Severe sepsis and septic shock are life-threatening consequences of infection. The urinary tract is commonly the source of infections resulting in severe sepsis and septic shock, accounting for as many as 35% of cases. Escherichia coli and other Enterobacteriaceae cause the majority of these infections. 

Over the last decade, strains have become increasingly resistant to fluoroquinolones (FQR), the antibiotics of choice to treat uncomplicated pyelonephritis. Also, strains producing extended-spectrum beta-lactamases (ESBL) have emerged, which accounts for some of the increasing resistance to fluoroquinolones. More recently, strains have started to show resistance to carbapenems, which has been an antibiotic class consistently active against ESBL-producing isolates. These strains are called carbapenem-resistant Enterobacteriaceae or CRE.

Multidrug-resistant Gram-negative bacteria pose a great risk to public health, with few treatment options. Patients with urosepsis represent a higher risk population, both for infections due to multidrug-resistant bacteria and to experience serious adverse outcomes, including death, related to lack of in vitro activity of empirically prescribed antibiotic regimens. We expect that the prevalence of infections due to ESBL-producing and CRE strains will continue to increase. 

Patients with severe illness and sepsis commonly present to EDs. Therefore, we propose to conduct a study among ED-presenting patients at EMERGEncy ID NET sites with the clinical diagnosis of urosepsis to determine the prevalence of and examine potential risk factors associated with infections due to ESBL-producing and CRE strains. We will attempt to determine the association of initial empirical antibiotic treatment in vitro activity discordance and concordance with clinical outcomes, controlling for recognized outcome predictors.

Secondary objectives are to:

• Determine the molecular characterization of ESBL-producing and CRE strains; 

• Describe empirical treatment practices; and

• Describe the microbiology of patients with urosepsis.

Primary objectives are to:

• Determine the prevalence of ESBL-producing Enterobacteriaceae and CRE among patients with urosepsis and pyelonephritis requiring hospital admission;

• Determine potential risk factors associated with ESBL-producing and CRE infections; and 

• Determine the association of concordant and discordant in vitro activity of the initial empirical antibiotic regimen with clinical outcomes (e.g., in-hospital mortality).