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      The impact of delayed biliary decompression and anti-microbial therapy in 260 patients with cholangitis-associated septic shock

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          Abstract

          Cholangitis-associated septic shock carries significant mortality. There is uncertainty regarding the most appropriate time to achieve biliary decompression.

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          Most cited references26

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          Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock.

          Our goal was to determine the impact of the initiation of inappropriate antimicrobial therapy on survival to hospital discharge of patients with septic shock. The appropriateness of initial antimicrobial therapy, the clinical infection site, and relevant pathogens were retrospectively determined for 5,715 patients with septic shock in three countries. Therapy with appropriate antimicrobial agents was initiated in 80.1% of cases. Overall, the survival rate was 43.7%. There were marked differences in the distribution of comorbidities, clinical infections, and pathogens in patients who received appropriate and inappropriate initial antimicrobial therapy (p < 0.0001 for each). The survival rates after appropriate and inappropriate initial therapy were 52.0% and 10.3%, respectively (odds ratio [OR], 9.45; 95% CI, 7.74 to 11.54; p < 0.0001). Similar differences in survival were seen in all major epidemiologic, clinical, and organism subgroups. The decrease in survival with inappropriate initial therapy ranged from 2.3-fold for pneumococcal infection to 17.6-fold with primary bacteremia. After adjustment for acute physiology and chronic health evaluation II score, comorbidities, hospital site, and other potential risk factors, the inappropriateness of initial antimicrobial therapy remained most highly associated with risk of death (OR, 8.99; 95% CI, 6.60 to 12.23). Inappropriate initial antimicrobial therapy for septic shock occurs in about 20% of patients and is associated with a fivefold reduction in survival. Efforts to increase the frequency of the appropriateness of initial antimicrobial therapy must be central to efforts to reduce the mortality of patients with septic shock.
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            Early combination antibiotic therapy yields improved survival compared with monotherapy in septic shock: a propensity-matched analysis.

            Septic shock represents the major cause of infection-associated mortality in the intensive care unit. The possibility that combination antibiotic therapy of bacterial septic shock improves outcome is controversial. Current guidelines do not recommend combination therapy except for the express purpose of broadening coverage when resistant pathogens are a concern. To evaluate the therapeutic benefit of early combination therapy comprising at least two antibiotics of different mechanisms with in vitro activity for the isolated pathogen in patients with bacterial septic shock. Retrospective, propensity matched, multicenter, cohort study. Intensive care units of 28 academic and community hospitals in three countries between 1996 and 2007. A total of 4662 eligible cases of culture-positive, bacterial septic shock treated with combination or monotherapy from which 1223 propensity-matched pairs were generated. The primary outcome of study was 28-day mortality. Using a Cox proportional hazards model, combination therapy was associated with decreased 28-day mortality (444 of 1223 [36.3%] vs. 355 of 1223 [29.0%]; hazard ratio, 0.77; 95% confidence interval, 0.67-0.88; p = .0002). The beneficial impact of combination therapy applied to both Gram-positive and Gram-negative infections but was restricted to patients treated with beta-lactams in combination with aminoglycosides, fluoroquinolones, or macrolides/clindamycin. Combination therapy was also associated with significant reductions in intensive care unit (437 of 1223 [35.7%] vs. 352 of 1223 [28.8%]; odds ratio, 0.75; 95% confidence interval, 0.63-0.92; p = .0006) and hospital mortality (584 of 1223 [47.8%] vs. 457 of 1223 [37.4%]; odds ratio, 0.69; 95% confidence interval, 0.59-0.81; p < .0001). The use of combination therapy was associated with increased ventilator (median and [interquartile range], 10 [0-25] vs. 17 [0-26]; p = .008) and pressor/inotrope-free days (median and [interquartile range], 23 [0-28] vs. 25 [0-28]; p = .007) up to 30 days. Early combination antibiotic therapy is associated with decreased mortality in septic shock. Prospective randomized trials are needed.
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              Early treatment of acute biliary pancreatitis by endoscopic papillotomy.

              Most patients with acute biliary pancreatitis have stones in the biliary tract or ampulla of Vater. Because these stones may be passed spontaneously soon after a patient is admitted to the hospital, the importance of early operative removal is not known. We tested the hypothesis that endoscopic papillotomy within 24 hours of admission decreased the incidence of complications in patients with acute biliary pancreatitis. We studied 195 patients with acute pancreatitis who were randomly assigned to one of two groups: 97 patients underwent within 24 hours after admission emergency endoscopic retrograde cholangiopancreatography (ERCP) followed by endoscopic papillotomy for ampullary and common-bile-duct stones, and 98 patients received initial conservative treatment and selective ERCP with or without endoscopic papillotomy only if their condition deteriorated. One hundred twenty-seven patients ultimately proved to have biliary stones. Emergency ERCP with or without endoscopic papillotomy resulted in a reduction in biliary sepsis as compared with conservative treatment (0 of 97 patients vs. 12 of 98 patients, P = 0.001). The decrease in biliary sepsis occurred both in patients predicted to have mild pancreatitis (0 of 56 patients in the group that received emergency ERCP vs. 4 of 58 patients in the conservative-treatment group, P = 0.14) and in patients predicted to have severe pancreatitis (0 of 41 patients vs. 8 of 40 patients, P = 0.008). In all patients who had unrelenting biliary sepsis, persistent ampullary or common-bile-duct stones were identified. There were no major differences in the incidence of local complications (10 patients in the group that received emergency ERCP vs. 12 patients in the conservative-treatment group) or systemic complications (10 patients vs. 14 patients) of acute pancreatitis between the two groups, but the hospital mortality rate was slightly lower in the group undergoing emergency ERCP with or without endoscopic papillotomy (5 patients vs. 9 patients, P = 0.4). Emergency ERCP with or without endoscopic papillotomy is indicated in the treatment of patients with acute pancreatitis.
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                Author and article information

                Journal
                Alimentary Pharmacology & Therapeutics
                Aliment Pharmacol Ther
                Wiley-Blackwell
                02692813
                October 2016
                October 10 2016
                : 44
                : 7
                : 755-766
                Affiliations
                [1 ]the Cooperative Antimicrobial Therapy of Septic Shock (CATSS) Database Research Group
                Article
                10.1111/apt.13764
                27506331
                c6c1fb5b-abe4-4162-8520-dc03ec87b313
                © 2016

                http://doi.wiley.com/10.1002/tdm_license_1.1

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