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

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

[Saksenaea caused invasive infection in an immunocompetent patient after trauma]. / Saksenaea-svamp gav invasiv infektion hos frisk traumapatient.

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.

Exploring therapeutic options for mild diabetic-related foot infections: a comparative in vitro study of cefditoren versus amoxicillin/clavulanic acid.

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.

Advances in contezolid: novel oxazolidinone antibacterial in Gram-positive treatment.

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.

Antifungal drug penetration in soft tissue abscesses: a comparative analysis.

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.

A National Quality Improvement Collaborative to Improve Antibiotic Use in Pediatric Infections.

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.

Skin and Soft Tissue Actinomycosis in Children and Adolescents.

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

Telodendrimer functionalized hydrogel platform for sustained antibiotics release in infection control.

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.

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

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

Significantly reduced duration of antibiotic prescription for erysipelas subsequent to the 2019 French guidelines on skin and soft tissue infection: A before-after study.

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.

Necrotising soft tissue infections. / Nekrotiserende bløtdelsinfeksjoner.

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.

Doxycycline versus cephalexin treatment of presumed streptococcal skin and soft tissue infection among adults presenting to the emergency department.

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.

Successful management of surgical site infection caused by Mycobacterium mageritense in a breast cancer patient.

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.

Current challenges in acute bacterial skin infection management.

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

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

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

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

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

Nanosecond pulsed electric fields increase antibiotic susceptibility in methicillin-resistant Staphylococcus aureus.

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.