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      Management and Novel Adjuncts of Necrotizing Soft Tissue Infections

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          Abstract

          <p id="d12140180e187">Necrotizing soft tissue infections (NSTI) have been recognized for millennia and continue to impose considerable burden on both patient and society in terms of morbidity, death, and the allocation of resources. With improvements in the delivery of critical care, outcomes have improved, although disease-specific therapies are lacking. The basic principles of early diagnosis, of prompt and broad antimicrobial therapy, and of aggressive debridement have remained unchanged. Clearly novel and new therapeutics are needed to combat this persistently lethal disease. This review emphasizes the pillars of NSTI management and then summarizes the contemporary evidence supporting the incorporation of novel adjuncts to the pharmacologic and operative foundations of managing this disease. </p>

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          Necrotizing soft-tissue infection: diagnosis and management.

          Necrotizing soft-tissue infections (NSTIs) are highly lethal. They are frequent enough that general and specialty physicians will likely have to be involved with the management of at least 1 patient with NSTI during their practice, but they are infrequent enough that familiarity with the disease will seldom be achieved. Establishing the diagnosis of NSTI can be the main challenge in treating patients with NSTI, and knowledge of all available tools is key for early and accurate diagnosis. The laboratory risk indicator for necrotizing fasciitis score can be helpful for distinguishing between cases of cellulitis, which should respond to medical management alone, and NSTI, which requires operative debridement in addition to antimicrobial therapy. Imaging studies are less helpful. The mainstay of treatment is early and complete surgical debridement, combined with antimicrobial therapy, close monitoring, and physiologic support. Novel therapeutic strategies, including hyperbaric oxygen and intravenous immunoglobulin, have been described, but their effect is controversial. Identification of patients at high risk of mortality is essential for selection of patients that may benefit from future novel treatments and for development and comparison of future trials.
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            High-dose vancomycin therapy for methicillin-resistant Staphylococcus aureus infections: efficacy and toxicity.

            Vancomycin hydrochloride treatment failure for infections caused by susceptible methicillin-resistant Staphylococcus aureus (MRSA) strains with high minimum inhibitory concentration (MIC) has prompted recent guidelines to recommend a higher vancomycin target trough of 15 to 20 microg/mL. A prospective cohort study of adult patients infected with MRSA was performed to determine the distribution of vancomycin MIC and treatment outcomes with vancomycin doses targeting an unbound trough of at least 4 times the MIC. The microbiology laboratory computer records were used to identify all patients from whom MRSA was isolated from August 1, 2004, through June 30, 2005. Primary outcome measures were clinical response, mortality, and nephrotoxicity. Patients were placed into subgroups based on target trough attainment and high vs low vancomycin MIC (>/=2 vs /=15 vs <15 microg/mL) for nephrotoxicity analyses. Of the 95 patients in the study, 51 (54%) were infected with high-MIC strains and had pneumonia (77%) and/or bacteremia. An initial response rate of 74% was achieved if the target trough was attained irrespective of MIC. However, despite achieving the target trough, the high-MIC group had lower end-of-treatment responses (24/39 [62%] vs 34/40 [85%]; P = .02) and higher infection-related mortality (11/51 [24%] vs 4/44 [10%]; P=.16) compared with the low-MIC group. High MIC (P = .03) and Acute Physiology and Chronic Health Evaluation II score (P = .009) were independent predictors of poor response in multivariate analysis. Nephrotoxicity occurred only in the high-trough group (11/63 [12%]), significantly predicted by concomitant therapy with other nephrotoxic agents. High prevalence of clinical MRSA strains with elevated vancomycin MIC (2 microg/mL) requires aggressive empirical vancomycin dosing to achieve a trough greater than 15 microg/mL. Combination or alternative therapy should be considered for invasive infections caused by these strains.
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              Determinants of mortality for necrotizing soft-tissue infections.

              The authors determined the risk factors of mortality in patients with necrotizing soft-tissue infections (NSTIs) and examined the incidence and mortality from NSTI secondary to Streptococcus pyogenes. All patients with NSTIs who were treated between January 1989 and June 1994 were analyzed for presentation, etiology, factors important in pathogenesis and treatment, and mortality. Sixty-five patients were identified with NSTIs secondary to postoperative wound complications (18), trauma (15), cutaneous disease (15), idiopathic causes (10), perirectal abscesses (3), strangulated hernias (2), and subcutaneous injections (2). Necrotizing soft-tissue infections were polymicrobial in 45 patients (69%). S. pyogenes was isolated in only 17% of the NSTIs, but accounted for 53% of monomicrobial infections. Eight of ten idiopathic infections were caused by a single bacterium (p = 0.0005), whereas 82% of postoperative infections were polymicrobial. An average of 3.3 operative debridements per patient and amputation in 12 patients were necessary to control infection. The overall mortality was 29%; mortality from S. pyogenes infection was only 18%. The average time from admission to operation was 90 hours in nonsurvivors versus 25 hours in survivors (p = 0.0002). Other risk factors previously associated with the development of NSTIs did not affect mortality. Early debridement of NSTI was associated with a significant decrease in mortality. S. pyogenes infection was the most common cause of monomicrobial NSTI, but was not associated with an increased mortality.
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                Author and article information

                Journal
                Surgical Infections
                Surgical Infections
                Mary Ann Liebert Inc
                1096-2964
                1557-8674
                April 2017
                April 2017
                : 18
                : 3
                : 250-272
                Article
                10.1089/sur.2016.200
                5393412
                28375805
                52c5045c-34b6-4459-9389-385953ca97fe
                © 2017
                History

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