Effects of Clinically Meaningful Concentrations of Antipseudomonal β-Lactams on Time to Detection and Organism Growth in Blood Culture Bottles

Abstract

The effectiveness of antimicrobial binding resins present in blood culture (BC) bottles in removing meropenem, ceftolozane-tazobactam, and ceftazidime-avibactam is unknown. We assessed the time to detection (TTD) and growth of 2 isolates in the presence of clinically meaningful concentrations of these antibiotics. Bactec Plus Aerobic/F and BacT/Alert FA Plus BC bottles were inoculated with one of two isolates (1 meropenem susceptible and 1 resistant), followed by fresh whole blood containing the peak, midpoint, or trough plasma concentrations for meropenem, ceftolozane-tazobactam, and ceftazidime-avibactam. Matching bottles were loaded into their respective detection instruments and a standard incubator at 37°C, with TTD and CFU being monitored for up to 72 h. Bacterial growth was observed for 11/48 (22.9%), 22/48 (45.8%), and 47/48 (97.9%) of all BC bottles inoculated with the peak, midpoint, and trough concentrations, respectively ( ≤ 0.001). When was isolated, the TTD was typically<26 h, and no differences between Bactec and BacT/Alert bottles were observed. In both systems, meropenem was removed to a greater degree than were ceftolozane and ceftazidime; however, concentrations for all antibiotics remained above the MIC for the susceptible organisms at 12 h. BC bottles containing antibiotic binding resins may not sufficiently inactivate achievable concentrations of meropenem, ceftolozane-tazobactam, and ceftazidime-avibactam. The consistent identification of both isolates was observed only in the presence of antibiotic trough concentrations. To minimize false-negative BC results for patients already receiving these antibiotics, cultures should be collected just prior to the next dose, when antibiotic concentrations are lowest.

Efficient Inactivation of Clinically Relevant Antimicrobial Drug Concentrations by BacT/Alert or Bactec Resin-Containing Media in Simulated Adult Blood Cultures

“…Our findings agree with the recent findings of other researchers that the present ex vivo (using human blood and simulated antibiotic concentrations)/in vitro study provides further support for a worthwhile use of BacT/Alert (FA Plus and FN Plus) or Bactec (Plus Aerobic/F and Plus Anaerobic/F) antimicrobial-inactivating BC media (13,14). We tested a range of Gram-negative and Gram-positive bacterial species against clinically effective concentrations of three to seven antibiotics per species.…”

“…media performances of BacT/Alert FA Plus bottles with those of Bactec Plus Aerobic/F bottles by testing bacteria and antibiotics (Pseudomonas aeruginosa and antipseudomonal ␤-lactams, in one case [14]). However, investigating both aerobic and anaerobic BC bottles is important for improving treatment outcomes in septic patients (15).…”

“…We tested a range of Gram-negative and Gram-positive bacterial species against clinically effective concentrations of three to seven antibiotics per species. Apart from the peak (P) concentration (i.e., C max ), we selected for each antibiotic two descending concentrations (i.e., C/2 and C/4) that were higher than the midpoint (M) and/or through (T) concentrations tested elsewhere (8,9,14). Therefore, consistent with the study by Mitteregger et al (10), we ensured that the antibiotic levels of C/2-or C/4-spiked BCs were still higher than the expected antibiotic-inactivating capability for aerobic/anaerobic BC media so that organism recoveries could occur in BC bottles containing still-active (above the MIC) antibiotic concentrations.…”

“…In fact, BacT/Alert FN Plus was able to recover K. pneumoniae isolates at all levels of meropenem, not just at C/4. In the study by Grupper et al (14), P. aeruginosa ATCC 27853, the sole bacterial species tested and able to be compared, grew in Ͻ26 h in all BacT/Alert FA Plus and Bactec Plus Aerobic/F bottles in the presence of meropenem T concentrations. In our study, the same species grew in ϳ13 and ϳ17 h in all BacT/Alert FA Plus and Bactec Plus Aerobic/F bottles, respectively in the presence of meropenem C/4 concentrations.…”

Monitoring Antibiotics and Inflammatory Markers in Human Blood: Impact in Choice of Antibiotic Therapy and Used Methods

“…Therefore, maintaining the MIC at this level for as long as possible is the key to antibiotic therapy, if the pathogen is sensitive to this drug [81]. In a study by Grupper et al, antibiotic therapy efficacy was assessed by the level of growth of Pseudomonas aeruginosa colonies at various time intervals after the administration of clinically significant concentrations of beta-lactam antibiotics [82]. Among these antibiotics are meropenem, ceftolosan/tazobactam, and ceftazidime/tazobactam, which belong to the subclass of carbapenems (imipenems).…”