The pathogenic bacterium Staphylococcus aureus is the most common pathogen isolated in skin-and-soft-tissue infections (SSTIs) in the United States. Most S. aureus SSTIs are caused by the epidemic clone USA300 in the USA. These infections can be serious; in 2019, SSTIs with S. aureus were associated with an all-cause, age-standardized mortality rate of 0.5 globally. Clinical presentations of S. aureus SSTIs vary from superficial infections with local symptoms to monomicrobial necrotizing fasciitis, which can cause systemic manifestations and may lead to serious complications or death. In order to cause skin infections, S. aureus employs a host of virulence factors including cytolytic proteins, superantigenic factors, cell wall-anchored proteins, and molecules used for immune evasion. The immune response to S. aureus SSTIs involves initial responders such as keratinocytes and neutrophils, which are supported by dendritic cells and T-lymphocytes later during infection. Treatment for S. aureus SSTIs is usually oral therapy, with parenteral therapy reserved for severe presentations; it ranges from cephalosporins and penicillin agents such as oxacillin, which is generally used for methicillin-sensitive S. aureus (MSSA), to vancomycin for methicillin-resistant S. aureus (MRSA). Treatment challenges include adverse effects, risk for Clostridioides difficile infection, and potential for antibiotic resistance.

An important limitation of traditional clinical guidelines is the frequent dissociation between quality of evidence and strength of recommendations.^1-6 As a result, some past guideline recommendations have endorsed harmful care, which was only subsequently recognized when high-quality, prospective controlled trials were conducted.⁷ To overcome this limitation, we developed a novel approach, called WikiGuidelines, to establish clear recommendations only when high-quality, hypothesis-confirming evidence is available (see group charter in Supplement 1).

The Centers for Disease Control and Prevention has promoted the appropriate use of antibiotics since 1995 when it initiated the National Campaign for Appropriate Antibiotic Use in the Community. This study examined upper respiratory tract infections included in the campaign to determine the degree to which antibiotics were appropriately prescribed and subsequent admission rates in a veteran population. This study was a retrospective chart review conducted among outpatients with a diagnosis of a respiratory tract infection, including bronchitis, pharyngitis, sinusitis, or nonspecific upper respiratory tract infection, between January 2009 and December 2011. The study found that 595 (35.8%) patients were treated appropriately, and 1,067 (64.2%) patients received therapy considered inappropriate based on the Get Smart Campaign criteria. Overall the subsequent readmission rate was 1.5%. The majority (77.5%) of patients were prescribed an antibiotic. The most common antibiotics prescribed were azithromycin (39.0%), amoxicillin-clavulanate (13.2%), and moxifloxacin (7.5%). A multivariate regression analysis demonstrated significant predictors of appropriate treatment, including the presence of tonsillar exudates (odds ratio [OR], 0.6; confidence interval [CI], 0.3 to 0.9), fever (OR, 0.6; CI, 0.4 to 0.9), and lymphadenopathy (OR, 0.4; CI, 0.3 to 0.6), while penicillin allergy (OR, 2.9; CI, 1.7 to 4.7) and cough (OR, 1.6; CI, 1.1 to 2.2) were significant predictors for inappropriate treatment. Poor compliance with the Get Smart Campaign was found in outpatients for respiratory infections. Results from this study demonstrate the overprescribing of antibiotics, while providing a focused view of improper prescribing. This article provides evidence that current efforts are insufficient for curtailing inappropriate antibiotic use.

BACKGROUND: The risk of vancomycin-associated nephrotoxicity varies greatly depending on the trough concentration. Recent guidelines suggest target vancomycin trough concentrations of 15–20 mg/L as a predictor of efficacy in the treatment of severe gram-positive infections. Limited data exist quantifying the risk for nephrotoxicity with various ranges of vancomycin troughs. OBJECTIVE: To determine the occurrence of nephrotoxicity during vancomycin therapy and up to 72 hours after its completion, in relation to the maximum trough concentration value, and identify risk factors that impact nephrotoxicity associated with vancomycin use. METHODS: We reviewed the medical records of veterans with a baseline serum creatinine less than 2 mg/dL who received 48 or more hours of vancomycin therapy and had 1 or more vancomycin trough samples obtained within 96 hours of therapy initiation from January 1, 2006, to November 1, 2008, to determine the occurrence of nephrotoxicity (as defined by RIFLE [Risk, Injury, Failure, Loss, and End-stage renal disease] criteria). RESULTS: Thirty-four (12.6%) patients developed nephrotoxicity. In multiple logistic regression analysis, maximum trough concentrations (OR 1.14; 95% CI 1.09 to 1.20), documented hypotension (OR 4.7; 95% CI 1.3 to 16.4), and weight (OR 1.02; 95% CI 1.0 to 1.03) were found to be significantly associated with the occurrence of nephrotoxicity. Once stratified into ranges of 5–10 mg/L (4.9%), 10.1–15 mg/L (3.1%), 15.1–20 mg/L (10.6%), 20.1–35 mg/L (23.6%), and greater than 35 mg/L (81.8%), increasing trough ranges were associated with a subsequently higher risk of nephrotoxicity. CONCLUSIONS: In the population evaluated, hypotension and trough concentrations were predictors of nephrotoxicity; elevated vancomycin trough concentration had the highest odds of association. These data reinforce the close therapeutic monitoring guidelines for vancomycin trough concentrations, especially when targeting troughs of 15–20 mg/L.