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      Appropriate and timely antimicrobial therapy in cirrhotic patients with spontaneous bacterial peritonitis-associated septic shock: a retrospective cohort study

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      Alimentary Pharmacology & Therapeutics

      Wiley-Blackwell

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          Abstract

          Spontaneous bacterial peritonitis (SBP)-associated septic shock carries significant mortality in cirrhosis.

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          Most cited references 28

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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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              Management of bacterial infections in cirrhosis.

              Bacterial infections are very frequent in advanced cirrhosis and become the first cause of death of these patients. Despite numerous experimental data and significant advances in the understanding of the pathogenesis of sepsis in cirrhosis, the outcome remains poor. Classical diagnostic parameters such as C-reactive protein and SIRS criteria have less diagnostic capacity in the cirrhotic population, often delaying the diagnosis and the management of bacterial infection. Prompt and appropriate empirical antibiotic treatment of infection and early resuscitation of patients with severe sepsis or septic shock are essential in determining patient's outcome. A strategy of careful restriction of prophylactic antibiotics to the high-risk populations could reduce the spread of multidrug resistant bacteria. This review is focused on the currently recommended diagnostic, therapeutic and prophylactic strategies for bacterial infections in the cirrhotic population. Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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                Author and article information

                Journal
                Alimentary Pharmacology & Therapeutics
                Aliment Pharmacol Ther
                Wiley-Blackwell
                02692813
                April 2015
                April 20 2015
                : 41
                : 8
                : 747-757
                Affiliations
                [1 ]the Cooperative Antimicrobial Therapy of Septic Shock (CATSS) Database Research Group
                Article
                10.1111/apt.13135
                25703246
                © 2015
                Product
                Self URI (article page): http://doi.wiley.com/10.1111/apt.13135

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