The pathogenesis of infection is a continuously evolving battle between the human host and the infecting microbe. The past decade has brought a burst of insights into the molecular mechanisms of innate immune responses to bacterial pathogens. In parallel, multiple specific mechanisms by which microorganisms subvert these host responses have been uncovered. This Review highlights recently characterized mechanisms by which bacterial pathogens avoid killing by innate host responses, including autophagy pathways and a proinflammatory cytokine transcriptional response, and by the manipulation of vesicular trafficking to avoid the toxicity of lysosomal enzymes.
Warmth is a characteristic but nondiagnostic feature of cellulitis. We assessed the diagnostic utility of skin surface temperature in differentiating cellulitis from pseudocellulitis. Adult patients presenting to the emergency department of a large urban hospital with presumed cellulitis were enrolled. Patients were randomized to dermatology consultation (n = 40) versus standard of care (n = 32). Thermal images of affected and unaffected skin were obtained for each patient. Analysis was performed on dermatology consultation patients to establish a predictive model for cellulitis, which was then validated in the other cohort. Of those evaluated by dermatology consultation, pseudocellulitis was diagnosed in 28%. Cellulitis patients had an average maximum affected skin temperature of 34.1°C, which was 3.7°C warmer than the corresponding unaffected area (95% confidence interval = 2.7-4.8°C, P < 0.00001). Pseudocellulitis patients had an average maximum affected temperature of 31.5°C, which was 0.2°C warmer than the corresponding unaffected area (95% confidence interval = -1.1 to 1.5°C, P = 0.44). Temperature differences between sites were greater in cellulitis patients than in pseudocellulitis patients (3.7 vs. 0.2°C, P = 0.002). A logistic regression model showed that a temperature difference of 0.47°C or greater conferred a 96.6% sensitivity, 45.5% specificity, 82.4% positive predictive value, and 83.3% negative predictive value for cellulitis diagnosis. When validated in the other cohort, this model gave the correct diagnosis for 100% of patients with cellulitis and 50% of those with pseudocellulitis. A difference threshold of 0.47°C or greater between affected and unaffected skin showed an 87.5% accuracy in cellulitis diagnosis.
IMPORTANCE Each year, cellulitis leads to 650 000 hospital admissions and is estimated to cost $3.7 billion in the United States. Previous literature has demonstrated a high misdiagnosis rate for cellulitis, which results in unnecessary antibiotic use and health care cost. OBJECTIVE To determine whether dermatologic consultation decreases duration of hospital stay or intravenous antibiotic treatment duration in patients with cellulitis. DESIGN, SETTING, AND PARTICIPANTS This randomized clinical trial was conducted in a large urban tertiary care hospital between October 2012 and January 2017, with 1-month follow-up duration. Patients were randomized to the control group, which received the standard of care (ie, treatment by primary medicine team), or the intervention group, which received dermatology consultation. Medical chart review of demographic information and hospital courses was performed. Adult patients hospitalized with presumed diagnosis of cellulitis were eligible. A total of 1300 patients were screened, 1125 were excluded, and 175 were included. Statistical analysis was employed to identify significant outcome differences between the 2 groups. INTERVENTIONS Dermatology consultation within 24 hours of hospitalization. MAIN OUTCOMES AND MEASURES Length of hospital stay and duration of intravenous antibiotic treatment. RESULTS Of 175 participants, 70 (40%) were women and 105 (60%) were men. The mean age was 58.8 years. Length of hospital stay was not statistically different between the 2 groups. The duration of intravenous antibiotic treatment (<4 days: 86.4% vs 72.5%; absolute difference, 13.9%; 95% CI, 1.9%-25.9%; P = .04) and duration of total antibiotic treatment was significantly lower in patients who had early dermatology consultation (<10 days: 50.6% vs 32.5%; absolute difference, 18.1%; 95% CI, 3.7%-32.5%; P = .01). Clinical improvement at 2 weeks was significantly higher for those in the intervention group (79 [89.3%] vs 59 [68.3%]; absolute difference, 21.0%; 95% CI, 9.3%-32.7%; P < .001). There was no significant difference in 1-month readmission rate between the groups (4 [4.5%] vs 6 [6.9%]; absolute difference, −2.4%; 95% CI, −9.3% to 4.5%; P = .54). In the intervention group, the rate of cellulitis misdiagnosis was 30.7% (27 of 88 participants). Among the entire cohort, 101 (57.7%) patients were treated with courses of antibiotics longer than what is recommended by guidelines. CONCLUSIONS AND RELEVANCE Early dermatologic consultation can improve outcomes in patients with suspected cellulitis by identifying alternate diagnoses, treating modifiable risk factors, and decreasing length of antibiotic treatment. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01706913
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