Background
Acute pulmonary exacerbations of cystic fibrosis in patients colonized with pseudomonas aeruginosa are recommended to be treated by dual antipseudomonal agents.
Methods
We conducted a single-center two-year prospective cohort study in adult cystic fibrosis patients colonized with mucoid pseudomonas to determine if attaining recommended pharmacokinetics/pharmacodynamics index of aminoglycoside correlated with clinical outcomes.
Results
There were 14 admissions with acute pulmonary exacerbations in nine patients. Dual antipseudomonal regimes used included amikacin in 10 and the remaining included gentamicin. ( Table 1) The average empirical dose of amikacin was 30.9 ± 2 mg/kg, while for gentamicin it was 10.5±0.7 mg/kg. The target Cmax:MIC ratio of 8-10 in our study was achieved in only 50% of the amikacin group, and none in the gentamicin group. However, all patients had significant clinical improvement with a mean improvement in FEV1 from admission to discharge of 8%.
| PK Parameter | Amikacin (n=10) |
Gentamicin (n=4) |
| Ke (hr-1) | 0.32 | 0.27 |
| Vd (L/kg) | 0.26 | 0.68 |
| t1/2 (hr) | 2.14 (13.8%) | 2.56 (20.2%) |
| AUC 0 ? 24 h (mg.hr/L) | 360.60(82.8%) | 53.97 (16.5%) |
Conclusions
Despite not achieving the target Cmax:MIC ratio in the majority of the patients, a significant clinical improvement in patients admitted with acute pulmonary exacerbations of cystic fibrosis was seen. Our findings warrant revisiting the rationale of using a dual antibiotic regime as a blanket guideline in cystic fibrosis patients colonized with pseudomonas as either a single agent may be enough or the aminoglycosides are effective despite not achieving the recommended Cmax:MIC and the target level may need to be revised.