201 Bolus and Continuous Infusion of Antibiotics Achieves Effective Therapeutic Levels of Antibiotics Better Than Traditional Dosing in Burn Patients

Abstract

Previous publications show that traditional dosing of amikacin, vancomycin, ciprofloxacin and daptomycin leads to sub-therapeutic dosing of these antibiotics in burn patients. At the same time, levels of effective minimum inhibitory concentrations (MIC) for antibiotics are rising, making traditional dosing regimes even more ineffective. We tested a new protocol in burn patients whose burn was greater than 20% TBSA using bolus dosing followed by a continuous drip for delivering common antibiotics used in burn patients. Over a nine month period we treated eleven burn patients with vancomycin, ceftazidime, piperacillin/tazobactam (pip/tazo) or cefepime using bolus and drip dosing protocols previously established for critically ill non-burn patients. For amikacin and meropenem we used higher than normal doses and did not change frequency of dosing. We measured serum peak, trough and random levels of these drugs to assess how well we reached target levels of these antibiotics and to derive pharmacokinetic parameters. Monte Carlo simulations with these derived kinetic parameters, standard MIC’s of pip/tazo for pseudomonas and vancomycin MIC’s for methicillin resistant staph aureus (MRSA) compared the efficacy of bolus and continuous drip dosing versus traditional intermittent dosing. No patients were sub-therapeutic for beta-lactam or amino glycoside antibiotics. We achieved 80% successful dosing with vancomycin. Several patients were super therapeutic with our protocols, but none of them had any adverse reactions to the higher levels of antibiotics. Traditional dosing for vancomycin was predicted to be only 72% effective for MRSA strains with an MIC of 1 and 1.2% effective for strains of MRSA with an MIC of 2. Currently, 20% of MRSA strains in the Unites States have an MIC of 2. Our new dosing protocol provided 100% and 20% efficacy for MRSA with MIC’s of 1 and 2 respectively. Traditional dosing of pip/tazo was only be 84%, 52% and 3% effective for pseudomonas strains with MIC’s of 4, 8 and 16 respectively, while our new protocol would be 100%, 100% and 35% effective for these MIC’s. It is important to note that Pseudomonas strains with an MIC of 16 or less are considered sensitive to pip/tazo. Intermittent dosing is not effective at achieving pharmacodynamic goals with vancomycin for MRSA and pip/tazo for pseudomonas in burn patients. Bolus dosing followed by a continuous drip of antibiotics is superior. Effective antibiotic dosing in burn patients needs careful evaluation of MIC’s for the bacteria being treated. Moreover, we should consider using bolus dosing followed by continuous drip therapy for effective antibacterial therapy in burn patients.