Gram-negative bacteraemia; a multi-centre prospective evaluation of empiric antibiotic therapy and outcome in English acute hospitals

Abstract

Increasing antibiotic resistance makes choosing antibiotics for suspected Gram-negative infection challenging. This study set out to identify key determinants of mortality among patients with Gram-negative bacteraemia, focusing particularly on the importance of appropriate empiric antibiotic treatment. We conducted a prospective observational study of 679 unselected adults with Gram-negative bacteraemia at ten acute english hospitals between October 2013 and March 2014. Appropriate empiric antibiotic treatment was defined as intravenous treatment on the day of blood culture collection with an antibiotic to which the cultured organism was sensitive in vitro. Mortality analyses were adjusted for patient demographics, co-morbidities and illness severity. The majority of bacteraemias were community-onset (70%); most were caused by Escherichia coli (65%), Klebsiella spp. (15%) or Pseudomonas spp. (7%). Main foci of infection were urinary tract (51%), abdomen/biliary tract (20%) and lower respiratory tract (14%). The main antibiotics used were co-amoxiclav (32%) and piperacillin-tazobactam (30%) with 34% receiving combination therapy (predominantly aminoglycosides). Empiric treatment was inappropriate in 34%. All-cause mortality was 8% at 7 days and 15% at 30 days. Independent predictors of mortality (p <0.05) included older age, greater burden of co-morbid disease, severity of illness at presentation and inflammatory response. Inappropriate empiric antibiotic therapy was not associated with mortality at either time-point (adjusted OR 0.82; 95% CI 0.35-1.94 and adjusted OR 0.92; 95% CI 0.50-1.66, respectively). Although our study does not exclude an impact of empiric antibiotic choice on survival in Gram-negative bacteraemia, outcome is determined primarily by patient and disease factors.

Levels of outpatient prescribing for four major antibiotic classes and rates of septicemia hospitalization in adults in different US states

“…On the other hand, macrolides are used relatively infrequently in the treatment of urinary tract and gastrointestinal infections. A UK study found that for a high proportion of Gram-negative bacteremia, the main foci of infection were either urinary tract or abdomen/biliary tract [51]. Overall, the potential benefits of antibiotic stewardship for penicillins may be the most important findings of this paper, while options for antibiotic replacement require further investigation.…”

Strategy to reduceE. colibacteraemia based on cohort data from a London teaching hospital

“…Based on our local susceptibility data and a small number of bacteraemic isolates that were ESBL producers and only amikacin susceptible, we would advocate single-dose amikacin prophylaxis prior to these procedures, although we recognise that increased usage of a ‘reserve’ antibiotic could lead to increased resistance. Amikacin compared with gentamicin has a higher barrier to resistance,17 and nationally we are yet to see the emergence of amikacin resistance rates >5% 18. Further attention is also required regarding placement of central intravascular devices using a care bundle and, where possible, avoiding femoral vein placement.…”

Management and outcome of bloodstream infections: a prospective survey in 121 French hospitals (SPA-BACT survey)

“…Our model did not take into account time-dependent variables such as length of stay within the hospital before BSI happened, and we did not consider time to treatment as a time-dependent variable. This was decided to be consistent with previous literature and because of the design of the survey which aimed at investigating short-term mortality 6. Furthermore, correct antibiotic regimen was started before 48 hours for >80% of patients, suggesting that few biases could be introduced due to events happening between blood culture and appropriate treatment.…”