Health & Medical intensive care

Procalcitonin for Reduction of Antibiotic Use in Asthma

Procalcitonin for Reduction of Antibiotic Use in Asthma

Methods

Patients and Study Design


This was a randomized controlled trial. The study was approved by the Shanghai Fifth People's Hospital Research Ethics Committee, and all patients or their legally authorized representatives provided written informed consent.

From January 2009 to December 2011, consecutive patients ages 18 to 65 years who were hospitalized in the Fifth People's Hospital of Shanghai with severe acute exacerbations of asthma were eligible for enrollment in the study. Asthma was defined according to the guidelines of the Global Initiative for Asthma. A severe asthma exacerbation was defined as at least one of the following: (1) need for systemic corticosteroids, or an increase from a stable maintenance dose, for at least 3 days and/or (2) hospitalization or ED visit because of asthma requiring systemic corticosteroids. Excluded were patients with antibiotic use within the previous 14 days, psychiatric disorders or other inability to give written informed consent, not being available for follow-up, severe immunosuppression, heart failure, cystic fibrosis, active tuberculosis, pregnancy and chest radiography–confirmed pneumonia.

Baseline assessment included asthma and medical history, vital signs, physical examination, routine blood tests, chest radiography, spirometry and clinical events related to asthma within the previous year, including asthma exacerbations, need for systemic corticosteroids, ED visits and hospitalizations for asthma. Spontaneously expectorated sputum samples were obtained to identify potential pathogenic microorganisms.

Serum PCT was measured using the B.R.A.H.M.S. PCT sensitive Kryptor (B.R.A.H.M.S., Hennigsdorf, Germany), a rapid sensitive assay with a functional sensitivity of 0.06 μg/L and a lower detection limit of 0.02 μg/L with an assay time of less than 30 minutes.

Study Intervention


Eligible patients were randomized to either PCT-guided (PCT group) or standard antimicrobial therapy (control group). Allocation to either intervention was conducted according to computer-generated random numbers produced by an independent statistician. After randomization, an opaque, sealed, sequentially numbered envelope containing the PCT or control protocol was prepared for each subject according to group assignment. The control group received antibiotic according to the discretion of the treating physician, who was unaware of the patient's PCT levels. PCT levels of patients in the PCT group were provided to their attending physicians. Patients in the PCT group were treated with antibiotics on the basis of a PCT algorithm validated in previous studies: antibiotic treatment was strongly discouraged when serum PCT level was less than 0.1 μg/L; antibiotic treatment was discouraged when serum PCT level was less than 0.25 μg/L; and antibiotic treatment was encouraged when serum PCT level was higher than 0.25 μg/L. When antibiotics were withheld from patients, a second measurement of the PCT level was mandatory within 6 to 24 hours for safety reasons. The use of antibiotics was recommended if this second measurement was higher than 0.25 μg/L. The physicians were permitted to overrule the algorithm, but they had to indicate the reasons for overruling. The patients were reevaluated 12 months after discharge.

Outcome Measures


The primary end point was antibiotic use, expressed as rate of antibiotic prescriptions in percentage and relative risk of antibiotic exposure. Secondary end points included measures of treatment success; length of hospital stay; clinical, laboratory and spirometry outcomes at discharge; and results of spirometry at the 12-month follow-up examination, as well as the results of the Asthma Control Test (ACT), the results of the Asthma Quality of Life Questionnaire (AQLQ) at the 12-month follow-up visit and the clinical events during the 12-month follow-up period, including numbers of asthma exacerbations, ED visits, hospitalizations and need for systemic corticosteroid use for treatment of asthma.

The ACT was used to determine the level of disease control. The overall ACT score varies from 5 (very poor asthma control) to 25 (full asthma control), with scores ranging from 20 to 24 defining controlled asthma, scores ranging from 16 to 19 partly indicating controlled asthma and scores ≤15 identifying uncontrolled asthma. The AQLQ was used to evaluate quality of life. The AQLQ consists of 32 items covering asthma-related symptoms and limitations during the 2 weeks preceding administration of the questionnaire, and responses are scored on a scale of 1 to 7, with higher numbers indicating a better quality of life. The validity and reliability of the ACT and the AQLQ have been evaluated for use in Chinese patients with asthma.

Statistical Analysis


Discrete variables are expressed as percentages and continuous variables as mean ± standard deviation (SD) for variables normally distributed and as median with interquartile range (IQR) for nonnormally distributed data. Comparability of groups was analyzed by χ test, two-sampled t-test and/or Mann-Whitney U test as appropriate. Relative risk (RR) was calculated with 95% confidence interval (CI). P < 0.05 was defined as statistically significant.

Assuming 90% of the patients in the control group would use antibiotics and anticipating a 15% decrease in antibiotic usage in the PCT group, a sample size of 158 patients (79 patients per group) was necessary to detect a significant difference in antibiotic prescription rate between the groups with 80% power and an α error of 0.05. To account for possible loss of patients to follow-up, we planned to enroll 180 patients.

The time to the first occurrence of asthma-related clinical events (exacerbation and hospitalization) was analyzed using Kaplan-Meier survival curves and by the logrank test. For outcomes during the follow-up period, we performed per-protocol analyses. Data were analyzed using SPSS version 16 for Windows statistical software (SPSS, Chicago, IL, USA).

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