Necrotizing Fasciitis Within 72 hours After Presentation with Skin and Skin Structure Infection

Introduction: A small percentage of patients with skin infections later develop necrotizing fasciitis (NF). Diagnostic testing is needed to identify patients with skin infections at low risk of NF who could be discharged from the emergency department (ED) after antibiotic initiation. Elevated lactate has been associated with NF; existing estimates of the frequency of NF are based on retrospective reviews, and cases often lack testing for lactate. We present the incidence of patients with skin infections who developed NF and their baseline lactates.Methods: In four phase-3 trials, 2883 adults with complicated or acute bacterial skin and skin structure infections were randomized to dalbavancin or comparator, with early and late follow-up visits through Day 28. We prospectively collected baseline plasma lactates in one trial to assess an association with NF.Results: NF was diagnosed in 3/2883 patients (0.1%); all three survived. In the study with prospectively collected baseline lactates (n = 622), 15/622 (2.4%) had a lactate ≥4 millimoles per liter (mmol/L), including 3/622 (0.5%) with a lactate ≥7 mmol/L. NF was not seen in patients with a lactate <4 mmol/L; NF was seen in 1/15 (6.7%) with a lactate ≥4 mmol/L, including 1/3 (33.3%) with lactate ≥7 mmol/L.Conclusions: NF incidence within 72 hours of antibiotic initiation in patients with complicated or acute bacterial skin and skin structure infections was extremely low (0.1%) and occurred in 6.7% with a lactate ≥4 mmol/L. Lactate <4 mmol/L can be used to identify patients at low risk of NF who could be safely discharged from the ED after antibiotic initiation

Treatment of acute bacterial skin and skin structure infection with single-dose dalbavancin in persons who inject drugs

Background: Persons who inject drugs (PWID) are at increased risk of acute bacterial skin and skin structure infections (ABSSSIs), a growing healthcare concern. Multiple medical, social, and economic issues, including adherence and comorbidities, complicate the medical care of the PWID population, adversely affecting patient outcomes. Methods: We assessed demographics and outcomes for the PWID population in a double-blind trial of 698 patients randomized to dalbavancin 1500 mg as a single intravenous (IV) infusion or as a 2-dose regimen (1000 mg IV on day 1; 500 mg IV on day 8) for ABSSSI. The primary endpoint was ≥20% reduction in erythema at 48–72 hours in the intent-to-treat population; clinical status was also assessed at days 14 and 28. Results: There were 212/698 (30.4%) patients with a history of injection drug use in this clinical trial. Dalbavancin efficacy was similar between the single- and 2-dose therapy groups in the PWID and non-PWID populations at all timepoints. Dalbavancin was well tolerated in the PWID population, with similar rates of adverse events as the non-PWID population. Conclusion: Dalbavancin as a single-dose or 2-dose regimen had similar efficacy for the treatment of ABSSSI at all timepoints in the PWID and non-PWID populations. A single 30-minute IV infusion would eliminate the need for indwelling IV access. The convenience of a single dose supervised in a health setting may also optimize treatment adherence in the PWID population

The Ability of Virulence Factor Expression by <em>Pseudomonas aeruginosa</em> to Predict Clinical Disease in Hospitalized Patients

<div><h3>Background</h3><p><em>Pseudomonas aeruginosa</em> is an opportunistic pathogen that frequently causes hospital acquired colonization and infection. Accurate identification of host and bacterial factors associated with infection could aid treatment decisions for patients with <em>P. aeruginosa</em> cultured from clinical sites.</p> <h3>Methods</h3><p>We identified a prospective cohort of 248 hospitalized patients with positive <em>P. aeruginosa</em> cultures. Clinical data were analyzed to determine whether an individual met predefined criteria for infection versus colonization. <em>P. aeruginosa</em> isolates were tested for the expression of multiple phenotypes previously associated with virulence in animal models and humans. Logistic regression models were constructed to determine the degree of association between host and bacterial factors with <em>P. aeruginosa</em> infection of the bloodstream, lung, soft tissue and urinary tract.</p> <h3>Results</h3><p>One host factor (i.e. diabetes mellitus), and one bacterial factor, a Type 3 secretion system positive phenotype, were significantly associated with <em>P. aeruginosa</em> infection in our cohort. Subgroup analysis of patients with <em>P. aeruginosa</em> isolated from the urinary tract revealed that the presence of a urinary tract catheter or stent was an additional factor for <em>P. aeruginosa</em> infection.</p> <h3>Conclusions</h3><p>Among hospitalized patients with culture-documented <em>P. aeruginosa,</em> infection is more likely to be present in those with diabetes mellitus and those harboring a Type 3 secretion positive bacterial strain.</p> </div

Clinical criteria for infection based on site of culture.

<p>Clinical criteria for infection based on site of culture.</p

Patient characteristics as a function of colonization vs. infection status.

<p>Patient characteristics as a function of colonization vs. infection status.</p

Parsimonious multivariate analysis of factors associated with risk of <i>P. aeruginosa</i> infection.

<p>Parsimonious multivariate analysis of factors associated with risk of <i>P. aeruginosa</i> infection.</p