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Background: Skin and soft-tissue infections (SSI) caused by Staphylococcus aureus remain a significant concern in both community and hospital settings. Mupirocin resistance among these isolates poses challenges for infection management and control strategies. Aims and Objectives: The aim of this study was to determine the prevalence and patterns of mupirocin resistance among staphylococcus isolates responsible for cutaneous and soft-tissue infections in patients attending a tertiary health-care facility. Along with that, the study investigated into mupirocin resistance prevalence and identified risk factors. Materials and Methods: A prospective study was conducted at a medical college, including 256 non-consecutive staphylococcal isolates from SSI. Antibiotic susceptibility testing was performed using Clinical and Laboratory Standards Institute recommended methods. Mupirocin resistance was determined through disk diffusion testing using 5 μg and 200 μg Mupirocin disks for low-level and high-level resistance, respectively. Results: Among the samples, 16.4% were methicillin-resistant S. aureus (MRSA) and 9.37% were methicillin-resistant coagulase-negative staphylococci. Mupirocin high-level resistance was found in 16.6% of S. aureus isolates, and mupirocin low-level resistance in 19% of MRSA isolates. The prevalence of resistance was lower in inpatient departments compared to outpatient departments. Associations were observed between resistance and patient demographics, history of mupirocin use, surgical site infections, hospitalization history, and diabetes. Conclusion: Mupirocin resistance presents a multifaceted challenge in the context of both patient demographics and clinical settings. The prevalence of resistance was influenced by factors such as patient age, gender, and prior mupirocin usage.

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

Background: Skin and soft-tissue infections (SSI) caused by Staphylococcus aureus remain a significant concern in both community and hospital settings. Mupirocin resistance among these isolates poses challenges for infection management and control strategies. Aims and Objectives: The aim of this study was to determine the prevalence and patterns of mupirocin resistance among staphylococcus isolates responsible for cutaneous and soft-tissue infections in patients attending a tertiary health-care facility. Along with that, the study investigated into mupirocin resistance prevalence and identified risk factors. Materials and Methods: A prospective study was conducted at a medical college, including 256 non-consecutive staphylococcal isolates from SSI. Antibiotic susceptibility testing was performed using Clinical and Laboratory Standards Institute recommended methods. Mupirocin resistance was determined through disk diffusion testing using 5 μg and 200 μg Mupirocin disks for low-level and high-level resistance, respectively. Results: Among the samples, 16.4% were methicillin-resistant S. aureus (MRSA) and 9.37% were methicillin-resistant coagulase-negative staphylococci. Mupirocin high-level resistance was found in 16.6% of S. aureus isolates, and mupirocin low-level resistance in 19% of MRSA isolates. The prevalence of resistance was lower in inpatient departments compared to outpatient departments. Associations were observed between resistance and patient demographics, history of mupirocin use, surgical site infections, hospitalization history, and diabetes. Conclusion: Mupirocin resistance presents a multifaceted challenge in the context of both patient demographics and clinical settings. The prevalence of resistance was influenced by factors such as patient age, gender, and prior mupirocin usage. [ABSTRACT FROM AUTHOR]

Skin and soft-tissue infections (SSTIs) encompass a variety of pathological conditions that involve the skin and underlying subcutaneous tissue, fascia, or muscle, ranging from simple superficial infections to severe necrotizing infections.Together, the World Society of Emergency Surgery, the Global Alliance for Infections in Surgery, the Surgical Infection Society-Europe, The World Surgical Infection Society, and the American Association for the Surgery of Trauma have jointly completed an international multi-society document to promote global standards of care in SSTIs guiding clinicians by describing reasonable approaches to the management of SSTIs.An extensive non-systematic review was conducted using the PubMed and MEDLINE databases, limited to the English language. The resulting evidence was shared by an international task force with different clinical backgrounds.

Background and aims: Injection drug use‐associated bacterial and fungal infections are increasingly common, and social contexts shape individuals' injecting practices and treatment experiences. We sought to synthesize qualitative studies of social–structural factors influencing incidence and treatment of injecting‐related infections. Methods: We searched PubMed, EMBASE, Scopus, CINAHL and PsycINFO from 1 January 2000 to 18 February 2021. Informed by Rhodes' 'risk environment' framework, we performed thematic synthesis in three stages: (1) line‐by‐line coding; (2) organizing codes into descriptive themes, reflecting interpretations of study authors; and (3) consolidating descriptive themes into conceptual categories to identify higher‐order analytical themes. Results: We screened 4841 abstracts and included 26 qualitative studies on experiences of injecting‐related bacterial and fungal infections. We identified six descriptive themes organized into two analytical themes. The first analytical theme, social production of risk, considered macro‐environmental influences. Four descriptive themes highlighted pathways through which this occurs: (1) unregulated drug supply, leading to poor drug quality and solubility; (2) unsafe spaces, influenced by policing practices and insecure housing; (3) health‐care policies and practices, leading to negative experiences that discourage access to care; and (4) restrictions on harm reduction programmes, including structural barriers to effective service provision. The second analytical theme, practices of care among people who use drugs, addressed protective strategies that people employ within infection risk environments. Associated descriptive themes were: (5) mutual care, including assisted‐injecting and sharing sterile equipment; and (6) self‐care, including vein health and self‐treatment. Within constraining risk environments, some protective strategies for bacterial infections precipitated other health risks (e.g. HIV transmission). Conclusions: Injecting‐related bacterial and fungal infections are shaped by modifiable social–structural factors, including poor quality unregulated drugs, criminalization and policing enforcement, insufficient housing, limited harm reduction services and harmful health‐care practices. People who inject drugs navigate these barriers while attempting to protect themselves and their community. [ABSTRACT FROM AUTHOR]

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

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

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

IntroductionOver the last 5 years, the American Association for the Surgery of Trauma has developed grading scales for emergency general surgery (EGS) diseases. In a previous validation study using diverticulitis, the grading scales were predictive of complications and length of stay. As EGS encompasses diverse diseases, the purpose of this study was to validate the grading scale concept against a different disease process with a higher associated mortality. We hypothesized that the grading scale would be predictive of complications, length of stay, and mortality in skin and soft-tissue infections (STIs).MethodsThis multi-institutional trial encompassed 12 centers. Data collected included demographic variables, disease characteristics, and outcomes such as mortality, overall complications, and hospital and ICU length of stay. The EGS scale for STI was used to grade each infection and two surgeons graded each case to evaluate inter-rater reliability.Results1170 patients were included in this study. Inter-rater reliability was moderate (kappa coefficient 0.472-0.642, with 64-76% agreement). Higher grades (IV and V) corresponded to significantly higher Laboratory Risk Indicator for Necrotizing Fasciitis scores when compared with lower EGS grades. Patients with grade IV and V STI had significantly increased odds of all complications, as well as ICU and overall length of stay. These associations remained significant in logistic regression controlling for age, gender, comorbidities, mental status, and hospital-level volume. Grade V disease was significantly associated with mortality as well.ConclusionThis validation effort demonstrates that grade IV and V STI are significantly predictive of complications, hospital length of stay, and mortality. Though predictive ability does not improve linearly with STI grade, this is consistent with the clinical disease process in which lower grades represent cellulitis and abscess and higher grades are invasive infections. This second validation study confirms the EGS grading scale as predictive, and easily used, in disparate disease processes.Level of evidencePrognostic/Epidemiologic retrospective multicenter trial, level III.

Introduction: Aeromonas spp., the emerging human pathogens, can cause various diseases like gastrointestinal infections, Skin and Soft-Tissue Infections (SSTIs), respiratory tract infections, urinary tract infection, hepatobiliary tract infection, blood stream infections etc. Aeromonas consists of important pathogenic species like Aeromonas hydrophila being the most common one followed by A.sobria, A.veroni, A.caviae and A.salmonicida. SSTIs due to Aeromonads are most often associated with pre-existing ulcer, traumatic wound and exposure to water. Aim: The present study was carried out to analyse socio-epidemiological factors, clinical features, risk factors and antibiotic resistance potential of Aeromonas spp., SSTIs. Materials and Methods: In this prospective study, all Gram-negative fermenting motile isolates which are positive for oxidase, H2S production, indole reaction, lysine decarboxylase were further identified by Vitek 2 compact system (Biomerieux, France). The study period was 2 years. Results: A total of 39 patients with Aeromonas spp., SSTIs were identified during the period from 2020 to 2022. Majority of patients hailed from urban areas, were in middle age group and were farmers. A.hydrophila (n=24, 62%) was the predominant isolate. Majority of the infections were superinfection of wound (n=16, 41%) and chronic non healing ulcer (n=13, 33.3%). A total of 33.3% of infections were polymicrobial, common concomitant pathogens being, Pseudomonas aeruginosa and Methicillin Resistant Staphylococcus aureus (MRSA). Trauma and water exposure were main risk factors with co-morbidities like diabetes, hypertension and liver cirrhosis. A 20.5% of patients were immunocompromised. There was one case of Necrotising Fasciitis (NF) which resulted in patient’s death. Co-trimoxazole, 3rd and 4th generation cephalosporins. Aztreonam and Tigecycline were the most effective antibiotics while eight of the isolates were Multidrug Resistant (MDR). Thirty-three patients recovered completely and three patients died of complications. Conclusion: Aeromonas hydrophila must be regarded as an emerging pathogen of SSTIs mainly in patients with pre-existing ulcers and can be MDR. Such infections have a good prognosis if prompt medical, surgical and supportive treatment is given.

Abstract Skin and soft-tissue infections (SSTIs) encompass a variety of pathological conditions that involve the skin and underlying subcutaneous tissue, fascia, or muscle, ranging from simple superficial infections to severe necrotizing infections. Together, the World Society of Emergency Surgery, the Global Alliance for Infections in Surgery, the Surgical Infection Society-Europe, The World Surgical Infection Society, and the American Association for the Surgery of Trauma have jointly completed an international multi-society document to promote global standards of care in SSTIs guiding clinicians by describing reasonable approaches to the management of SSTIs. An extensive non-systematic review was conducted using the PubMed and MEDLINE databases, limited to the English language. The resulting evidence was shared by an international task force with different clinical backgrounds.

Population-based studies of Staphylococcus aureus contribute to understanding the epidemiology of S. aureus infection. We enrolled surgical inpatients admitted to an African tertiary-care hospital in order to prospectively analyze the nosocomial impact of S. aureus. Data collection included an active sampling of the anterior nares and infectious foci within 48 h after admission and subsequently when clinically indicated. All S. aureus isolates were spa and agr genotyped. Possession of Panton-Valentine leukocidin (PVL) and other toxin genes was determined. We analyzed antibiotic susceptibility profiles by VITEK 2 systems and verified methicillin-resistant S. aureus (MRSA) by mecA/C PCR. Among 325 patients, 15.4% carried methicillin-susceptible S. aureus (MSSA) at admission, while 3.7% carried MRSA. The incidence densities of nosocomial infections due to MSSA and MRSA were 35.4 and 6.2 infections per 10,000 patient-days, respectively. Among all 47 nosocomial infections, skin and soft-tissue (40.4%) and bones or joints' (25.5%) infections predominated. Six (12.7%) infection-related S. aureus isolates harbored PVL genes including two (4.2%) MRSA: overall, seventeen (36.2%) isolates carried pyrogenic toxin superantigens or other toxin genes. This study illustrates the considerable nosocomial impact of S. aureus in a Nigerian University hospital. Furthermore, they indicate a need for effective approaches to curtail nosocomial acquisition of multidrug-resistant S. aureus. [ABSTRACT FROM AUTHOR]

Background: Rapidly growing mycobacteria (RGM) are increasingly being recognized as potential pathogens. RGM, particularly Mycobacterium abscessus, Mycobacterium fortuitum, and Mycobacterium chelonae, have been observed in both pulmonary and extrapulmonary infections including cutaneous, soft-tissue, and wound infections. However, there are limited reports of these potential pathogens from skin and soft-tissue infections. Moreover, the drug susceptibility profile of RGM is largely unknown in several regions of the world. Methods: We analyzed reports on RGM isolated from skin and soft-tissue infections globally for details of RGM species and drug susceptibility profile. We also analyzed the drug susceptibility profile of four RGM isolates, obtained from skin and soft-tissue infections in our laboratory, by broth microdilution method. Results: In the reports reviewed, the most common RGM isolated from skin and soft-tissue infections were M. abscessus (184/475, 38.7%), M. fortuitum (150/475, 31.5%), M. chelonae (72/475, 15%), and M. chelonae–M. abscessus complex (46/475, 9.6%). However, drug susceptibility was tested only in 26/39 (66.6%) reports. In our own laboratory, we obtained three isolates of M. abscessus and one isolate of M. fortuitum from one case of breast abscess and three cases of postsurgical wound infections. Maximum susceptibility of M. abscessus was observed to clarithromycin, amikacin, and linezolid. The M. fortuitum isolate was susceptible to clarithromycin, amikacin, clofazimine, and linezolid. Conclusion: Paucity of information available on RGM isolated from skin and soft-tissue infections highlights the need to be aware of the pathogenic potential and the drug susceptibility profile of these organisms.

Population-based studies of Staphylococcus aureus contribute to understanding the epidemiology of S. aureus infection. We enrolled surgical inpatients admitted to an African tertiary-care hospital in order to prospectively analyze the nosocomial impact of S. aureus. Data collection included an active sampling of the anterior nares and infectious foci within 48 h after admission and subsequently when clinically indicated. All S. aureus isolates were spa and agr genotyped. Possession of Panton-Valentine leukocidin (PVL) and other toxin genes was determined. We analyzed antibiotic susceptibility profiles by VITEK 2 systems and verified methicillin-resistant S. aureus (MRSA) by mecA/C PCR. Among 325 patients, 15.4% carried methicillin-susceptible S. aureus (MSSA) at admission, while 3.7% carried MRSA. The incidence densities of nosocomial infections due to MSSA and MRSA were 35.4 and 6.2 infections per 10,000 patient-days, respectively. Among all 47 nosocomial infections, skin and soft-tissue (40.4%) and bones or joints’ (25.5%) infections predominated. Six (12.7%) infection-related S. aureus isolates harbored PVL genes including two (4.2%) MRSA: overall, seventeen (36.2%) isolates carried pyrogenic toxin superantigens or other toxin genes. This study illustrates the considerable nosocomial impact of S. aureus in a Nigerian University hospital. Furthermore, they indicate a need for effective approaches to curtail nosocomial acquisition of multidrug-resistant S. aureus.

Background: Rapidly growing mycobacteria (RGM) are increasingly being recognized as potential pathogens. RGM, particularly Mycobacterium abscessus, Mycobacterium fortuitum, and Mycobacterium chelonae, have been observed in both pulmonary and extrapulmonary infections including cutaneous, soft-tissue, and wound infections. However, there are limited reports of these potential pathogens from skin and soft-tissue infections. Moreover, the drug susceptibility profile of RGM is largely unknown in several regions of the world. Methods: We analyzed reports on RGM isolated from skin and soft-tissue infections globally for details of RGM species and drug susceptibility profile. We also analyzed the drug susceptibility profile of four RGM isolates, obtained from skin and soft-tissue infections in our laboratory, by broth microdilution method. Results: In the reports reviewed, the most common RGM isolated from skin and soft-tissue infections were M. abscessus (184/475, 38.7%), M. fortuitum (150/475, 31.5%), M. chelonae (72/475, 15%), and M. chelonae–M. abscessus complex (46/475, 9.6%). However, drug susceptibility was tested only in 26/39 (66.6%) reports. In our own laboratory, we obtained three isolates of M. abscessus and one isolate of M. fortuitum from one case of breast abscess and three cases of postsurgical wound infections. Maximum susceptibility of M. abscessus was observed to clarithromycin, amikacin, and linezolid. The M. fortuitum isolate was susceptible to clarithromycin, amikacin, clofazimine, and linezolid. Conclusion: Paucity of information available on RGM isolated from skin and soft-tissue infections highlights the need to be aware of the pathogenic potential and the drug susceptibility profile of these organisms. [ABSTRACT FROM AUTHOR]

Introduction: National guidelines suggest that most skin abscesses do not require antibiotics, and that cellulitis antibiotics should target streptococci, not community-associated MRSA (CA-MRSA). The objective of this study is to describe antimicrobial treatment of skin infections in U.S. emergency departments (EDs) and analyze potential quality measures.Methods: The National Hospital Ambulatory Medical Care Survey (NHAMCS) is a 4-stage probability sample of all non-federal U.S. ED visits. In 2007 NHAMCS started recording whether incision and drainage was performed at ED visits. We conducted a retrospective analysis, pooling 2007-2010 data, identified skin infections using diagnostic codes, and identified abscesses by performance of incision and drainage. We generated national estimates and 95% confidence intervals using weighted analyses; quantified frequencies and proportions; and evaluated antibiotic prescribing practices. We evaluated 4 parameters that might serve as quality measures of antibiotic stewardship, and present 2 of them as potentially robust enough for implementation.Results: Of all ED visits, 3.2% (95% confidence interval 3.1-3.4%) were for skin infection, and 2.7% (2.6-2.9%) were first visits for skin infection, with no increase over time (p=0.80). However, anti-CA-MRSA antibiotic use increased, from 61% (56-66%) to 74% (71-78%) of antibiotic regimens (p

People who inject drugs (PWID) experience significant injection-related infections (IRIs) at significant healthcare system cost. This study used and validated an algorithm based on the International Classification of Diseases, Tenth Revision, to estimate hospitalized PWID populations, assess the total statewide morbidity for IRIs among PWID, and calculate associated costs of care. [ABSTRACT FROM AUTHOR]

In patients infected with human immunodeficiency virus (HIV)-1 at our hospital, we observed increases in skin and soft-tissue infections (SSTIs) by community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). Therefore, we analyzed factors related to CA-MRSA infection and performed a molecular epidemiological investigation. HIV-1-infected patients were diagnosed with SSTIs related to S. aureus between 2007 and 2017, and MRSA was classified into community and hospital-acquired types according to published criteria. Information was collected retrospectively from clinical records, and multivariate analysis by logistic regression was performed concerning factors related to CA-MRSA infection. We evaluated the staphylococcal cassette chromosome mec (SCC mec) type, multilocus sequence type, and the presence of genes encoding Panton–Valentine leucocidin (PVL) in 27 MRSA samples isolated during and after 2015. We found 218 episodes of SSTIs in 169 patients, and among initial episodes of SSTIs, the MRSA ratio was higher from 2015 to 2017 relative to that from 2007 to 2014 (88% vs. 44%; p < 0.0001). Multivariate analysis showed that in men having sex with men [MSM; odds ratio (OR): 13] and exhibiting onset during and after 2015 (OR: 5.4), CD4+ cell count ≥200 cells/μL (OR: 5.6) and the presence of lesions in the lower abdomen or buttocks (OR: 9.5) were independent factors related to CA-MRSA infection. Additionally, PVL+/ST8/SCCmec type IV MRSA was the predominant pathogen (22 cases; 81%). These data describe an increased prevalence of SSTIs due to PVL-positive ST8-MRSA-IV, not previously considered epidemic in Japan, in MSM infected with HIV-1 in Osaka, Japan. [ABSTRACT FROM AUTHOR]

Clinical results of wound healing dynamics were studied in 60 patients with soft-tissue infection against the background of diabetes mellitus type II. At the same time the study considered indices of intercellular contacts protein tissue expression such as connexin 43(Cx43) and basic fibroblast growth factor receptors (bFGFR). The basic therapy of biopsy material of wound borders was applied. The reduction of bFGFR expression and the minor growth of Cx43 expression were observed. The pain syndrome proceeded for a long time and there were signs of perifocal inflammation, retard wound healing with granulation tissue. The application of combined method of ozone therapy which included autohemotherapy with ozone and an external management of wound by ozone-oxygen mixture facilitated to considerable shortening of inflammatory phase and regeneration. It was associated with increased Cx43 expression (in 1,9 times) in comparison with initial level and bFGFR was enlarged in 1,7 times to eighth day of postoperative period.

The vancomycin-resistance associated sensor/regulator, VraSR two-component regulatory-system (VraSR), regulates virulence and the response of Staphylococcus aureus (SA) to environmental stress. To investigate the role of VraSR in SA skin and soft tissue infections (SSTI), we inactivated the VraSR of a clinical CA-MRSA ST30 strain by insertional mutation in vraR gene using the TargeTron-Gene Knockout System. We constructed an organotypic keratinocyte fibroblast co-culture (3D-skin model) and a humanized mouse as SSTI infection models. In the 3D-skin model, inactivation of VraSR in the strains ST30 and USA300 showed 1-log reduction in adhesion and internalization (p < 0.001) compared to the respective wildtype. The mutant strains of ST30 (p < 0.05) and USA300-LAC (p < 0.001) also exhibited reduced apoptosis. The wildtype ST30 infection in the humanized mouse model demonstrated increased skin lesion size and bacterial burden compared to BALB/c mice (p < 0.01). The response of the humanized mouse towards the MRSA infection exhibited human similarity indicating that the humanized mouse SSTI model is more suitable for evaluating the role of virulence determinants. Inactivation of VraSR in ST30 strain resulted in decreased skin lesion size in the humanized mouse SSTI model (p < 0.05) and reduction in apoptotic index (p < 0.01) when compared with the wildtype. Our results reveal that inactivating the VraSR system may be a potent anti-virulence approach to control MRSA infection.

Introduction: Skin and soft-tissue infections (SSTIs) are an important cause of infectious disease morbidity among military populations. Due to the high direct and indirect costs associated with SSTIs, particularly with methicillin-resistant Staphylococcus aureus (MRSA) infections, there remains a critical need for the development and evaluation of SSTI prevention strategies among high-risk military personnel. Herein, we review efforts of the Infectious Disease Clinical Research Program (IDCRP) related to the prevention of SSTIs in the military.Methods: The IDCRP of the Uniformed Services University has conducted clinical research protocols on SSTI epidemiology and prevention among military personnel since 2009. Observational studies have examined the epidemiology of Staphylococcus aureus colonization and SSTI in training and deployment settings. Two randomized controlled trials of personal hygiene strategies for SSTI prevention at Marine Corps Base Quantico (Virginia) and Fort Benning (Georgia) were performed. Lastly, two vaccine trials have been conducted by the IDCRP, including a Phase 2 S. aureus vaccine trial (currently ongoing) among military trainees.Results: Military recruits and deployed personnel experience an intense and prolonged exposure to S. aureus, the major causative agent of SSTI. The burden of S. aureus colonization and SSTI is particularly high in military trainees. Hygiene-based trials for S. aureus decolonization among military trainees were not effective in reducing rates of SSTI. In January 2018, the IDCRP initiated a Phase 2 S. aureus vaccine trial among the US Army Infantry training population at Fort Benning.Conclusions: In the military, a disproportionate burden of SSTIs is borne by the recruit population. Strategies relying upon routine application of agents for S. aureus decolonization have not been effective in preventing SSTIs. A novel S. aureus vaccine candidate is being currently evaluated in a military training population and may represent a new opportunity to prevent SSTIs for the military. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus (S. aureus) is a leading cause of skin and soft-tissue infections (SSTIs) in the community. In this study, we characterized a collection of 34 S. aureus from SSTIs in ambulatory patients in Portugal and analyzed the presence of Panton–Valentine leucocidin (PVL)-encoding genes and antibiotic-resistance profile, which was correlated with genetic determinants, plasmid carriage, and clonal lineage. Nearly half of the isolates (15, 44.1%) were methicillin-resistant Staphylococcus aureus (MRSA) and/or multidrug resistant (MDR). We also detected resistance to penicillin (33/34, 97.1%), fluoroquinolones (17/34, 50.0%), macrolides and lincosamides (15/34, 44.1%), aminoglycosides (6/34, 17.6%), and fusidic acid (2/34, 5.9%), associated with several combinations of resistance determinants (blaZ, erm(A), erm(C), msr(A), mph(C), aacA-aphD, aadD, aph(3′)-IIIa, fusC), or mutations in target genes (fusA, grlA/gyrA). The collection presented a high genetic diversity (Simpson’s index of 0.92) with prevalence of clonal lineages CC5, CC22, and CC8, which included the MRSA and also most MDR isolates (CC5 and CC22). PVL-encoding genes were found in seven isolates (20.6%), three methicillin-susceptible Staphylococcus aureus (MSSA) (ST152-agrI and ST30-agrIII), and four MRSA (ST8-agrI). Plasmid profiling revealed seventeen distinct plasmid profiles. This work highlights the high frequency of antimicrobial resistance and PVL carriage in SSTIs-related S. aureus outside of the hospital environment.

Nontuberculous mycobacteria (NTM) diseases mainly manifest as pulmonary illnesses, but 20 - 30% of NTM isolates originate from extrapulmonary diseases. These diseases cause a variety of clinical syndromes, including skin and soft-tissue infections, musculoskeletal infections, lymphadenitis, and disseminated disease. In skin and soft-tissue infections, musculoskeletal infections, prolonged treatment with combinations of antibiotics is effective in the treatment of NTM diseases, with surgery as an important complementary tool. The recommended duration of therapy for skin and soft-tissue infection is usually 2 - 4 months for mild disease and 6 months for severe disease, while treatment of musculoskeletal NTM disease usually requires at least 6 -12 months. Management options of NTM lymphadenitis include surgical intervention, medical therapy, or observation. Treatment of disseminated NTM disease generally requires 6 to 12 months after immune restoration. However, despite a considerable increase in knowledge about NTM diseases, determining optimal treatment approaches remains a complex and challenging task. [ABSTRACT FROM AUTHOR]

Chao Liu,1,* Zhi Mao,1,* Mengmeng Yang,1 Hongjun Kang,1 Hui Liu,1 Liang Pan,1 Jie Hu,1 Jun Luo,2 Feihu Zhou1 1Department of Surgical Intensive Care Unit, Chinese People’s Liberation Army General Hospital, Beijing, 2Department of Surgical Intensive Care Unit, Xuanhan People’s Hospital, Sichuan, People’s Republic of China *These authors contributed equally to this work Background: Skin and soft tissue infections (SSTIs) are significant indications for antibiotic treatment. Daptomycin, a novel antibiotic, has been registered and licensed to be used in the treatment of these infections. However, its efficacy and safety remain controversial. Objective: The objective of this study was to conduct a systematic review with trial sequential analysis (TSA) to evaluate the efficacy and safety of daptomycin for the treatment of SSTIs and to analyze whether the available sample size has been large enough and is conclusive. Methods: PubMed, the Cochrane Library, and EMBASE were searched for published randomized controlled trials (RCTs) that compared daptomycin with other antibiotics in adult patients with SSTIs up to February 2016.Results: This meta-analysis included eight randomized controlled trials (n=2,002). There was no difference in either the clinical success rate (intention-to-treat population: relative risk [RR] =1.04, 95% confidence interval [CI] =0.99–1.10, P=0.12; clinically evaluable population: RR =1.00, 95% CI =0.97–1.04, P=0.82) or the microbiological success rate (RR =1.00, 95% CI =0.95–1.06, P=0.92) between the daptomycin and comparator groups for treating SSTIs, which was confirmed by TSA. Compared with vancomycin, daptomycin exhibited no advantage in increasing the clinical success rate (RR =1.03, 95% CI =0.95–1.13, P=0.47), and this was also confirmed by TSA. All-cause mortality, overall treatment-related adverse events, and creatine phosphokinase events were similar between these two groups. Conclusion: Daptomycin and comparator drugs are equally efficacious with regard to clinical and microbiological success for patients with SSTIs, and TSA showed that no additional randomized controlled trials are required. Although daptomycin is a good alternative when other antibiotics are contraindicated for patients with SSTIs and it can serve as a first-line treatment for SSTIs, clinicians should be aware of potential adverse events, such as daptomycin-induced acute eosinophilic pneumonia and creatine phosphokinase, when treating patients with daptomycin. Keywords: daptomycin, skin and soft tissue infections, vancomycin, meta-analysis, trial sequential analysis

We evaluated if the introduction of a clinical pathway for skin and soft-tissue infections (SSTIs) would reduce methicillin-resistant Staphylococcus aureus (MRSA)-directed therapy for simple cellulitis and antibiotic use for simple abscess after drainage. We compared the treatment of SSTI during a 3-month prepathway and 11-month postpathway period. We included patients 57 days to 18 years old discharged from the emergency department (ED) with a diagnosis of cellulitis or abscess. Balancing measures included 72-hour revisit rate and ED length of stay (LOS). A total of 291 patients prepathway and 781 patients postpathway were included. The proportion of patients with simple cellulitis prescribed MRSA-directed therapy decreased from 81% to 54% postpathway. The proportion of patients with a drained abscess prescribed systemic antibiotics decreased from 88% to 75%. There was no increase in 72-hour revisit rates (3.8% vs 3.2%, P = .64) or ED LOS (2.8 vs 2.7 hours, P = .05). [ABSTRACT FROM AUTHOR]

Background The number of antibiotics in the pipeline targeting Gram-positive pathogens has increased in recent years. Aims This narrative review aims to provide a summary of existing evidence on efficacy, microbiological spectrum and safety of novel systemic antibiotics that have either recently been licensed or completed phase III trials, and possess activity predominantly against Gram-positive organisms. Sources A review of the published literature via the MEDLINE database was performed. In addition, ongoing trials were identified through a search of the clinical trial registration platform clinicaltrials.gov , and when necessary, pharmaceutical companies responsible for the development of the drug were contacted for further information. Content Data on development, microbiological spectrum, pharmacokinetic/pharmacodynamic properties, clinical efficacy, safety and cost are presented for the new cephalosporins ceftaroline and ceftobiprole; the lipoglycopeptides dalbavancin, oritavancin and telavancin; the fluoroquinolones delafloxacin, nemonoxacin and zabofloxacin; the dihydrofolate-reductase inhibitor iclaprim; the pleuromutilin lefamulin; and the tetracycline omadacycline. Implications Although promising, these new antibiotics have so far been tested in non-severe infections whose treatment is generally uncomplicated and whose aetiologies were not predominantly multidrug-resistant pathogens. None of the new antibiotics have shown superiority to standard care, and none have been investigated for patient-relevant outcomes. Safety and pharmacokinetic data continue to be lacking. How these new drugs are to be integrated into the current armamentarium remains to be established. [ABSTRACT FROM AUTHOR]

Non-tuberculous mycobacterial infections in immunocompetent children are generally limited to cervical lymphadenitis. However, spreading cutaneous infections are another rare presentation of nontuberculous mycobacterial infection. Here, we present a previously healthy 14 year-old male with a rapidly desquamating and spreading cutaneous lesion encompassing the entire left face. A multi-disciplinary approach was necessary to diagnose a cutaneous atypical mycobacterial infection. The patient was treated with a combination of debridement, antibiotics, and local wound care. Pediatric otolaryngologists should be aware of this rare presentation of mycobacterial infection in order to facilitate prompt and accurate diagnosis and expedite treatment for these children. [ABSTRACT FROM AUTHOR]

Risk for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections has increased due to the ongoing opioid epidemic and unsafe injection practices. We estimated the prevalence and incidence of HIV and HCV diagnoses among people who inject drugs from hospital-based clinical encounters. We linked clinical encounters at an Atlanta hospital during 2012–2018 with state HIV and HCV surveillance records to examine the prevalence of infections at discharge and incidence of infections post clinical encounter. At discharge, 32.9% and 28.6% of patients with injection drug use-related clinical encounters had an HIV or HCV diagnosis, respectively. HIV and HCV diagnoses at the time of discharge were mostly among 40–64 years old patients, males, and Black/African Americans. Post clinical encounter, 3.8% of patients were later diagnosed with HIV, and 16.5% were later diagnosed with HCV, translating to incidence rates of 9.3 per 1000 person-years and 41.5 per 1000 person-years, respectively. The majority of HIV and HCV diagnoses post clinical encounter occurred among Black/African Americans and males. Of patients with HIV and HCV diagnoses post clinical encounter, 27.3% and 11.9% had been tested during their clinical encounter, respectively. Targeted interventions for HIV/HCV prevention, screening, diagnosis, and linkage to treatment are needed to reduce the incidence of new infections among people who inject drugs. [ABSTRACT FROM AUTHOR]

Background: Methicillin-resistant Staphylococcus aureus (MRSA) USA300 is the leading cause of MRSA infections in the United States and has caused an epidemic of skin and soft-tissue infections. Recurrent infections with USA300 MRSA are common, yet intrahost evolution during persistence on an individual has not been studied. This gap hinders the ability to clinically manage recurrent infections and reconstruct transmission networks.Methods: To characterize bacterial intrahost evolution, we examined the clinical courses of 4 subjects with 3-6 recurrent USA300 MRSA infections, using patient clinical data, including antibiotic exposure history, and whole-genome sequencing and phylogenetic analysis of all available MRSA isolates (n = 29).Results: Among sequential isolates, we found variability in diversity, accumulation of mutations, and mobile genetic elements. Selection for antimicrobial-resistant populations was observed through both an increase in the number of plasmids conferring multidrug resistance and strain replacement by a resistant population. Two of 4 subjects had strain replacement with a genetically distinct USA300 MRSA population.Discussions: During a 5-year period in 4 subjects, we identified development of antimicrobial resistance, intrahost evolution, and strain replacement among isolates from patients with recurrent MRSA infections. This calls into question the efficacy of decolonization to prevent recurrent infections and highlights the adaptive potential of USA300 and the need for effective sampling. [ABSTRACT FROM AUTHOR]

Illicit drug use can result in a wide range of medical complications. As the availability, synthesis, and popularity of illicit drugs evolve over time, new syndromes associated with their use may mimic infections. Some of these symptoms are anticipated drug effects, and others are complications of adulterants mixed with drugs or complications from the method of using drugs. Some illicit drugs are associated with rare infections, which are difficult to diagnosis with standard microbiological techniques. The goal of this review is to orient a wide range of clinicians--including general practitioners, emergency medicine providers, and infectious diseases specialists--to complications of illicit drug use that may be underrecognized. Improving awareness of infectious and noninfectious complications of illicit drug can expedite diagnosis and medical treatment of persons who use drugs and facilitate targeted harm reduction counseling to prevent future complications. [ABSTRACT FROM AUTHOR]

Background Given its nonspecific physical examination findings, accurately distinguishing cellulitis from a cellulitis mimicker (pseudocellulitis) is challenging. Objective We sought to investigate the national incidence of cellulitis misdiagnosis among inpatients. Methods We conducted a retrospective review of inpatient dermatology consultations at Massachusetts General Hospital, University of Alabama at Birmingham Medical Center, University of California Los Angeles Medical Center, and University of California San Francisco Medical Center in 2008. All consults requested for the evaluation of cellulitis were included. The primary outcomes were determining the incidence of cellulitis misdiagnosis, evaluating the prevalence of associated risk factors, and identifying common pseudocellulitides. Results Of the 1430 inpatient dermatology consultations conducted in 2008, 74 (5.17%) were requested for the evaluation of cellulitis. In all, 55 (74.32%) patients evaluated for cellulitis were given a diagnosis of pseudocellulitis. There was no statistically significant difference in the rate of misdiagnosis across institutions ( P = .12). Patient demographics and associated risk factor prevalence did not statistically vary in patients given a diagnosis of cellulitis versus those with pseudocellulitis ( P > .05). Limitations This study was unable to evaluate all patients admitted with cellulitis and was conducted at tertiary care centers, which may affect the generalizability of the results. Conclusions Cellulitis is commonly misdiagnosed in the inpatient setting. Involving dermatologists may improve diagnostic accuracy and decrease unnecessary antibiotic use. [ABSTRACT FROM AUTHOR]

Objectives In Spain, despite the high rates of healthcare-associated methicillin-resistant Staphylococcus aureus (MRSA), the incidence of community-associated (CA) MRSA seems to be low on the basis of a small number of studies. We analysed the evolution of CA-MRSA in Spain from 2004 to 2012, and identified the clonal lineages and population structure. Methods The study included 8326 MRSA strains. Susceptibility to 18 antimicrobials was determined. Isolates were tested for the presence of mecA, Panton–Valentine leucocidin (PVL) and the arginine catabolic mobile element (ACME) by PCR, and typed by staphylococcal cassette chromosome mec, PFGE, spa, multilocus sequence typing and agr. Results Among the 8326 isolates, 246 (2.9%) were CA-MRSA. We identified genotypically 226 PVL-positive CA-MRSA isolates (88% agr type I, 10.2% agr type III and 1.8% agr type II) and 20 PVL-negative CA-MRSA isolates (all agr type I) from children and adults (82.1% from wounds) from 13 different geographical areas. A significant increase in the rates of CA-MRSA was observed when comparing 2004–07 (0.43%) with 2008–12 (5.44%). Resistance rates were as follows: only β-lactams, 84.5%; erythromycin, 12.8%; tetracycline, 8.8%; clindamycin, 4.9%; ciprofloxacin, 3.1%; fusidic acid, 2.0%; others, 0.4%; and multiresistant, 6.2% (six isolates USA300). The strains belonged to the PVL-positive clones ST8-IVc (69.9%), ST8-IVa-ACME-positive (USA300, 8.9%), ST8-IVa-ACME-negative (0.8%), ST30-IVc (4.5%), ST80-IVc (2.0%), ST5-IVc (1.2%) and others (ST59, ST72, ST88, ST642, ST1472 and ST1829; 4.5%) and to the PVL-negative ST398-V (8.1%). Conclusions We confirm an increase in CA-MRSA in Spain, the predominance of the ST8-IVc clone, the emergence of the USA300 clone, a high genetic diversity among PVL-positive CA-MRSA isolates and the recent emergence of the pig-associated ST398-V clone. [ABSTRACT FROM PUBLISHER]

Objectives Methicillin-resistant Staphylococcus aureus (MRSA) strains carrying the mecC gene have been reported from humans and animals from several European countries, but never from Spain. We describe the first isolates of mecC-positive MRSA of human origin collected in Spain and report a fatal case of bacteraemia. Methods Isolates were tested for phenotypic resistance using cefoxitin, tested for the mecA/mecC genes and toxin genes by PCR, and typed by staphylococcal cassette chromosome mec (SCCmec), PFGE, spa, multilocus sequence typing and agr. Results During 2008–13 five MRSA isolates showing resistance to cefoxitin and carrying the mecC gene were recovered at one hospital in Spain. In a review of 5505 S. aureus strains received at the Spanish National Reference Centre for Staphylococci from the same period, we found two additional mecC-positive isolates. The isolates were recovered from blood (two), wounds (two), joint fluid (one), urine (one) and a nasal swab (one). All MRSA were mecA negative, presented SCCmecXI, belonged to agr group III and to clonal complex 130, and were negative for the production of the toxin genes tst1, eta, etb, etd and Panton–Valentine leucocidin. Six isolates belonged to spa type t843 (ST130 and ST1945, where ST stands for sequence type) and one to spa type t6220 (ST1945). One patient with mecC-positive MRSA sepsis died in the emergency department. Conclusions We confirm the presence of MRSA carrying the mecC gene in Spain, the ability of this livestock-associated MRSA to cause severe infections in humans and the need to perform culture-based susceptibility testing methods in order to detect these emerging strains. [ABSTRACT FROM PUBLISHER]

Background: Skin and soft tissue infections (SSTIs) are commonly occurring infections with wide-ranging clinical manifestations, from mild to life-threatening. There are few population-based studies of SSTIs in the period after the rapid increase in community-acquired methicillin-resistant Staphyloccus aureus (MRSA). Methods: We used electronic databases to describe the incidence, microbiology, and patient characteristics of clinically-diagnosed skin and soft tissue infections (SSTIs) among members of a Northern California integrated health plan. We identified demographic risk factors associated with SSTIs and MRSA infection. Results: During the three-year study period from 2009 to 2011, 376,262 individuals experienced 471,550 SSTI episodes, of which 23% were cultured. Among cultured episodes, 54% were pathogen-positive. Staphylococcus aureus (S. aureus) was isolated in 81% of pathogen-positive specimens, of which nearly half (46%) were MRSA. The rate of clinically-diagnosed SSTIs in this population was 496 per 10,000 person-years. After adjusting for age group, gender, race/ethnicity and diabetes, Asians and Hispanics were at reduced risk of SSTIs compared to whites, while diabetics were at substantially higher risk compared to non-diabetics. There were strong age group by race/ ethnicity interactions, with African Americans aged 18 to <50 years being disproportionately at risk for SSTIs compared to persons in that age group belonging to other race/ethnicity groups. Compared to Whites, S. aureus isolates of African-Americans and Hispanics were more likely to be MRSA (Odds Ratio (OR): 1.79, Confidence Interval (CI): 1.67 to 1.92, and, OR: 1.24, CI: 1.18 to 1.31, respectively), while isolates from Asians were less likely to be MRSA (OR: 0.73, CI: 0.68 to 0.78). Conclusions: SSTIs represent a significant burden to the health care system. The majority of culture-positive SSTIs were caused by S. aureus, and almost half of the S. aureus SSTIs were methicillin-resistant. The reasons for African-Americans having a higher likelihood, and Asians a lower likelihood, for their S. aureus isolates to be methicillin-resistant, should be further investigated. [ABSTRACT FROM AUTHOR]

Abstract: This retrospective analysis of patients from eight countries included in the European Cubicin® Outcomes Registry and Experience (EU-CORESM) captures the first post-approval years of clinical experience with daptomycin in its licensed indications. Of the total 1127 patients enrolled in EU-CORE between 2006 and 2008, 373 had a primary complicated skin and soft-tissue infection (cSSTI), most commonly surgical-site infection (48%), and 244 had bacteraemia, 55% of which were catheter-related. The most common pathogens were Staphylococcus aureus in cSSTIs (43%) and coagulase-negative staphylococci in bacteraemia (36%). The most frequently prescribed daptomycin doses were 4mg/kg and 6mg/kg for cSSTIs, and 6mg/kg for bacteraemia. The median duration of inpatient and outpatient treatment, respectively, was 13 days and 8 days for cSSTIs and 8 days and 10 days for bacteraemia. Clinical success was reported for 81% of patients with cSSTIs and 77% with bacteraemia, with 82% success overall for infections caused by S. aureus. A trend towards higher clinical success was noted with higher daptomycin doses in bacteraemia (78% for 6mg/kg vs. 90% for doses >6mg/kg). Daptomycin demonstrated a favourable safety profile. Adverse events regardless of relationship to study drug were reported for 11% of patients with cSSTIs and 24% with bacteraemia, most commonly septic shock [7 patients (2%) with cSSTIs and 5 patients (2%) with bacteraemia]. These results demonstrate that daptomycin is effective and well tolerated in the treatment of cSSTIs and bacteraemia caused by Gram-positive bacteria in clinical practice. [Copyright &y& Elsevier]

Abstract: Glycopeptides have been considered the antimicrobials of choice for serious meticillin-resistant Staphylococcus aureus (MRSA) and meticillin-resistant coagulase-negative staphylococci (MR-CoNS) infections for several years. Daptomycin is a new option for the treatment of these infections, including those exhibiting reduced susceptibility to glycopeptides. The aim of this study was to compare glycopeptides and daptomycin for the treatment of infections caused by MRSA or MR-CoNS. Data for 106 patients with bloodstream infections (bacteraemia or infective endocarditis) or skin and soft-tissue infections (SSTIs) were retrospectively reviewed, of which 43 were treated with daptomycin (DAP group) and 63 were treated with vancomycin or teicoplanin (GLYCO group). Patients included in the two comparison groups were homogeneous in terms of age, risk factors and clinical severity. Aetiology was mainly represented by MRSA in both groups, followed by various species of MR-CoNS. Daptomycin was used more frequently in patients with central venous catheter-associated bacteraemia or pacemaker-associated infection. Patients with SSTIs included in the GLYCO group had a longer mean duration of antibiotic therapy (18.2 days vs. 14.6 days; P =0.009) and a longer mean length of hospital stay (28.2 days vs. 19.6 days; P =0.01) compared with those included in the DAP group. A longer mean duration of antibiotic therapy was also observed in patients with bloodstream infections receiving glycopeptide therapy (25.6 days vs. 18 days; P =0.004). In conclusion, the good clinical efficacy of daptomycin is associated with a more rapid resolution of the clinical syndrome and a reduced length of hospitalisation. This latter aspect may have important pharmacoeconomic implications, promoting the use of daptomycin in the clinical setting. [Copyright &y& Elsevier]

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OBJECTIVE: To determine the interrater reliability of clinical examination by pediatric emergency medicine physicians for the diagnosis of skin and soft-tissue infections (SSTIs). METHODS: A cross-sectional study of patients presentingto a pediatric emergency department with SSTIs was performed. Each lesion was examined by a treating physician and a study physician (from a pool of 62 physicians) at the bedside during the emergency department visit. The primary outcome was reliability, as measured with the weighted K statistic, for determining whether the lesion was an abscess and whether the lesion required a drainage procedure. RESULTS: Atotal of 371 lesions were analyzed for interrater reliability. The weighted i value for diagnosis of the lesion as an abscess was 0.39 (95% confidence interval: 0.32-0.47), and that for assessment of the need for drainage was 0.43 (95% confidence interval: 0.36-0.51). Agreement was statistically more likely for lesions in children ⩽4 years of age but was not more likely for lesions in nonblack patients, lesions in patients with a history of or exposure to a close contact with a SSTI, or lesions examined by 2 experienced pediatric emergency medicine physicians. CONCLUSIONS: Among the 62 participating physicians at our site, the reliability of the clinical examination was poor. This may indicate that improved education and/or more-objective means for diagnosing these infections in the acute care setting are warranted. Additional studies are needed to determine whether these results are generalizable to other settings. [ABSTRACT FROM AUTHOR]

The vancomycin-resistance associated sensor/regulator, VraSR two-component regulatory-system (VraSR), regulates virulence and the response of Staphylococcus aureus (SA) to environmental stress. To investigate the role of VraSR in SA skin and soft tissue infections (SSTI), we inactivated the VraSR of a clinical CA-MRSA ST30 strain by insertional mutation in vraR gene using the TargeTron-Gene Knockout System. We constructed an organotypic keratinocyte fibroblast co-culture (3D-skin model) and a humanized mouse as SSTI infection models. In the 3D-skin model, inactivation of VraSR in the strains ST30 and USA300 showed 1-log reduction in adhesion and internalization (p < 0.001) compared to the respective wildtype. The mutant strains of ST30 (p < 0.05) and USA300-LAC (p < 0.001) also exhibited reduced apoptosis. The wildtype ST30 infection in the humanized mouse model demonstrated increased skin lesion size and bacterial burden compared to BALB/c mice (p < 0.01). The response of the humanized mouse towards the MRSA infection exhibited human similarity indicating that the humanized mouse SSTI model is more suitable for evaluating the role of virulence determinants. Inactivation of VraSR in ST30 strain resulted in decreased skin lesion size in the humanized mouse SSTI model (p < 0.05) and reduction in apoptotic index (p < 0.01) when compared with the wildtype. Our results reveal that inactivating the VraSR system may be a potent anti-virulence approach to control MRSA infection. [ABSTRACT FROM AUTHOR]

Complicated skin and soft-tissue infections (cSSTIs) are a significant clinical problem, partially owing to increasing resistance of infecting bacteria to current antibiotic therapies. Two case studies that illustrate complications that can arise when treating cSSTIs are outlined, and methods that can be used to address the problem and the final treatment outcome are detailed. Although these are specific examples, intolerance of and bacterial resistance to current antibacterial therapies are problems that are often seen in the clinical setting and must be addressed appropriately. The use of new antibiotic agents is one potential solution to these problems, and some of these agents are highlighted. Selecting the most appropriate therapy for an infection is often crucial for patient welfare. This article presents some potential approaches to the treatment of cSSTIs. [ABSTRACT FROM AUTHOR]

Abstract: Background: Community-acquired methicillin-resistant Staphylococcus aureus (MRSA) rates are at an all time high. MRSA rates as high as 60% have been reported in patients presenting with skin and soft-tissue infections (SSTIs). Our objectives were to (1) examine the incidence of MRSA over a 7-year period in surgical patients with SSTIs, (2) examine the choice of empiric antibiotic therapy, and (3) evaluate the vancomycin minimum inhibitory concentration (MIC) in MRSA isolates. Methods: The medical records of all patients who underwent operative debridement of SSTIs from 2000 to 2006 were retrospectively reviewed. Demographic data such as age, race, and gender as well as co-morbid risk factors were collected. Preoperative American Society of Anesthesiologists (ASA) score, temperature, WBC, creatinine, HgbA1c, albumin, and empiric antimicrobial of choice were also included. Microbiology of all operative cultures was recorded. Available vancomycin MIC data were collected. All data are presented as mean ± standard error of the mean. A chi-square test was used for statistical analysis. Results: From 2000 to 2006, 288 patients with operative debridement for SSTIs were identified. The mean age was 54 ± 11 years. Fifty-two percent of patients had diabetes mellitus, 55% were tobacco users, 34% alcohol users, and 23% had hepatitis C. The mean temperature at presentation was 99.2° ± 1.5°F. The mean white blood cell count was 13.8 ± .9. The mean HgbA1c was 8.6 ± 2.5. The mean body mass index was 30.1 ± 8. Sixty-seven percent of patients had an ASA ≥ 3. There was a significant increase in MRSA SSTIs in 2006 (77%) compared with 2000 (34%, P < .001). Correspondingly, there was a significant increase in empiric administration of vancomycin in 2006 (93%) compared with 2000 (18%, P < .001). The examination of vancomycin MIC shows a shift for MRSA isolates over this time period (MIC ≤ = .5 μg/mL, 62%, MIC = 1 μg/mL, 7%, and MIC = 2 μg/mL, 31%). Conclusion: Our study shows a significant and ongoing increase in the incidence of MRSA in patients with SSTIs. Empiric coverage with an MRSA antimicrobial should be used as first-line therapy. However, given the observed increase in vancomycin MIC, alternative MRSA antimicrobials should be considered. [Copyright &y& Elsevier]

Three collections of Staphylococcus aureus isolates ( n = 1058) were investigated to assess the spread of Panton–Valentine leukocidin (PVL)-producing strains in Greece and their association with skin and soft-tissue infections (SSTIs). The isolates were collected during 2001–2003 from inpatients and outpatients with invasive infections in two distinct geographical areas. Clonal types were identified according to their ClaI- mecA:: ClaI-Tn 554::pulsed-field gel electrophoresis patterns, and the presence of the lukS-PV and lukF-PV genes was assessed by PCR. In total, 287 (27%) S. aureus isolates carried the PVL genes: 45% of methicillin-resistant S. aureus (MRSA) and 12% of methicillin-sensitive S. aureus (MSSA). All the PVL-positive MRSA isolates belonged to a single clone that was disseminated in the community and hospitals. The PVL-positive MSSA isolates were polyclonal, with 14 of 65 isolates being associated with hospital-acquired infections. The community-acquired isolates were from SSTIs, while the hospital-acquired isolates were associated with surgical wound infections, especially those involving prosthetic devices. Thus, a unique clone of PVL-positive MRSA has spread in both the community and the hospital setting in Greece, and has replaced older clonal types. [ABSTRACT FROM AUTHOR]