Comparing the Outcomes of Adults with Enterobacteriaceae Bacteremia Receiving Short-Course vs Prolonged-Course Antibiotic Therapy

Abstract

BackgroundThe recommended duration of antibiotic treatment for Enterobacteriaceae bacteremia is between 7 and 14 days. We compared the clinical outcomes of patients receiving short-course (6–10 days) vs prolonged-course (11–15 days) antibiotic therapy for Enterobacteriaceae bacteremia.MethodsA retrospective cohort study was conducted at The Johns Hopkins Hospital, The University of Maryland Medical Center, and The Hospital of the University of Pennsylvania including patients with monomicrobial Enterobacteriaceae bacteremia treated with in vitro active antibiotic therapy in the range of 6–15 days between 2008 and 2014. 1:1 nearest neighbor propensity score matching without replacement was performed, prior to regression analysis, to estimate the risk of all-cause mortality within 30 days after the end of antibiotic treatment for patients receiving short vs. prolonged durations of antibiotic therapy. Secondary outcomes included Clostridium difficile infection (CDI) and the emergence of multidrug-resistant Gram-negative (MDRGN) bacteria within 30 days after the end of antibiotic therapy.ResultsA total of 1,769 patients met eligibility criteria. There were 385 matched pairs who were well-balanced on baseline characteristics. The median duration of therapy in the short-course group and prolonged-course group was 8 days (interquartile range (IQR) 7–9 days) and 15 days (IQR 13–15 days), respectively. No difference in all-cause mortality between short- and prolonged-course treatment groups was observed (adjusted hazard ratio [aHR] 1.00; 95% CI 0.62–1.63). Rates of CDI were similar between the treatment groups (OR 1.17; 95% CI 0.39–3.51). There was a non-significant protective effect of short-course antibiotic therapy on the emergence of MDRGN bacteria (OR 0.59; 95% CI 0.32–1.09 P = 0.09).ConclusionShort courses of antibiotic therapy yields similar clinical outcomes to prolonged courses of antibiotic therapy for Enterobacteriaceae bacteremia, and may protect against subsequent MDRGN emergence.Disclosures All authors: No reported disclosures.

Intravenous push versus intravenous piggyback beta‐lactams for the empiric management of gram‐negative bacteremia

“…In‐hospital mortality occurred in 9 (9%) and 3 (3%) patients in the IVPB and IVP groups, respectively. This is lower but comparable to the 9.8% mortality rate identified by Chotiprasitsakul and colleagues in a study of patients with Enterobacteriaceae bacteremia of a primarily urinary or intra‐abdominal source and similar baseline characteristics to ours 14 . We hypothesize the time of infusion between IVP over 5 min and IVPB over 30 min did not lead to differences in clinical response given the low MICs of our organisms to FEP and MEM, the previously described lack of pharmacokinetic differences in time above MIC between these two forms of administration, and the more favourable outcomes in patients with a low inoculum urinary or intra‐abdominal source of Enterobacteriaceae bacteremia 1,14 …”

“…More specifically, our population included a limited number of patients with either deep seated infections such as meningitis, osteomyelitis and endocarditis or biofilm‐forming organisms such as P aeruginosa , all of which may be more difficult to eradicate and treat. Although our primary endpoint of escalation of therapy is not consistent with those used in other Gram‐negative bacteremia studies, this endpoint was chosen to minimize confounders in the assessment of IVPB versus IVP forms of administration 14 . Furthermore, close to half of the patients received at least 1 dose of another susceptible antibiotic prior to receiving the study drug, potentially influencing the ability to evaluate microbiological clearance between IVP and IVPB in a population of patients with a urinary source of bacteremia.…”

“…There was no assessment of adherence to or duration of outpatient use of antibiotics after discharge, which may impact 90‐day mortality and 90‐day infection‐related readmission. However, the median inpatient duration of therapy was 7 to 8 days, which may be adequate treatment for GNB from a urinary or intra‐abdominal source 14 …”

Effect of C-Reactive Protein–Guided Antibiotic Treatment Duration, 7-Day Treatment, or 14-Day Treatment on 30-Day Clinical Failure Rate in Patients With Uncomplicated Gram-Negative Bacteremia

“…Most patients with bacterial bloodstream infections still receive between 10 and 14 days of antibiotics, although these durations are based largely on expert opinion, and recent evidence from retrospective analyses and a randomized trial indicate clinical noninferiority between 7-day and 14-day courses. 4,5 Fixed antibiotic durations provide straightforward guidance but do not take into account host characteristics or treatment response. Given high diversity among pathogens and their hosts, another approach would be to individualize durations via biomarker-assisted guidance.…”

Duration of antibiotic therapy for common infections

“…(102) Subsequent to this meta-analysis several randomized controlled trials of 7-8 versus 14-15 days of antibiotics in patients with Gram-negative bacteremia (of which the majority had a urinary tract source) found that the shorter course was non-inferior to longer courses in clinical outcome. (80,103,104) A more recent meta-analysis comparing ≤ 10 days to> 10 days of therapy in patients with bacteremia showed no differences in clinical or microbiologic cure nor mortality, however there were only 4 studies available to assess specifically this duration. (105) In an observational study, when source control had been achieved, investigators found that patients with Pseudomonas bacteremia receiving a median of 9 days of therapy (IQR 8-10) had a similar odds of recurrent infection and death as patients who received a median of 16 days (IQR, [14][15][16][17].…”