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

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

Haemolysin Ahh1 secreted from Aeromonas dhakensis activates the NLRP3 inflammasome in macrophages and mediates severe soft tissue infection.

Severe soft tissue infections caused by Aeromonas dhakensis, such as necrotizing fasciitis or cellulitis, are prevalent in southern Taiwan and around the world. However, the mechanism by which A. dhakensis causes tissue damage remains unclear. Here, we found that the haemolysin Ahh1, which is the major virulence factor of A. dhakensis, causes cellular damage and activates the NLR family pyrin domain containing 3 (NLRP3) inflammasome signalling pathway. Deletion of ahh1 significantly downregulated caspase-1, the proinflammatory cytokine interleukin 1ß (IL-1ß) and gasdermin D (GSDMD) and further decreased the damage caused by A. dhakensis in THP-1 cells. In addition, we found that knockdown of the NLRP3 inflammasome confers resistance to A. dhakensis infection in both THP-1 NLRP3-/- cells and C57BL/6 NLRP3-/- mice. In addition, we demonstrated that severe soft-tissue infections treated with antibiotics combined with a neutralizing antibody targeting IL-1ß significantly increased the survival rate and alleviated the degree of tissue damage in model mice compared control mice. These findings show that antibiotics combined with therapies targeting IL-1ß are potential strategies to treat severe tissue infections caused by toxin-producing bacteria.

Cellulitis caused by Roseomonas mucosa in a child: a case report.

BACKGROUND: Roseomonas mucosa (R. mucosa) is a pink-pigmented, Gram-negative short rod bacterium. It is isolated from moist environments and skin, resistant to multiple drugs, including broad-spectrum cephalosporins, and a rare cause of infection with limited reports. R. mucosa mostly causes catheter-related bloodstream infections, with even fewer reports of skin and soft tissue infections. CASE PRESENTATION: A 10-year-old boy received topical steroid treatment for sebum-deficient eczema. A few days before the visit, he was bitten by an insect on the front of his right lower leg and scratched it due to itching. The day before the visit, redness, swelling, and mild pain in the same area were observed. Based on his symptoms, he was diagnosed with cellulitis. He was treated with sulfamethoxazole/trimethoprim, and his symptoms improved. Pus culture revealed R. mucosa. CONCLUSIONS: We report a rare case of cellulitis caused by R. mucosa. Infections caused by rare organisms that cause opportunistic infections, such as R. mucosa, should be considered in patients with compromised skin barrier function and regular topical steroid use. Gram stain detection of organisms other than Gram-positive cocci should be considered.

Case Commentary: Another prong of attack? Topical antibiotic instillation with negative pressure wound therapy for nontuberculous mycobacterial skin and soft tissue infections.

Nontuberculous mycobacteria (NTM) skin infections remain therapeutically challenging. Given the diversity in infections, host responses, and antimicrobials, clinical guidelines are often built on case series and observational studies. In this commentary, we respond to a paper by Stemkens et al. that introduces an emerging strategy: adjunctive negative pressure wound therapy with instillation and dwell time combined with topical antibiotics for refractory NTM skin and soft tissue infections. We delve into the primary considerations surrounding this innovative approach.

Skin and soft tissue infection incidence before and during the COVID-19 pandemic.

Skin and Soft Tissue Infections (SSTIs) are common bacterial infections. We hypothesized that due to the COVID-19 pandemic, SSTI rates would significantly decrease due to directives to avoid unneeded care and attenuated SSTIs risk behaviours. We retrospectively examined all patients with an ICD-10 diagnosis code in the Los Angeles County Department of Health Services, the second largest U.S. safety net healthcare system between 16 March 2017 and 15 March 2022. We then compared pre-pandemic with intra-pandemic SSTI rates using an interrupted time series analysis. We found 72,118 SSTIs, 46,206 during the pre-pandemic period and 25,912 during the intra-pandemic period. Pre-pandemic SSTI rate was significantly higher than the intra-pandemic rate (3.27 vs. 2.31 cases per 1,000 empanelled patient-months, P < 0.0001). The monthly SSTI cases decreased by 1.19 SSTIs/1,000 empanelled patient-months between the pre- and intra-pandemic periods (P = 0.0003). SSTI subgroups (inpatient, observation unit, emergency department, and outpatient clinics), all had significant SSTI decreases between the two time periods (P < 0.05) except for observation unit (P = 0.50). Compared to the pre-COVID-19 pandemic period, medically attended SSTI rates in our large U.S. safety net healthcare system significantly decreased by nearly 30%. Whether findings reflect true SSTI decreases or decreased health system utilization for SSTIs requires further examination.

Antimicrobial treatment of skin and soft tissue infections.

Bacterial skin infections are common in children, and frequently do not require systemic antibiotic therapy, particularly for superficial forms. In these cases, washing (with soap and water) and careful rinsing of the lesion are the key points of treatment. A semiotic analysis must precede any therapeutic decision to assess the appropriateness of antibiotic therapy, need for drainage (which may be spontaneous or surgical) and possible existence of symptoms related to toxin production, which are frequent signs of severity. The bacterial species most frequently implicated in children are Staphylococcus aureus and Streptococcus pyogenes. Given the low incidence of methicillin-resistant S. aureus in France (<10%), the first-line antibiotic treatment is amoxicillin-clavulanate, to which an anti-toxin treatment such as clindamycin may be added for patients with overt toxin signs.

Streptococcal pharyngitis in a Child, Complicated with a Necrotizing Myositis: Diagnosis, Management and Follow-Up.

BACKGROUND Group A streptococcus is a common cause of pharyngitis and can also cause a wide variety of invasive infections, including necrotizing soft-tissue infections. The presented case is one of the rare occurrences of necrotizing soft-tissue infection as a consequence of hematogenous spread and is the first described pediatric case of streptococcal myositis that was clearly preceded by pharyngitis. CASE REPORT A 2.5-year-old boy, previously healthy, fell ill 3 days before admission with high-grade fever, diffuse erythematous truncal rash and, later, with pain in the left lower leg. The next day, scarlet fever was diagnosed, and he was started on oral penicillin V. In the following 2 days, the fever and pain in the leg did not subside; edema and redness of the left shin appeared. On admission, he was febrile and had tachycardia, and the mouth examination was consistent with bacterial pharyngitis. The left shin was grossly edematous, with diffuse bluish skin discoloration. Empiric antibiotic treatment with benzylpenicillin and clindamycin was started. An ultrasound scan of the left shin revealed extensive myonecrosis. Urgent fasciotomy was done, and necrotic muscles were surgically excised. CONCLUSIONS Streptococcal necrotizing myositis is exceedingly rare. Due to potentially life-threatening complications and a need for urgent surgical intervention, clinicians must have a low threshold of suspicion, even in atypical pathogenesis and presentation.

Functionalized Rhodium Nanoparticles as Antimicrobial Agents for Treatment of Drug-Resistant Skin and Soft Tissue Infections.

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

[Invasive group A streptococcal infections in the Netherlands]. / Invasieve groep A-streptokokkeninfecties in Nederland.

Group A streptococcal (GAS) infections are caused by the Gram-positive bacterium Streptococcus pyogenes. Infection can occur via droplet infection from the throat and via (in)direct contact with infected people. GAS can cause a wide variety of diseases, ranging from superficial skin infections, pharyngitis and scarlet fever, to serious invasive diseases such as puerperal sepsis, pneumonia, necrotising soft tissue infections (NSTI) (also known as necrotising fasciitis/myositis), meningitis and streptococcal toxic shock syndrome (STSS). In invasive GAS infections, the bacteria has penetrated into a sterile body compartment (such as the bloodstream, deep tissues, or the central nervous system). Invasive GAS infections are rare but serious, with high morbidity and mortality. Since March 2022, the National Institute for Public Health and the Environment (RIVM) reported a national increase in notifiable invasive GAS infections (NSTI, STSS and puerperal fever). Particularly NSTI has increased compared to the years before the SARS-CoV-2 pandemic. Remarkably, the proportion of children aged 0 to 5 years with invasive GAS-infections is higher in 2022 than in the previous years (12% compared to 4%). While seasonal peaks occur, the current elevation exceeds this variation. To promote early recognition and diagnosis of invasive GAS infections different clinical cases are presented.

Pharmacokinetics of intravenous daptomycin in Japanese pediatric patients: Pharmacokinetic comparisons supporting dosing recommendations in Japanese pediatric patients.

INTRODUCTION: The pharmacokinetics (PK) of daptomycin has not been previously characterized in Japanese pediatric patients with complicated skin and soft tissue infections (cSSTI) or bacteremia. An aim of the study includes evaluation of PK of daptomycin in Japanese pediatric patients and an appropriateness of the age-specific, weight-based dosing regimens in Japanese pediatric patients based on PK comparison with Japanese adult patients. METHODS: The phase 2 trial enrolled Japanese pediatric patients (age 1-17 years) with cSSTI (n = 14) or bacteremia (n = 4) caused by gram-positive cocci in order to evaluate safety, efficacy and PK. The Phase 3 trial in Japanese adult patients (SSTI n = 65, septicemia/right-sided infective endocarditis (RIE) n = 7) was referred to for PK comparison between adult and pediatric. Daptomycin concentrations in plasma were analyzed by reverse-phase high-performance liquid chromatography (HPLC). PK parameters were determined using non-compartmental analysis in Japanese pediatric and Japanese adult patients. The exposures in Japanese pediatric patients were graphically compared with those in Japanese adult patients. The relationship between daptomycin exposures and creatine phosphokinase (CPK) elevation was explored visually. RESULTS: Following administration of the age-specific, weight-based dosing regimens, daptomycin exposures were overlapping across age groups in pediatric patients with cSSTI with similar observations based on clearance. The distribution of individual exposure in Japanese pediatric patients was overlapping with that in Japanese adult patients. No apparent relationship between daptomycin exposures and CPK elevation in Japanese pediatric patients was observed. CONCLUSIONS: The results suggested that the age-specific, weight-based dosing regimens are considered to be appropriate in Japanese pediatric patients.

Microbiology of Facial Skin Infections-Strains, Susceptibility, and Therapeutic Consequences.

BACKGROUND: Skin and soft tissue infections (SSTIs) are common conditions with severe and potentially life-threatening outcomes. However, the use of antibiotics to treat these infections is controversial. PURPOSE: This study was to identify the microorganisms responsible for facial SSTIs, their antibiotic sensitivities, and the therapeutic outcomes of treatment. STUDY DESIGN, SETTING, AND SAMPLE: This was a retrospective, observational cohort study conducted at a single oral and maxillofacial plastic surgery department. The study sample included 103 patients with facial SSTIs (61 men, 42 women) with a mean age of 41.8 years (standard deviation ± 20.4). PREDICTOR/EXPOSURE/INDEPENDENT VARIABLES: The predictor variables included patient characteristics, antibiotic use before the clinic visit, and the infection's site and origin. MAIN OUTCOME VARIABLE(S): The primary outcome variable was the presence of antibiotic resistance in the bacterial strains isolated from the infections. METHODS: The data were collected by reviewing the results of microbiological swabs and patient records obtained from patients with facial SSTIs. Categorical variables were described using absolute and relative frequencies, and continuous variables were described using mean and standard deviation. The association between antibiotic resistance and the predictor variables was analyzed using Pearson's χ2 test and student's t test. RESULTS: The most common cause of SSTI was an infected epidermal cyst (60.1%). Of all the microorganisms identified, 80.6% were Gram-positive, and 55.8% showed antibiotic resistance against one or more of the evaluated antibiotics, including several backup antibiotics. There were no identified risk factors that significantly influenced the probability of resistance, and there were no adverse events observed. CONCLUSION: The results of this study suggest that surgery should be the primary approach for treating SSTIs, as antibiotic administration may not be effective due to the unknown susceptibility of the causative strains. Antibiotics should be reserved for severe cases and high-risk patients, and if deemed necessary for SSTI management, a broad-spectrum antibiotic should be administered to cover resistant organisms.

Rapid diagnostics for skin and soft tissue infections: the current landscape and future potential.

PURPOSE OF REVIEW: Managing antimicrobial therapy in patients with complicated skin and soft tissue infections (SSTI) constitutes a growing challenge due to the wide spectrum of potential pathogens and resistance phenotypes. Today, microbiological documentation relies on cultural methods. This review summarizes the available evidence regarding the clinical input of rapid microbiological diagnostic tools (RMDT) and their impact on the management of antimicrobial therapy in SSTI. RECENT FINDINGS: Accurate tools are already available for the early detection of methicillin-resistant Staphylococcus aureus (MRSA) in SSTI samples and may help avoiding or shortening empirical anti-MRSA coverage. Further research is necessary to develop and evaluate RMDT detecting group A streptococci (e.g., antigenic test) and Gram-negative pathogens (e.g., multiplex PCR assays), including through point-of-care utilization. Next-generation sequencing (NGS) methods could provide pivotal information for the stewardship of antimicrobial therapy, especially in case of polymicrobial or fungal SSTI and in the immunocompromised host; however, a shortening in the turnaround time and prospective data regarding their therapeutic input are needed to better appraise the clinical positioning of these promising approaches. SUMMARY: The clinical input of RMDT in SSTI is currently limited due to the scarcity of available dedicated assays and the polymicrobial feature of certain cases. NGS appears as a relevant tool but requires further developments before its implementation in routine clinical practice.

The second nationwide surveillance of antibacterial susceptibility patterns of pathogens isolated from skin and soft-tissue infections in dermatology departments in Japan.

The present study compared trends in antimicrobial resistance patterns in pathogens isolated from skin and soft-tissue infections (SSTIs) in Japan with those of a nationwide survey conducted in 2013. Three organisms that caused most of the SSTIs were collected from 12 dermatology departments in medical centers and 12 dermatology clinics across Japan between April 2019 and August 2020. A total of 390 strains, including 267 Staphylococcus aureus, 109 coagulase-negative staphylococci (CNS), and 14 Streptococcus pyogenes strains were submitted to a central laboratory for antimicrobial susceptibility testing. Patient demographic and clinical information was collated. Methicillin-resistant S. aureus (MRSA) was detected in 25.8% (69/267) of the S. aureus strains. The prevalence of MRSA between the present study and the 2013 survey did not differ significantly. Furthermore, there were no significant differences in MIC values and susceptibility patterns of the MRSA strains to other agents, regardless of a history of hospitalization within 1 year or invasive medical procedures. Methicillin-resistant CNS (MRCNS) was detected in 48.6% (53/109) of CNS isolates, higher than the 35.4% prevalence in the 2013 survey. This difference could be attributed to the heterogeneity in the members of the MRCNS, which comprises multiple staphylococci species, between the 2013 and 2019 surveys. However, it was noted that the susceptibility profiles of the MRCNS to each antibiotic were not significantly different from those identified in the 2013 survey. Most strains of S. pyogenes were susceptible to each antibiotic, similar to the 2013 survey. Continuous monitoring of trends in pathogen and susceptibility profiles is important to advise local public health efforts regarding the appropriate treatment of SSTIs.

[Vibrio vulnificus infection of the skin and soft parts. Communication of a case diagnosed in Argentina]. / Infección de piel y partes blandas por Vibrio vulnificus. Comunicación de un caso diagnosticado en Argentina.

Vibrio vulnificus is one of the most virulent Vibrio species known. It is a bacterium with universal distribution. The first case registered in Uruguay occurred in 2001 and, since then, several infections have occurred per year. Recently, in this country, V. vulnificus was responsible for a fatal soft tissue infection. Although no cases of human infection with this species have been reported in Argentina, researchers have recently identified V. vulnificus in samples associated with microplankton in the Rio Negro estuary. We present the case of a severe skin and soft tissue infection by V. vulnificus from an open wound in a patient in contact with a marine aquatic environment on the coast of the River Plate, in Uruguay. Isolation of vibrios from wound specimens can cause rapidly progressing tissue damage, particularly V. vulnificus which has a high mortality rate without early and appropriate intervention. In our case, the rapid identification of the microorganism allowed us to support the empirical treatment used, which a good clinical evolution.

Vibrio vulnificus es una de las especies de Vibrio más virulentas que se conocen. Es una bacteria de distribución universal. El primer caso registrado en Uruguay se produjo en 2001, y desde entonces ocurren varias infecciones por año. Recientemente, en ese país, V. vulnificus fue responsable de una infección de partes blandas de curso letal. Aunque no han sido comunicados casos de infección humana por esta especie en Argentina, se ha identificado recientemente Vibrio vulnificus en muestras asociadas con microplancton en el estuario del Río Negro. Presentamos el caso de una infección grave de piel y partes blandas por V. vulnificus a partir de una herida abierta en un paciente en contacto con medio acuático marino en la costa de Uruguay del Río de la Plata. El aislamiento de vibrios en muestras de heridas puede causar un daño en los tejidos con rápida progresión, en particular V. vulnificus, que tiene una alta mortalidad sin la precoz y apropiada intervención. En nuestro caso, la rápida identificación del microorganismo permitió avalar el tratamiento empírico utilizado, con una buena evolución clínica.

ICU Management of Invasive ß-Hemolytic Streptococcal Infections.

ß-hemolytic streptococci (BHS) are a leading cause of invasive bacterial disease worldwide. They are subtyped based on the presence of the surface polysaccharide antigens and include Group A Streptococcus (GAS; Streptococcus pyogenes), Group B Streptococcus (GBS; Streptococcus agalactiae), and non-group A, non-group B Streptococci (NABS). Invasive BHS infection is defined as isolation from the normally sterile site in patients with a compatible clinical syndrome which include, but is not limited to, streptococcal toxic shock syndrome (STSS), Necrotizing soft tissue infection (NSTI), bacteremia, meningitis lower respiratory tract, musculoskeletal and puerperal/postpartum infections. Resuscitation, source control, and ß-lactam therapy are the cornerstone of therapy.

Frequency and Antibiotic Susceptibility Pattern of Community-associated Methicillin-resistant Staphylococcus Aureus (CA-MRSA) in Uncomplicated Skin and Soft Tissue Infections.

OBJECTIVE: To determine the frequency and antibiotic susceptibility pattern of CA-MRSA in patients with uncomplicated skin and soft tissue infections reporting to the dermatology outpatient of a tertiary health care hospital. STUDY DESIGN: A descriptive study. PLACE AND DURATION OF STUDY: Dermatology outpatient of a tertiary care hospital in Punjab province of Pakistan, from September 2020 to August 2021. METHODOLOGY: Patients of all age groups and both genders reporting during the study period with community-associated uncomplicated bacterial skin and soft tissue infections were enrolled in the study. Samples were collected from skin lesions and cultured on blood agar and MacConkey agar plates. Antimicrobial susceptibility testing using the modified Kirby Baur disc diffusion technique was performed. RESULTS: A total of 157 patients were included in the study. Impetigo was most common infection (n=80, 51%), followed by Furunculosis (n=47, 29.9%). The frequency of MRSA isolates was 54.1% (n=85). MRSA was significantly more frequently isolated from patients with furunculous, carbuncle and cutaneous abscesses as compared to impetigo. All MRSA isolates were sensitive to linezolid, teicoplanin, and vancomycin. 97.6%, 84.7%, and 72.9% of MRSA isolates were sensitive to rifampicin, minocycline, and fusidic acid respectively. 89.4% of MRSA were sensitive to amikacin and clindamycin. 63.5% were sensitive to doxycycline and 58.8% were sensitive to co-trimoxazole. Only 20% of MRSA were sensitive to ciprofloxacin. CONCLUSION: The antibiotics active against CA-MRSA including rifampicin, minocycline, amikacin, and clindamycin may be used empirically in patients with furunculosis, cutaneous abscess, and carbuncles. Linezolid, teicoplanin, and vancomycin should be reserved for severe infections. KEY WORDS: Uncomplicated skin and soft tissue infections, Community-associated Methicillin-resistant staphylococcus aureus (CA-MRSA), Antibiotic susceptibility pattern.

Clinical Diagnosis, Management and Microbiological Profiling of Necrotizing Soft Tissue Infections - A Prospective Study of North India Region.

Background: Necrotizing Soft Tissue Infections (NSTIs) are rapidly progressive, potentially fatal illnesses characterized by necrosis of soft tissue. The disease is highly lethal if left untreated. However, its early diagnosis and management can result in significant decrease in mortality, saving the life of patient and preventing limb loss ; but its diagnosis in early stage is difficult. Therefore, the present work describes a step-by-step protocol for early diagnosis of NSTIs and its application for successful management of NSTIs (type III) in the North Indian population. Methods: This prospective study was conducted over a period of 1 year and 9 months (December 2017 to September, 2019) in a single tertiary center (Dayanand Medical College and Hospital, Ludhiana, Punjab, India) with 115 patients suffering from NSTIs. Demographic, symptomatic and clinical features were recorded. After initial resuscitation, debridement or amputation was done and collected samples were subjected to microbial profiling and drug sensitivity tests. Based on results, suitable pharmacological treatment was started to minimize the risk of mortality and fasten the recovery of patient. Results: The present work showed that in the selected population, monomicrobial gram negative infections are more prominent, more so, among diabetic males. The most prominent pathogen was found to be "Escherichia coli" (40% of cases). Enrolled patients had NSTIs in stage 1 and had no blood infection which means they sought medical attention in the early stages of the disease and the clinician was able to detect it. Debridement or amputation resulted in a significant decrease in the mortality rate (10.4%) even when the selected population had lethal Type III NSTIs. Conclusion: The presented approach can aid in early detection and management of NSTIs, thus, helping in saving patient's life and limb.

Extensive Subcutaneous Abscess due to Panton-Valentine Leucocidin-Positive Community-Associated Methicillin-Resistant Staphylococcus aureus in an Infant.

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections have increased worldwide in people without underlying diseases. CA-MRSA can often cause serious bacterial infections, especially skin and soft tissue infections (SSTI). Here, we describe a case of severe subcutaneous abscess due to Panton-Valentine leucocidin (PVL)-positive CA-MRSA in an infant without underlying diseases. A 4-month-old girl presented with a 4-day history of fever, with extensive redness and swelling of the lumbar region and buttocks. She was diagnosed with extensive subcutaneous abscess of the lumbar region and buttocks. Surgical drainage was performed, and a substantial volume of pus was drained. MRSA was detected in the pus on culture. Antibiotic therapy that covered MRSA was also administered for 3 weeks, and the abscess healed. As it was a severe SSTI due to MRSA, analysis of MRSA revealed PVL-positive MRSA. This patient had no underlying disease or history of antibiotic administration, and as MRSA was present in the nasopharyngeal cavity, it was considered a case of CA-MRSA. Furthermore, the prevalence of PVL-positive CA-MRSA in MRSA isolated from patients with SSTI has also increased in Japan. The Infectious Diseases Society of America recommends surgical intervention and empirical antibiotic therapy for MRSA-complicated SSTI cases in an era of CA-MRSA. Pediatricians must strongly consider the possibility of MRSA in children with severe SSTIs.

The phenomenon of staphylococcal interbacterial aggregate and net structures (SIAN) in community-associated methicillin-resistant Staphylococcus aureus CA-MRSA/J.

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) usually causes skin and soft tissue infections (SSTIs), but occasionally causes invasive infections with a broad range of manifestations. Virulence factors and pathogenesis of CA-MRSA have been investigated in details with genotype ST8/SCCmecIVa (USA300), which first emerged in the United States. However, CA-MRSA evolves rapidly, with different clones dominating in different world regions; their pathogenesis remains unclear. CA-MRSA with genotype ST8/SCCmecIVl (CA-MRSA/J) emerged in 2003 in Japan, spreading widely with a fatal case. We have studied the genetic characteristics of CA-MRSA/J, and during the course of this study, we found that CA-MRSA/J has bacteriophage-like spikes with or without a hexagonal cap (spikes X and Xc). Here, we report that CA-MRSA/J strain NN55 has non-phage-like, one-µm-long/jerky spikes with or without a hexagonal cap (LSX/LSXc), and also that LSX/LSXc forms (staphylococcal) interbacterial aggregate/net structures (SIAN). Regarding the phenomenon of SIAN, NN55 first formed single short spike X, followed by multiple molecules of long and jerky LSX/LSXc, leading to the interbacterial construction of SIAN, in colonies with high cell densities. The LSX/LSXc and SIAN structures have not been reported in S. aureus. NN55 was invasive in a HEp-2 cell assay, exhibiting SIAN. The novel SIAN structures may be foci-skeletons or toxic aggregates in NN55's invasive infections. The phenomenon of SIAN suggests novel staphylococcal cell-surface dynamism, providing a new structure-and-function relationship model and advancing the understanding of CA-MRSA pathogenesis.

Regional Variations in Microbiology and Outcomes of Necrotizing Soft Tissue Infections: A Systematic Review and Meta-Analysis.

Background: Frequency, microbiology, and outcomes of necrotizing soft tissue infections (NSTIs) could vary across the United States because of differences in locoregional and environmental factors. We synthesized the literature from across the regions of the United States on NSTIs in a systematic review/meta-analysis. Methods: PubMed, ProQuest, Scopus, and Web of Science databases were systematically searched and screened. DerSimonian-Laird random-effects meta-analyses were performed using 'meta' package in R to determine pooled prevalences. Meta-regression analyses examined moderator effects of risk factors. Results: Twenty-seven studies (2,242 total patients) were included. Pooled prevalences of polymicrobial and monomicrobial infections were 52.2% and 39.9%, respectively. The prevalence of monomicrobial NSTIs increased over the last two decades (p = 0.018), whereas polymicrobial infections declined (p = 0.003). Meta-regression analysis showed that most polymicrobial NSTIs were Fournier gangrene (p < 0.001), whereas monomicrobial NSTIs mostly affected extremities (p < 0.001). Staphylococcus aureus was the most common organism isolated (predominantly in the South), followed by Bacteroides spp. (predominately in the East) and Streptococcus pyogenes. Methicillin-resistant Staphylococcus aureus (MRSA) accounted for 11.9% of NSTIs, mainly in the South. The overall mortality rate was 17.8% and declined over last two decades (p < 0.001), with the lowest rate reported in the last decade at 13% without any regional differences. Conclusions: Advancement in the management of NSTIs may have contributed to the observed decline in NSTI-related mortality in the United States. However, the proportion of monomicrobial NSTIs seems to be increasing, possibly because of increased comorbidities affecting extremities. Causative organisms varied by region. Multi-center observational studies are warranted to confirm our observations.