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Am J Respir Crit Care Med. 2018 Nov 1;198(9):1177-1187. doi: 10.1164/rccm.201802-0215OC.

Azithromycin for Early Pseudomonas Infection in Cystic Fibrosis. The OPTIMIZE Randomized Trial.

Collaborators (145)

Retsch-Bogart G, Accurso FJ, Buckingham R, Howenstine M, Jacob S, Kronmal R, Kuhn R, Mayer-Hamblett N, McCoy K, Nichols D, Ramsey BW, Rosenfeld M, Sagel S, Saiman L, Sheridan J, Wilfond B, Zemanick E, Bondick I, Braam L, Brassil M, Buckingham R, Cianciola M, Heltshe S, Jacob S, Johnson M, Kirihara J, Kloster M, Kong A, Ma S, McNamara S, Mann L, Moormann K, Myers M, Mayer-Hamblett N, Ramsey BW, Retsch-Bogart G, Seidel K, Skalland M, Ufret-Vincenty C, VanDalfsen J, Goss CH, Horne DJ, Kross EK, Leary PJ, Ramos KJ, Roush P, Salerno JC, Omlor G, Ouellette D, Green D, Hosler K, Savant A, Ashrafi Z, Berlinski A, Ross A, Sawicki G, Fowler R, Ulles M, Albers G, Branch F, Kirchner K, DiBenardo K, Kerby G, Anthony M, Keens T, Franquez A, Reyes C, Abdulhamid I, Van Wagnen C, Orenstein D, Hartigan E, Mihlo C, Williams R, Lessard M, Sass L, McAndrews E, Parrott J, Noe J, Hastings P, Kump T, Clancy J, Niehaus S, Saiman L, Zhou J, Mueller G, Bartosik S, Fullmer J, Millian C, Stecenko A, Dangerfield J, Graff G, Kitch D, Cairns A, Milliard C, Zanni R, Marra B, McCoy K, Guittar P, Smith M, Schaeffer D, DeLuca E, Welter J, Gallagher M, Ramirez A, Cornell A, Simeon E, Roberts D, Nelson K, Chmiel J, Schaefer C, Davis SD, Shively L, Wallace J, Richter A, Ramsey B, McNamara S, Pittman J, Hicks T, Brown P, Durham D, Milla C, Zirbes J, Fortner C, Suttmore V, Black P, Thompson R, Daines C, Varela M, Starner T, Teresi M, Nasr S, Kruse D, Thomas H, Houdesheldt L, Retsch-Bogart G, Barlow C, Cunnion R, Srinivasan S, Horobetz C, Asfour F, Francis J, Rock M, Makholm L, Egan M, Guzman C.

Author information

1 Department of Pediatrics and.
3 Department of Biostatistics, University of Washington, Seattle, Washington.
2 Seattle Children's Hospital, Seattle, Washington.
4 Department of Pediatrics, University of North Carolina, Chapel Hill, North Carolina.
5 Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado.
6 Children's Hospital Colorado, Aurora, Colorado.
7 Department of Pediatrics, Saint Louis University School of Medicine, Saint Louis, Missouri.
8 Children's Mercy Hospital, Kansas City, Missouri.
9 St. Luke's Regional Medical Center, Boise, Idaho.
10 Maine Medical Center, Portland, Maine.
11 Indiana University Hospital, Indianapolis, Indiana.
12 James Whitcomb Riley Hospital for Children, Indianapolis, Indiana.
13 Hershey Medical Center, Hershey, Pennsylvania.
14 Penn State Children's Hospital, Hershey, Pennsylvania; and.
15 UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania.



New isolation of Pseudomonas aeruginosa (Pa) is generally treated with inhaled antipseudomonal antibiotics such as tobramycin inhalation solution (TIS). A therapeutic approach that complements traditional antimicrobial therapy by reducing the risk of pulmonary exacerbation and inflammation may ultimately prolong the time to Pa recurrence.


To test the hypothesis that the addition of azithromycin to TIS in children with cystic fibrosis and early Pa decreases the risk of pulmonary exacerbation and prolongs the time to Pa recurrence.


The OPTIMIZE (Optimizing Treatment for Early Pseudomonas aeruginosa Infection in Cystic Fibrosis) trial was a multicenter, double-blind, randomized, placebo-controlled, 18-month trial in children with CF, 6 months to 18 years of age, with early Pa. Azithromycin or placebo was given 3× weekly with standardized TIS.


The primary endpoint was the time to pulmonary exacerbation requiring antibiotics and the secondary endpoint was the time to Pa recurrence, in addition to other clinical and safety outcomes. A total of 221 participants (111 placebo, 110 azithromycin) out of a planned 274 were enrolled. Enrollment was stopped early by the NHLBI because the trial had reached the prespecified interim boundary for efficacy. The risk of pulmonary exacerbation was reduced by 44% in the azithromycin group as compared with the placebo group (hazard ratio, 0.56; 95% confidence interval, 0.37-0.83; P = 0.004). Weight increased by 1.27 kg in the azithromycin group compared with the placebo group (95% confidence interval, 0.01-2.52; P = 0.046). No significant differences were seen in microbiological or other clinical or safety endpoints.


Azithromycin was associated with a significant reduction in the risk of pulmonary exacerbation and a sustained improvement in weight, but had no impact on microbiological outcomes in children with early Pa. Clinical trial registered with (NCT02054156).


Pseudomonas aeruginosa; clinical trial; eradication; pulmonary exacerbation

[Available on 2019-11-01]

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