Exploring Outcomes of Extended Infusions for Gram-Negative Bacteremia

In the infectious disease community there has been a growing interest in the use of extended infusion beta-lactams for gram-negative bacteremia. However, as clinician interest has increased, a team of investigators from Detroit Medical Center and Michigan Medicine noticed that available data on these infusions are “conflicting” and solely focus on clinical cure and/or mortality outcomes.

As a result, the investigators launched a study to assess outcomes of patients receiving extended infusion beta-lactams compared to patients receiving intermittent infusions for gram-negative bacteria. To date, 96 patient outcomes have been evaluated, the results of which were presented in a poster session at the Making a Difference in Infectious Diseases 2019 (MAD-ID) annual meeting.

In an exclusive interview at the conference, Contagion® spoke with Kieu-Nhi (Nikki) Tran, PharmD, a PGY1 Pharmacy Resident at Detroit Medical Center, who also presented the poster (see video).

The retrospective, cohort study enrolled adult patients who received Cefepime (FEP), Piperacillin/Tazobactam (TZP), or Meropenem (MEM) for gram-negative bacteria via intermittent infusion (30 minutes) or extended infusion (3 hours) between 2010 and 2018. For enrollment, patients were required to receive the study drug within 24 hours of the onset of the bacteremia and continue the drug for >48 hours. Patients who did not receive the drug for at least 48 hours or had a mixed infection were excluded.

The patients were matched 1:1 into the intermittent and extended groups based upon sepsis severity, source of bacteremia, causative pathogen, and intensive care unit status. The median age of the participant population was 64.5 years (range: 58-75 years) and 39% of the patients were female.

At the time of enrollment 42 (44%) participants were patients in the ICU and severe sepsis/septic shock was detected in 38 (40%) participants. Fifteen percent of participants had congestive heart failure and 25% had chronic kidney disease, with an overall Charlson Comorbidity Index of 2 (range 1-3).

The investigators observed that the most commonly isolated organisms were E coli (41%), Pseudomonas aeruginosa (20%), and Klebsiella pneumoniae (16%). Further, FEP was the most commonly used agent, used in 52% of the participants, with TZP and MEM were used in 25% and 23% of patients, respectively.

According to the abstract, there were no differences between the 2 groups with regards to any baseline or infection-related characteristics.

Mortality was documented in 1 patient of the 48 in extended infusion (p=1) group, with no reported mortality in the intermittent group. Treatment failure was documented for 5 patients in the intermittent group and 1 individual in the extended group (p=0.20). The length of stay from study drug in days, median was 8 (5-14) in the intermittent group and 6 (4-10) in the extended group (p=0.06). The duration of study antibiotic in days + SD was 4.9 + 4.9 in the intermittent group and 3.8 + 2.7 in the extended group (p=0.20). Two recurrences were reported in the intermittent group.

While the preliminary results did not find any statistically significant difference in outcomes between the 2 groups, this could be attributable to the small sample size.

Tran, who is an incoming PGY2 Infectious Disease Resident at the University of Michigan, also shared her biggest takeaway from the research with Contagion® (see video).

“There were signals toward improved outcomes with [extended infusion] and an increased sample size will help fully assess these endpoints,” the authors conclude.

The poster “Clinical Outcomes with Extended Infusion (EI) versus Intermittent Infusion (II) of Cefepime (FEP), Piperacillin/Tazobactam (TZP), and Meropenem (MEM) in Patients with Gram-negative Bacteremia (GNB),” was presented on Thursday, May 9, 2019 at MAD-ID 2019 in Orlando, Florida.