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Clinical Investigations: CYSTIC FIBROSIS |

The Efficacy and Safety of Meropenem and Tobramycin vs Ceftazidime and Tobramycin in the Treatment of Acute Pulmonary Exacerbations in Patients With Cystic Fibrosis*

Jeffrey L. Blumer, PhD, MD; Lisa Saiman, MD, MPH; Michael W. Konstan, MD; David Melnick, MD
Author and Funding Information

Affiliations: *From the Rainbow Babies and Children’s Hospital (Drs. Blumer and Konstan), Case Western Reserve University School of Medicine, Cleveland, OH; Columbia University (Dr. Saiman), New York, NY; and AstraZeneca (Dr. Melnick), Wilmington, DE.,  A complete list of coordinating investigators for each study site is located in the Appendix.

Correspondence to: Jeffrey L. Blumer, PhD, MD, Tulane University School of Medicine, 1430 Tulane Ave, SL-37, New Orleans, LA 70112; e-mail: jblumer@tulane.edu



Chest. 2005;128(4):2336-2346. doi:10.1378/chest.128.4.2336
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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 ≥ 8 μg/mL and a trough of < 2 μg/mL), as treatment for CF patients with APEs.

Methods: Patients who were ≥ 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 ≥ 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.

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