Antibiotics in addition to systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease.
BACKGROUND
The role of antibiotics in acute exacerbations is controversial and their efficacy when added to systemic corticosteroids is unknown.


OBJECTIVE
We conducted a randomized, placebo-controlled trial to determine the effects of doxycycline in addition to corticosteroids on clinical outcome, microbiological outcome, lung function, and systemic inflammation in patients hospitalized with an acute exacerbation of chronic obstructive pulmonary disease.


METHODS
Of 223 patients, we enrolled 265 exacerbations defined on the basis of increased dyspnea and increased sputum volume with or without increased sputum purulence. Patients received 200 mg of oral doxycycline or matching placebo for 7 days in addition to systemic corticosteroids. Clinical and microbiological response, time to treatment failure, lung function, symptom scores, and serum C-reactive protein were assessed.


RESULTS
On Day 30, clinical success was similar in intention-to-treat patients (odds ratio, 1.3; 95% confidence interval, 0.8 to 2.0) and per-protocol patients. Doxycycline showed superiority over placebo in terms of clinical success on Day 10 in intention-to-treat patients (odds ratio, 1.9; 95% confidence interval, 1.1 to 3.2), but not in per-protocol patients. Doxycycline was also superior in terms of clinical cure on Day 10, microbiological outcome, use of open label antibiotics, and symptoms. There was no interaction between the treatment effect and any of the subgroup variables (lung function, type of exacerbation, serum C-reactive protein, and bacterial presence).


CONCLUSIONS
Although equivalent to placebo in terms of clinical success on Day 30, doxycycline showed superiority in terms of clinical success and clinical cure on Day 10, microbiological success, the use of open label antibiotics, and symptoms. Clinical trial registered with www.clinicaltrials.gov (NCT00170222).
Daniels
Johannes M A
JM
Department of Pulmonary Diseases, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. j.daniels@vumc.nl
Snijders
Dominic
D
de Graaff
Casper S
CS
Vlaspolder
Fer
F
Jansen
Henk M
HM
Boersma
Wim G
WG
D000208:Acute Disease; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000378:metabolism; D004311:Double-Blind Method; D004318:Doxycycline / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000627:therapeutic use; D011241:Prednisone / Q000627:therapeutic use; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D015996:Survival Rate
D000305:Adrenal Cortex Hormones; D000900:Anti-Bacterial Agents; D001993:Bronchodilator Agents; D002097:C-Reactive Protein; D011239:Prednisolone; D004318:Doxycycline; D011241:Prednisone