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.