Cellulitis in the Emergency Department: A prospective cohort study with patient-centred follow-up.

OBJECTIVE: There is substantial practice variation in the management of cellulitis with limited prospective studies describing the course of cellulitis after diagnosis. We aimed to describe the demographics, clinical features (erythema, warmth, swelling and pain), patient-reported disease trajectory and medium-term follow-up for ED patients with cellulitis. METHODS: Prospective observational cohort study of adults diagnosed with cellulitis in two EDs in Southeast Queensland, Australia. Patients with (peri)orbital cellulitis and abscess were excluded. Data were obtained from a baseline questionnaire, electronic medical records and follow-up questionnaires at 3, 7 and 14 days. Clinician adjudication of day 14 cellulitis cure was compared to patient assessment. Descriptive analyses were conducted. RESULTS: Three-hundred patients (mean age 50 years, SD 19.9) with cellulitis were enrolled, predominantly affecting the lower limb (75%). Cellulitis features showed greatest improvement between enrolment and day 3. Clinical improvement continued gradually at days 7 and 14 with persistent skin erythema (41%) and swelling (37%) at day 14. Skin warmth was the feature most likely to be resolved at each time point. There was a discrepancy in clinician and patient assessment of cellulitis cure at day 14 (85.8% vs. 52.8% cured). CONCLUSIONS: A clinical response of cellulitis features can be expected at day 3 with ongoing slower improvement over time. Over one third of patients had erythema or swelling at day 14. Patients are less likely than clinicians to deem their cellulitis cured at day 14. Future research should include parallel patient and clinician evaluation of cellulitis to help develop clearer definitions of treatment failure and cure.

Restriction of Arginine Induces Antibiotic Tolerance in Staphylococcus aureus.

Staphylococcus aureus is responsible for a substantial number of invasive infections globally each year. These infections are problematic because they are frequently recalcitrant to antibiotic treatment, particularly when they are caused by Methicillin-Resistant Staphylococcus aureus (MRSA). Antibiotic tolerance, the ability for bacteria to persist despite normally lethal doses of antibiotics, is responsible for most antibiotic treatment failure in MRSA infections. To understand how antibiotic tolerance is induced, S. aureus biofilms exposed to multiple anti-MRSA antibiotics (vancomycin, ceftaroline, delafloxacin, and linezolid) were examined using both quantitative proteomics and transposon sequencing. These screens indicated that arginine metabolism is involved in antibiotic tolerance within a biofilm and led to the hypothesis that depletion of arginine within S. aureus communities can induce antibiotic tolerance. Consistent with this hypothesis, inactivation of argH, the final gene in the arginine synthesis pathway, induces antibiotic tolerance under conditions in which the parental strain is susceptible to antibiotics. Arginine restriction was found to induce antibiotic tolerance via inhibition of protein synthesis. Finally, although S. aureus fitness in a mouse skin infection model is decreased in an argH mutant, its ability to survive in vivo during antibiotic treatment with vancomycin is enhanced, highlighting the relationship between arginine metabolism and antibiotic tolerance during S. aureus infection. Uncovering this link between arginine metabolism and antibiotic tolerance has the potential to open new therapeutic avenues targeting previously recalcitrant S. aureus infections.

Shewanella algae bacteraemia in a patient with a chronic ulcer after contact with seawater on vacation in Turkey: A case report from a German maximum-care hospital.

After seawater baths in Antalya, Turkey, a 55-year-old man suffered from Shewanella algae bacteraemia. Imported/travel-related S. algae infections should be kept in mind, also in usually rather cold geographical areas, as patterns of seawater-associated bacilli infections might change due to warming of seawater caused by climate change.

A community-based study of abscess self-treatment and barriers to medical care among people who inject drugs in the United States.

Skin and soft tissue infections (SSTIs) are the most common medical complication of injection drug use in the United States, though little work has been done assessing SSTI treatment among people who inject drugs (PWID). We examined past-3-month abscess characteristics, treatment utilization, and barriers to medical treatment among N = 494 community-recruited PWID. We used descriptive statistics to determine the frequencies of self-treatment and medical treatment for their most recent past-3-month abscess as well as barriers to seeking medical treatment. We then used bivariate and multivariate logistic regression to identify factors associated with having an abscess in the past 3 months. Overall, 67% of participating PWID ever had an abscess and 23% had one in the past 3 months. Only 29% got medical treatment for their most recent abscess whereas 79% self-treated. Methods for self-treatment included pressing the pus out (81%), applying a hot compress (79%), and applying hydrogen peroxide (67%). Most (91%) self-treated abscesses healed without further intervention. Barriers to medical treatment included long wait times (56%), being afraid to go (49%), and not wanting to be identified as a PWID (46%). Factors associated independently with having an abscess in the past 3 months were injecting purposely into muscle tissue (adjusted odds ratio [AOR] = 2.64), having difficulty finding a vein (AOR = 2.08), and sharing injection preparation equipment (AOR = 1.74). Our findings emphasize the importance of expanding community-based access to SSTI education and treatment services, particularly at syringe service programs where PWID may be more comfortable seeking resources.

Comparative Effectiveness Study of Home-Based Interventions to Prevent CA-MRSA Infection Recurrence.

Recurrent skin and soft tissue infections (SSTI) caused by Community-Associated Methicillin-Resistant Staphylococcus aureus (CA-MRSA) or Methicillin-Sensitive Staphylococcus aureus (CA-MSSA) present treatment challenges. This community-based trial examined the effectiveness of an evidence-based intervention (CDC Guidelines, topical decolonization, surface decontamination) to reduce SSTI recurrence, mitigate household contamination/transmission, and improve patient-reported outcomes. Participants (n = 186) were individuals with confirmed MRSA(+)/MSSA(+) SSTIs and their household members. During home visits; Community Health Workers/Promotoras provided hygiene instructions; a five-day supply of nasal mupirocin; chlorhexidine for body cleansing; and household disinfecting wipes (Experimental; EXP) or Usual Care Control (UC CON) pamphlets. Primary outcome was six-month SSTI recurrence from electronic health records (EHR). Home visits (months 0; 3) and telephone assessments (months 0; 1; 6) collected self-report data. Index patients and participating household members provided surveillance culture swabs. Secondary outcomes included household surface contamination; household member colonization and transmission; quality of life; and satisfaction with care. There were no significant differences in SSTI recurrence between EXP and UC in the intent-to-treat cohort (n = 186) or the enrolled cohort (n = 119). EXP participants showed reduced but non-significant colonization rates. EXP and UC did not differ in household member transmission, contaminated surfaces, or patient-reported outcomes. This intervention did not reduce clinician-reported MRSA/MSSA SSTI recurrence. Taken together with other recent studies that employed more intensive decolonization protocols, it is possible that a promotora-delivered intervention instructing treatment for a longer or repetitive duration may be effective and should be examined by future studies.

Staphylococcus aureus Skin and Soft Tissue Infection Recurrence Rates in Outpatients: A Retrospective Database Study at 3 US Medical Centers.

BACKGROUND: Staphylococcus aureus skin and soft tissue infections (SA-SSTIs) are common in healthcare and community settings, and recurrences occur at variable frequency, even after successful initial treatment. Knowing the exact burden and timing of recurrent disease is critical to planning and evaluating interventions to prevent recurrent SSTIs. METHODS: In this retrospective study, SSTI cases in patients aged ≥18 years at 3 US medical centers (Columbia, Chicago, Vanderbilt) between 2006 and 2016 were analyzed according to a biennial cohort design. Index SSTIs (with or without key comorbidities), either microbiologically confirmed to be SA-SSTI or not microbiologically tested (NMT-SSTI), were recorded within 1 calendar year and followed up for 12 months for recurrent infections. The number of index cases, proportion of index cases with ≥1 recurrence(s), time to first recurrence, and number of recurrences were collected for both SA-SSTI and NMT-SSTI events. RESULTS: In the most recent cohorts, 4755 SSTI cases were reported at Columbia, 2873 at Chicago, and 6433 at Vanderbilt. Of these, 452, 153, and 354 cases were confirmed to be due to S. aureus. Most cases were reported in patients without key comorbidities. Across centers, 16.4%-19.0% (SA-SSTI) and 11.0%-19.2% (NMT-SSTI) of index cases had ≥1 recurrence(s). In patients without key comorbidities, more than 60% of index SSTIs with recurrences had only 1 recurrence, half of which occurred in the first 3 months following primary infection. CONCLUSIONS: SA-SSTI recurrences are common among healthy adults and occur in at least 1 in 6 individuals during the 1 year following the primary event.

Obligate anaerobes are abundant in human necrotizing soft tissue infection samples - a metagenomics analysis.

Necrotizing soft tissue infections (NSTIs) are associated with high morbidity and mortality and are increasing in incidence. Proper identification of the microbial causes of NSTIs is a crucial step in diagnosis and treatment, but the majority of data collected are culture based, which is biased against fastidious organisms, including obligate anaerobes. The goal of this study was to address this gap in knowledge by characterizing NSTI microbial communities through molecular diagnostics. We performed 16S rRNA sequencing on human NSTI samples and identified five genera most commonly found in NSTIs (Prevotella, Bacteroides, Peptoniphilus, Porphyromonas, and Enterococcus). We found that a >70% contribution of obligate anaerobes to the bacterial population distribution was associated with NSTI mortality, and that NSTI samples, from both survivors and non-survivors, had an increased relative abundance of gram negative bacteria compared to those of abscess patients. Based on our data, we conclude that obligate anaerobes are abundant in NSTIs and a high relative abundance of anaerobes is associated with a worse outcome. We recommend increasing anaerobe antibiotic coverage during the treatment of NSTIs even when anaerobes are not found by traditional clinical microbiology methods, and especially when there is a clinical suspicion for anaerobe involvement.

Cationic Au(I) complexes with aryl-benzothiazoles and their antibacterial activity.

Two cationic Au(I) complexes derived from aryl-benzothiazoles, namely [(PPh3)Au(pbt)](OTf) (1) and [(PPh3)Au(qbt)](OTf) (2) (where pbt = 2­(pyridyl)benzothiazole and qbt = (quinolyl)benzothiazole, and OTf- = trifluoromethanesulfonate anion), have been synthesized and structurally characterized by X-ray crystallography. Both complexes exhibit strong antibacterial effects against Gram-negative bacteria such as Acinetobacter baumannii and Pseudomonas Aeruginosa. Results of examination of the reactions of 1 and 2 indicate that these cationic Au(I) complexes rapidly cross the bacterial membrane and exert drug action by disrupting cellular function(s) through binding of cytosolic thiol-containing peptides (such as glutathione) and proteins to the highly reactive (PPh3)Au+ intermediate formed upon in situ dissociation of pbt or qbt.

Human Memory B Cells Targeting Staphylococcus aureus Exotoxins Are Prevalent with Skin and Soft Tissue Infection.

Staphylococcus aureus is a Gram-positive opportunistic pathogen that causes superficial and invasive infections in the hospital and community. High mortality from infection emphasizes the need for improved methods for prevention and treatment. Although S. aureus possesses an arsenal of virulence factors that contribute to evasion of host defenses, few studies have examined long-term humoral and B-cell responses. Adults with acute-phase skin and soft tissue infections were recruited; blood samples were obtained; and S. aureus isolates, including methicillin-resistant strains, were subjected to genomic sequence analysis. In comparisons of acute-phase sera with convalescent-phase sera, a minority (37.5%) of patients displayed 2-fold or greater increases in antibody titers against three or more S. aureus antigens, whereas nearly half exhibited no changes, despite the presence of toxin genes in most infecting strains. Moreover, enhanced antibody responses waned over time, which could reflect a defect in B-cell memory or long-lived plasma cells. However, memory B cells reactive with a range of S. aureus antigens were prevalent at both acute-phase and convalescent-phase time points. While some memory B cells exhibited toxin-specific binding, those cross-reactive with structurally related leucocidin subunits were dominant across patients, suggesting the targeting of conserved epitopes. Memory B-cell reactivity correlated with serum antibody levels for selected S. aureus exotoxins, suggesting a relationship between the cellular and humoral compartments. Overall, although there was no global defect in the representation of anti-S. aureus memory B cells, there was evidence of restrictions in the range of epitopes recognized, which may suggest potential therapeutic approaches for augmenting host defenses.IMPORTANCE The contribution of B-cell memory and long-term antibody responses to host defenses against S. aureus exotoxins remains poorly understood. Our studies confirmed that infection did not commonly lead to enhanced long-term humoral responses. Whereas circulating memory B cells against S. aureus secreted exotoxins were prevalent, they were dominated by cross-reactivity with structurally related leucocidin subunits, consistent with recognition of conserved epitopes. These findings also provide the first evidence of a relationship between the reactivity of antistaphylococcal circulating memory B cells and serum antibody levels. In general, infection was not associated with a global defect in B-cell memory for S. aureus secreted factors, and responses were highly dominated by cross-reactivity to structurally related exotoxins, which arguably may alone be suboptimal in providing host defenses. Our studies illuminate aspects of the S. aureus-host relationship that may better inform strategies for the development of an effective protective vaccine.

Current and future treatment options for community-associated MRSA infection.

INTRODUCTION: Community-associated MRSA (CA-MRSA) represents a global epidemic which beautifully encapsulates the fascinating ability of bacterial organisms to adapt quickly on an evolutionary basis to the extreme selective pressure of antibiotic exposure. In stark contrast to Healthcare-associated MRSA (HA-MRSA), it has become apparent that CA-MRSA is less straight forward of a challenge in terms of controlling its transmission, and has forced clinicians to adjust empiric management of clinical syndromes such as skin and soft tissue infection (SSTI) as well as pneumonia. AREAS COVERED: This review details the history and epidemiology of CA-MRSA, while covering both current and future treatment options that are and may be available to clinicians. The authors reviewed both historic and more recent literature on this ever-evolving topic. EXPERT OPINION: While development of new anti-MRSA agents should be encouraged, the importance of antimicrobial stewardship in the battle to stay ahead of the curve with regards to the ongoing control of the MRSA epidemic should be emphasised.

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

To investigate the trends of antimicrobial resistance in pathogens isolated from skin and soft-tissue infections (SSTI) at dermatology departments in Japan, a Japanese surveillance committee conducted the first nationwide survey in 2013. Three main organisms were collected from SSTI at 30 dermatology departments in medical centers and 10 dermatology clinics. A total of 860 strains - 579 of Staphylococcus aureus, 240 of coagulase-negative Staphylococci, and 41 of Streptococcus pyogenes - were collected and shipped to a central laboratory for antimicrobial susceptibility testing. The patient profiles were also studied. Among all 579 strains of S. aureus, 141 (24.4%) were methicillin-resistant (MRSA). Among 97 Staphylococcus epidermidis strains, 54 (55.7%) were methicillin-resistant (MRSE). MRSA and MRSE were more frequently isolated from inpatients than from outpatients. Furthermore, these methicillin-resistant strains were also isolated more frequently from patients with histories of taking antibiotics within 4 weeks and hospitalization within 1 year compared to those without. However, there were no significant differences in MIC values and susceptibility patterns of the MRSA strains between patients with a history of hospitalization within 1 year and those without. Therefore, most of the isolated MRSA cases at dermatology departments are not healthcare-acquired, but community-acquired MRSA. S. pyogenes strains were susceptible to most antibiotics except macrolides. The information in this study is not only important in terms of local public health but will also contribute to an understanding of epidemic clones of pathogens from SSTI.

Differences in prevalence of community-associated MRSA and MSSA among U.S. and non-U.S. born populations in six New York Community Health Centers.

BACKGROUND: Staphylococcus aureus is the most common cause of Skin and Soft Tissue Infections (SSTIs) in the community in the United States of America. Community Health Centers (CHC) serve as primary care providers for thousands of immigrants in New York. METHODS: As part of a research collaborative, 6 New York City-area CHCs recruited patients with SSTIs. Characterization was performed in all S. aureus isolates from wounds and nasal swabs collected from patients. Statistical analysis examined the differences in wound and nasal cultures among immigrant compared to native-born patients. RESULTS: Wound and nasal specimens were recovered from 129 patients and tested for antibiotic susceptibility. 40 patients were immigrants from 15 different countries. Although not statistically significant, immigrants had lower rates of MRSA infections (n = 15) than did native-born participants, and immigrants showed significantly higher rates of MSSA wound cultures (n = 11) (OR = 3.5, 95% CI: 1.3, 9.7). CONCLUSIONS: In our study, immigrants were more likely to present with SSTIs caused by MSSA than US-born patients. Immigants also reported lower frequencies of antibiotic prescription or consumption in the months prior to SSTI infection. This suggests that antibiotic resistance may vary regionally and that immigrants presenting with SSTIs may benefit from a broader range of antibiotics.

Vancomycin Use in Patients Discharged From the Emergency Department: A Retrospective Observational Cohort Study.

BACKGROUND: Infections due to methicillin-resistant Staphylococcus aureus (MRSA) are associated with significant morbidity and mortality and are typically treated with intravenous vancomycin. Given vancomycin's time-dependent mechanism of action, it is unlikely that vancomycin administration in the emergency department (ED) prior to disposition home could be beneficial. STUDY OBJECTIVES: To characterize the indications, dosing, and appropriateness of vancomycin use in patients discharged from the ED. METHODS: This is a single-center retrospective observational cohort study of patients who received vancomycin in an urban, academic, tertiary care ED. The subjects were consecutive adult patients administered intravenous vancomycin in the ED and then discharged home over an 18-month period. Outcomes were measured 1) to characterize patients receiving vancomycin prior to discharge home from the ED; and 2) to identify patients that did not meet indications for appropriate use based on the 2011 Infectious Diseases Society of America guidelines for treating MRSA infections. RESULTS: There were 526 patients that received vancomycin in the ED prior to discharge during the study period. In this cohort, 368 (70%) patients were diagnosed with skin and soft tissue infections. A MRSA risk factor was present in 396 (75%) patients. Prior to discharge, one dose of vancomycin was administered to 357 (68%) patients. Underdosing of vancomycin occurred in 239 (73%) patients. CONCLUSIONS: Vancomycin was given frequently to patients discharged home from the ED, most commonly for conditions where vancomycin was not indicated, such as skin and soft tissue infections. The majority of these patients received a vancomycin dosing strategy that is not only unlikely to lead to clinical improvement, but also has the potential to contribute adversely to the development of antibiotic resistance. Further investigation is needed into the impact of vancomycin use, the emergence of vancomycin resistance, and the role of ED-based antibiotic stewardship.

The shared microbiota of humans and companion animals as evaluated from Staphylococcus carriage sites.

BACKGROUND: Staphylococcus aureus and other coagulase-positive staphylococci (CPS) colonize skin and mucous membrane sites and can cause skin and soft tissue infections (SSTIs) in humans and animals. Factors modulating methicillin-resistant S. aureus (MRSA) colonization and infection in humans remain unclear, including the role of the greater microbial community and environmental factors such as contact with companion animals. In the context of a parent study evaluating the households of outpatients with community MRSA SSTI, the objectives of this study were 1) to characterize the microbiota that colonizes typical coagulase-positive Staphylococcus spp. carriage sites in humans and their companion pets, 2) to analyze associations between Staphylococcus infection and carriage and the composition and diversity of microbial communities, and 3) to analyze factors that influence sharing of microbiota between pets and humans. RESULTS: We enrolled 25 households containing 56 pets and 30 humans. Sampling locations were matched to anatomical sites cultured by the parent study for MRSA and other CPS. Bacterial microbiota were characterized by sequencing of 16S ribosomal RNA genes. Household membership was strongly associated with microbial communities, in both humans and pets. Pets were colonized with a greater relative abundance of Proteobacteria, whereas people were colonized with greater relative abundances of Firmicutes and Actinobacteria. We did not detect differences in microbiota associated with MRSA SSTI, or carriage of MRSA, S. aureus or CPS. Humans in households without pets were more similar to each other than humans in pet-owning households, suggesting that companion animals may play a role in microbial transfer. We examined changes in microbiota over a 3-month time period and found that pet staphylococcal carriage sites were more stable than human carriage sites. CONCLUSIONS: We characterized and identified patterns of microbiota sharing and stability between humans and companion animals. While we did not detect associations with MRSA SSTI, or carriage of MRSA, S. aureus or CPS in this small sample size, larger studies are warranted to fully explore how microbial communities may be associated with and contribute to MRSA and/or CPS colonization, infection, and recurrence.

Lower Limb Infection in an Infant with <i>Haemophilus influenzae</i> Serotype b / General Medicine

We describe a rare case of lower leg infection caused by <i>Haemophilus influenzae</i> serotype b (Hib) in a previously healthy 14-month-old boy. In primary care, <i>H. influenzae</i> is a common pathogen affecting children, and which causes respiratory and central nervous system infection alike. Conversely, skin and soft tissue infections caused by Hib are a somewhat rare occurrence. Beta-lactamase-negative ampicillin-resistant strains have been spreading throughout Japan, although the type of Hib in our case was cephalosporin-sensitive. As a result, we need to pay attention to Hib infection in various clinical settings.

Incidence of Community-associated Methicillin-resistant Staphylococcus aureus Infections in a Regional Hospital.

BACKGROUND AND OBJECTIVE: Since the early 2000s, the incidence of methicillin-resistant Staphylococcus aureus (MRSA) infections among the community of people lacking known healthcare risk factors has increased. This MRSA infection is referred to as community-associated MRSA (CA-MRSA) infection and is distinct from hospital-associated MRSA (HA-MRSA) infection, which occurs among people with known healthcare risk factors. Understanding the epidemiology of CA-MRSA infections is critical; however, this has not been investigated in detail in Japan. Our objective was to investigate the incidence of CA-MRSA infections in a regional hospital. PATIENTS AND METHODS: We investigated CA-MRSA isolates and infections in a rural regional hospital by reviewing medical records of one year. Infections were classified as CA-MRSA if no established risk factors were identified. RESULTS: During 2008, 31 Staphylococcus aureus (S. aureus) isolates were detected in 29 unique patients, with 1 methicillin-sensitive S. aureus (MSSA) isolates obtained from 19 patients (66%) and MRSA obtained from 10 patients (34%). In the 10 patients with MRSA, the number of HA-MRSA and CA-MRSA cases were nine (32% of patients with S. aureus isolates) and one (3%), respectively. The patient with CA-MRSA was diagnosed with cellulitis due to CA-MRSA. All nine patients with HA-MRSA exhibited colonization. CONCLUSION: We observed a CA-MRSA case in a regional hospital in Japan, suggesting that incidence trends of CA-MRSA should be considered in future research and treatment.

Incidence of Community-associated Methicillin-resistant Staphylococcus aureus Infections in a Regional Hospital / Journal of Rural Medicine

<b>Background and Objective:</b> Since the early 2000s, the incidence of methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) infections among the community of people lacking known healthcare risk factors has increased. This MRSA infection is referred to as community-associated MRSA (CA-MRSA) infection and is distinct from hospital-associated MRSA (HA-MRSA) infection, which occurs among people with known healthcare risk factors. Understanding the epidemiology of CA-MRSA infections is critical; however, this has not been investigated in detail in Japan. Our objective was to investigate the incidence of CA-MRSA infections in a regional hospital. <BR><b>Patients and Methods:</b> We investigated CA-MRSA isolates and infections in a rural regional hospital by reviewing medical records of one year. Infections were classified as CA-MRSA if no established risk factors were identified. <BR><b>Results:</b> During 2008, 31 <i>Staphylococcus aureus</i> (<i>S. aureus</i>) isolates were detected in 29 unique patients, with 1 methicillin-sensitive <i>S. aureus</i> (MSSA) isolates obtained from 19 patients (66%) and MRSA obtained from 10 patients (34%). In the 10 patients with MRSA, the number of HA-MRSA and CA-MRSA cases were nine (32% of patients with <i>S. aureus</i> isolates) and one (3%), respectively. The patient with CA-MRSA was diagnosed with cellulitis due to CA-MRSA. All nine patients with HA-MRSA exhibited colonization. <BR><b>Conclusion:</b> We observed a CA-MRSA case in a regional hospital in Japan, suggesting that incidence trends of CA-MRSA should be considered in future research and treatment.