Concomitant antibiotics
The interaction between various intravenous medications for APE is considered important to ensure optimal treatment (28, 29). This was assessed retrospectively in 162 adult CF patients with continuous intravenous infusion of BL antibiotics, in combination with intravenous tobramycin (19). The BL clearance rate increased by nearly 21% while the tobramycin clearance rate decreased by 6.3% between admission and discharge (19). A specific combination of antibiotics appears to change the basic PK properties of tobramycin. This synergy introduces further variability when treating an APE and may be an important factor to consider when evaluating dosing strategies.
Tobramycin concomitant to ceftazidime and to piperacillin/tazobactam were the only combinations that significantly impacted the composite criterion in this study, increasing the probability of a positive outcome. Given their wide confidence interval, specific recommendations cannot be made. However, ceftazidime in combination with tobramycin has been previously shown effective in the treatment of an APE and our results support the superiority of this combination (30). Anaerobic organisms identified by non-culture methods appear prevalent in APEs (31), antibiotic treatment covering these organisms may be more effective.
The presence of microorganisms other than P. aeruginosa is rarely investigated and may need to be integrated in the rationale behind the treatment of an APE. Although not significant in our study, the presence of such organisms showed a trend towards impacting the clinical efficacy of current treatments, especially resistant organisms. Higher-powered studies are needed to evaluate the impact of these additional organisms and how to manage them.