title: The efficacy and safety of meropenem and tobramycin vs ceftazidime and tobramycin in the treatment of acute pulmonary exacerbations in patients with cystic fibrosis.
abstract: 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.
authors.affiliation: Rainbow Babies and Children's Hospital, Case Western Reserve University School of Medicine, Cleveland, OH, USA. jblumer@tulane.edu
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Blumer
authors.forename: Lisa
authors.initials: L
authors.lastname: Saiman
authors.forename: Michael W
authors.initials: MW
authors.lastname: Konstan
authors.forename: David
authors.initials: D
authors.lastname: Melnick
mesh_terms: D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D019121:Burkholderia Infections / Q000188:drug therapy; D016956:Burkholderia cepacia / Q000302:isolation & purification; D002442:Ceftazidime / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000145:classification / Q000188:drug therapy* / Q000503:physiopathology; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005541:Forced Expiratory Volume; D006801:Humans; D000077731:Meropenem; D008875:Middle Aged; D011552:Pseudomonas Infections / Q000188:drug therapy; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification; D012129:Respiratory Function Tests; D013183:Sputum / Q000382:microbiology; D013845:Thienamycins / Q000627:therapeutic use*; D014031:Tobramycin / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D013845:Thienamycins; D002442:Ceftazidime; D000077731:Meropenem; D014031:Tobramycin