Disclosure of a Promising Lead to Tackle Complicated Skin and Skin Structure Infections: Antimicrobial and Antibiofilm Actions of Peptide PP4-3.1

Efficient antibiotics are being exhausted, which compromises the treatment of infections, including complicated skin and skin structure infections (cSSTI) often associated with multidrug resistant (MDR) bacteria, methicillin-resistant S. aureus (MRSA) being the most prevalent. Antimicrobial peptides (AMP) are being increasingly regarded as the new hope for the post-antibiotic era. Thus, future management of cSSTI may include use of peptides that, on the one hand, behave as AMP and, on the other, are able to promote fast and correct skin rebuilding. As such, we combined the well-known cosmeceutical pentapeptide-4 (PP4), devoid of antimicrobial action but possessing collagenesis-boosting properties, with the AMP 3.1, to afford the chimeric peptide PP4-3.1. We further produced its N-methyl imidazole derivative, MeIm-PP4-3.1. Both peptide-based constructs were evaluated in vitro against Gram-negative bacteria, Gram-positive bacteria, and Candida spp. fungi. Additionally, the antibiofilm activity, the toxicity to human keratinocytes, and the activity against S. aureus in simulated wound fluid (SWF) were assessed. The chimeric peptide PP4-3.1 stood out for its potent activity against Gram-positive and Gram-negative bacteria, including against MDR clinical isolates (0.8 ≤ MIC ≤ 5.7 µM), both in planktonic form and in biofilm matrix. The peptide was also active against three clinically relevant species of Candida fungi, with an overall performance superior to that of fluconazole. Altogether, data reveal that PP4-3.1 is as a promising lead for the future development of new topical treatments for severe skin infections.

Interrelationships between Skin Structure, Function, and Microbiome of Pregnant Females and Their Newborns: Study Protocol for a Prospective Cohort Study

Background. Pregnancy leads to several skin changes, but evidence about structural and functional skin changes is scarce. Findings on skin structure and function in children in their first year reveal rapid skin maturation, but evidence indicates that in particular, water holding and transport mechanisms are different from adults. Important questions include whether maternal cutaneous properties predict infant skin condition, and if so, how. This is especially relevant for the skin’s microbiome because it closely interacts with the host and is assumed to play a role in many skin diseases. Therefore, the study objective is to explore characteristics of skin and hair of pregnant women and their newborns during pregnancy and in the first six months after delivery and their associations. Methods. The study has an observational longitudinal design. We are recruiting pregnant females between 18 and 45 years using advertisement campaigns in waiting areas of gynecologists and hospital’s outpatient services. A final sample size of n = 100 women is the target. We perform noninvasive, standardized skin, hair, and skin microbiome measurements. We establish the baseline visit during pregnancy until at the latest four weeks before delivery. We schedule follow-up visits four weeks and six months after birth for mothers and their newborns. We will calculate descriptive statistical methods using frequencies and associations over time depending on scale levels of the measurements. Discussion. The majority of previous studies that have investigated infants’ skin microbiome and its associations used cross-sectional designs and focused on selected characteristics in small samples. In our longitudinal study, we will characterize a broad range of individual and environmental characteristics of mothers and their newborns to evaluate interrelationships with skin parameters and their changes over time. Considering the combination of these multiple variables and levels will allow for a deeper understanding of the complex interrelationship of the newborn’s skin maturation. This trial is registered with ClinicalTrials.gov (Identifier: NCT04759924).

1245. In Vitro Activities of Ceftaroline and Comparator Agents Against Bacterial Pathogens Collected from Patients with Skin and Skin Structure Infections: ATLAS Global Surveillance Program 2012-2019

Background Ceftaroline fosamil, the prodrug of ceftaroline, is a parenteral cephem approved for the treatment of patients with skin and skin structure infections (SSSIs) caused by Staphylococcus aureus (both methicillin-susceptible [MSSA] and methicillin-resistant [MRSA] isolates), β-hemolytic streptococci (Streptococcus pyogenes, S. agalactiae, S. dysgalactiae), and select species of Enterobacterales (Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca). The current study is part of the ATLAS (Antimicrobial Testing Leadership and Surveillance) program and evaluated the current activities of ceftaroline and comparator agents against commonly encountered bacterial isolates associated with SSSIs. Methods From 2012 to 2019 the ATLAS program received 124,694 bacterial isolates that had been cultured by 493 clinical laboratories in 71 countries from samples of patients diagnosed with SSSIs. All isolates were transported to IHMA, (Schaumburg, IL, USA) where their identities were confirmed using MALDI-TOF mass spectrometry and antimicrobial susceptibility testing performed following standardized CLSI broth microdilution methodology (M07). Percent susceptibilities were determined using 2021 CLSI MIC breakpoints. Phenotypic extended-spectrum β-lactamase (ESBL) screening and confirmatory testing were performed using the CLSI M100 method. Results The in vitro activity of ceftaroline is summarized in the following table. Overall, >99.9% of MSSA and 92.8% of MRSA from SSSI were susceptible to ceftaroline (MIC ≤1 µg/ml); 7.1% of MRSA isolates were ceftaroline-susceptible dose-dependent (MIC 2-4 µg/ml) with greatest proportion being from Chile (53.3% of 392 isolates), S. Korea (29.3% of 321 isolates), and China (24.7% of 652 isolates). Twelve ceftaroline-resistant MRSA were observed, consisting of 11 of 109 isolates from Thailand (10.1%) and 1 of 161 from China (0.6%). All S. pyogenes and 88.0% of ESBL-negative Enterobacterales were susceptible to ceftaroline. Results Table Conclusion Ceftaroline continues to demonstrate potent in vitro activity against clinically relevant pathogens associated with SSSIs. Disclosures Meredith Hackel, PhD MPH, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Gregory Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)

1365. Clinical and Financial Implication of Dalbavancin Utilization on Length of Stay Avoidance in Acute Bacterial Skin and Skin Structure Infection

Background Our institution admits 650 patients annually for acute bacterial skin and skin structure infection (ABSSSI). These patients may require intravenous antibiotics, potentially complicated by social factors and loss to follow up. Dalbavancin is a long-acting lipoglycopeptide given as a single dose regimen for ABSSSI. A previous review conducted at our institution identified 117 potential avoidable hospital days over 4 months with outpatient dalbavancin use. The objective of this prospective study was to evaluate the clinical and financial impact of avoided admissions with outpatient dalbavancin use. Methods The Institutional Review Board approved this single-site, prospective study. All patients who presented to the emergency department (ED) with ABSSSI from December 15, 2020 to April 15, 2021 were included in the study. Dalbavancin eligibility criteria were given to providers. Eligible patients were given a single dose of dalbavancin and then discharged. The primary outcome was the difference between percentage of avoidable admissions from the ED with dalbavancin use in the retrospective cohort and prospective cohort. The secondary outcomes were estimated length of stay avoidance, percentage of treatment success without ED re-visit within 30 days, estimated hospital cost avoidance and drug cost reimbursement. The primary outcome was assessed using the Chi-square test. Descriptive statistics were used for the secondary outcomes. Results Fourteen patients received dalbavancin and avoided hospital admissions. The percentages of admissions avoided in the retrospective and prospective cohorts were 16.02% and 6.67%, respectively (Figure 1). A difference of 9.35% was found to be statistically significant (p=0.01). The total estimated length of stay avoidance was 50 days. No patients re-visited the ED within 30 days with treatment failure. The total estimated hospital cost avoidance was &148,852 (Table 1). The net reimbursement for dalbavancin over drug cost was &5,100 (Table 2). Conclusion Dalbavancin use decreased avoidable admissions. At our institution, annual hospital cost savings can reach &1,015,794 if dalbavancin was utlilized to all eligible patients. Disclosures All Authors: No reported disclosures

Induction of Apoptotic Temperature in Photothermal Therapy under Various Heating Conditions in Multi-Layered Skin Structure

Recently, photothermal therapy has attracted attention as an alternative treatment to conventional surgical techniques because it does not lead to bleeding and patients quickly recover after treatment compared to incisional surgery. Photothermal therapy induces tumor cell death through an increase in the temperature using the photothermal effect, which converts light energy into thermal energy. This study was conducted to perform numerical analysis based on heat transfer to induce apoptosis of tumor tissue under various heating conditions in photothermal therapy. The Monte Carlo method was applied to evaluate a multi-layered skin structure containing squamous cell carcinoma. Tissue-equivalent phantom experiments verified the numerical model. Based on the effective apoptosis retention ratio, the numerical analysis results showed the quantitative correlation for the laser intensity, volume fraction of gold nanorods injected into the tumor, and cooling time. This study reveals optimal conditions for maximizing apoptosis within tumor tissue while minimizing thermal damage to surrounding tissues under various heating conditions. This approach may be useful as a standard treatment when performing photothermal therapy.