The efficacy and safety of meropenem and tobramycin vs ceftazidime and tobramycin in the treatment of acute pulmonary exacerbations in patients with cystic fibrosis

Chest. 2005 Oct;128(4):2336-46. doi: 10.1378/chest.128.4.2336.


Background: Cystic fibrosis (CF) is characterized by chronic pulmonary infection with acute pulmonary exacerbations (APEs) requiring IV antibiotic treatment. We report on a blinded comparative trial of IV meropenem (40 mg/kg to 2 g q8h) or ceftazidime (5 mg/kg to 2 g q8h), each of which was administered with IV tobramycin (at a serum peak of > or = 8 microg/mL and a trough of < 2 microg/mL), as treatment for CF patients with APEs.

Methods: Patients who were > or = 5 years of age who were infected with ceftazidime-susceptible Pseudomonas aeruginosa were stratified by lung function and randomized to treatment with meropenem/tobramycin or ceftazidime/tobramycin. Patients infected with Burkholderia cepacia complex or ceftazidime-resistant P aeruginosa were assigned to receive open-label meropenem/tobramycin. Clinical response was assessed by spirometry to determine the change in percent predicted FEV1 and by a clinical acute change score (ACS).

Results: One hundred two patients were randomized to meropenem/tobramycin (n = 50) or ceftazidime/tobramycin (n = 52). Nineteen patients received open-label meropenem/tobramycin. FEV1 was improved at the end of treatment (EOT) with meropenem/tobramycin (mean [+/- SD] increase, 38.8 +/- 52.3%) and with ceftazidime/tobramycin (mean increase, 29.4 +/- 35.1%; p < 0.0001 vs baseline values). The proportion of patients with > or = 15% relative increase from baseline FEV1 (satisfactory response) at day 7 was 62% for the meropenem/tobramycin group and 44% for the ceftazidime/tobramycin group (p = 0.04). The median time to FEV1 response was 4 days for meropenem/tobramycin therapy vs 6 days for ceftazidime/tobramycin therapy. Similarly, FEV1 improved in the open-label group (mean increase, 12.5 +/- 25.7%; p = 0.05). ACS improved in all three groups at EOT (p < 0.0001 vs baseline values).

Conclusions: Therapy with both meropenem/tobramycin and ceftazidime/tobramycin improved pulmonary and clinical status and reduced sputum bacterial burden in CF patients with APEs. A larger proportion of patients receiving meropenem/tobramycin therapy demonstrated a satisfactory FEV1 response at day 7. Resistant P aeruginosa emerged infrequently during treatment with both regimens.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Anti-Bacterial Agents / therapeutic use
  • Burkholderia Infections / drug therapy
  • Burkholderia cepacia / isolation & purification
  • Ceftazidime / therapeutic use*
  • Child
  • Child, Preschool
  • Cystic Fibrosis / classification
  • Cystic Fibrosis / drug therapy*
  • Cystic Fibrosis / physiopathology
  • Disease Progression
  • Drug Therapy, Combination
  • Forced Expiratory Volume
  • Humans
  • Meropenem
  • Middle Aged
  • Pseudomonas Infections / drug therapy
  • Pseudomonas aeruginosa / isolation & purification
  • Respiratory Function Tests
  • Sputum / microbiology
  • Thienamycins / therapeutic use*
  • Tobramycin / therapeutic use*


  • Anti-Bacterial Agents
  • Thienamycins
  • Ceftazidime
  • Meropenem
  • Tobramycin