Effect of Clinically Meaningful Antibiotic Concentrations on Recovery of Escherichia coli and Klebsiella pneumoniae Isolates from Anaerobic Blood Culture Bottles with and without Antibiotic Binding Resins

Abstract

Blood cultures are routinely collected in pairs of aerobic and anaerobic bottles. Artificial sterilization of Gram-negative bacteria in aerobic bottles containing clinically meaningful antibiotic concentrations has previously been observed. This study assessed recovery from anaerobic bottles with and without antibiotic binding resins. We studied the recovery of Escherichia coli and Klebsiella pneumoniae when exposed to meropenem, imipenem, cefepime, cefazolin, levofloxacin, and piperacillin-tazobactam in resin-containing BacT/Alert FN Plus and BD Bactec Plus anaerobic/F bottles as well as resin-free BacT/Alert SN and BD Bactec standard anaerobic bottles. Bottles were inoculated with bacteria and whole blood containing peak, midpoint, or trough concentrations and incubated for up to 120 hours in their respective detection systems. In E. coli resin-containing bottles, recovery was observed in 10/24 (42%), 17/24 (71%), and 18/24 (75%) (P = 0.034) of those exposed to peak, midpoint, and trough concentrations, respectively. In K. pneumoniae resin-containing bottles, recovery was observed in 8/16 (50%), 10/16 (63%), and 10/16 (63%) (P = 0.710), respectively. No growth was detected in bottles containing cefepime regardless of concentration, while recovery was observed in the presence of all concentrations of cefazolin and piperacillin-tazobactam. Recovery in bottles with meropenem and imipenem was more frequently observed in BacT/Alert FN Plus bottles compared with Bactec Plus bottles. Resin-free bottles demonstrated significantly lower recovery than bottles containing binding resin. Clinical concentrations of certain antibiotics can adversely affect detection of E. coli and K. pneumoniae in anaerobic blood culture bottles. Obtaining blood cultures immediately before a dose and utilizing resin-containing anaerobic bottles will maximize the likelihood of recovery.

Inactivation of Clinically Frequently Used Antimicrobial Agents By BacT/ALERT FAN Plus and BACTEC Aerobic and Anaerobic Culture Media in Simulated Blood Cultures: First Comparative Evaluation in China Mainland

“…It is worth noting that the anaerobic bottles contained different media, which could influence the recovery of many pathogens, especially when exposed to antimicrobial agents. 10 In addition, the resin-free BACTEC Lytic/10 Anaerobic/F bottle evaluated here is the only type of BD anaerobic blood culture media approved by the Chinese National Medical Products Administration (NMPA), which to some extent has lead to the relative lower positive rate of BACTEC system. In comparison, the resin-free BacT/ALERT SN anaerobic bottles that functioned to ensure the activities of antimicrobials involved showed 0/48 (0.0%) recovery when evaluated with antimicrobial agents at peak serum concentrations.…”

Simulated Pediatric Blood Cultures to Assess the Inactivation of Clinically Relevant Antimicrobial Drug Concentrations in Resin-Containing Bottles

“…However, it should be noted that the bacterial inoculum (50 to 100 CFU per bottle) used by Menchinelli et al. (2019b) was much higher than the inoculum (7 to 30 CFU per bottle) used by Chen et al. (2019) , and this difference might have caused the dissimilar performance of BC bottles observed in the two studies.…”

“…Similarly, our previous study (albeit in the adult setting) showed no recovery for E. coli when tested in the presence of meropenem at the lowest but clinically relevant concentration in both BacT/Alert (FA Plus and FN Plus) and Bactec (Plus Aerobic/F and Plus Anaerobic/F) bottles ( Menchinelli et al., 2019b ). Concomitantly, Chen et al. (2019) showed that the recovery of E. coli exposed to meropenem midpoint and trough concentrations was more successful in BacT/Alert FN Plus bottles than in Bactec Plus Anaerobic/F bottles.…”

“…To the best of our knowledge, this is the first study to evaluate BacT/Alert PF Plus bottles after 2013, the year these bottles became commercially available. Indeed, published studies until now ( Chen et al., 2019 ; Chung et al., 2019 ; Menchinelli et al., 2019b ; Xu et al., 2021 ) have simulated adult BCs—using human, horse, or sheep blood sources—to assess the antibiotic inactivation capability of Bactec Plus Aerobic/F or Anaerobic/F bottles in comparison with BacT/Alert FA Plus (aerobic) or FN Plus (anaerobic) bottles. In our study, both BacT/Alert PF Plus and Bactec Peds Plus bottles showed 100% recovery in two instances (piperacillin/tazobactam with P. aeruginosa and oxacillin with MSSA), which suggests that antibiotic-binding resins might be effective regardless of bacteria or antibiotic levels in blood samples.…”

Modern Blood Culture

“…Resins can neutralize select antibacterial agents (including common empirically utilized antibiotics such as piperacillin-tazobactam, vancomycin, and some cephalosporins), but have lower to no ability to neutralize other agents (eg, carbapenems and fluoroquinolones). 1 , 2 , 3 Resins improve the yield of blood cultures for patients who are on antibiotics at the time of blood collection; this has clear advantages for initial blood cultures but also results in more positive cultures for patients subsequently on therapy, and thus more laboratory expense. The clinical significance of subsequent positive cultures in bottles with resins is unclear.…”