Staph Aureus and Pseudomonas Infections in Adult CF Patients
Staph Aureus and Pseudomonas Infections in Adult CF Patients
This retrospective cross-sectional cohort study included all patients followed at the Montreal Chest Institute (McGill University Health Centre, QC, Canada) Adult CF clinic who were alive in January 2012. Inclusion criteria were as follows: age >18 years old; diagnosis of CF; at least one sputum microbiology culture; at least one routine visit between January 2011 and February 2013. The baseline visit was defined as the first routine visit during which the patient was in a stable clinical condition within the study period. A stable clinical condition was defined as a period of at least 28 days without intravenous (IV) or oral antibiotics (excluding chronic antibiotic treatment). Patients were excluded if they had no routine visit during our study period (n = 6) or were colonized with Burkholderia cepacia complex (n = 1). All study participants provided written informed consent. The study was approved by the Research Ethics Board of the McGill University Health Center.
The demographic and clinical data were collected from the CF clinic database, a prospective database of all clinic patients and visits. Demographic data included age and sex. The body mass index (BMI) was calculated from the weight and height. Spirometry, including forced expiratory volume in 1 s (FEV 1) and forced vital capacity (FVC) expressed as a percentage of predicted values, was performed according to the American Thoracic Society standards and was measured at the baseline visit for this study. Pulmonary exacerbations are episodes of clinical deterioration diagnosed clinically by the treating physician, defined as episodes requiring IV antibiotic treatment at home or in the hospital. The exacerbation rate was calculated using the number of pulmonary exacerbations during the calendar year.
We used the Matouk clinical score, a previously described and validated measure of CF disease activity. The total clinical score includes key manifestations of CF disease with clinical (signs and symptoms), radiographic (chest radiographic findings), pulmonary function and complication subscores as previously described. For this study, we excluded the microbiology subscore (originally described in) to avoid a collinearity effect between the total clinical score and the airway infection status. The total clinical score (out of total of 95 points) is scaled to indicate more severe diseases with lower scores.
All spontaneously expectorated sputum samples collected from patients, during both routine and non-routine visits as well as hospitalisations, were analyzed by the McGill University Health Centre clinical microbiology laboratory according to standard protocols for CF samples. Briefly, sputum samples were cultured on sheep blood agar, MacConkey agar, and B. cepacia agar plates (BD), and the presence of PA, SA, and B. cepacia were confirmed through standard biochemical testing. The patients' infection status was determined based on the microbiology results of all sputum cultures collected during the calendar year of the baseline visit, including both routine and exacerbation visits. Patients were defined as infected with PA and/or SA if ≥50 % of their sputum samples were positive. In the case of insufficient samples, sputum microbiology results from the previous calendar year were used. No differentiation was made between MSSA and MRSA infections in our primary analyses because of the small number of patients with MRSA in our clinic (n = 4). Plasma C-reactive protein (CRP) levels were measured from plasma samples collected during the baseline visit using ELISA.
Continuous variables (age, body mass index, FEV 1 and FVC % predicted, clinical score and subscores, and CRP) were compared among the different infection groups using one-way analysis of variance (ANOVA) or student's t-test. Post-hoc analysis was done in conjunction with ANOVA using Tukey's test. Categorical variables (sex) were compared using the Mantel-Haenszel chi-square test. Differences in exacerbation rate and hospitalization rate were calculated using Poisson regression. P-values of ≤0.05 were considered statistically significant. To assess the association between airway infection and the patient's clinical status, we used FEV 1 % predicted and exacerbation rate as primary outcomes, and plasma CRP and clinical scores as secondary outcomes. Multivariable analyses included variables (age and sex) determined a priori. Linear regression was used for continuous outcomes (FEV 1 % predicted, plasma CRP and clinical scores), and Poisson regression was used for count data outcomes (exacerbation rate). Variables were tested for collinearity using a correlation matrix. In multivariable analyses, the infection category "PA" was used as a reference group, as this was the largest group. Statistical analyses were conducted using SAS 9.2 statistical package (SAS Institute Inc., USA).
Methods
Study Design
This retrospective cross-sectional cohort study included all patients followed at the Montreal Chest Institute (McGill University Health Centre, QC, Canada) Adult CF clinic who were alive in January 2012. Inclusion criteria were as follows: age >18 years old; diagnosis of CF; at least one sputum microbiology culture; at least one routine visit between January 2011 and February 2013. The baseline visit was defined as the first routine visit during which the patient was in a stable clinical condition within the study period. A stable clinical condition was defined as a period of at least 28 days without intravenous (IV) or oral antibiotics (excluding chronic antibiotic treatment). Patients were excluded if they had no routine visit during our study period (n = 6) or were colonized with Burkholderia cepacia complex (n = 1). All study participants provided written informed consent. The study was approved by the Research Ethics Board of the McGill University Health Center.
Demographic and Clinical Data
The demographic and clinical data were collected from the CF clinic database, a prospective database of all clinic patients and visits. Demographic data included age and sex. The body mass index (BMI) was calculated from the weight and height. Spirometry, including forced expiratory volume in 1 s (FEV 1) and forced vital capacity (FVC) expressed as a percentage of predicted values, was performed according to the American Thoracic Society standards and was measured at the baseline visit for this study. Pulmonary exacerbations are episodes of clinical deterioration diagnosed clinically by the treating physician, defined as episodes requiring IV antibiotic treatment at home or in the hospital. The exacerbation rate was calculated using the number of pulmonary exacerbations during the calendar year.
We used the Matouk clinical score, a previously described and validated measure of CF disease activity. The total clinical score includes key manifestations of CF disease with clinical (signs and symptoms), radiographic (chest radiographic findings), pulmonary function and complication subscores as previously described. For this study, we excluded the microbiology subscore (originally described in) to avoid a collinearity effect between the total clinical score and the airway infection status. The total clinical score (out of total of 95 points) is scaled to indicate more severe diseases with lower scores.
Microbiology and Laboratory Data
All spontaneously expectorated sputum samples collected from patients, during both routine and non-routine visits as well as hospitalisations, were analyzed by the McGill University Health Centre clinical microbiology laboratory according to standard protocols for CF samples. Briefly, sputum samples were cultured on sheep blood agar, MacConkey agar, and B. cepacia agar plates (BD), and the presence of PA, SA, and B. cepacia were confirmed through standard biochemical testing. The patients' infection status was determined based on the microbiology results of all sputum cultures collected during the calendar year of the baseline visit, including both routine and exacerbation visits. Patients were defined as infected with PA and/or SA if ≥50 % of their sputum samples were positive. In the case of insufficient samples, sputum microbiology results from the previous calendar year were used. No differentiation was made between MSSA and MRSA infections in our primary analyses because of the small number of patients with MRSA in our clinic (n = 4). Plasma C-reactive protein (CRP) levels were measured from plasma samples collected during the baseline visit using ELISA.
Statistical Analysis
Continuous variables (age, body mass index, FEV 1 and FVC % predicted, clinical score and subscores, and CRP) were compared among the different infection groups using one-way analysis of variance (ANOVA) or student's t-test. Post-hoc analysis was done in conjunction with ANOVA using Tukey's test. Categorical variables (sex) were compared using the Mantel-Haenszel chi-square test. Differences in exacerbation rate and hospitalization rate were calculated using Poisson regression. P-values of ≤0.05 were considered statistically significant. To assess the association between airway infection and the patient's clinical status, we used FEV 1 % predicted and exacerbation rate as primary outcomes, and plasma CRP and clinical scores as secondary outcomes. Multivariable analyses included variables (age and sex) determined a priori. Linear regression was used for continuous outcomes (FEV 1 % predicted, plasma CRP and clinical scores), and Poisson regression was used for count data outcomes (exacerbation rate). Variables were tested for collinearity using a correlation matrix. In multivariable analyses, the infection category "PA" was used as a reference group, as this was the largest group. Statistical analyses were conducted using SAS 9.2 statistical package (SAS Institute Inc., USA).