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.

Clinical Evaluation of BacT/Alert FA Plus and FN Plus Bottles Compared with Standard Bottles

“…Although it is helpful that the resin-containing bottles and standard bottles were handled the same way in this regard, it is possible that lengthy room temperature storage affected the outcome of the study. In the in vitro experiments, resin or charcoal clearly suppressed the activities of antibiotics in the blood culture bottles (14,15). Although one possible mechanism of resin or charcoal is the adsorption of antibiotics present in the blood culture bottles, this hypothesis remains to be confirmed.…”

Continuous and Prolonged Intravenous β-Lactam Dosing: Implications for the Clinical Laboratory

“…In another study, time to detection for resin-containing blood culture bottles of BacT/Alert FAN with or without defined concentrations of various antimicrobials was investigated. Using a predefined, clinically relevant 3-h delay in the time to positivity, it was found that piperacillin-tazobactam was incompletely neutralized, and some strains did not demonstrate growth in bottles containing the betalactam antibiotics, i.e., amoxicillin-clavulanate, cefepime, cefotaxime, and meropenem (110). Importantly, the use of prolonged or continuous beta-lactam administration, combined with more aggressive doses, will result in longer intervals of higher antibiotic concentrations than with traditional intermittent dosing (13) (Fig.…”

“…These systems contain various binding resins and proprietary materials to prevent antibiotic carryover and inhibition of bacteria. However, the concentration of antibiotic and the duration that concentrations remain elevated may influence the time to positivity or overall positivity of some systems (107)(108)(109)(110)(111). A recent study that compared head to head the blood culture media of BacT/Alert Fan and Bactec Plus found the former to be superior in the ability to neutralize peak and middle simulated concentrations of piperacillin.…”

Sepsis in standard care: patients’ characteristics, effectiveness of antimicrobial therapy and patient outcome—a cohort study

“…Since starting antimicrobial treatment before having taken patient samples for microbiological diagnostics is a well-known yet unsolved and apparently unavoidable predicament in clinical routine, it was not assessed as a major limitation. In addition, the blood culture flasks used contain resin particles, which decreased the concentration of or completely absorbed antimicrobial substances present in patients' blood [39].…”