for Emergency Department Implementation and Cost Savings.

BACKGROUND: A pathway for the treatment of acute bacterial skin and skin structure infections (ABSSSI) with a single intravenous (IV) dose of dalbavancin was previously shown to reduce hospital admissions and shorten inpatient length of stay (LOS). OBJECTIVES: To describe pathway implementation at the emergency department (ED) and evaluate cost-effectiveness of a single-dose dalbavancin administered to ED patients who would otherwise be hospitalized to receive usual care with multidose IV antibiotics. METHODS: The dalbavancin pathway was previously implemented at 11 U.S. EDs (doi:10.1111/acem.14258). Patients with ABSSSI, without an unstable comorbidity or infection complication requiring complex management, were treated with a single dose of dalbavancin. At the emergency physicians' discretion, patients were either discharged and received outpatient follow-up or were hospitalized for continued management. A decision analytic cost-effectiveness model was developed from the U.S. healthcare's perspective to evaluate costs associated with the dalbavancin pathway compared with inpatient usual care. Costs (2021 USD) were modeled over a 14-day horizon and included ED visits, drug costs, inpatient stay, and physician visits. One-way and probabilistic sensitivity analyses examined input parameter uncertainty. RESULTS: Driven largely by the per diem inpatient cost and LOS for usual care, the dalbavancin pathway was associated with savings of $5133.20 per patient and $1211.57 per hospitalization day avoided, compared with inpatient usual care. The results remained robust in sensitivity and scenario analyses. CONCLUSION: The new single-dose dalbavancin ED pathway for ABSSSI treatment, which was previously implemented at 11 U.S. EDs, offers robust cost savings compared to inpatient usual care.

A rare case of primary cutaneous Nocardia vinacea in an immunocompetent patient: A case report and a review of the literature.

The nocardiae are a complex group of bacteria belonging to the aerobic saprophytes actinomycetes. Although nocardiosis typically occurs in immunocompromised patients, infection may occasionally develop in immunocompetent patients as well. Here we describe a rare case of primary cutaneous nocardiosis due to Nocardia vinacea in an immunocompetent 79-year-old patient. Since cutaneous nocardiosis presents variably and mimics other cutaneous infections, acid-fast and Gram stainings on clinical samples are significant to obtain a rapid and presumptive diagnosis.

Reactive Microneedle Patches with Antibacterial and Dead Bacteria-Trapping Abilities for Skin Infection Treatment.

Bacterial skin infections are highly prevalent and pose a significant public health threat. Current strategies are primarily focused on the inhibition of bacterial activation while disregarding the excessive inflammation induced by dead bacteria remaining in the body and the effect of the acidic microenvironment during therapy. In this study, a novel dual-functional MgB2 microparticles integrated microneedle (MgB2 MN) patch is presented to kill bacteria and eliminate dead bacteria for skin infection management. The MgB2 microparticles not only can produce a local alkaline microenvironment to promote the proliferation and migration of fibroblasts and keratinocytes, but also achieve >5 log bacterial inactivation. Besides, the MgB2 microparticles effectively mitigate dead bacteria-induced inflammation through interaction with lipopolysaccharide (LPS). With the incorporation of these MgB2 microparticles, the resultant MgB2 MN patches effectively kill bacteria and capture dead bacteria, thereby mitigating these bacteria-induced inflammation. Therefore, the MgB2 MN patches show good therapeutic efficacy in managing animal bacterial skin infections, including abscesses and wounds. These results indicate that reactive metal borides-integrated microneedle patches hold great promise for the treatment of clinical skin infections.

Skin and Soft Tissue Actinomycosis in Children and Adolescents.

BACKGROUND: Pediatric actinomycosis studies are limited to case reports or small case series. In this retrospective cohort study, we aimed to describe characteristics of skin and soft tissue actinomycosis in adolescents and children. METHODS: We conducted the study from January 2019 to December 2022, including patients ≤21 years of age with at least 1-year follow-up data. All clinical cultures obtained under sterile conditions with Actinomyces growth were included. RESULTS: One hundred four patients met inclusion criteria; median age 19 (interquartile range: 17-20) years, 68.3% female, 46.2% Black and 47.1% Hispanic. The median antibiotic treatment duration was 10 (7-10) days, and majority of patients received treatment with non-first-line Actinomyces antibiotics. Infectious disease consultation was requested for only 7 patients during their initial skin and soft tissue actinomycosis treatment. One-third of the patients with skin and soft tissue actinomycosis had documented recurrence within a median of 10 (interquartile range: 6-16) months of the initial episode. Monobacterial culture growth (85.7% vs. 63.8%, P = 0.02), patients with body mass index >25 (75% vs. 52.6%, P = 0.04) and patients with prior abscess in the same area (18.8% vs. 51.4%, P = 0.001) were significantly higher in patients with recurrent actinomycosis compared to the nonrecurrent group. In a univariate logistic regression model, they were found to be significantly associated with recurrence; monobacterial growth [odds ratio (OR): 3.4; 95% confidence interval (CI): 1.2-9.9], body mass index >25 (OR: 2.7; 95% CI, 1.1-7.0) and prior abscess (OR: 4.6; 95% CI: 1.9-11.2). CONCLUSIONS: Our study results highlight the importance of considering Actinomyces species in skin and soft tissue infections, especially in recurrent ones, and risk factors for recurrence. Suboptimal antibiotic utilization, very low numbers of consultations with infectious diseases and high recurrence rate suggest that providers should be informed and updated regarding this rare but hard-to-treat infection.

Secondary Bacterial Infections in Patients with Atopic Dermatitis or Other Common Dermatoses.

Secondary bacterial infections of common dermatoses such as atopic dermatitis, ectoparasitosis, and varicella zoster virus infections are frequent, with Staphylococcus aureus and Streptococcus pyogenes being the bacteria most involved. There are also Gram-negative infections secondary to common dermatoses such as foot dyshidrotic eczema and tinea pedis. Factors favoring secondary bacterial infections in atopic dermatitis, ectoparasitosis, and varicella zoster virus infections mainly include an epidermal barrier alteration as well as itch. Mite-bacteria interaction is also involved in scabies and some environmental factors can promote Gram-negative bacterial infections of the feet. Furthermore, the bacterial ecology of these superinfections may depend on the geographical origin of the patients, especially in ectoparasitosis. Bacterial superinfections can also have different clinical aspects depending on the underlying dermatoses. Subsequently, the choice of class, course, and duration of antibiotic treatment depends on the severity of the infection and the suspected bacteria, primarily targeting S. aureus. Prevention of these secondary bacterial infections depends first and foremost on the management of the underlying skin disorder. At the same time, educating the patient on maintaining good skin hygiene and reporting changes in the primary lesions is crucial. In the case of recurrent secondary infections, decolonization of S. aureus is deemed necessary, particularly in atopic dermatitis.

Case report: Cutaneous anthrax diagnosed using mNGS of a formalin-fixed paraffin-embedded tissue sample.

The metagenomic next-generation sequencing (mNGS) method is preferred for genotyping useful for the identification of organisms, illumination of metabolic pathways, and determination of microbiota. It can accurately obtain all the nucleic acid information in the test sample. Anthrax is one of the most important zoonotic diseases, infecting mainly herbivores and occasionally humans. The disease has four typical clinical forms, cutaneous, gastrointestinal, inhalation, and injection, all of which may result in sepsis or meningitis, with cutaneous being the most common form. Here, we report a case of cutaneous anthrax diagnosed by mNGS in a butcher. Histopathology of a skin biopsy revealed PAS-positive bacilli. Formalin-fixed paraffin-embedded (FFPE) tissue sample was confirmed the diagnosis of anthrax by mNGS. He was cured with intravenous penicillin. To our knowledge, this is the first case of cutaneous anthrax diagnosed by mNGS using FFPE tissue. mNGS is useful for identifying pathogens that are difficult to diagnose with conventional methods, and FFPE samples are simple to manage. Compared with traditional bacterial culture, which is difficult to cultivate and takes a long time, mNGS can quickly and accurately help us diagnose anthrax, so that anthrax can be controlled in a timely manner and prevent the outbreak of epidemic events.

Doxycycline monotherapy for pyoderma vegetans: a case report.

Background: Pyoderma vegetans (PV) is a rare neutrophilic dermatosis of unknown etiology. Currently, there are no treatment guidelines for PV. Systemic steroids are often used as first-line therapy, but recurrence upon discontinuation or tapering is common.Materials and methods: We tested the efficacy of doxycycline at a dose of 200 mg/d to treat resistant PV.Results: After 4 weeks of treatment we noticed a significant improvement in the clinical appearance of PV.Conclusions: Our case demonstrates the potential utility of doxycycline as a systemic steroid-sparing agent in the treatment of PV.

In vitro activity of ceftazidime-avibactam against gram-negative bacteria in patients with bacteremia and skin and soft-tissue infections in Colombia 2019-2021.

OBJECTIVES: Ceftazidime-avibactam (CAZ-AVI) is an option for infections caused by MDR gram-negative bacilli. In this study, we aimed to analyze the in vitro antimicrobial activity of CAZ-AVI and other antimicrobial agents against gram-negative bacilli that were collected in Colombia between 2019 and 2021 from patients with bacteremia and skin and soft-tissue infections (SSTIs). METHODS: A total of 600 Enterobacterales and 259 P. aeruginosa strains were analyzed. The phenotypic resistance of isolates, particularly non-susceptibility to meropenem, multidrug-resistant (MDR) isolates, and difficult-to-treat (DTR) P. aeruginosa, was evaluated according to CLSI breakpoints. RESULTS: Enterobacterales had the most susceptibility to CAZ-AVI (96.5 %) and tigecycline (95 %). Tigecycline and CAZ-AVI were the antimicrobial agents with the most in vitro activity against carbapenem-resistant Enterobacterales (CRE). CAZ-AVI was the antimicrobial treatment with the most activity against P. aeruginosa. CONCLUSIONS: Tigecycline and CAZ-AVI were the antimicrobial agents with the most activity against CRE and MDR Enterobacterales. For P. aeruginosa, CAZ-AVI was the antimicrobial treatment with the most in vitro activity.

Stenotrophomonas maltophilia skin infection in an immunocompetent patient: Primary cutaneous CD30+ T-cell lymphoproliferative disorder or pseudolymphoma?

Cutaneous pseudolymphomas are a wide group of diseases mimicking cutaneous lymphoma. They comprise several skin conditions with different etiopathogenesis, clinical-pathological features, and prognosis, which may occur in the absence of an identifiable trigger factor or after administration of medications or vaccinations, tattoos, infections, or arthropod bites. They present with different manifestations: from solitary to regionally clustered lesions, up to generalized distribution and, in rare cases, erythroderma. They persist variably, from weeks to years, and resolve spontaneously or after antibiotics, but may recur in some cases. CD30+ T-cell pseudolymphomas are characterized by the presence of large, activated lymphoid cells, generally in response to viral infections, arthropod assault reactions, and drug eruptions. Stenotrophomonas maltophilia is a ubiquitous Gram-negative bacillus responsible for opportunistic infections in immunocompromised patients. Infection of intact skin in immunocompetent patients is particularly rare. Here, we report a case of a man presenting an isolated nodule histopathologically mimicking a primary cutaneous CD30+ T-cell lymphoproliferative disorder.

Antibacterial activity of plant-derived compounds and cream formulations against canine skin bacteria.

An urgent need to find alternative antimicrobial compounds effective in the prevention and treatment of skin infections led us to study the inhibitory activity of eight plant-derived bioactive compounds (betulin, curcumin, glycyrrhizic acid, guaiazulene, piperine, quercetin, quinine, tannic acid) against 14 canine skin isolates (11 Gram-positive and three Gram-negative bacteria) selected based on antibiotic resistance and virulence features. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) were determined using the broth microdilution method. In detail, the results for the eight different plant compounds showed their inhibitory activity in the concentration range from 0.04 to more than 16 mg/ml (MIC) and from 0.25 to more than 16 mg/ml (MBC). The most potent compounds appear to be tannic acid, followed by quinine and curcumin (MIC 0.04-16.0 mg/ml). The most susceptible strain to the tested agents in general was Bacillus cereus AE13, while Enterococcus faecium AA14 was the most resistant strain (the highest MICs) among the tested bacteria. The two most potent plant-derived compounds (tannic acid and quinine) were tested in mixture in different ratios (1:1, 1:2, 2:1). The lowest MIC and MBC values were observed for the 1:2 ratio, which was used for preparation of creams with different cream bases. One of the cream formulations (cream F) was effective up to 63.0 mg/ml (MIC) with a microbial inactivation time of 1-6 h according to the tested strain. This study provides evidence that some plant-derived compounds could have an antimicrobial effect against canine skin bacteria, the strength of which is bacterial strain dependent.

[Skin abscess caused by Actinomyces radingae]. / Hautabszess verursacht durch Actinomyces radingae.

We report a 77-year-old man with a skin abscess caused by Actinomyces radingae. Targeted antibiotic therapy with amoxicillin/clavulanic acid for 6 weeks resulted in clearing of the infection. A. radingae is a rare pathogenic agent of skin and soft tissue infections. As with other Actinomyces infections, the early identification of the pathogen and specific antibiotic therapy is crucial for successful resolution of the infection because of the chronic course and the long treatment time needed. Usually, A. radingae is sensitive to ß­lactam antibiotics.

Current challenges in acute bacterial skin infection management.

PURPOSE OF REVIEW: There are aspects of skin and soft tissue infections (SSTIs) that remain unresolved, such as current numbers, classification criteria, how best to define severity and predict the outcome, what diagnostic tests to perform, what new treatment options are available, or what the duration of antibiotic treatment should be. We have reviewed the literature over the last 18 months to clarify these issues and provide our opinion. RECENT FINDINGS: SSTIs are common and among the top 10 most frequent infections worldwide. They represent a burden on the healthcare system and have a major impact on the quality of life of patients. Regarding classification, the Infectious Diseases Society of America (IDSA) provides a practical guide that distinguishes between uncomplicated and complicated infections, acute and chronic wound infections, and necrotising and nonnecrotizing infections based on skin extension and tissue necrosis. With new microbiological and imaging diagnostic techniques, SSTIs can now be better diagnosed. New PCR techniques are available, and mass spectrometry can be applied to samples collected in liquid transport media. Moreover, new treatment methods such as photodynamic therapy, reactive oxygen, and phages are emerging. SSTI patients can be treated with shorter antibiotic courses if they receive an active drug with good tissue penetration. Antibiotic treatment in necrotizing infections can be shortened to 48 h after the last debridement. SUMMARY: SSTIs remain a challenge regarding rapid and accurate diagnosis and clinical management.

Emerging treatment options for skin and soft tissue infections tailoring drug selection to individual patients.

PURPOSE OF REVIEW: To provide a brief overview of drugs in Phase II and III of development for the treatment of acute bacterial skin and skin structure infections (ABSSSI), offering insights into potential customized treatment options. RECENT FINDINGS: Several drugs are currently in advanced stages of evaluation for the treatment of ABSSSI, and numerous molecules are entering in the early development phases. Notably, many of these drugs exhibit unique mechanisms of action and interesting antimicrobial spectrum. SUMMARY: Tailoring antibiotic therapy based on patient characteristics, likely pathogens, type, site and severity of ABSSSI is crucial. Given the inherent limitations of available treatments, the development of novel agents is a pivotal avenue. Such advancements hold promise for enhancing treatment efficacy and simplifying drug selection for ABSSSI in everyday clinical practice.

Cutaneous Mycobacterium avium-intracellulare infection masquerading as sarcoidosis.

Mycobacterium avium-intracellulare (MAC) infection may have different skin manifestations, including cutaneous granulomas. Granulomatous skin reactions have distinct morphologic and histopathologic appearances. We present the case of an adolescent male with cutaneous MAC, misdiagnosed as sarcoidosis after initial biopsy results, demonstrated preservation of reticulin fibers and absence of organisms within granulomas. Sarcoidal granulomas often stain positive for reticulin fibers, which could be used to distinguish them from the infectious kind. This case should alert clinicians to the fact that the presence or quantity of intact reticular fibers may not be a reliable tool to differentiate between a sarcoidal and an infectious granuloma. Our case also highlights the diagnostic challenge of cutaneous MAC infection.

Subcutaneous infection caused by Mycobacterium abscessus following botulinum toxin injections: A case report and literature review.

BACKGROUND: The rapid development of cosmetic injections has led to an increased incidence of nontuberculous mycobacterial (NTM) infection. PATIENTS AND METHODS: Here, we presented a case of cutaneous Mycobacterium abscessus infection subsequent to botulinum toxin injection for treating masseter hypertrophy, and reviewed the literature on skin and soft tissue infections caused by NTM after cosmetic injections. RESULTS AND CONCLUSIONS: The patient underwent surgical excision and regular antibiotic therapy and has had nearly 2 months of follow-up without any signs of infection. The diagnosis and treatment of NTM infection have always been challenging, and further research is needed to standardize and guide the treatment.