Allosteric Probe-Based Colorimetric Assay for Direct Identification and Sensitive Analysis of Methicillin Resistance of Staphylococcus aureus.

The accurate and rapid detection of methicillin-resistance of Staphylococcus aureus (SA) holds significant clinical importance. However, the methicillin-resistance detection strategies commonly require complicated cell lysis and gene extraction. Herein, we devised a novel colorimetric approach for the sensitive and accurate identification of methicillin-resistance of SA by combining allosteric probe-based target recognition with self-primer elongation-based target recycling. The PBP2a aptamer in the allosteric probe successfully identified the target MRSA, leading to the initiation of self-primer elongation based-cascade signal amplification. The peroxidase-like hemin/G-quadruplex undergo an isothermal autonomous process that effectively catalyzes the oxidation of ABTS2- and produces a distinct blue color, enabling the visual identification of MRSA at low concentrations. The method offers a shorter duration for bacteria cultivation compared to traditional susceptibility testing methods, as well as simplified manual procedures for gene analysis. The overall amplification time for this test is 60 min, and it has a detection limit of 3 CFU/ml. In addition, the approach has exceptional selectivity and reproducibility, demonstrating commendable performance when tested with real samples. Due to its advantages, this colorimetric assay exhibits considerable potential for integration into a sensor kit, thereby offering a viable and convenient alternative for the prompt and on-site detection of MRSA in patients with skin and soft tissue infections.

Epidemiology and clinical features of Skin and Soft Tissue Infections Caused by PVL-Positive and PVL-Negative Methicillin-Resistant Staphylococcus aureus Isolates in inpatients in China: a single-center retrospective 7-year study.

Previous studies have mainly focused on outpatient cases of skin and soft tissue infections (SSTIs), with limited attention to inpatient occurrences. Thus, we aimed to compare the clinical parameters of inpatients with SSTIs, performed genomic characterization, and determined the subtypes of Panton-Valentine leucocidin (PVL) bacteriophages of methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from these patients. We found that PVL-positive patients had shorter hospital stays (mean, 9 vs. 24 days; p < 0.001) and abscess resolution durations (mean, 8 vs. 13 days; p < 0.01). PVL-positive MRSA-induced SSTIs were more frequently associated with abscesses [36/55 (65.5%) vs. 15/124 (12.1%), p < 0.001], with 52.7% undergoing incision and drainage; over 80% of PVL-negative patients received incision, drainage, and antibiotics. In PVL-positive patients receiving empirical antibiotics, anti-staphylococcal agents such as vancomycin and linezolid were administered less frequently (32.7%, 18/55) than in PVL-negative patients (74.2%, 92/124), indicating that patients with PVL-positive SSTIs are more likely to require surgical drainage rather than antimicrobial treatment. We also found that the ST59 lineage was predominant, regardless of PVL status (41.3%, 74/179). Additionally, we investigated the linear structure of the lukSF-PV gene, revealing that major clusters were associated with specific STs, suggesting independent acquisition of PVL by different strain types and indicating that significant diversity was observed even within PVL-positive strains detected in the same facility. Overall, our study provides comprehensive insights into the clinical, genetic, and phage-related aspects of MRSA-induced SSTIs in hospitalized patients and contributes to a more profound understanding of the epidemiology and evolution of these pathogens in the Chinese population.

Efficacy and safety of omadacycline for treating complicated skin and soft tissue infections: a meta-analysis of randomized controlled trials.

OBJECTIVE: In the present study, we aimed to compare the clinical efficacy and safety of omadacycline (OMC) with its comparators for the treatment of complicated skin and soft tissue infections (cSSTIs) in adult patients. METHODS: Randomized controlled trials (RCTs) evaluating OMC for cSSTIs were searched in databases of PubMed, Embase, Cochrane, Web of Science, and Clinical Trial, up to July 2022. The primary outcomes were clinical efficacy and microbiological response, with secondary outcome was safety. RESULTS: Four RCTs consisting of 1,757 patients were included, with linezolid (LZD) as a comparator drug. For clinical efficacy, OMC was not inferior to LZD in the modified intent-to-treat (MITT) (OR: 1.24, 95% Cl: [0.93, 1.66], P = 0.15) and clinically evaluable (CE) populations (OR: 1.92, 95% Cl: [0.94, 3.92], P = 0.07). For microbiological response, OMC was numerically higher than LZD in the microbiologically evaluable (ME) (OR: 1.74, 95% Cl: [0.81, 3.74], P = 0.16) and microbiological MITT (micro-MITT) populations (OR: 1.27, 95% Cl: [0.92, 1.76], P = 0.14). No significant difference was found in subpopulations of monomicrobial or polymicrobial mixed infection populations. The mortality and adverse event rates were similar between OMC and LZD. CONCLUSIONS: OMC was as good as LZD in terms of clinical efficacy and microbiological response, and has similar safety issues in treating cSSTIs. OMC might be a promising option for treating cSSTIs in adult patients.

Community-acquired Staphylococcus aureus skin and soft tissue infection risk assessment using hotspot analysis and risk maps: the case of California emergency departments.

BACKGROUND: Community-acquired Staphylococcus aureus (CA-Sa) skin and soft tissue infections (SSTIs) are historically associated with densely populated urban areas experiencing high poverty rates, intravenous drug use, and homelessness. However, the epidemiology of CA-Sa SSTIs in the United States has been poorly understood since the plateau of the Community-acquired Methicillin-resistant Staphylococcus aureus epidemic in 2010. This study examines the spatial variation of CA-Sa SSTIs in a large, geographically heterogeneous population and identifies neighborhood characteristics associated with increased infection risk. METHODS: Using a unique neighborhood boundary, California Medical Service Study Areas, a hotspot analysis, and estimates of neighborhood infection risk ratios were conducted for all CA-Sa SSTIs presented in non-Federal California emergency departments between 2016 and 2019. A Bayesian Poisson regression model evaluated the association between neighborhood-level infection risk and population structure, neighborhood poverty rates, and being a healthcare shortage area. RESULTS: Emergency departments in more rural and mountainous parts of California experienced a higher burden of CA-Sa SSTIs between 2016 and 2019. Neighborhoods with high infection rates were more likely to have a high percentage of adults living below the federal poverty level and be a designated healthcare shortage area. Measures of population structure were not associated with infection risk in California neighborhoods. CONCLUSIONS: Our results highlight a potential change in the epidemiology of CA-Sa SSTIs in California emergency departments. Future studies should investigate the CA-Sa burden in other geographies to identify whether this shift in epidemiology holds across other states and populations. Further, a more thorough evaluation of potential mechanisms for the clustering of infections seen across California neighborhoods is needed.

Automatic Extraction of Skin and Soft Tissue Infection Status from Clinical Notes.

The reliable identification of skin and soft tissue infections (SSTIs) from electronic health records is important for a number of applications, including quality improvement, clinical guideline construction, and epidemiological analysis. However, in the United States, types of SSTIs (e.g. is the infection purulent or non-purulent?) are not captured reliably in structured clinical data. With this work, we trained and evaluated a rule-based clinical natural language processing system using 6,576 manually annotated clinical notes derived from the United States Veterans Health Administration (VA) with the goal of automatically extracting and classifying SSTI subtypes from clinical notes. The trained system achieved mention- and document-level performance metrics of the range 0.39 to 0.80 for mention level classification and 0.49 to 0.98 for document level classification.

Epidemiology of acute infections in people who inject drugs in Australia.

ISSUES: People who inject drugs are at risk of acute infections, such as skin and soft tissue infections, infective endocarditis, bone and joint infections and bloodstream infections. There has been an increase in these infections in people who inject drugs internationally over the past 10 years. However, the local data regarding acute infections in Australia has not been well described. APPROACH: We review the epidemiology of acute infections and associated morbidity and mortality amongst people who inject drugs in Australia. We summarise risk factors for these infections, including the concurrent social and psychological determinants of health. KEY FINDINGS: The proportion of people who report having injected drugs in the prior 12 months in Australia has decreased over the past 18 years. However, there has been an increase in the burden of acute infections in this population. This increase is driven largely by skin and soft tissue infections. People who inject drugs often have multiple conflicting priorities that can delay engagement in care. IMPLICATIONS: Acute infections in people who inject drugs are associated with significant morbidity and mortality. Acute infections contribute to significant bed days, surgical requirements and health-care costs in Australia. The increase in these infections is likely due to a complex interplay of microbiological, individual, social and environmental factors. CONCLUSION: Acute infections in people who inject drugs in Australia represent a significant burden to both patients and health-care systems. Flexible health-care models, such as low-threshold wound clinics, would help directly target, and address early interventions, for these infections.

Descriptive evaluation of patients receiving one-time intravenous vancomycin doses at a large academic medical center emergency department.

BACKGROUND: Intravenous (IV) vancomycin is commonly used to treat a variety of infections caused by methicillin-resistant Staphylococcus aureus (MRSA). The practice of administering a single dose of IV vancomycin prior to emergency department (ED) discharge may be clinically ineffective and foster antimicrobial resistance. Furthermore, this practice introduces an unnecessary infection risk along with preventable adverse effects while potentially increasing ED length of stay (LOS). There is a paucity of literature identifying patient characteristics and objective findings in this patient population, which may foster future antimicrobial stewardship initiatives in the ED. METHODS: This was a single-center, retrospective, descriptive analysis of adult patients seen in the ED between January 2020 and January 2023 who received a single dose of IV vancomycin and were subsequently discharged from the ED without hospital admission. Information was collected on patient demographics and select comorbidities, vancomycin indication and dosing, ED LOS, initial vitals and labs, concomitant antibiotics administered, culture results, 30-day return ED visits and admissions, and antibiotics prescribed at ED discharge. RESULTS: A total of 295 patients met inclusion criteria. A total of 32.1% of patients met SIRS criteria. The most commonly selected order indication for IV vancomycin was "skin and skin structure infection" (41%). A total of 86.1% of patients received concomitant antibiotics in the ED and only 54.6% of patients were prescribed oral antibiotics at ED discharge. A total of 80% of patients had at least one culture obtained during the ED visit. In those who had at least one culture obtained, 78.4% of patients had negative cultures and 4.2% of patients had MRSA positive cultures, with MRSA skin cultures being the most common (3.1%). Return ED visits and admissions within 30 days were not statistically significantly different between patients who did and did not receive oral antibiotics at ED discharge. CONCLUSIONS: Despite a lack of clinical efficacy reported in prior literature and the potential risks, administration of a one-time dose of IV vancomycin prior to ED discharge is commonly encountered in clinical practice. There are opportunities for enhanced antimicrobial stewardship related to IV vancomycin use in the ED. Areas of future focus include the utilization of oral antimicrobials when clinically appropriate, particularly for skin and soft tissue infections, and clarification of antibiotic allergies.

Vibrio parahaemolyticus infection caused by market sewage: A case report and literature review.

Vibrio parahaemolyticus is distributed worldwide in seafood such as fish, shrimp, and shellfish and is a major cause of seafood-borne diarrhoeal disease. Previous studies have reported infections contacting with contaminated seafood seawater. So far, 11 cases reported of skin and soft tissue infections (SSTIs) caused by V. parahaemolyticus, which 5 patients died and 6 survived. We found that transmission through contact with contaminated water also causes infection. We report a 46-year-old male contracted V. parahaemolyticus after being splashed with market sewage. His condition deteriorated rapidly and he died eventually, suggesting that more atypical modes of V. parahaemolyticus transmission may be possible in the future. Literature review revealed that SSTIs due to V. parahaemolyticus are rare, so, detailed questioning of the patient's exposure history can help with empirical drug administration early. Patients with immunodeficiency disease and progressive blistering need mandatory debridement urgently. If fascial necrosis is found during debridement, early amputation may save the patient's life.

The Etiology, Antibiotic Therapy and Outcomes of Bacteremic Skin and Soft-Tissue Infections in Onco-Hematological Patients.

OBJECTIVES: to assess the current epidemiology, antibiotic therapy and outcomes of onco- hematological patients with bacteremic skin and soft-tissue infections (SSTIs), and to identify the risk factors for Gram-negative bacilli (GNB) infection and for early and overall mortality. METHODS: episodes of bacteremic SSTIs occurring in cancer patients at two hospitals were prospectively recorded and retrospectively analyzed. RESULTS: Of 164 episodes of bacteremic SSTIs, 53% occurred in patients with solid tumors and 47% with hematological malignancies. GNB represented 45.5% of all episodes, led by Pseudomonas aeruginosa (37.8%). Multidrug resistance rate was 16%. Inadequate empirical antibiotic therapy (IEAT) occurred in 17.7% of episodes, rising to 34.6% in those due to resistant bacteria. Independent risk factors for GNB infection were corticosteroid therapy and skin necrosis. Early and overall case-fatality rates were 12% and 21%, respectively. Risk factors for early mortality were older age, septic shock, and IEAT, and for overall mortality were older age, septic shock and resistant bacteria. CONCLUSIONS: GNB bacteremic SSTI was common, particularly if corticosteroid therapy or skin necrosis. IEAT was frequent in resistant bacteria infections. Mortality occurred mainly in older patients with septic shock, resistant bacteria and IEAT. These results might guide empirical antibiotic therapy in this high-risk population.

Prevalence and incidence of emergency department presentations and hospital separations with injecting-related infections in a longitudinal cohort of people who inject drugs.

People who inject drugs are at risk of acute bacterial and fungal injecting-related infections. There is evidence that incidence of hospitalizations for injecting-related infections are increasing in several countries, but little is known at an individual level. We aimed to examine injecting-related infections in a linked longitudinal cohort of people who inject drugs in Melbourne, Australia. A retrospective descriptive analysis was conducted to estimate the prevalence and incidence of injecting-related infections using administrative emergency department and hospital separation datasets linked to the SuperMIX cohort, from 2008 to 2018. Over the study period, 33% (95%CI: 31-36%) of participants presented to emergency department with any injecting-related infections and 27% (95%CI: 25-30%) were admitted to hospital. Of 1,044 emergency department presentations and 740 hospital separations, skin and soft tissue infections were most common, 88% and 76%, respectively. From 2008 to 2018, there was a substantial increase in emergency department presentations and hospital separations with any injecting-related infections, 48 to 135 per 1,000 person-years, and 18 to 102 per 1,000 person-years, respectively. The results emphasize that injecting-related infections are increasing, and that new models of care are needed to help prevent and facilitate early detection of superficial infection to avoid potentially life-threatening severe infections.

Successful addition of topical antibiotic treatment after surgery in treatment-refractory nontuberculous mycobacterial skin and soft tissue infections.

Treatment of skin and soft tissue infections with nontuberculous mycobacteria sometimes fails despite repeated debridements and long-term systemic antibiotic therapy. These treatment-refractory infections can cause significant morbidity and pose a treatment challenge. Following surgery, we treated three patients with negative pressure wound therapy with the instillation and dwell time of topical antibiotics, in addition to systemic antibiotic treatment. Treatment was successful and well tolerated, except for some local irritation.

In vitro activity of ceftaroline against bacterial isolates causing skin and soft tissue and respiratory tract infections collected in Latin American countries, ATLAS program 2016-2020.

OBJECTIVES: Ceftaroline, a broad-spectrum cephalosporin, has activity against Gram-positive and several Gram-negative bacteria (GNB). This study aimed to evaluate the antimicrobial activity of ceftaroline and comparators against isolates causing skin and soft tissue infections (SSTIs) and respiratory tract infections (RTIs) collected in Latin America (LATAM) in 2016-2020 as part of the Antimicrobial Testing Leadership and Surveillance program (ATLAS). METHODS: Minimum inhibitory concentrations were determined using both Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. RESULTS: Ceftaroline demonstrated potent activity against methicillin-susceptible Staphylococcus aureus (CLSI/EUCAST: MIC90 0.25 mg/L; susceptibility 100%), whereas activity against methicillin-resistant S. aureus varied for SSTIs (MIC90 1 mg/L; susceptibility 92.5%) and RTIs isolates (MIC90 2 mg/L; susceptibility 72.9%) isolates. For Streptococcus pneumoniae, particularly penicillin-resistant isolates commonly causing respiratory infections, high ceftaroline activity (MIC90 0.25 mg/L; susceptibility 100%/98.4%) was noted. All isolates of ß-hemolytic streptococci were susceptible to ceftaroline (S. agalactiae: MIC90 0.03 mg/L [SSTIs]; MIC90 0.015 mg/L (RTIs); susceptibility 100%; S. pyogenes: MIC90 0.008 mg/L; susceptibility 100%). Ceftaroline was highly active against Haemophilus influenzae, including ß-lactamase positive isolates (MIC90 0.06 mg/L; susceptibility 100%/85.7%). Ceftaroline demonstrated high activity against non-ESBL-producing GNB (E. coli: MIC90 0.5 mg/L, susceptibility 91.9%; K. pneumoniae: MIC90 0.25 mg/L, susceptibility 95.1%; K. oxytoca, MIC90 0.5 mg/L; susceptibility 95.7%). CONCLUSION: Ceftaroline was active against the recent collection of bacterial pathogens commonly causing SSTIs and RTIs in LATAM. Local and regional surveillance of antimicrobial resistance patterns are crucial to understand evolving resistance and guide treatment management.

Molecular Epidemiologic and Geo-Spatial Characterization of Staphylococcus aureus Cultured from Skin and Soft Tissue Infections from United States-Born and Immigrant Patients Living in New York City.

(1) Background: With increasing international travel and mass population displacement due to war, famine, climate change, and immigration, pathogens, such as Staphylococcus aureus (S. aureus), can also spread across borders. Methicillin-resistant S. aureus (MRSA) most commonly causes skin and soft tissue infections (SSTIs), as well as more invasive infections. One clonal strain, S. aureus USA300, originating in the United States, has spread worldwide. We hypothesized that S. aureus USA300 would still be the leading clonal strain among US-born compared to non-US-born residents, even though risk factors for SSTIs may be similar in these two populations (2) Methods: In this study, 421 participants presenting with SSTIs were enrolled from six community health centers (CHCs) in New York City. The prevalence, risk factors, and molecular characteristics for MRSA and specifically clonal strain USA300 were examined in relation to the patients' self-identified country of birth. (3) Results: Patients born in the US were more likely to have S. aureus SSTIs identified as MRSA USA300. While being male and sharing hygiene products with others were also significant risks for MRSA SSTI, we found exposure to animals, such as owning a pet or working at an animal facility, was specifically associated with risk for SSTIs caused by MRSA USA300. Latin American USA300 variant (LV USA300) was most common in participants born in Latin America. Spatial analysis showed that MRSA USA300 SSTI cases were more clustered together compared to other clonal types either from MRSA or methicillin-sensitive S. aureus (MSSA) SSTI cases. (4) Conclusions: Immigrants with S. aureus infections have unique risk factors and S. aureus molecular characteristics that may differ from US-born patients. Hence, it is important to identify birthplace in MRSA surveillance and monitoring. Spatial analysis may also capture additional information for surveillance that other methods do not.

Dual-Toehold-Probe-Mediated Exonuclease-III-Assisted Signal Recycles Integrated with CHA for Detection of mecA Gene Using a Personal Glucose Meter in Skin and Soft Tissue Infection.

Staphylococcus aureus integrated with mecA gene, which codes for penicillin-binding protein 2a, is resistant to all penicillins and other beta-lactam antibiotics, resulting in poor treatment expectations in skin and soft tissue infections. The development of a simple, sensitive and portable biosensor for mecA gene analysis in S. aureus is urgently needed. Herein, we propose a dual-toehold-probe (sensing probe)-mediated exonuclease-III (Exo-III)-assisted signal recycling for portable detection of the mecA gene in S. aureus. When the target mecA gene is present, it hybridizes with the sensing probe, initiating Exo III-assisted dual signal recycles, which in turn release numerous "3" sequences. The released "3" sequences initiate catalytic hairpin amplification, resulting in the fixation of a sucrase-labeled H2 probe on the surface of magnetic beads (MBs). After magnet-based enrichment of an MB-H1-H2-sucrase complex and removal of a liquid supernatant containing free sucrase, the complex is then used to catalyze sucrose to glucose, which can be quantitatively detected by a personal glucose meter. With a limit of detection of 4.36 fM for mecA gene, the developed strategy exhibits high sensitivity. In addition, good selectivity and anti-interference capability were also attained with this method, making it promising for antibiotic tolerance analysis at the point-of-care.

In Vitro Activity of Ceftaroline and Comparators against Bacterial Isolates Collected Globally from Patients with Skin and Soft Tissue Infections: ATLAS Program 2019-2020.

The objective of this study was to assess the in vitro activity of ceftaroline and a panel of comparator agents against isolates causing skin and soft tissue infections (SSTIs) collected in Africa/Middle East, Asia-Pacific, Europe, and Latin America from 2019-2020. Minimum inhibitory concentrations (MIC) were determined using European Committee on Antimicrobial Susceptibility Testing criteria. All the methicillin-susceptible Staphylococcus aureus (MSSA) isolates were susceptible to ceftaroline. Across all regions, ceftaroline demonstrated potent activity against methicillin-resistant S. aureus (MRSA, susceptibility 89.5-93.7%) isolates. Susceptibility to vancomycin, daptomycin, linezolid, teicoplanin, trimethoprim sulfamethoxazole, and tigecycline was ≥94.1% in MSSA and MRSA isolates. Against ß-hemolytic streptococci isolates, ceftaroline demonstrated very potent activity (MIC90 0.008-0.03 mg/L) across all regions. All ß-hemolytic streptococci isolates were susceptible to linezolid, penicillin, and vancomycin (MIC90 0.06-2 mg/L). Among the extended-spectrum ß-lactamases (ESBL)-negative Enterobacterales tested (E. coli, K. pneumoniae, and K. oxytoca), susceptibility to ceftaroline was high (88.2-98.6%) in all regions. All ESBL-negative Enterobacterales were susceptible to aztreonam. Potent activity was observed for amikacin, cefepime, and meropenem (94.1-100%) against these isolates. Overall, ceftaroline showed potent in vitro activity against isolates of pathogens causing SSTIs. Continuous surveillance of global and regional susceptibility patterns is needed to guide appropriate treatment options against these pathogens.

Ultrasonography for Skin and Soft Tissue Infections, Noninfectious Cysts, Foreign Bodies, and Burns in the Critical Care Setting.

There are multiple opportunities for the use of ultrasonography in the diagnosis of skin and soft tissue differentials. Ultrasonography is inexpensive, easily reproducible, and able to provide real-time data in situations where condition changes and progression are common. Not only does bedside ultrasonography provide the clinician an in-depth look beyond epidermal structures into body cavities, it remains a safe, nonionizing radiating, effective, cost-efficient, reliable, and accessible tool for the emergency management of life- and limb-threatening integumentary infections. Unnecessary invasive procedures are minimized, providing improved patient outcomes. Integumentary abnormalities secondary to trauma, surgery, and hospitalization are common among critical care patients. This article provides a brief overview and evidence-based recommendations for the use of ultrasonography in the critical care setting for integumentary system conditions, including common skin and soft tissue differentials, foreign bodies, and burn depth assessment.

Development, acceptability and feasibility of a personalised, behavioural intervention to prevent bacterial skin and soft tissue infections among people who inject drugs: a mixed-methods Person-Based Approach study.

BACKGROUND: Skin and soft tissue infections (SSTI) among people who inject drugs (PWID) are a public health concern. This study aimed to co-produce and assess the acceptability and feasibility of a behavioural intervention to prevent SSTI. METHODS: The Person-Based Approach (PBA) was followed which involves: (i) collating and analysing evidence; (ii) developing guiding principles; (iii) a behavioural analysis; (iv) logic model development; and (v) designing and refining intervention materials. Co-production activities with target group representatives and key collaborators obtained feedback on the intervention which was used to refine its design and content. The intervention, harm reduction advice cards to support conversation between service provider and PWID and resources to support safer injecting practice, was piloted with 13 PWID by four service providers in Bristol and evaluated using a mixed-methods approach. Semi-structured interviews were conducted with 11 PWID and four service providers. Questionnaires completed by all PWID recorded demographic characteristics, SSTI, drug use and treatment history. Interviews were analysed thematically and questionnaires were analysed descriptively. RESULTS: Published literature highlighted structural barriers to safer injecting practices, such as access to hygienic injecting environments and injecting practices associated with SSTI included: limited handwashing/injection-site swabbing and use of too much acidifier to dissolve drugs. Co-production activities and the literature indicated vein care and minimisation of pain as PWID priorities. The importance of service provider-client relationships and non-stigmatising delivery was highlighted through the co-production work. Providing practical resources was identified as important to address environmental constraints to safer injecting practices. Most participants receiving the intervention were White British, male, had a history of SSTI and on average were 43.6 years old and had injected for 22.7 years. The intervention was well-received by PWID and service providers. Intervention content and materials given out to support harm reduction were viewed positively. The intervention appeared to support reflections on and intentions to change injecting behaviours, though barriers to safer injecting practice remained prominent. CONCLUSIONS: The PBA ensured the intervention aligned to the priorities of PWID. It was viewed as acceptable and mostly feasible to PWID and service providers and has transferability promise. Further implementation alongside broader harm reduction interventions is needed.

Fabrication and characterisation of poly(sulfonated) and poly(sulfonic acid) dissolving microneedles for delivery of antibiotic and antifungal agents.

Skin and soft tissue infections (SSTIs) arise from microbial ingress into the skin. In this study, poly(2-acrylamido-2-methyl-1-propanesulfonic acid) (polyAMPS), which has been reported to exhibit antimicrobial properties was synthesised for the manufacture of microarray patches (MAPs). The free acid and sodium salt of polyAMPS with controlled molar masses and narrow dispersity were synthesised via reversible addition - fragmentation chain-transfer (RAFT) polymerisation reaction with a monomer conversion of over 99%, as determined by 1H NMR. The polymers were shown to be biocompatible when evaluated using a fibroblast dermal cell line while agar plating assay using cultures of C. albican demonstrated that the acid form of polyAMPS exhibited antimicrobial inhibition, which is potentiated in the presence of antimicrobial agents. The synthesised polymers were then used to fabricate dissolving MAPs, which were loaded with either ITRA or levofloxacin (LEV). The MAPs displayed acceptable mechanical resistance and punctured ex vivo skin to a depth of 600 µm. Skin deposition studies revealed that the MAPs were able to administer up to âˆ¼ 1.9 mg of LEV (delivery efficiency: 94.7%) and âˆ¼ 0.2 mg of ITRA (delivery efficiency: 45.9%), respectively. Collectively, the synthesis and development of this novel pharmaceutical system may offer a strategy to manage SSTIs.

Acinetobacter baumannii in the critically ill: complex infections get complicated.

Acinetobacter baumannii is increasingly associated with various epidemics, representing a serious concern due to the broad level of antimicrobial resistance and clinical manifestations. During the last decades, A. baumannii has emerged as a major pathogen in vulnerable and critically ill patients. Bacteremia, pneumonia, urinary tract, and skin and soft tissue infections are the most common presentations of A. baumannii, with attributable mortality rates approaching 35%. Carbapenems have been considered the first choice to treat A. baumannii infections. However, due to the widespread prevalence of carbapenem-resistant A. baumannii (CRAB), colistin represents the main therapeutic option, while the role of the new siderophore cephalosporin cefiderocol still needs to be ascertained. Furthermore, high clinical failure rates have been reported for colistin monotherapy when used to treat CRAB infections. Thus, the most effective antibiotic combination remains disputed. In addition to its ability to develop antibiotic resistance, A. baumannii is also known to form biofilm on medical devices, including central venous catheters or endotracheal tubes. Thus, the worrisome spread of biofilm-producing strains in multidrug-resistant populations of A. baumannii poses a significant treatment challenge. This review provides an updated account of antimicrobial resistance patterns and biofilm-mediated tolerance in A. baumannii infections with a special focus on fragile and critically ill patients.

Photodynamic therapy: a new approach to the treatment of Nontuberculous Mycobacterial skin and soft tissue infections.

Nontuberculous mycobacterial skin and soft tissue infections are rising and are causing social concern due to the growth of cosmetic dermatology and immune-compromised populations. For the treatment of nontuberculous mycobacteria, several novel strategies have been investigated. One of them, photodynamic therapy, is a recently developed therapeutic strategy that has shown promise in managing nontuberculous mycobacterial skin and soft tissue infections. In this review, we first present an overview of the current status of the therapy and then summarize and analyze the cases of photodynamic therapy used to treat nontuberculous mycobacterial skin and soft tissue infections. We also discussed the feasibility of photodynamic therapy for treating nontuberculous mycobacterial skin soft tissue infections and the related mechanisms, providing a potential new option for clinical treatment.