Neutralization of antimicrobial substances in new BacT/Alert FA and FN Plus blood culture bottles

Abstract

Time to detection (TTD) in automated blood culture systems is delayed for sensitive microorganisms in the presence of antimicrobial substances and has been associated with worse outcomes for sepsis patients on inadequate empirical therapy. While resin addition removes antimicrobial substances to various degrees from blood culture media, media formulations and the blend of resins may influence performance. The BacT/Alert 3D system (bioMérieux) was investigated using the new resin-containing medium types FA Plus (aerobic) and FN Plus (anaerobic). TTD was compared between control and test bottles containing relevant bacteria or Candida albicans, with and without defined concentrations of antimicrobials. Failure of neutralization was defined as a negative blood culture on day 3. In general, growth delay was nonlinear, concentration dependent, bottle type specific, and reciprocally associated with MICs. Substance-specific serum drug concentrations corresponding to a predefined, clinically relevant 3-h delay of TTD were calculated. Where appropriate, a time interval allowing for drug elimination below this critical level was obtained by pharmacokinetic modeling. Clarithromycin, clindamycin, gentamicin, linezolid, tigecycline, vancomycin, and fluconazole were neutralized. For ciprofloxacin and piperacillin-tazobactam, which were only incompletely neutralized in combination with the most sensitive test strains, a maximum waiting time for blood draw of 1 h was determined based on pharmacokinetics. One or more test strains did not grow in bottles containing either amoxicillin-clavulanate, cefepime, cefotaxime, meropenem, or metronidazole, and we thus recommend particular caution in timing of blood draws if patients have been pretreated with these agents.

Fig 1

Differences in the TTDs with and without antimicrobial substances: (a) BacT/Alert FA Plus (aerobic) bottle; (b) BacT/Alert FN Plus (anaerobic) bottle. Arithmetic means of triplicates were used for the graphic illustration. Each column illustrates the difference in the TTD between bottles containing antimicrobial substances and controls. Consecutive columns along the x axis show the change in TTD (ΔTTD) related to decreasing concentrations of the antimicrobial substances. The ΔTTD for bottles that remained negative due to insufficient antimicrobial neutralization after 3 days was set as 72 h.