Ineffective Empiric Treatment Leads to Deadly Consequences in Late-Onset Sepsis Patients

Sepsis is a serious complication that can arise due to a bacterial infection. It occurs when the body releases chemicals into the blood stream to combat the infection. However, these chemicals elicit an inflammatory response that affects multiple organs, potentially causing them to fail. Sepsis can progress to septic shock, which can be fatal. Physicians treating patients with sepsis typically administer an antibiotic regimen with the hopes that the treatment will combat the bacteria responsible, as timely and effective treatment is key for positive outcomes.

In a new study accepted for publication in Antimicrobial Agents and Chemotherapy, co-authors Scott Micek, PharmD, Nicholas Hampton, PharmD, and Marin Kollef, MD, examined the differences between administering ineffective empiric treatment (IET) and effective empiric treatment (EET) in treating patients with sepsis. Briefly, IET involves administering an initial antibiotic regimen that is not effective against pathogens identified in the in vitro susceptibility testing.

The study was performed at Barnes-Jewish Hospital in St. Louis, Missouri, and included patients that were admitted between January 2010 and October 2015. To be included in the study, patients had to have a sterile site (such as blood, cerebrospinal fluid, or pericardial fluid) culture that tested positive for gram-negative bacteria. In addition, patients had to be diagnosed with either severe sepsis or be in septic shock to be included in the study. The goals of the study were to pinpoint the occurrence of early-onset or late-onset IET as well as to identify variables that can be used to predict IET in patients with gram-negative bacterial infections.

Patients were classified as having early-onset infections if the gram-negative bacterium was isolated within 48 hours of hospitalization. In addition, the authors defined IET as administering an initial antibiotic regimen that was not active against pathogens identified using in vitro susceptibility testing. An example of a scenario that would be classified as IET would be patients who received piperacillin-tazobactam but were diagnosed with species likely to produce AmpC β-lactamase as administering this antibiotic can lead to selection of resistant bacteria.

The study included 855 patients with severe sepsis or septic shock due to a gram-negative bacterial infection. The authors found that early infection occurred in 60.8% of patients and late infection occurred in the remaining 40% of patients. In addition, IET occurred in approximately 12% of patients with early-onset infections and was correlated with a higher comorbidity index, prior hospitalization, and higher incidence of prior intravenous antibiotic therapy to treat infections caused by the species Pseudomonas. For patients with late-onset infections, there was a correlation with prior hospitalization and previous administration of intravenous antibiotics.

Overall, for patients with early-onset gram-negative infections, the authors found no difference in survival between the IET and EET groups. However, for patients in the late-onset group, the authors found that patients receiving IET had lower survival rates in comparison to those receiving EET, suggesting that outcomes for IET can depend on the onset of infection. Furthermore, this study demonstrated that receiving previous intravenous antibiotic therapy is a risk factor for IET, irrespective of the onset of infection. Future work should center on developing better approaches to best use empiric therapy to treat patients with potentially fatal bacterial infections.