Impact of Appropriate Antimicrobial Therapy for Patients with Severe Sepsis and Septic Shock – A Quality Improvement Study

Background There is ample literature available on the association between both time to antibiotics and appropriateness of antibiotics and clinical outcomes from sepsis. In fact, the current state of debate surrounds the balance to be struck between prompt empirical therapy and care in the choice of appropriate antibiotics (both in terms of the susceptibility of infecting organism and minimizing resistance arising from use of broad-spectrum agents). The objective of this study is to determine sepsis bundle compliance and the appropriateness of antimicrobial therapy in patients with severe sepsis and septic shock and its impact on outcomes. Material This study was conducted in the ICU of a tertiary care, private hospital in São Paulo, Brazil. A retrospective cohort study was conducted from July 2005 to December 2012 in patients with severe sepsis and septic shock. Results A total of 1,279 patients were identified with severe sepsis and septic shock, of which 358 (32.1%) had bloodstream infection (BSI). The inpatient mortality rate was 29%. In evaluation of the sepsis bundle, over time there was a progressive increase in serum arterial lactate collection, obtaining blood cultures prior to antibiotic administration, administration of broad-spectrum antibiotics within 1 hour, and administration of appropriate antimicrobials, with statistically significant differences in the later years of the study. We also observed a significant decrease in mortality. In patients with bloodstream infection, after adjustment for other covariates the administration of appropriate antimicrobial therapy was associated with a decrease in mortality in patients with severe sepsis and septic shock (p = 0.023). Conclusions The administration of appropriate antimicrobial therapy was independently associated with a decline in mortality in patients with severe sepsis and septic shock due to bloodstream infection. As protocol adherence increased over time, the crude mortality rate decreased, which reinforces the need to implement institutional guidelines and monitor appropriate antimicrobial therapy compliance

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Risk factors associated with inadequate antimicrobial therapy in patients with severe sepsis or septic shock patients who had documented bloodstream infection.

<p>OR  =  Odds Ratio; CI  =  Confidance Interval; APACHE  =  Acute Physiology and Chronic Health Evaluation II.</p><p><b>ESKAPE  = </b><b><i>Enterococcus, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterobacter spp.</i></b></p><p>Risk factors associated with inadequate antimicrobial therapy in patients with severe sepsis or septic shock patients who had documented bloodstream infection.</p

Risk factors associated with death for patients with severe sepsis or septic shock and documented bloodstream infection.

<p>OR  =  Odds Ratio; CI  =  Confidence Interval; APACHE  =  Acute Physiology and Chronic Health Evaluation II.</p><p>Risk factors associated with death for patients with severe sepsis or septic shock and documented bloodstream infection.</p

Comparison between patients with and without positive blood cultures.

<p>163 patients without blood culture collected during the study period.</p><p>Comparison between patients with and without positive blood cultures.</p

The most prevalent microorganisms from monomicrobial bloodstream infections and clinical outcome stratified by adequacy of antimicrobial therapy during the study period.

<p>*resistant to fluconazole.</p><p>**resistant to 3rd and 4th generation cephalosporins.</p>#<p>resistant to carbapenems.</p>##<p>resistant to methicillin.</p>###<p>resistant to vancomycin.</p><p>The most prevalent microorganisms from monomicrobial bloodstream infections and clinical outcome stratified by adequacy of antimicrobial therapy during the study period.</p

Risk factors associated with death in all patients with severe sepsis or septic shock.

<p>OR  =  Odds Ratio; CI  =  Confidence Interval; APACHE: Acute Physiology and Chronic Health Evaluation II.</p><p>Risk factors associated with death in all patients with severe sepsis or septic shock.</p

Demographic and clinical characteristics of severe sepsis and septic shock patients from July 2005 to December 2012.

<p>-Analyses of antimicrobial appropriateness and value of central venous oxygen saturation were performed with the total of 199 and 358 patients, respectively.</p><p>-Extended data from the study published in Plos One 2011 (reference number 6).</p><p>Demographic and clinical characteristics of severe sepsis and septic shock patients from July 2005 to December 2012.</p