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Soft tissue and bone infections continue to be a serious complication in orthopedic and trauma surgery. Both can lead to a high burden for the patients and the healthcare system. Musculoskeletal infections can be induced by intraoperative contamination, bacterial contamination of open wounds or hematogenous bacterial spread. During the recent decades, advances were achieved in the understanding of pathogenesis and antibiotic resistance. Despite some progress in the diagnosis and advancing of therapeutic concepts, groundbreaking successful improvement of treatment concepts is still missing. Current therapy concepts are based on the two pillars consisting of surgical debridement with joint or bone reconstruction as well as prolonged antibiotic therapy. An improved understanding of both host and pathogen-related factors leading to treatment failure is essential in musculoskeletal infections. Therefore, this review aims to give an overview of pathogen-related pathophysiology in musculoskeletal infections. It describes defense strategies of pathogens such as (1) biofilm, its development, characteristics, and treatment options. In addition, (2) characteristics of small colony variants and (3) intracellular bacteria are highlighted. Lastly (4) an outlook for potential and promising future therapeutic strategies is provided., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Purpose: An advisory panel of experts was convened by the ASHP Foundation as a part of its Medication-Use Evaluation Resources initiative to provide commentary on an approach to antibiotic stewardship in the treatment of skin and soft tissue infections (SSTIs), with a focus on oral antibiotics in the emergency department (ED) setting for patients who will be treated as outpatients. Considerations include a need to update existing guidelines to reflect new antibiotics and susceptibility patterns, patient-specific criteria impacting antibiotic selection, and logistics unique to the ED setting., Summary: While national guidelines serve as the gold standard on which to base SSTI treatment decisions, our advisory panel stressed that institutional guidelines must be regularly updated and grounded in local antimicrobial resistance patterns, patient-specific factors, and logistical considerations. Convening a team of experts locally to establish institution-specific guidelines as part of a comprehensive antibiotic stewardship program can ensure patients receive the most appropriate oral therapy for the outpatient treatment of SSTIs in patients visiting the ED., Conclusion: SSTI treatment considerations for antibiotic selection in the ED supported by current, evidence-based guidelines, including guidance on optimal oral antibiotic selection for patients discharged for outpatient treatment, are a useful tool to improve the quality and efficiency of care, enhance patient-centric outcomes and satisfaction, decrease healthcare costs, and reduce overuse of antibiotics., (© American Society of Health-System Pharmacists 2024.)

Shortly after its introduction into clinical practice, Staphylococcus aureus isolates gained resistance to penicillin via the acquisition of β-lactamases. A number of centers have recently described an increase in the proportion of invasive methicillin-susceptible S. aureus (MSSA), which are also susceptible to penicillin (PSSA). Little data are available regarding the prevalence or impact of PSSA in skin and soft tissue infections (SSTI). Community-acquired MSSA SSTI isolates were obtained through a surveillance study at Texas Children's Hospital from January 2017 to December 2021. A total of 200 random isolates underwent PCR for blaZ β-lactamase; blaZ -negative isolates then underwent penicillin susceptibility testing using macrobroth dilution. Isolates which were blaZ negative and had a penicillin MIC ≤0.125 µg/mL were regarded as PSSA with the remainder regarded as penicillin-resistant MSSA (PR-MSSA). All PSSA underwent multilocus sequence typing. Medical records were reviewed. The median age of subjects was 4.2 years (IQR: 1.6-10.5). PSSA accounted for 9% of isolates during the study period. PSSA and PR-MSSA cases were similar with respect to age, demographics, and rates of prior antibiotic exposure. PSSA isolates less often had vancomycin MIC ≥1.5 µg/mL. Furthermore, 39% of PSSA were variants of sequence type 1. In multivariable analyses, penicillin susceptibility was independently associated with both hospital admission and surgical intervention. PSSA account for a small but significant proportion of MSSA SSTI in children. Clinically distinguishing patients with PSSA and PR-MSSA SSTI is challenging. However, PSSA SSTI were independently associated with higher rates of hospital admission as well as the need for surgical intervention suggesting a significant clinical impact.IMPORTANCEThe vast majority of Staphylococcus aureus in the US are penicillin resistant with most clinical labs no longer reporting penicillin susceptibility for this organism. A number of centers, however, have reported increasing penicillin susceptibility among invasive S. aureus infections. Skin and soft tissue infections (SSTI) are far more common than invasive infections, yet the frequency and impact of penicillin-susceptible S. aureus (PSSA) in this population are uncertain. Through active surveillance at a children's hospital, we found that 9% of methicillin-susceptible S. aureus SSTI isolates were PSSA. PSSA were independently associated with hospital admission for the management of SSTI as well as the need for debridement in the operating room. Given that most SSTI are managed in the outpatient setting, these findings suggest a clinical impact of this phenotype and the need for a reassessment of the value in susceptibility testing and potentially even treatment with penicillin., Competing Interests: J.C.M. receives grant support through Merck for unrelated research and is a site investigator on a clinical trial sponsored by Nabriva (also unrelated to the work under consideration). S.L.K. and K.G.H. receive support through Pfizer for unrelated work.

Background and Objectives: Although skin and soft tissue infections (SSTIs) are among the most common indications for pediatric hospitalization, little is known about outpatient care received for SSTI before and after hospitalization. We assessed peri-hospitalization care for SSTI, including antibiotic exposures and their impact on hospital length of stay (LOS)., Methods: This is a retrospective cohort study of 1229 SSTI hospitalizations in 2019 from children aged 1-to-18 years enrolled in Medicaid from 10 US states included in the Merative Marketscan Medicaid database. We characterized health service utilization (outpatient visits, laboratory and diagnostic tests, antibiotic exposures) 14 days before and 30 days after hospitalization and evaluated the effects of pre-hospitalization care on hospital LOS with linear regression., Results: Only 43.1% of children hospitalized with SSTI had a preceding outpatient visit with a SSTI diagnosis, 69.8% of which also filled prescription for an antibiotic. Median LOS for SSTI admission was 2 days (interquartile range 1-3). Pre-hospitalization visits with a diagnosis of SSTI were associated with a 0.7 day reduction (95% confidence interval: 0.6-0.81) in LOS (P < .001), but pre-hospital antibiotic exposure alone had no effect on LOS. Most children (81.7%) filled antibiotic prescriptions after hospital discharge and 74.5% had post-discharge ambulatory visits., Conclusions: Although most children did not receive pre-admission care for SSTI, those that did had a shorter hospitalization. Further investigation is necessary on how to optimize access and use of outpatient care for SSTI., Competing Interests: CONFLICT OF INTEREST DISCLOSURES: The authors have indicated they have no conflicts of interest relevant to this article to disclose., (Copyright © 2024 by the American Academy of Pediatrics.)

Background: Skin and soft tissue infections (SSTIs) are among the most common indications for antimicrobial prescribing in hospitals. Inappropriate antimicrobial use can lead to increased morbidity, unnecessary hospital re-admission and increased antimicrobial resistance. This study aimed to assess the quality of antimicrobial prescribing practices in SSTI management within Australian hospitals to provide guidance for future practice., Methods: A retrospective analysis was conducted with data from the National Antimicrobial Prescribing Survey (NAPS). SSTI prescribing data from Hospital NAPS (2013-2022) and surgical site infection data from Surgical NAPS (2016-2022) datasets were analysed. Variables assessed included guideline compliance, appropriateness as per the structured NAPS algorithm, and reasons for inappropriateness., Results: From the Hospital NAPS dataset, 40,535 antimicrobial prescriptions for SSTIs were analysed. The most common indication was cellulitis (34.1%, N=13,822), and the most prescribed antimicrobial was flucloxacillin (18.8%, N=7,638). SSTI indications had a lower rate of guideline compliance but a higher rate of appropriateness compared with all other indications for antimicrobial prescriptions (guideline compliance 66.3%, N=21,035 vs 67.4%, N=156,285; appropriateness 75.6%, N=30,639 vs 72.7%, N=209,383). The most common reason for inappropriateness was incorrect dose or frequency (29.3%, N=2367). From the Surgical NAPS dataset, 5674 prescriptions for surgical site infections were analysed. Of these, 68.2% (N=3867) were deemed to be appropriate. The most common reason for inappropriateness was incorrect dose or frequency (27.7%, N=350)., Conclusions: As SSTIs are a common indication for prescribing an antimicrobial in Australian hospitals, identifying effective antimicrobial stewardship strategies to optimize antimicrobial use for SSTI management is recommended to improve patient outcomes., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: This study compared the costs and nursing time associated with the delivery of continuous infusion of antibiotics via elastomeric infusion pumps (EIP) versus conventional intermittent infusion (CII) across different care pathways., Design: Retrospective real-world data informed a cost comparison analysis that compared costs and nursing hours between infusion of antibiotics via EIP versus CII across eight care pathways in inpatient or outpatient care during infection episodes. Real-world data were obtained from patients treated within a year with parenteral antimicrobial therapy in Päijät-Häme Region, Finland., Setting: Inpatient care with hospital admission and outpatient care at hospital at home in Päijät-Häme Region in Finland., Participants: 3778 patients with a total of 4214 infection episodes treated with intravenous antimicrobial therapy., Interventions: Eight treatment strategies with various combinations of EIP and CII administered in inpatient or outpatient care., Primary and Secondary Outcome Measures: Direct costs and nursing time., Results: Skin and soft tissue infections accounted for the highest number of episodes treated with EIP overall (30.8%; 74 out of 240 episodes) and in outpatient care specifically (53.3%; 128 out of 240 episodes). Compared with inpatient care costs with CII (€4590 per episode), treating skin and soft tissue infections in outpatient care with EIP or CII incurred only 24% (€1104) and 35% (€1620) of the costs, respectively. Across all treatment strategies and infections studied, the use of EIP consistently required less nursing time. The highest nursing time in the outpatient care was observed in sepsis episodes treated with CII (37 hours with CII vs 7 hours with EIP per episode)., Conclusion: Delivery of antimicrobial therapy using continuous infusions with EIP instead of CII can significantly decrease the nursing time and cost in both inpatient and outpatient care. For skin and soft tissue infections and sepsis, the utilisation of EIP is a cost-saving option in outpatient care compared with the use of CII., Competing Interests: Competing interests: TH, ML and EH received consulting fees paid directly to their employer by Baxter Healthcare SA. JS and TG are employees of Baxter Healthcare SA, and they did not participate in data capture nor data-analysis, nor data interpretation., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: This study conducted a network meta-analysis comparing linezolid, teicoplanin, daptomycin, tigecycline, and ceftaroline fosamil with vancomycin for treating MRSA-related diseases, addressing the lack of comprehensive evaluations in existing research on antibiotic therapy for MRSA infections., Methods: We systematically searched databases including PubMed, Embase, Web of Science, the Cochrane Librar up to August 22, 2023. All eligible randomized controlled trials of the six antibiotics were included in the NMA, and their effectiveness and safety were compared across various MRSA-related diseases. Categorical data were used for the odds ratio (OR), and continuous data were used for mean difference (SMD). The surface under the cumulative ranking (SUCRA) was employed to evaluate the incidence rate., Results: According to SUCRA results, daptomycin was the most effective treatment (73.0%) in bloodstream infections. In pulmonary infections and skin and soft tissue infections, linezolid out-performed other antibiotics in effectiveness rate (90.6% and 86.3%), microbial killing rate (93.3% and 93.1%). Vancomycin showed lower adverse reactions than teicoplanin, with less hepatotoxicity compared to linezolid and tigecycline. Linezolid had higher thrombocytopenia risk but lower nephrotoxicity risk than others. Vancomycin was less effective in microbial killing rates than linezolid across various infections., Conclusion: The present research suggests that in pulmonary infections and skin and soft tissue infections, linezolid may be a better option for treating MRSA-related diseases. However, caution is warranted due to the association of linezolid with thrombocytopenia., Trial Registration: Our study protocol was registered with the International Prospective Register of SystematicReviews (PROSPERO); Registration number: CRD42024535142., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Three family members attended their general practice and emergency department over a 3-month period with recurrent skin and soft tissue infections (SSTIs) such as paronychia, submandibular carbuncle and groin and gluteal abscess requiring surgical drainage. Only when two family members were concurrently admitted with abscesses requiring drainage under general anaesthetic was the definitive diagnosis reached. The wound swabs identified methicillin-resistant Staphylococcus aureus (MRSA) and subsequent identification of the exotoxin Panton-Valentine leukocidin (PVL). Following MRSA decolonisation therapy with mupirocin and octenidine, only one family member has had one recurrence of an SSTI with MRSA isolated from the wound. When patients present with a history of recurrent SSTIs or a family all have had similar presentations, the clinician should consider MRSA with PVL exotoxin infection. Then patients must be referred for confirmation to ensure management is effective for the SSTI and prescribe MRSA decolonisation therapy concurrently to reduce recurrence., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

The clinical microbiology laboratory is capable of identifying microorganisms in clinical specimens faster and more accurately than ever before. At face value, this should enable patient care providers to make better-informed decisions and target antimicrobial therapies to deliver individualized care. Ironically, more complete and specific reporting of microorganisms isolated from specimens may result in overtreatment based on the presence of a pathogen, even in the absence of clear signs of clinical infection. This conundrum calls into question the role of the laboratory in contributing to care through selective or "exception" reporting whereby some results are selectively withheld when there is a low probability that laboratory findings correlate with the clinical infection. In a recent article published in the Journal of Clinical Microbiology , Bloomfield et al. (J Clin Microbiol 62:e00342-24, 2024, https://doi.org/10.1128/jcm.00342-24) examine the impact and safety of an exception reporting strategy applied to wound swab specimens. Canonical pathogens associated with skin and soft tissue infections including S. aureus and beta-hemolytic streptococci are withheld from the laboratory report if certain patient criteria are met that would put them at low risk of adverse outcomes if untreated, or if treated with guideline-recommended empiric therapy. Their central finding was an approximately 50% reduction in post-laboratory report antibiotic initiation without adverse events or increased 30-day admission rate (indicative of infection-related complications, e.g., disseminated disease). While effectively achieving their goal, the premise of exception reporting and other modified reporting strategies raises questions about the potential risk of underreporting and how to ensure that the message is being interpreted, and acted upon, by care providers as was intended by the laboratory., Competing Interests: The author declares no conflict of interest.

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.

Purpose: Soft tissue infections can be severe and life-threatening. Their treatment consists currently in radical surgical wound debridement and combined systemic antimicrobial therapy. Different side effects are possible. Local antibiotic therapy represents a new approach to reduce side effects and improve healing. The aim of this study is to assess the effectiveness of the local sprayed use of antibiotics with fibrin sealing compared with negative pressure wound therapy as an established treatment of soft-tissue infections., Methods: In this retrospective study, patients with soft tissue infections who underwent surgical treatment were analysed. One group consists of patients, who received local fibrin-antibiotic spray (FAS) (n = 62). Patients treated by vacuum-assisted wound therapy (VAWT) as the established treatment were the control group (n = 57). Main outcomes were differences in the success of healing, the duration until healing and the number of needed operations., Results: Clinical healing could be achieved for 55 patients (98.21%) in the FAS group vs. 47 patients (92.16%) in the VAWT group (p = 0.19). Time to require this was 10.65 ± 10.38 days in the FAS group and 22.85 ± 14.02 days in the VAWT group (p < 0.001). In the FAS group, patients underwent an average of 1.44 ± 0.72 vs.3.46 ± 1.66 operations in the VAWT group (p < 0.001)., Conclusion: Compared to vacuum-assisted wound therapy in soft tissue infections, local fibrin-antibiotic spray shows faster clinical healing and less needed operations. Leading to shorter hospital stays and more satisfied patients. The combination of sprayed fibrin and antibiotics can be seen as a promising and effective method., (© 2024. The Author(s).)

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., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Mycobacterium mageritense (M. mageritense), a nontuberculous mycobacterium, is classified as a rapidly growing mycobacterium, class IV in the Runyon Classification. This bacterium is found in soil, water, and other habitats. Infections caused by M. mageritense are relatively rare and no treatment protocol has been established. Herein, we report a case of skin and soft tissue infection caused by M. mageritense. A 49-year-old woman underwent surgery for right breast cancer. Four months after surgery, a surgical site infection was found, and M. mageritense was identified in the wound culture using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Based on the sensitivity results, the patient was treated with levofloxacin and doxycycline for 4 months. In addition to antimicrobial agents, aggressive surgical interventions led to a favorable course of treatment. In conclusion, successful treatment of skin and soft tissue infections with M. mageritense requires surgical intervention whenever possible, aggressive susceptibility testing, and appropriate antimicrobial therapy., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Objectives: Mastitis is mainly caused by Gram-positive bacteria and usually involves treatment with beta-lactam antibiotics and clindamycin. Oxazolidinones show good results in the treatment of skin and soft tissue infections (SSTIs) due to its pharmacokinetic characteristics. We aimed to describe clinical characteristics and outcomes of patients who received oxazolidinones for the treatment of SSTIs of the mammary tissue., Methods: Retrospective single-centre study of patients with a diagnosis of breast infection who received treatment with oxazolidinones as initial or salvage therapy between September 2016 and November 2022. Patients were identified through the pharmacy database. The primary outcome was clinical cure., Results: Twenty-nine patients received oxazolidinones: 27 received linezolid and 2 tedizolid. Median age was 41 years (IQR 31.0-56.5) and 28 patients were female. Ten patients (35%) had a history of breast cancer, while three (10%) had an immunosuppressive condition. Microbiological isolation was obtained in 24 individuals (83%). Predominant isolations were methicillin-resistant Staphylococcus aureus (8, 28%) and methicillin-susceptible S. aureus (7, 24%). Twenty-four patients (83%) received oxazolidinones as a salvage therapy, with a median duration of 14 days (IQR 10-17). Clinical cure was achieved in 24 patients (83%), while 4 relapsed after a median of 15 days (IQR 4-34). One was lost to follow-up. Three patients (10%) were taking selective serotonin reuptake inhibitors, and one of them concurrently received linezolid for 4 days with no adverse events recorded. Cytopenia during treatment was observed in 2/12 individuals. Oxazolidinones allowed hospital discharge in 11/13 hospitalized patients., Conclusions: Oxazolidinones could be considered as an alternative for treating breast infections., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Skin and soft tissue infections (SSTIs), and particularly diabetic-related foot infections (DFI), present diagnostic and therapeutic complexities, often leading to severe complications. This study aims to evaluate the in vitro efficacy of cefditoren and amoxicillin/clavulanic acid against typical DFI pathogens. Clinical samples from 40 patients with mild SSTIs were analyzed, revealing a predominance of Staphylococcus spp. and Streptococcus spp. species. Cefditoren exhibited activity against 90% of isolates, with superior potency over amoxicillin/clavulanic acid. These findings underscore the utility of cefditoren in empirical treatment of DFI, although a larger sample size would be desirable for further validation., (©The Author 2024. Published by Sociedad Española de Quimioterapia. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)(https://creativecommons.org/licenses/by-nc/4.0/).)

Background: Knowing the natural history of acute infections in primary care, defined as the course of a disease over time in the absence of specific therapy or treatment, can inform clinicians' and patients' expectations about illness recovery, but this evidence is fragmented across the literature. This scoping review aimed to map existing research and research gaps relevant to the natural history of acute infections., Methods: We searched MEDLINE, Embase and CENTRAL using a 2-phase hierarchical search approach. In Phase A, we focused on identifying systematic reviews synthesising natural history data for eligible infections (acute respiratory, urinary, and skin and soft tissue) and systematic reviews of treatment effectiveness (of RCTs with placebo or no treatment arm, or cohort studies). For infections without existing reviews, in Phase B, we searched for primary studies (placebo-controlled RCTs or cohort studies). Two reviewers independently screened and extracted the data (study characteristics, outcome data - e.g., symptom duration, proportion with resolution at various time points)., Results: We identified 40 systematic reviews, reporting on 45 infections, most commonly (90%) respiratory tract infections. Six (15%) of these aimed to synthesise natural history information. Most reviews reported the proportion of participants with symptom resolution at various time point/s, with 58% providing data on mean symptom duration. Recovery data show the spontaneous resolution of some infections in some people. We found no eligible studies for cellulitis, ecthyma, carbuncle, and erysipelas., Conclusions: Our review has shown that natural history evidence exists for many common acute infections. It can be utilised by clinicians in implementing patient-centred antibiotic stewardship strategies in primary care. Future research should focus on generating natural history evidence for skin and soft tissue infections and urinary tract infections., (© 2024. The Author(s).)

Background: Invasive fungal infections (IFIs) are severe and difficult-to-treat infections affecting immunocompromised patients. Antifungal drug penetration at the site of infection is critical for outcome and may be difficult to achieve. Data about antifungal drug distribution in infected human tissues under real circumstances of IFI are scarce., Methods: Multiple samples were obtained from soft tissue abscesses of a lung transplant patient with Candida albicans invasive candidiasis who underwent recurrent procedures of drainage, while receiving different consecutive courses of antifungal therapy [itraconazole (ITC), fluconazole, caspofungin]. Antifungal drug concentrations were measured simultaneously at the site of infection (surrounding inflammatory tissue and fluid content of the abscess) and in plasma for calculation of the tissue/plasma ratio (R). The concentration within the infected tissue was interpreted as appropriate if it was equal or superior to the MIC of the causal pathogen., Results: A total of 30 tissue samples were collected for measurements of ITC (n = 12), fluconazole (n = 17) and caspofungin (n = 1). Variable concentrations were observed in the surrounding tissue of the lesions with median R of 2.79 (range 0.51-15.9) for ITC and 0.94 (0.21-1.37) for fluconazole. Concentrations ranges within the fluid content of the abscesses were 0.39-1.83 for ITC, 0.66-1.02 for fluconazole and 0.23 (single value) for caspofungin. The pharmacodynamic target (tissue concentration ≥ MIC) was achieved in all samples for all three antifungal drugs., Conclusions: This unique dataset of antifungal drug penetration in infected human soft tissue abscesses suggests that ITC, fluconazole and caspofungin could achieve appropriate concentrations in soft tissue abscesses., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

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.

This text discusses a rare case of soft tissue infection caused by the fungus Saksenaea in a young, immunocompetent woman following an all-terrain vehicle accident abroad. Despite initial treatment, her wound worsened, necessitating multiple surgical revisions and aggressive antifungal therapy with liposomal Amphotericin B. The interdisciplinary collaboration among orthopedic surgeons, infectious disease specialists, and plastic surgeons played a vital role in her successful treatment. Prompt identification of the fungus and immediate intervention were crucial. This case emphasizes the importance of awareness among healthcare providers regarding this rare condition and underscores the significance of early diagnosis and timely surgical and medical interventions for a positive outcome.

We aimed to describe the frequency of treatment failure and associated risk factors for treatment failure amongst neonates with skin and soft tissue infections (SSTIs). We conducted a retrospective cohort study of neonates 0 to 28 days old with uncomplicated SSTIs presenting to the emergency department of a quaternary care children's hospital from 2009 to 2017. Data were collected via chart review. Skin and soft tissue infections included the following: cellulitis, abscess, mastitis, perirectal SSTI, carbuncle, and furuncle. Of the 202 neonates in the study, most were term, afebrile with mastitis, or perirectal SSTI. Treatment failure occurred in 8% (17/202) of neonates receiving oral antibiotics; 10 of these neonates had perirectal SSTIs and 2 had clindamycin and methicillin-resistant Staphylococcus aureus . Neonates with treatment failure had increased odds of having perirectal SSTIs (odds ratio [OR] = 4.08, 95% confidence interval [CI] = 1.46-11.31). Further studies are needed to identify strategies to prevent treatment failure in neonates with perirectal SSTIs., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Elkin Lemos-Luengas, works in Medical Affairs Pfizer S.A.S Colombia Sixta Renteria, works in Medical Affairs Pfizer S.A.S Colombia Diana Marcela Almario Muñoz, works in Medical Affairs Pfizer S.A.S Colombia Cinthya Katherine Galindo Gonzalez, works in Medical Affairs Pfizer S.A.S Colombia Jorge Andres Ramos-Castaneda, has provided consulting services for Pfizer S.A.S, (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: The principal objective of this project was to review and thoroughly examine the chemical characteristics, pharmacological activity, and quantification methods associated with contezolid., Methods: The article was based on published and ongoing preclinical and clinical studies on the application of contezolid. These studies included experiments on the physicochemical properties of contezolid, in vitro antimicrobial research, in vivo antimicrobial research, and clinical trials in various phases. There were no date restrictions on these studies., Results: In June 2021, contezolid was approved for treating complicated skin and soft tissue infections. The structural modification of contezolid has resulted in better efficacy compared to linezolid. It inhibits bacterial growth by preventing the production of the functional 70S initiation complex required to translate bacterial proteins. The current evidence has indicated a substantial decline in myelosuppression and monoamine oxidase inhibition without impairing its antibacterial properties. Contezolid was found to have a more significant safety profile and to be metabolised by flavin monooxygenase 5, reducing the risk of harmful effects due to drug-drug interactions. Adjusting doses is unnecessary for patients with mild to moderate renal or hepatic insufficiency., Conclusion: As an oral oxazolidinone antimicrobial agent, contezolid is effective against multi-drug resistant Gram-positive bacteria. The introduction of contezolid provided a new clinical option., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Nearly 25% of antibiotics prescribed to children are inappropriate or unnecessary, subjecting patients to avoidable adverse medication effects and cost., Methods: We conducted a quality improvement initiative across 118 hospitals participating in the American Academy of Pediatrics Value in Inpatient Pediatrics Network 2020 to 2022. We aimed to increase the proportion of children receiving appropriate: (1) empirical, (2) definitive, and (3) duration of antibiotic therapy for community-acquired pneumonia, skin and soft tissue infections, and urinary tract infections to ≥85% by Jan 1, 2022. Sites reviewed encounters of children >60 days old evaluated in the emergency department or hospital. Interventions included monthly audit with feedback, educational webinars, peer coaching, order sets, and a mobile app containing site-specific, antibiogram-based treatment recommendations. Sites submitted 18 months of baseline, 2-months washout, and 10 months intervention data. We performed interrupted time series (analyses for each measure., Results: Sites reviewed 43 916 encounters (30 799 preintervention, 13 117 post). Overall median [interquartile range] adherence to empirical, definitive, and duration of antibiotic therapy was 67% [65% to 70%]; 74% [72% to 75%] and 61% [58% to 65%], respectively at baseline and was 72% [71% to 72%]; 79% [79% to 80%] and 71% [69% to 73%], respectively, during the intervention period. Interrupted time series revealed a 13% (95% confidence interval: 1% to 26%) intercept change at intervention for empirical therapy and a 1.1% (95% confidence interval: 0.4% to 1.9%) monthly increase in adherence per month for antibiotic duration above baseline rates. Balancing measures of care escalation and revisit or readmission did not increase., Conclusions: This multisite collaborative increased appropriate antibiotic use for community-acquired pneumonia, skin and soft tissue infections, and urinary tract infection among diverse hospitals., (Copyright © 2024 by the American Academy of Pediatrics.)

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., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: New skin and soft tissue infections (SSTI) guidelines were published in 2019 in France, changing the recommended duration for antibiotic treatment. The objective of the present study was to assess the impact of the publication of the 2019 French guidelines on SSTIs on the duration of antibiotic prescription for erysipelas., Methods: In a before-after study (a year before and a year after April 1st, 2019), we included all adult patients diagnosed with erysipelas in Reims University Hospital medical wards and the emergency department. We retrospectively retrieved antibiotic prescription duration in the patients' medical files., Results: Among 50 patients in the "before" and 39 in the "after" group, the mean duration of antibiotic prescription was significantly shorter in the "after" group (9.4 ± 2.8 vs. 12.4 ± 3.8 days, p = 0.0001)., Conclusions: A 25% decrease in the duration of antibiotic prescription for erysipelas was observed following the implementation of these guidelines, providing useful information for an antibiotic stewardship policy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Wound infection commonly causes delayed healing, especially in the setting of chronic wounds. Local release of antibiotics is considered a viable approach to treat chronic wounds. We have developed a versatile telodendrimer (TD) platform for efficient loading of charged antibiotic molecules via a combination of multivalent and synergistic charge and hydrophobic interactions. The conjugation of TD in biocompatible hydrogel allows for topical application to provide sustained antibiotic release. Notably, a drug loading capacity as high as 20 % of the drug-to-resin dry weight ratio can be achieved. The payload content (PC) and release profile of the various antibiotics can be optimized by fine-tuning TD density and valency in hydrogel based on the charge and hydrophobic features of the drug, e.g., polymyxin B (PMB), gentamycin (GM), and daptomycin (Dap), for effective infection control. We have shown that hydrogel with moderately reduced TD density demonstrates a more favorable release profile than hydrogel with higher TD density. Antibiotics loaded in TD hydrogel have comparable antimicrobial potency and reduced cytotoxicity compared to the free antibiotics due to a prolonged, controlled drug release profile. In a mouse model of skin and soft tissue infection, the subcutaneous administration of PMB-loaded TD hydrogel effectively eliminated the bacterial burden. Overall, these results suggest that engineerable TD hydrogels have great potential as a topical treatment to control infection for wound healing. STATEMENT OF SIGNIFICANCE: Wound infection causes a significant delay in the wound healing process, which results in a significant financial and resource burden to the healthcare system. PEGA-telodendrimer (TD) resin hydrogel is an innovative and versatile platform that can be fine-tuned to efficiently encapsulate different antibiotics by altering charged and hydrophobic structural moieties. Additionally, this platform is advantageous as the TD density in the resin can also be fine-tuned to provide the desired antibiotic payload release profile. Sustained antibiotics release through optimization of TD density provides a prolonged therapeutic window and reduces burst release-induced cytotoxicity compared to conventional antibiotics application. Studies in a preclinical mouse model of bacteria-induced skin and soft tissue infection demonstrated promising therapeutic efficacy as evidenced by effective infection control and prolonged antibacterial efficacy of antibiotics-loaded PEGA-TD resin. In conclusion, the PEGA-TD resin platform provides a highly customizable approach for effective antibiotics release with significant potential for topical application to treat various bacterial wound infections to promote wound healing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:, (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

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., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Necrotising soft tissue infections can affect the skin, subcutaneous tissue, superficial fascia, deep fascia and musculature. The infections are severe, they spread quickly and can result in extensive tissue loss. Although rare, morbidity and mortality rates are high. Early clinical identification is crucial for the outcome, and rapid infection control through surgery and targeted antibiotic treatment is needed to save lives. Few prospective clinical trials have been conducted for the treatment of this type of infection. Specific challenges include rapid identification of the condition and the uncertain efficacy of the various treatment options. In this clinical review article, we describe clinical characteristics, diagnostics and treatment.

Among 100 propensity score-matched emergency department patients receiving ≤14 days doxycycline versus cephalexin monotherapy for outpatient treatment of nonpurulent (presumed streptococcal) skin and soft tissue infection, a low rate of 14-day clinical failure was observed [6% each group; odds ratio (OR), 1.34 (0.21-8.69); P = 0.745], defined as hospital admission, i.v. antibiotic therapy, or change in oral antibiotic. Doxycycline may represent a reasonable therapeutic alternative for this indication in regions with low tetracycline resistance., Competing Interests: Dr. Nailor has served as a consultant for Shionogi, AbbVie, and Merck. All other authors declare no conflicts of interest.

Importance: We have found that treatment with short electric pulses potentiates the effects of multiple antibiotics against methicillin-resistant Staphylococcus aureus . By reducing the dose of antibiotic necessary to be effective, co-treatment with electric pulses could amplify the effects of standard antibiotic dosing to treat S. aureus infections such as skin and soft-tissue infections (SSTIs). SSTIs are accessible to physical intervention and are good candidates for electric pulse co-treatment, which could be adopted as a step-in wound and abscess debridement., Competing Interests: The authors declare no conflict of interest.

Background: Severe skin and soft tissue infections related to injection drug use have increased in concordance with a shift to heroin and illicitly manufactured fentanyl. Opioid agonist therapy medications (methadone and buprenorphine) may improve long-term outcomes by reducing injection drug use. We aimed to examine the association of medication use with mortality among people with opioid use-related skin or soft tissue infections., Methods: An observational cohort study of Medicaid enrollees aged 18 years or older following their first documented medical encounters for opioid use-related skin or soft tissue infections during 2007-2018 in North Carolina. The exposure was documented medication use (methadone or buprenorphine claim) in the first 30 days following initial infection compared with no medication claim. Using Kaplan-Meier estimators, we examined the difference in 3-year incidence of mortality by medication use, weighted for year, age, comorbidities, and length of hospital stay., Results: In this sample, there were 13,286 people with opioid use-related skin or soft tissue infections. The median age was 37 years, 68% were women, and 78% were white. In Kaplan-Meier curves for the total study population, 12 of every 100 patients died during the first 3 years. In weighted models, for every 100 people who used medications, there were four fewer deaths over 3 years (95% confidence interval = 2, 6)., Conclusion: In this study, people with opioid use-related skin and soft tissue infections had a high risk of mortality following their initial healthcare visit for infections. Methadone or buprenorphine use was associated with reductions in mortality., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: The authors declare no conflict of interest.

Nontuberculous mycobacteria (NTM) skin infections remain therapeutically challenging. Given the diversity in infections, host responses, and antimicrobials, clinical guidelines are often built on case series and observational studies. In this commentary, we respond to a paper by Stemkens et al. that introduces an emerging strategy: adjunctive negative pressure wound therapy with instillation and dwell time combined with topical antibiotics for refractory NTM skin and soft tissue infections. We delve into the primary considerations surrounding this innovative approach., Competing Interests: The authors declare no conflict of interest.

Skin and soft tissue infections are a common reason for patients seeking inpatient and outpatient medical care. Surgery is an essential part of managing in many episodes. Careful evaluation of antibiotic therapy could help clinicians in early identification to patients with treatment failure and to consider an alternative approach or a new surgical revision in "focus control". With the arrival of new drugs, there is a need to refine the appropriate drug's decision-making. Drugs with a long half-life (long-acting lipoglycopeptides such as dalbavancin or oritavancin), which allows weekly administration (or even greater), can reduce hospital admission and length of stay with fewer healthcare resources through outpatient management (home hospitalization or day hospitals). New anionic fluoroquinolones (e.g. delafloxacin), highly active in an acidic medium and with the possibility of switch from the intravenous to the oral route, will also make it possible to achieve these new healthcare goals and promote continuity of care. Therefore, management should rely on a collaborative multidisciplinary group with experience in this infectious syndrome., (©The Author 2023. Published by Sociedad Española de Quimioterapia. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)(https://creativecommons.org/licenses/by-nc/4.0/).)

Objectives: This study aimed to detect heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) among methicillin-resistant S. aureus (MRSA) isolated from healthcare-associated infections and identify staphylococcal cassette chromosome mec (SCC mec ) types., Methods: This study was conducted from February 2019 to March 2020 and included patients admitted in 4 tertiary care hospitals in Karnataka, India. Isolation and identification of MRSA were done using standard bacteriological methods. Antimicrobial susceptibility testing was done using Kirby-Bauer disc diffusion; macrolide-lincosamide-streptogramin B phenotypes were identified using the D test. The minimum inhibitory concentration (MIC) of vancomycin was determined using agar dilution. hVISA were confirmed by the modified population analysis profile-area under the curve test. SCC mec types and the Panton-Valentine leukocidin ( pvl ) gene were detected using multiplex polymerase chain reaction., Results: Of 220 MRSA stains, 14 (6.4%) were hVISA. None of the MRSA isolates was vancomycin-intermediate or -resistant and all hVISA were susceptible to linezolid and teicoplanin. The macrolide-streptogramin B phenotype was present in 42.9% of hVISA; 92.9% of the hVISA strains had vancomycin MIC in the range of 1-2 μg/mL. Majority of the hVISA and vancomycin-susceptible MRSA were isolated from patients with skin and soft tissue infections. SCC mec III and IV were present in 50% and 35.7% of hVISA, respectively; 14.3% of the hVISA harboured SCC mec V., Conclusion: The prevalence rate of hVISA among MRSA was 6.4%. Therefore, MRSA strains should be tested for hVISA before starting vancomycin treatment. None of the isolates was vancomycin-intermediate or -resistant and all the hVISA strains were susceptible to linezolid and teicoplanin. The majority of the hVISA were isolated from patients with skin and soft tissue infections and harboured SCC mec III and IV., Competing Interests: CONFLICT OF INTEREST The authors declare no conflicts of interests., (© Copyright 2023, Sultan Qaboos University Medical Journal, All Rights Reserved.)

Bacterial skin infections are common in children, and frequently do not require systemic antibiotic therapy, particularly for superficial forms. In these cases, washing (with soap and water) and careful rinsing of the lesion are the key points of treatment. A semiotic analysis must precede any therapeutic decision to assess the appropriateness of antibiotic therapy, need for drainage (which may be spontaneous or surgical) and possible existence of symptoms related to toxin production, which are frequent signs of severity. The bacterial species most frequently implicated in children are Staphylococcus aureus and Streptococcus pyogenes. Given the low incidence of methicillin-resistant S. aureus in France (<10%), the first-line antibiotic treatment is amoxicillin-clavulanate, to which an anti-toxin treatment such as clindamycin may be added for patients with overt toxin signs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: Early initiation of broad-spectrum antibiotic agents is a cornerstone of the care of necrotizing skin and soft tissue infections (NSTI). However, the optimal duration of antibiotic agents is unclear. We sought to characterize antibiotic prescribing patterns for patients with NSTI, as well as associated complications. Patients and Methods: Using an NSTI registry, we characterized antibiotic use at a quaternary referral center. Kaplan-Meier analyses were used to describe overall antibiotic duration and relative to operative source control, stratified by presence of other infections that independently influenced antibiotic duration. Factors associated with successful antibiotic discontinuation were identified using logistic regression. Results: Between 2015 and 2018, 441 patients received antibiotic agents for NSTI with 18% experiencing a complicating secondary infection. Among those without a complicating infection, the median duration of antibiotic administration was 9.8 days (95% confidence interval [CI], 9.2-10.5) overall, and 7.0 days after the final debridement. Perineal NSTI received fewer days of antibiotic agents (8.3 vs. 10.6) compared with NSTI without perineal involvement. White blood cell (WBC) count and fever were not associated with failure of antibiotic discontinuation, however, a chronic wound as the underlying infection etiology was associated with greater odds of antibiotic discontinuation failure (odds ratio [OR], 4.33; 95% CI, 1.24-15.1). Conclusions: A seven-day course of antibiotic agents after final operative debridement may be sufficient for NSTI without any secondary complicating infections, because clinical characteristics do not appear to be associated with differences in successful antibiotic discontinuation.

Background: A previous review demonstrated that the majority of NTM infections in the Northern Territory (NT) are pulmonary in nature [1], however skin and soft tissue (SST) are likely the next most common sites of disease. The current epidemiology of NTM SST infections across the NT is not known. We aimed to establish the current and historical incidence rates, and the organisms involved., Methods: All NTM cases reported to the Centre for Disease Control in Darwin from 1989-2021 were retrospectively reviewed., Results: 226 NTM notifications were reviewed. 73 (32%) cases were SST infections. The incidence of SST cases increased over the study period. Female cases were more common (p=0·002). Disease occurred across a wide age range (1-85 years). Only 16% of cases occurred in Aboriginal individuals which may reflect immunological factors requiring further investigation. Many cases had no clear provocation, but localised skin trauma was the most common risk factor. The most common organism identified was M. fortuitum (41%). Diagnosis was often delayed, with a median time to diagnosis of 69 days (IQR=31-149). Most cases (60%) underwent surgical intervention with adjunctive anti-mycobacterial medical therapy., Conclusion: NTM SST incidence rates increased over the study period. NTM SST infections are a rare but important differential diagnosis for non-healing cutaneous wounds., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest No conflict of interests exits in the submission of this manuscript, and manuscript is approved by all authors for publication. I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part. All the listed authors have approved the manuscript that is enclosed. Wang Xiao, Wang Xiaoyu, He Yongqing, Xiao Tianzhen, (Copyright © 2023. Published by Elsevier B.V.)

Objective: To observe the clinical characteristics and impact on mortality of carbapenem-resistant Pseudomonas aeruginosa (CRPA) colonized or infected patients with hematological disorders in order to provide evidence for the prevention and treatment of CRPA., Methods: The patients who were colonized or infected with CRPA in the Department of Hematology of The First Affiliated Hospital of Zhejiang Chinese Medical University from January 2020 to March 2021 were selected as the research subjects, the clinical data such as hospitalization time, primary disease treatment regimen, granulocyte count, previous infection and antibiotic regimen of these patients were analyzed, meanwhile, antibiotic regimen and efficacy during CRPA infection, 30-day and long-term survival were also analyzed., Results: A total of 59 patients were included in this study, and divided into CRPA infection group (43 cases) and CRPA colonization group (16 cases). Univariate logistic regression analysis showed that ECOG score ( P =0.003), agranulocytosis ( P <0.001), and exposure to upper than 3 rd generations of cephalosporins and tigecycline within 30 days ( P =0.035, P =0.017) were the high-risk factors for CRPA infection. Multivariate logistic regression analysis showed that ECOG score of 3/4 ( OR =10.815, 95% CI : 1.260-92.820, P =0.030) and agranulocytosis ( OR =13.82, 95% CI : 2.243-85.176, P =0.005) were independent risk factors for CRPA infection. There was a statistically significant difference in cumulative survival rate between CRPA colonization group and CRPA infection group ( χ 2 =14.134, P < 0.001). Kaplan-Meier survival analysis showed that the influencing factors of 30-day survival in patients with CRPA infection were agranulocytosis ( P =0.022), soft tissue infection ( P =0.03), and time of hospitalization before CRPA infection ( P =0.041). Cox regression analysis showed that agranulocytosis was an independent risk factor affecting 30-day survival of patients with CRPA infection ( HR =3.229, 95% CI :1.093-3.548, P =0.034)., Conclusions: Patients with hematological disorders have high mortality and poor prognosis after CRPA infection. Bloodstream infection and soft tissue infection are the main causes of death. Patients with high suspicion of CRPA infection and high-risk should be treated as soon as possible.

In recent years, the unprecedented rise of bacterial antibiotic resistance together with the lack of adequate therapies have made the treatment of skin infections and chronic wounds challenging, urging the scientific community to focus on the development of new and more efficient treatment strategies. In this context, there is a growing interest in the use of natural molecules with antimicrobial features, capable of supporting wound healing i.e., antimicrobial peptides (AMPs), for the treatment of skin and soft tissue infections. In this review, we give a short overview of the bacterial skin infections as well as some of the classic treatments used for topical application. We then summarize the AMPs classes, stressing the importance of the appropriate selection of the peptides based on their characteristics and physicochemical properties in order to maximize the antibacterial efficacy of the therapeutic systems against multi-drug resistant pathogens. Additionally, the present paper provides a comprehensive and rigorous assessment of the latest clinical trials investigating the efficacy of AMPs in the treatment of skin and soft tissue infections, highlighting the relevant outcomes. Seeking to obtain novel and improved compounds with synergistic activity, while also decreasing some of the known side effects of AMPs, we present two employed strategies using AMPs: (i) AMPs-conjugated nanosystems for systemic and topical drug delivery systems and (ii) antibiotics-peptide conjugates as a strategy to overcome antibiotics resistance. Finally, an important property of some of the AMPs used in wound treatment is highlighted: their ability to help in wound healing by generally promoting cell proliferation and migration, and in some cases re-epithelialization and angiogenesis among others. Thus, as the pursuit of improvement is an ongoing effort, this work presents the advances made in the treatment of skin and soft tissue infections along with their advantages and limitations, while the still remaining challenges are addressed by providing future prospects and strategies to overcome them., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Skin and soft tissue infections (SSTIs) are among the most common bacterial infections reported in outpatients. Drug-resistant bacteria are the major cause of treatment failure and increased mortality rate in patients with SSTIs, posing significant challenges to human health. In this study, new-generation rhodium nanoplates (RhNPs) and glycol chitosan- and polydopamine-functionalized RhNPs (Rh@GCS) are developed for the treatment of drug-resistant SSTIs. RhNPs exhibited favorable antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and Ag-resistant MRSA. The modified Rh@GCS exhibited enhanced antibacterial activity and can directly kill various drug-resistant bacteria by increasing the permeability of cell membranes, including gram-positive MRSA and gram-negative multidrug-resistant Escherichia coli (E.coli) and Pseudomonas aeruginosa (PA). Moreover, Rh@GCS effectively inhibited bacterial growth and promoted the healing of skin lesions in MRSA-induced SSTI mouse models. These results suggest that Rh@GCS is a promising nonantibiotic antimicrobial agent for the treatment of drug-resistant SSTIs., (© 2023 Wiley-VCH GmbH.)