Search

Background: Colistin is used to treat multidrug-resistant gram-negative bacteria. Rising colistin resistance worldwide has created challenges in effective treatment and raised treatment costs. Our study aimed to understand the prevalence of colistin resistance in carbapenem-resistant gram-negative bacteria, associated pathogens and their antimicrobial susceptibility pattern at our institute, to help limit further development of resistance. Methods: An observational, cross-sectional study was conducted at the Microbiology laboratory of Indus Hospital & Health Network, Karachi, Pakistan from January 1, 2022 to December 31, 2023. Variables extracted from the electronic patient care database included the type of patient samples, clinical diagnoses, frequency of carbapenem-resistant gram-negative bacteria and antimicrobial susceptibility profiles. Microsoft Excel software (Microsoft Excel 2013 {15.0.5553.1000} 32-bit) was used for analysis. Susceptibility results were interpreted in accordance with the M100 guidelines of the Clinical and Laboratory Standards Institute. Results: A total of 1,785 carbapenem-resistant gram-negative bacteria were isolated during the study period. Thirty (1.7%) of these exhibited colistin minimum inhibitory concentrations of ≥ 4 µg/ml and were characterized as colistin-resistant. Most patients with colistin-resistant gram-negative bacterial infections were males (57%), aged 31–49 and ≥ 50 years (37% each), and in-patients (60%). Majority had urinary tract infection (34%), followed by bloodstream infection (30%), ventilator-associated pneumonia (23%), and skin and soft tissue infection (13%). Organisms included Klebsiella species (77%), Acinetobacter baumanii (20%) and Pseudomonas aeruginosa (3%). Tigecycline was the most susceptible antibiotic among isolates (96%) while, fosfomycin (53%), minocycline (50%), doxycycline (45%) and tetracycline (42%) exhibited moderate susceptibility. Conclusion: Our study highlights a concerning prevalence of colistin resistance (1.7%) among carbapenem-resistant gram-negative bacteria, particularly Klebsiella species, predominantly affecting male in-patients aged 31–49 and ≥ 50 years. This significant therapeutic challenge is underscored by the limited efficacy of available antibiotics, with only tigecycline showing high susceptibility (96%) and others like fosfomycin (53%) and minocycline (50%) offering moderate alternatives. [ABSTRACT FROM AUTHOR]

Infections after orthotopic heart transplantation (OHT) cause significant morbidity and mortality. Concurrent with increased pre-OHT temporary mechanical circulatory support (MCS), there have been recent concerns of a perceived increase in infections post-OHT. We examined the association between pre-OHT temporary versus durable MCS and post-OHT infection. We performed a single-center retrospective review of patients who received OHT at Tufts Medical Center between January 2014 and April 2022. Our composite outcome was the occurrence of bacteremia, invasive fungal infections, opportunistic infections, or skin/soft tissue infections of device sites within 1-year post-OHT. We used Cox proportional hazards models to assess the relationship between the type of pre-OHT MCS and time to the first infection, treating death from other causes as a competing risk. We addressed confounding with 2 statistical methods: propensity score (PS) with inverse probability weighting (IPW) and an instrumental variable (IV) analysis. Of the 320 OHT recipients, 268 required MCS before OHT; 192 were managed with durable MCS and 76 with temporary MCS. Patients receiving pre-OHT temporary MCS had no difference in time to first infection (unadjusted hazard ratio [HR] 0.77, 95% CI 0.41-1.44) compared to durable MCS. Results were similar in the model employing PS with IPW (HR 0.61, 95% CI 0.29-1.27) and the IV analysis (HR 0.28, 95% CI 0.26-2.36). Pre-OHT temporary MCS was not associated with the composite outcome of bacteremia, invasive fungal infections, opportunistic infections, or skin/device site infections post-OHT compared to durable MCS in this single-center cohort. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus is a versatile organism, capable of existing as a commensal organism while also possessing pathogenic potential. The emergence of clinically and genetically distinct strains of methicillin-resistant S. aureus (MRSA), termed community-onset MRSA (CO-MRSA), resulted in an epidemic of invasive and skin and soft tissue infections (SSTI) in otherwise healthy individuals without traditional risk factors. Colonization with S. aureus is a risk factor for developing infection and also a source of transmission to close contacts. Outbreaks of S. aureus SSTI have been described in crowded settings and within households. Thus, preventive strategies are essential to interrupt recurrent infections. The objective of this narrative review is to provide a comprehensive, evidence-based approach to prevent transmission of CO-MRSA. We highlight key clinical trials that emphasize the importance of household and environmental S. aureus colonization in propagating household transmission. Finally, we highlight research priorities to prevent S. aureus infection. We cite primary literature from peer-reviewed publications as sources for this review. Our recommended approach to the management of individuals presenting with skin abscesses includes optimal treatment of the initial infection and hygiene education. Decolonization measures should be recommended for individuals with recurrent SSTIs or whose household members have SSTIs. Targeted decolonization with topical antimicrobials should be prescribed to all affected individuals within the household. S. aureus infections result in substantial mortality and morbidity because of the high incidence of recurrent skin infections. Although current decolonization strategies are beneficial, interventions are often costly to families and effectiveness wanes over time. Results from a recently completed trial evaluating integrated periodic decolonization and household environmental hygiene will further add to our understanding of what constitutes a sustainable decolonization approach. In addition, novel preventive strategies are being developed such as S. aureus vaccines, lytic agents, probiotics, microbiota transplants, and phage therapy. [ABSTRACT FROM AUTHOR]

Objective: We evaluated the impact of a methicillin-resistant Staphylococcus aureus (MRSA) nasal polymerase chain reaction (PCR) protocol on the vancomycin length of therapy (LOT) for skin and soft tissue infections (SSTIs). Design: Retrospective quasi-experimental pre- and post- MRSA nasal PCR protocol implementation study. Setting: Tertiary-care academic medical center in Jacksonville, Florida. Patients: Eligible patients received empiric vancomycin for SSTIs from January 1st to September 30th 2020 (pre-implementation group) and from January 1st to September 30th 2022 (post-implementation group). Intervention: The electronic health system software was modified to provide a best-practice advisory (BPA) prompt to the pharmacist upon order verification of vancomycin for patients with SSTIs. Methods: We reviewed patient records to determine the time from vancomycin prescription to de-escalation. The secondary outcomes were incidence of acute kidney injury (AKI), number of vancomycin levels collected, and hospital length of stay (LOS). Results: The study included 131 patients (pre-implementation, n = 86 and post-implementation, n = 45). There was no significant difference in vancomycin length of therapy (LOT) between implementation groups: mean LOT in days and standard deviation (SD) were 2.7 (1.9) and 2.6 (1.3), respectively, p-value 0.493. Of significance, in the post-implementation group, vancomycin LOT between patients with a negative and positive MRSA PCR were 2.3 (1.1) and 3.9 (1.6), p-value 0.006. There was no difference in secondary outcomes. Conclusion: The utilization of the MRSA nasal PCR to guide vancomycin de-escalation did not significantly change the vancomycin LOT, however in the post-implementation group there was a significant difference in vancomycin LOT between negative and positive MRSA PCRs. [ABSTRACT FROM AUTHOR]

Purpose: Following the COVID-19 pandemic, group A Streptococcus (GAS) infection has been surging worldwide. We aimed to compare the disease burden between notified cases of streptococcal toxic shock syndrome (STSS) and unreported GAS infections. Methods: This is a multicentral observational study, retrospectively performed at seven hospitals in Okayama prefecture in Japan from January 2022, to June 2024. Clinical and microbiological data of patients with positive cultures of GAS were collected from the medical records. Primary outcomes were defined as rates of surgical procedures, intensive care unit (ICU) admission, and in-hospital mortality, which were compared among patients with locally-defined STSS, invasive GAS (iGAS), and non-iGAS infection. Results: GAS was detected in 181 patients, with 154 active cases of GAS infection. The number of patients with GAS infection surged in late 2023. The most common source of infection was skin and soft tissue infections, accounting for 83 cases, including 15 cases of necrotizing fasciitis, and 12 cases (7.8%) were notified to public health authorities as STSS. Among the 25 unreported iGAS cases, 9 (36.0%) underwent surgical intervention, and 4 patients (16.0%) required ICU admission. The mortality rates in the unreported iGAS cases were comparable to those observed in the notified STSS. Conclusions: We highlighted that the number of iGAS infections was twofold higher than that of notified STSS, with comparable mortality rate between these groups, indicating substantial underestimation of the true burden of iGAS. This epidemiological investigation has significant implications for enhancing infectious disease surveillance frameworks and public health policy development. [ABSTRACT FROM AUTHOR]

Background: Recent literature demonstrated a 24-hour reduction in vancomycin duration of therapy (DOT) for skin and soft tissue infections (SSTIs) with a negative methicillin-resistant staphylococcus aureus (MRSA) nasal screening versus a positive nasal screening. Objective of this study was to investigate vancomycin DOT in patients with SSTIs who received MRSA nasal polymerase chain reaction (PCR) screening versus those who did not receive MRSA nasal PCR screening. Methods: A retrospective, multi-center, cohort study was completed in admitted adult patients on vancomycin for SSTI from 01/01/2020 to 09/30/2022. Hospital policy permits any clinician to order a MRSA nasal PCR screening test for various indications, including SSTIs, pneumonia and sepsis. Results: One-hundred-fifty-one patients were included, of which 71 had MRSA nasal PCR screening tests obtained, and 80 did not. The median vancomycin DOT in patients with MRSA nasal PCR screening tests was 19.9 versus 36.7 hours (P =.014) in patients without screening tests. Conclusion: Patients with SSTIs who receive MRSA nasal PCR screening tests have a shortened vancomycin DOT. These results contribute to current data in support of the efficacy and clinical utility of obtaining MRSA nasal PCR screening tests for SSTIs. [ABSTRACT FROM AUTHOR]

AbstractThe mouth cavity is the second most complex microbial community in the human body. It is composed of bacteria, viruses, fungi, and protozoa. An imbalance in the oral microbiota may lead to various conditions, including caries, soft tissue infections, periodontitis, root canal infections, peri-implantitis (PI), pulpitis, candidiasis, and denture stomatitis. Additionally, several locally administered antimicrobials have been suggested for dentistry in surgical and non-surgical applications. The main drawbacks are increased antimicrobial resistance, the risk of upsetting the natural microbiota, and hypersensitivity responses. Because of their unique physiochemical characteristics, nanoparticles (NPs) can circumvent antibiotic-resistance mechanisms and exert antimicrobial action via a variety of new bactericidal routes. Because of their anti-microbial properties, carbon-based NPs are becoming more and more effective antibacterial agents. Periodontitis, mouth infections, PI, dentin and root infections, and other dental diseases are among the conditions that may be treated using carbon NPs (CNPs) like graphene oxide and carbon dots. An outline of the scientific development of multifunctional CNPs concerning oral disorders will be given before talking about the significant influence of CNPs on dental health. Some of these illnesses include Periodontitis, oral infections, dental caries, dental pulp disorders, dentin and dental root infections, and PI. We also review the remaining research and application barriers for carbon-based NPs and possible future problems. [ABSTRACT FROM AUTHOR]

The article from the Canadian Medical Association Journal discusses zoonotic infections in the Canadian Arctic, emphasizing the importance of understanding the unique epidemiology and modes of transmission of these diseases. It highlights the significance of considering Indigenous cultures and customs when assessing patients in Arctic communities to identify exposure risks accurately. The document provides detailed information on key zoonotic infections in the Arctic, such as trichinellosis, toxoplasmosis, echinococcosis, diphyllobothriasis, brucellosis, seal finger, and rabies, along with their clinical characteristics, diagnosis, and management. The article also addresses evolving issues affecting Arctic zoonoses, including the impact of warming climates and the interconnectedness of human health, animal health, and ecosystems under the One Health concept. [Extracted from the article]

Background: Sepsis and shock are common complications of necrotising soft tissue infections (NSTI). Sepsis encompasses different endotypes that are associated with specific immune responses. Hyperbaric oxygen (HBO2) treatment activates the cells oxygen sensing mechanisms that are interlinked with inflammatory pathways. We aimed to identify gene expression patterns associated with effects of HBO2 treatment in patients with sepsis caused by NSTI, and to explore sepsis-NSTI profiles that are more receptive to HBO2 treatment. Methods: An observational cohort study examining 83 NSTI patients treated with HBO2 in the acute phase of NSTI, fourteen of whom had received two sessions of HBO2 (HBOx2 group), and another ten patients (non-HBO group) who had not been exposed to HBO2. Whole blood RNA sequencing and clinical data were collected at baseline and after the intervention, and at equivalent time points in the non-HBO group. Gene expression profiles were analysed using machine learning techniques to identify sepsis endotypes, treatment response endotypes and clinically relevant transcriptomic signatures of response to treatment. Results: We identified differences in gene expression profiles at follow-up between HBO2-treated patients and patients not treated with HBO2. Moreover, we identified two patient endotypes before and after treatment that represented an immuno-suppressive and an immune-adaptive endotype respectively, and we characterized the genetic profile of the patients that transition from the immuno-suppressive to the immune-adaptive endotype after treatment. We discovered one gene MTCO2P12 that distinguished individuals who altered their endotype in response to treatment from non-responders. Conclusion: The global gene expression pattern in blood changed in response to HBO2 treatment in a direction associated with clinical biochemistry improvement, and the study provides potential novel biomarkers and pathways for monitoring HBO2 treatment effects and predicting an HBO2 responsive NSTI-sepsis profile. Trial registration: Biological material was collected during the INFECT study, registered at ClinicalTrials.gov (NCT01790698) 04/02/2013. [ABSTRACT FROM AUTHOR]

Background: The main aim of this study is evaluating the patients functional and the radiological outcomes after receiving iliosacral screws for their unstable posterior ring injuries in the pelvis. Methods: Thirty participants with posterior pelvic ring disruption were included in this prospective study. All patients are assessed by plain radiographs and CT. Results: Satisfactory rate of the surgical technique showing that 73.3% were satisfied and 26.7% were unsatisfied. The overall Majeed score shows that 76.7% of the study patients had Satisfactory score and 23.3% had unsatisfactory score. As regarding the Xray evaluation 16.7% of the study population were Excellent, 70% of the study population were good and only 13.3 % were fair. As regarding complications, 5% had neurological damage and 5% had Hematoma and 2% had Soft tissue infection. Conclusion: Our study conclude that Percutaneous sacroiliac fixation has a good result in fixation of the posterior pelvic ring disruption. [ABSTRACT FROM AUTHOR]

Introduction: Difficult-to-treat-resistant (DTR) infections caused by Pseudomonas aeruginosa represent a global public health threat, prioritizing the search and development of new antibiotics for this microorganism. Methods: We present the real-life experience of the compassionate use of imipenem/cilastatin/relebactam in a descriptive study involving 14 patients with DTR-P. aeruginosa infection and limited treatment options. Results: The primary source of infection was skin and soft tissue infection, 57.1% (8/14), followed by respiratory infection-pneumonia, 28.6% (4/14). At the onset of infection, 71.4% (10/14) of patients were in the intensive care unit (ICU). All our patients had a Charlson Score of ≥ 3. Septic shock was observed in 64.3% (9/14) of patients. The median treatment duration was 15 days, and no patient experienced an adverse event that required treatment interruption. All-cause 30-day mortality was observed in 42.9% of cases (6/14), while clinical efficacy and microbiological success were observed in 64.3% (9/14). Conclusions: Imipenem/cilastatin/relebactam may represent a treatment option for patients with DTR-P. aeruginosa infections, which should be validated in prospective clinical trials. [ABSTRACT FROM AUTHOR]

Snakebite envenomings continue to represent a major public health concern in Taiwan because of the presence of various venomous snakes whose habitats intersect with human activities. This review provides a comprehensive analysis of the clinical characteristics, complications, and management strategies associated with snakebite envenomings in Taiwan. Taiwan is inhabited by six principal venomous snakes: Trimeresurus stejnegeri stejnegeri, Protobothrops mucrosquamatus, Deinagkistrodon acutus, Daboia siamensis, Naja atra, and Bungarus multicinctus, each presenting distinct clinical challenges. The clinical manifestations vary from local symptoms such as pain, swelling, and necrosis to systemic complications including neurotoxicity, coagulopathy, and organ failure, depending on the species. Notable complications arising from these snakebite envenomings include necrotizing soft tissue infection, compartment syndrome, respiratory failure, and acute kidney injury, often necessitating intensive medical interventions. This review highlights the critical importance of early diagnosis, the prompt administration of antivenoms, and multidisciplinary care to improve patient outcomes and reduce healthcare costs. Future research is encouraged to enhance treatment efficacy, improve public awareness, and develop targeted prevention strategies. By identifying gaps in current knowledge and practice, this work contributes to the global literature on envenoming management and serves as a foundation for advancing clinical protocols and reducing snakebite-related morbidity and mortality in Taiwan. [ABSTRACT FROM AUTHOR]

Antibacterial activity can be classified as either bactericidal or bacteriostatic, using methods such as the MBC/MIC ratio and time–kill curves. However, such categorization has proven challenging in clinical practice, as these definitions only apply under specific laboratory conditions, which may differ from clinical settings. Several factors, such as the specific bacteria or infectious medium, can affect the action of antibiotics, with many antibacterials exerting both activities. These definitions have also led to the belief that bactericidal antibacterials are superior to bacteriostatic, especially in more severe cases, such as endocarditis, neutropenia and bacteraemia. Additionally, current dogma dictates against the combination of bactericidal and bacteriostatic antibacterials in clinical practice, due to potential antagonism. This review aimed to assess the differences in antibacterial activity of bactericidal and bacteriostatic antibacterials based on in vitro and in vivo studies and examine their antagonistic or synergistic effects. Our findings show that specific bacteriostatic agents, such as linezolid and tigecycline, are clinically non-inferior to bactericidals in multiple infections, including pneumonia, intra-abdominal infections, and skin and soft tissue infections. Studies also support using several bacteriostatic agents as salvage therapies in severe infections, such as neutropenic fever and endocarditis. Additionally, not all combinations of bacteriostatic and bactericidal agents appear to be antagonistic, with many combinations, such as linezolid and rifampicin, already being used. The findings should be interpreted with caution, as most evidence is from observational studies and there is a need for randomized controlled trials to assess their effectiveness and combinations, especially within the context of rising antimicrobial resistance. [ABSTRACT FROM AUTHOR]

Introduction: necrotizing fasciitis (NF) is a rare soft tissue infection that leads to sepsis and death without an early surgical treatment. LRINEC (laboratory risk indicator for necrotizing fasciitis) scale is one of the most accepted tests for diagnosis. This study presents a retrospective evaluation of the usefulness of the LRINEC scale in the diagnosis and prognosis of NF. Material and methods: retrospective study of 41 cases of NF in extremities between 2010 and 2019. Based on the score obtained on the LRINEC scale the cases were assigned to: LRINEC lower than 5 in Group 1 with 12 cases, score 6 or 7 in Group 2 also 12 cases, and finally score of 8 or above in Group 3, 17 cases. Results: the mean LRINEC score was 7.04 (range: 1-13). 30 patients (73%) had scores above 6, the threshold for suspicion of NF. The mean mortality rate was 26.8%, and was highest in group 3 (5 deaths). The mean amputation rate was 17% (seven patients). Conclusions: the LRINEC may facilitate early diagnosis, but as we see in our study its main strength is its ability to assess the severity of the septic process and therefore to provide a prognosis. [ABSTRACT FROM AUTHOR]

Background: Necrotizing fasciitis (NF) is a severe soft tissue infection typified by swiftly spreading necrosis of the fascia and subcutaneous fat with successive necrosis of the skin which affects all age groups. Objective: To compare the clinical presentation and treatment outcome of NF between children and adults. Materials and Methods: A prospective descriptive study of all patients presenting with NF to the (Usmanu Danfodiyo Univrersity Teaching Hospital, Sokoto), from September 2018 to August 2019. Participants were stratified into adults and children for comparison during data analysis. Results: A total of 32 patients were analyzed, 24 (75.0%) were adults. The age range was 2 weeks to 75 years with a median age of 35 years. Necrotic skin patches and skin erythema were the most common cutaneous findings. The lower limb was the most commonly affected region in adults (58.3%), whereas the head and neck and abdominal wall were equally commonly involved in children (37.5%). Children had more multiple isolates than adults, 87.5% compared to 62.5%, respectively, and it was significant (P value 0.04). Escherichia coli and Klebsiella species were both significantly commoner in isolates of children than adults (P value 0.01 and 0.04, respectively). The method of wound coverage was significantly different (P value 0.003) as fewer children required skin grafting. The mortality rate was 6.25%, the two deaths occurred in adults. Conclusion: NF is commoner in adults in our region. The predilection sites of the disease in the two groups differ and healing by secondary intention was more possible in children. [ABSTRACT FROM AUTHOR]

Summary: Objective: Peritonsillar abscess (PTA) is a common soft tissue infection of the head and neck. It remains unclear to what extent inflammatory diseases of the palatine tonsils or other infections contribute to the development of PTA. This study examines the demographic characteristics and seasonal variations of acute tonsillitis (aT) and PTA in ENT practices in Germany using a practice database. Methods: Retrospective analysis based on data from the German-wide IQVIA™ Disease Analyzer database for the period 2019 to 2023. Data include diagnoses of aT (ICD-10: J03) and PTA (ICD-10: J36) as well as patient demographics (age, sex). Seasonal variations were identified by analysing the monthly diagnosis rates. The Pearson correlation between the monthly case numbers of aT and PTA was determined. Results: 59,934 cases of aT and 5,024 cases of PTA were recorded. The mean age was 30.3 years (aT) and 39.4 years (PTA). The proportion of female patients was 60% (aT) and 49% (PTA). Both diagnoses showed seasonal variations with peaks in winter and spring and a decline in summer, although the decline was less pronounced for PTA. The monthly case numbers of aT and PTA showed high correlations between r = 0.75 (2019) and r = 0.94 (2020). The average correlation for the period 2019–2023 was r = 0.81. During the coronavirus pandemic, a significant decrease in the case numbers of both diseases was observed, while the typical seasonal variations disappeared. After the pandemic, the case numbers increased to higher levels than before the pandemic. Conclusions: aT and PTA both show seasonal variations with peaks in winter and spring and a decline in summer. The correlation between the variations of aT and PTA could be related to a partly common aetiology or to the specific sample of the practice database. The attenuation of seasonal variation during the coronavirus pandemic illustrates the impact of COVID-19 on the incidence of other diseases and on the use of healthcare pathways by patients. [ABSTRACT FROM AUTHOR]

Vancomycin-intermediate Staphylococcus aureus (VISA) is a multi-drug-resistant pathogen of significant clinical concern. Various S. aureus strains can cause infections, from skin and soft tissue infections to life-threatening conditions such as bacteremia and pneumonia. VISA infections, particularly bacteremia, are associated with high mortality rates, with 34% of patients succumbing within 30 days. This study aimed to develop predictive models for VISA (including hVISA) bacteremia outcomes using data mining techniques, potentially improving patient management and therapy selection. We focused on three endpoints in patients receiving traditional vancomycin therapy: VISA persistence in bacteremia after 7 days, after 30 days, and patient mortality. Our analysis incorporated 29 risk factors associated with VISA bacteremia. The resulting models demonstrated high predictive accuracy, with 82.0–86.6% accuracy for 7-day VISA persistence in blood cultures and 53.4–69.2% accuracy for 30-day mortality. These findings suggest that data mining techniques can effectively predict VISA bacteremia outcomes in clinical settings. The predictive models developed have the potential to be applied prospectively in hospital settings, aiding in risk stratification and informing treatment decisions. Further validation through prospective studies is warranted to confirm the clinical utility of these predictive tools in managing VISA infections. [ABSTRACT FROM AUTHOR]

Staphylococcus caprae is a coagulase-negative staphylococcus commonly associated with animals which can also be a zoonotic human pathogen. To date, there is little data available on S. caprae infections. The aim of this study was to characterize the S. caprae infections identified in two hospitals located, respectively, in rural and urban areas of Catalonia, Spain. In this retrospective, observational study, data were compiled from clinical records of all S. caprae infections diagnosed between January 2010 and December 2023. Over the study period, altogether 31 cases of S. caprae infection were identified, with most (23) of these cases occurring in the second half of the period (2017–2023). The mean age of patients was 58.87 ± 20.65 years, and 58.1% were males. Eight patients had had livestock exposure. The most frequent manifestation of infection was skin and soft subcutaneous tissue infections (10; 32.3%), osteomyelitis (6; 19.4%), and joint prosthetic infections (5; 16.1%). All the strains were susceptible to oxacillin, fluoroquinolones, rifampicin, and trimethoprim–sulfamethoxazole. Twenty-two (71%) of the patients required surgical treatment. Only one patient (3.2%) died, because of aortic prosthetic valve infective endocarditis. Skin and soft tissue infections were the most frequently identified manifestations of S. caprae infection. Over 75% of the cases occurred in the last six years, and 25.8% involved significant exposure to livestock. Ongoing surveillance is necessary to better understand the prevalence and transmission dynamics of this emerging zoonotic pathogen. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance in disease-causing microbes is seen as a severe problem that affects the entire world, makes therapy less effective, and raises mortality rates. Dermal antimicrobial therapy becomes a desirable choice in the management of infectious disorders since the rising resistance to systemic antimicrobial treatment frequently necessitates the use of more toxic drugs. Nanoparticulate systems such as nanobactericides, which have built-in antibacterial activity, and nanocarriers, which function as drug delivery systems for conventional antimicrobials, are just two examples of the treatment methods made feasible by nanotechnology. Silver nanoparticles, zinc oxide nanoparticles, and titanium dioxide nanoparticles are examples of inorganic nanoparticles that are efficient on sensitive and multidrug-resistant bacterial strains both as nanobactericides and nanocarriers. To stop the growth of microorganisms that are resistant to standard antimicrobials, various antimicrobials for dermal application are widely used. This review covers the most prevalent microbes responsible for skin and soft tissue infections, techniques to deliver dermal antimicrobials, topical antimicrobial safety concerns, current issues, challenges, and potential future developments. A thorough and methodical search of databases, such as Google Scholar, PubMed, Science Direct, and others, using specified keyword combinations, such as "antimicrobials," "dermal," "nanocarriers," and numerous others, was used to gather relevant literature for this work. [ABSTRACT FROM AUTHOR]

Wounds are physical injuries that results in an opening or breaking of the skin. Proper healing of wounds is very essential for the restoration of disrupted anatomical continuity and disturbed functional status of the skin. Wound healing is a complex but generally orderly process. Sequential waves of specialized cell types first clear the inciting injury and then progressively build the scaffolding to fill in any resulting defect. The antibacterial potential of the crude leaves extracts of Psidium guajava Linn. against some bacteria associated with surgical wound, burns, skin and soft tissue infections were investigated under different conditions. Tridax procumbens (L.) is a spreading annual herb found throughout India. The plant is a native of tropical America and naturalized in tropical Africa, Asia, and Australia. Local people known it as "Ghamara," in English popularly called "coat buttons" and is dispensed for "Bhringraj" by some of the practitioners of Ayurveda. The plant has many pharmacological applications such as hepatoprotective activity, anti-infl ammatory, wound healing, anti-diabetic activity, hypotensive effect, immunomodulating property, bronchial catarrh, dysentery, and diarrhea and to prevent falling of hair promotes the growth of hair, and antimicrobial activity against both Gram-positive and Gram-negative bacteria. The leaf juice possesses antiseptic, insecticidal and parasiticidal properties, as a remedy against conjunctivitis and is used also to check hemorrhage from cuts, bruises and wounds insect repellent. [ABSTRACT FROM AUTHOR]

BACKGROUND: Antibiotic lengths of therapy (LOT) vary widely, based on infection type, antibiotic regimen, and patient characteristics. Longer LOT are associated with increased risk of antibiotic resistance, adverse effects, and health care costs. There are increasing data supporting shorter LOT for many infections based on randomized, controlled trials (RCTs). OBJECTVE: To evaluate RCTs supporting shorter antibiotic LOT for common infections, with an emphasis on applying the data to older adults. DATA SOURCES: A list of RCTs that evaluated shorter LOT for common infections was first gathered from the website of Brad Spellberg, MD, at https://www. bradspellberg.com/shorter-is-better. The list was then verified through a PubMed search using the terms for each infection and LOT. DATA SYNTHESS: Of the 28 identified RCTs, 27 supported shorter antibiotic LOT. These trials were categorized by disease states: complicated urinary tract infections including pyelonephritis (n = 9), community-acquired pneumonia (n = 6), hospital-acquired pneumonia/ ventilator-associated pneumonia (n = 3), skin and soft tissue infections (n = 4), complicated intra-abdominal infections (n = 2), and gram-negative bacteremia (n = 3). The single incongruent trial was conducted on male patients with complicated urinary tract infections, and the results could be explained by a lower than usual dose of antibiotic utilized in the study. DSCUSSON: Many RCTs have demonstrated the safety and efficacy of shorter antibiotic LOT for the disease states included in this review. Several of these trials enrolled older adults. CONCLUSON: There are sufficient data to support using shorter antibiotic LOT in older patients. Implementing this strategy can help pharmacists and other health care professionals optimize antibiotic use in older adults. [ABSTRACT FROM AUTHOR]

Background: Bacteriophages are neutralized by the sera of patients undergoing phage therapy (PT), particularly during local or concomitant local and oral phage administration in bone infections, soft tissue infections, or upper respiratory tract infections. Methods: The antiphage activity of the sera (AAS) level of 27 patients with bacterial infections such as bone infections, soft tissue infections, or upper respiratory tract infections undergoing PT was performed using the plate phage neutralization test. Results: Our preliminary results suggest that high levels of antiphage antibodies appear late in the treatment period, at the earliest in the 3rd–8th week of PT. Patients with bone infections treated locally with the S. aureus phage Staph_1N and patients with upper respiratory tract infections administered locally and orally with the S. aureus phage Staph_A5L had elevated levels of antiphage antibodies in sera during PT. In parallel to these results, it has been shown that a strong antiphage humoral response does not prevent a positive outcome of phage treatment. Conclusions: The earliest time point at which high levels of antiphage antibodies in sera appear during local and oral PT is day 21 of therapy. We noticed that the high level of antiphage antibodies in sera occurring during local or both local and oral PT was correlated with the type of infection and phage type. [ABSTRACT FROM AUTHOR]

Since its standardization, clinical antimicrobial susceptibility testing (AST) has relied upon a standard medium, Mueller-Hinton Broth/Agar (MHB/A), to determine antibiotic resistance. However, this microbiologic medium bears little resemblance to the host milieu, calling into question the physiological relevance of resistance phenotypes it reveals. Recent studies investigating antimicrobial susceptibility in mammalian cell culture media, a more host-mimicking environment, demonstrate that exposure to host factors significantly alters susceptibility profiles. One such factor is bicarbonate, an abundant ion in the mammalian bloodstream/tissues. Importantly, bicarbonate sensitizes methicillin-resistant Staphylococcus aureus (MRSA) to early-generation β-lactams used for the treatment of methicillin-susceptible S. aureus (MSSA). This "NaHCO3-responsive" phenotype is widespread among US MRSA USA300/CC8 bloodstream and skin and soft tissue infection isolates. Translationally, β-lactam therapy has proven effective against NaHCO3-responsive MRSA in both ex vivo simulated endocarditis vegetation (SEV) and in vivo rabbit infective endocarditis (IE) models. Mechanistically, bicarbonate appears to influence mecA expression and PBP2a production/localization, as well as key elements for PBP2a functionality, including the PBP2a chaperone PrsA, components of functional membrane microdomains (FMMs), and wall teichoic acid (WTA) synthesis. The NaHCO3-responsive phenotype highlights the critical role of host factors in shaping antibiotic susceptibility, emphasizing the need to incorporate more physiological conditions into AST protocols. [ABSTRACT FROM AUTHOR]

Background: The emergence of multidrug-resistant hypervirulent Klebsiella pneumoniae (hvKp) has made it difficult to treat and control infections caused by this bacterium. Previously, the therapeutic effectiveness of phage-encoded depolymerase Dep_kpv74 in a mouse model of K. pneumoniae-induced thigh soft tissue infection was reported. In this study, the effect of Dep_kpv74 on blood parameters in mice, the proliferation and subpopulation composition of spleen lymphocytes, and the activity and stability of the enzyme at different pH and temperatures were further explored. Results: The stability tests showed that Dep_kpv74 remained active in the temperature range from 8 °C to 55 °C. The optimal pH value for maintaining the activity of Dep_kpv74 ranged from 5.0 to 9.0. The depolymerase was detected in the blood, spleen, and lungs of mice 10 min after intraperitoneal administration, reaching maximum activity values after 1–3 h and maintaining activity a day after administration. The introduction of Dep_kpv74 at the therapeutic dose (10 μg/mouse) or at a 10-fold higher dose did not lead to reliable changes in bloodstream cell content compared with the reference values of intact mice. The biochemical results of the studies indicated that Dep_kpv74 did not exert any toxic effects on liver and kidney functions. The results of the analysis of lymphocyte proliferative activity demonstrated that Dep_kpv74 depolymerase has a mild immunomodulatory effect. Conclusions: Thus, the results of this study provide one more confirmation that depolymerase Dep_kpv74 is a potential candidate for the treatment of infections caused by hvKp expressing K2 capsular polysaccharides. [ABSTRACT FROM AUTHOR]

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a significant burden globally, particularly in the Arabian Gulf region. The United Arab Emirates (UAE) has experienced rising MRSA prevalence, with increasing diversity in the clonal complexes (CCs) identified. The COVID-19 pandemic, with its increased hospitalization rates and antibiotic use, may have further influenced MRSA's genetic evolution and epidemiology in the country. Methods: To investigate this influence, genomic profiling of 310 MRSA clinical isolates collected between February and November 2022 was performed using a DNA microarray-based assay. Results: Isolates were assigned to 22 clonal complexes and 72 distinct strain assignments. The predominant clonal complexes were CC5, CC6, CC361, CC22, CC1, and CC8. Community-acquired MRSA lineages were dominant, with only one healthcare-associated MRSA lineage isolate identified. Upward trends of CC1153 were observed along with rare CCs, such as CC121-MRSA and CC7-MRSA, with the latter being reported for the first time in the Arabian Gulf region. The presence of pandemic strains USA300 CC8-MRSA-[IVa + ACME1] and CC8-MRSA-IV strains were also observed, including variants lacking Panton–Valentine leukocidin (pvl) genes and missing tst1 or enterotoxin genes. The PVL-negative CC772-MRSA-V/VT was identified, representing its first report in the UAE. A novel variant, CC361-MRSA-IV (tst1+/PVL+), was identified. Pvl genes were observed in 36% of the isolates, primarily from skin and soft tissue infections, while fusC (SCC-borne fusidic acid resistance) was identified in 13% of the isolates. Conclusions: The findings highlight the ongoing evolution of MRSA in the UAE, with the persistence and emergence of diverse and rare clonal complexes, driving the need for continuous genomic surveillance. [ABSTRACT FROM AUTHOR]

Background: In recent years, with the increase of antibiotic resistance, tigecycline has attracted much attention as a new broad-spectrum glycylcycline antibiotic. It is widely used in the treatment of complex skin and soft tissue infections, complex abdominal infections and hospital-acquired pneumonia by inhibiting bacterial protein synthesis. Tigecycline can exhibit significant time-dependent bactericidal activity, and its efficacy is closely related to pharmacokinetics. It can be evaluated by the ratio of AUC0-24 to the minimum inhibitory concentration (MIC) of pathogens. However, tigecycline may cause nausea, vomiting, diarrhea and a few patients have elevated serum aminotransferase, especially in critically ill patients. The safety of patients still needs further study. Methods: In this study, the clinical data of 263 patients with pulmonary infection in Shengjing Hospital of China Medical University and the Second Affiliated Hospital of Dalian Medical University were collected retrospectively, and the hepatotoxicity prediction model was established. The potential correlation between the toxic and side effects of tigecycline and the number of hospitalization days was preliminarily discussed, and the correlation analysis between the number of hospitalization days and continuous variables was established. Finally, the deep learning model was used to predict the hospitalization days of patients through simulated blood drug concentration and clinical laboratory indicators. Results: The degree of abnormal liver function was significantly correlated with AST, GGT, MCHC and hospitalization days. Secondly, the correlation between hospitalization time and clinical test indexes and simulated drug concentration was analyzed. It was found that multiple clinical laboratory parameters of patients (such as EO #, HCT, HGB, MCHC, PCT, PLT, WBC, AST, ALT, Urea), first dose (Dose), age and APACHE II score were significantly correlated with hospitalization days. The simulated blood drug concentration was correlated with the length of hospital stay from 12 h after administration, and reached the strongest between 24 and 48 h. The AUC of the liver function prediction model can reach 0.90. Further analysis showed that there was a potential correlation between hepatotoxicity and hospitalization days. The median hospitalization days of patients in the non-hepatotoxicity group, liver function injury group and hepatotoxicity group were 20, 23, and 30 days, respectively. Based on these results, the length of hospital stay was predicted by the deep learning prediction model with an error within 1 day. Conclusion: In this study, the hospitalization days of infected patients were predicted by deep learning model with low error. It was found that it was related to clinical test parameters, hepatotoxicity and dosage after administration. The results provided an important reference for the clinical application of tigecycline, and emphasized the need to pay attention to its toxic and side effects in use. [ABSTRACT FROM AUTHOR]

The article discusses a multicentre retrospective case series on Mycobacterium chelonae cutaneous infections unrelated to invasive procedures. The study collected 38 cases of M. chelonae skin infections of undetermined origin, mainly affecting women in their seventies, with a high prevalence of immunocompromised patients. Treatment involved antimicrobial therapy, surgery, or a combination of both, with varying success rates and side effects. The study highlights the challenges in treating these infections and the importance of considering the risk-benefit balance in fragile patients. [Extracted from the article]

Antibiotic resistance by methicillin-resistant Staphylococcus aureus (MRSA) is an urgent threat to human health. The biofilm and persister cells formation ability of MRSA and Staphylococcus epidermidis often companied with extremely high antimicrobial resistance. Pinaverium bromide (PVB) is an antispasmodic compound mainly used for irritable bowel syndrome. Here we demonstrate that PVB could rapidly kill MRSA and S. epidermidis planktonic cells and persister cells avoiding resistance occurrence. Moreover, by crystal violet staining, viable cells counting and SYTO9/PI staining, PVB exhibited strong biofilm inhibition and eradication activities on the 96-well plates, glass surface or titanium discs. And the synergistic antimicrobial effects were observed between PVB and conventional antibiotics (ampicillin, oxacillin, and cefazolin). Mechanism study demonstrated the antimicrobial and antibiofilm effects by PVB were mainly mediated by proton motive force disrupting as well as reactive oxygen species inducing. Although, relatively poor pharmacokinetics were observed by systemic use, PVB could significantly reduce the viable bacterial cell loads and inflammatory infiltration in abscess in vivo caused by the biofilm forming strain ATCC 43,300. In all, our results indicated that PVB could be an alternative antimicrobial reagent for the treatment of MRSA, S. epidermidis and its biofilm related skin and soft tissue infections. Key points: Pinaverium bromide (PVB) exhibited strong antimicrobial effects against Staphylococcus planktonic cells. Significant biofilm inhibitory and eradicating activities by PVB. Proton motive force disrupting and reactive oxygen species inducing are the main antimicrobial and antibiofilm mechanisms. PVB reduce the viable bacterial cell loads and inflammatory infiltration in vivo. [ABSTRACT FROM AUTHOR]

Acinetobacter baumannii, an opportunistic and notorious nosocomial pathogen, is responsible for many infections affecting soft tissues, skin, lungs, bloodstream, and urinary tract, accounting for more than 722,000 cases annually. Despite the numerous advancements in therapeutic options, no approved vaccine is currently available for this particular bacterium. Consequently, this study focused on creating a rational vaccine design using bioinformatics tools. Three outer membrane proteins with immunogenic potential and properties of good vaccine candidates were used to select epitopes based on good antigenic properties, non-allergenicity, high binding scores, and a low IC50 value. A multi-epitope peptide (MEP) construct was created by sequentially linking the epitopes using suitable linkers. ClusPro 2.0 and C-ImmSim web servers were used for docking analysis with TLR2/TLR4 and immune response respectively. The Ramachandran plot showed an accurate model of the MEP with 100% residue in the most favored and allowed regions. The construct was highly antigenic, stable, non-allergenic, non-toxic, and soluble, and showed maximum population coverage. Additionally, molecular docking demonstrated strong binding between the designed MEP vaccine and TLR2/TLR4. In silico immunological simulations showed significant increases in T-cell and B-cell populations. Finally, codon optimization and in silico cloning were conducted using the pET-28a (+) plasmid vector to evaluate the efficiency of the expression of vaccine peptide in the host organism (Escherichia coli). This designed MEP vaccine would support and accelerate the laboratory work to develop a potent vaccine targeting MDR Acinetobacter baumannii. [ABSTRACT FROM AUTHOR]

The document provides guidelines for identifying and managing maternal sepsis during and after pregnancy, emphasizing prompt recognition and treatment. Recommendations include early referral to hospital, administration of antibiotics, and involvement of senior clinicians. It also highlights the importance of tailored antibiotic therapy, source control, and seeking expert advice in severe cases. The text discusses complications like Group A Beta-hemolytic Streptococcus and necrotizing fasciitis, as well as the need for specialized care for critically ill pregnant women and their neonates. Future research areas include developing pregnancy-specific diagnostic criteria and improving quality of care in maternal sepsis. [Extracted from the article]

Background: Debates persist on the optimal surgical approach for treating Periprosthetic joint infection (PJI) following total hip arthroplasty (THA). This meta-analysis aimed to compare the reinfection rate of one-stage revision versus two-stage revision for PJI after THA. Methods: A comprehensive search was performed in four databases (PubMed, Embase, Web of Science, and Cochrane Library) to locate articles that assessed the reinfection rate of one-stage revision compared to two-stage revision. Meta-analyses of reinfection rate were performed. Results: A total of 14 articles including of 1429 patients were chosen for inclusion in this meta-analysis, with 561 patients in the one-stage group and 868 patients in the two-stage group. The meta-analysis of the 14 trials revealed that there was no statistically significant disparity in the reinfection rate between the two groups(OR = 1.34, 95% CI 0.92 ~ 1.93, P = 0.12, I2 = 0). A subgroup analysis was conducted based on the presence of a well-defined algorithm for decision making in either a one-stage or two-stage revision. There was no statistically significant difference in reinfection rate between one-stage and two-stage revision if there was a decision algorithm(OR = 0.83, 95% CI 0.44 ~ 1.54, P = 0.55, I2 = 0). If not, the reinfection rate of one-stage revision was significantly higher than that of two-stage revision(OR = 1.79, 95% CI 1.11 ~ 2.88, P = 0.02, I2 = 0). Postoperative hip function score was significantly better in the one-stage revision group than that of the two-stage revision group(SMD = 0.54, 95% CI 0.31 ~ 0.78, P<0.05, I2 = 79%). Conclusions: A strategy that is clearly defined and can be used for decision making in one-stage or two-stage revision is necessary for the treatment of PJI after THA. When there is significant damage to the soft tissue and/or the presence of strong microorganisms, a two-stage revision is recommended in order to decrease the reinfection rate. One-stage revision is recommended for patients with low-toxic infections and intact soft tissue. Trial registration: PROSPERO (CRD42023450842, 17 August 2023) https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023450842. [ABSTRACT FROM AUTHOR]

Background The population pharmacokinetics/pharmacodynamics (PK/PD) of minocycline, rifampicin and linezolid in patients with complicated skin and soft tissue infections (cSSTIs) caused by MRSA are described. Methods Samples were collected in a Phase 4 study of oral minocycline plus rifampicin versus linezolid showing minocycline plus rifampicin to be non-inferior to linezolid. Antibiotics were assayed by HPLC or LC-MS, and a population PK model was developed using Pmetrics. The association between PK/PD indices and patient outcomes was explored. Results A three-compartment model (with an absorption compartment) with first-order input and elimination best described the data for the three drugs. No covariates were included in the final model. The population median values (95% credibility limits) of the clearance and volume of distribution were 7.412 L/h (5.121–8.361) and 14.155 L (6.799–33.901) for minocycline, 5.683 L/h (3.703–7.726) and 7.736 L (6.031–8.948) for rifampicin, and 1.970 L/h (1.326–2.499) and 20.169 L (12.857–32.629) for linezolid, respectively. Maximum a posteriori probability-Bayesian estimation plots of observed versus predicted had a slope of 0.999 r 20.967 for minocycline, slope 0.998 r 20.769 for rifampicin and slope 0.998 r 20.895 for linezolid. PK/PD indices were not related to clinical outcome. Taking a translational minocycline f AUC24h/MIC target of >0.5 for minocycline in the presence of rifampicin, 96% (49/51) of patients reached the target. Conclusions Population PK models of minocycline, rifampicin and linezolid were developed in patients with MRSA cSSTI and almost all patients reached the predefined PD index targets. As a result, neither AUC, MIC nor the AUC/MIC ratio could be related to clinical outcome. [ABSTRACT FROM AUTHOR]

Background Cefiderocol may potentially be used to treat skin and soft tissue infections (SSTIs). However, the pharmacokinetics of cefiderocol in human soft tissues have not yet been determined. The objective of the present PK study was to investigate whether target-site concentrations of cefiderocol are sufficiently high for the treatment of SSTIs. Methods In this pharmacokinetic study, a single intravenous dose of 2 g cefiderocol was administered to eight healthy male volunteers. Drug concentrations were determined in plasma, muscle and subcutis over 8 h. Free plasma concentrations were calculated using the plasma protein binding determined with ultrafiltration. Free tissue concentrations were obtained using microdialysis. Penetration ratios were calculated as AUC0-8h_free_tissue/AUC0-8h_free_plasma. A population pharmacokinetic model was developed, and the probability of target attainment (PTA) was determined using Monte Carlo simulations. Results Cefiderocol showed good tissue penetration, with mean penetration ratios ± standard deviation of 0.99 ± 0.33 and 0.92 ± 0.30 for subcutis and muscle, respectively. Cefiderocol pharmacokinetics in plasma were best described with a two-compartment model, and tissue concentrations were described by scaling the tissue concentrations to concentrations in the peripheral compartment of the plasma model. For a thrice-daily regimen with 2 g doses intravenously infused over 3 h, PTA was ≥90% for MIC values up to 4 mg/L, both based on free plasma and soft tissue pharmacokinetics. Conclusions This study indicates that a dose of 2 g cefiderocol achieves concentrations in plasma considered sufficient for treating relevant bacterial species. Assuming a comparable PK/PD target for soft tissues, sufficiently high concentrations would also be achieved in soft tissues. [ABSTRACT FROM AUTHOR]