Introduction
Methods
Study design and participants
Study objectives
Microbiology
Statistical analyses
Results
Study participants
Evaluable participants (N = 191) | |
---|---|
Age (mean ± SD), months | 39.84 ± 17.76 |
Female, n (%) | 92 (48.2) |
Weight (mean ± SD), kg | 14.67 ± 3.83 |
Height (mean ± SD), cm | 96.04 ± 13.10 |
Age distribution, n (%) | |
6–11 months | 14 (7.3) |
12–23 months | 29 (15.2) |
24–35 months | 32 (16.8) |
36–47 months | 38 (19.9) |
48–59 months | 52 (27.2) |
60–71 months | 26 (13.6) |
Indications observed, n (%) | |
Cough | 151 (79.1) |
Wheezing | 86 (45.0) |
Pathologic auscultation | 74 (38.7) |
Infiltrates/atelectasis (diagnosed by X-ray) | 131 (68.6) |
Any pre-existing respiratory conditions, n (%) | |
Asthma | 72 (37.7) |
Pneumonia | 114 (59.7) |
Bronchiolitis | 85 (44.5) |
Bronchiectasis | 15 (7.9) |
Bronchitis | 143 (74.9) |
Rhinitis | 15 (7.9) |
Pre-existing otitis media conditions, n (%) | |
Acute otitis media | 53 (27.8) |
Otitis media with effusion or “glue ear” | 6 (3.1) |
Otitis media with perforation and discharge | 8 (4.2) |
Relevant vaccination history, n (%) | |
Any PCVa | 168 (88.0) |
≥ 2 doses of PCV7 | 13 (6.8) |
≥ 2 doses of PCV13 or PHiD-CV | 120 (62.8) |
Hib vaccine, ≥ 2 doses | 186 (97.4) |
Influenza vaccine, ≥ 1 dose | 58 (30.4) |
Antibiotic takenb, n (%) | 153 (80.1) |
Penicillin | 83 (43.5) |
Amoxicillin/ clavulanate | 76 (39.8) |
Azithromycin | 57 (29.8) |
Cephalosporins | 24 (12.6) |
Clarithromycin | 8 (4.2) |
Otherc | 6 (3.0) |
Culture and bacterial load
BALF
Cultures with any bacterial load, % (95% CI) | Cultures meeting the cut-off for infectiona, % (95% CI) | ||
---|---|---|---|
BALF (N = 190) | NPS (N = 191) | BALF (N = 190) | |
S. pneumoniae
| 30.5 (24.1–37.6) | 51.8 (44.5–59.1) | 10.5 (6.5–15.8) |
H. influenzae
| 51.1 (43.7–58.4) | 46.6 (39.4–53.9) | 8.9 (5.3–13.9) |
M. catarrhalis
| 49.5 (42.2–56.8) | 56.0 (48.7–63.2) | 6.3 (3.3–10.8) |
Any of the three | 74.2 (67.4–80.3) | 80.6 (74.3–86.0) | 22.1 (16.4–28.7) |
Other pathogens | 6.3 | 3.7 | – |
NPS
Clinical characteristics
S. pneumoniae
|
H. influenzae
|
M. catarrhalis
| ||||
---|---|---|---|---|---|---|
Positive | Negative | Positive | Negative | Positive | Negative | |
N = 20 | N = 170 | N = 17 | N = 173 | N = 12 | N = 178 | |
Indication observed in the patient, n (%) | ||||||
Cough | 14 (70.0) | 136 (80.0) | 16 (94.1) | 134 (77.5) | 10 (83.3) | 140 (78.7) |
Wheezing | 5 (25.0) | 80 (47.1) | 6 (35.3) | 79 (45.7) | 6 (50.0) | 79 (44.4) |
Pathologic auscultation | 9 (45.0) | 64 (37.7) | 6 (35.3) | 67 (38.7) | 6 (50.0) | 67 (37.6) |
Infiltrates/atelectasis (diagnosed by X-ray) | 12 (60.0) | 119 (70.0) | 12 (70.6) | 119 (68.8) | 7 (58.3) | 124 (69.7) |
Main fibro-bronchoscopy indication in patients, n (%) | ||||||
Wet cough for > 4 weeks without associated symptomsa | 5 (25.0) | 57 (33.5) | 4 (23.5) | 58 (33.5) | 2 (16.7) | 60 (33.7) |
Persistent wheezing (lasting > 3 months)a | 1 (5.0) | 7 (4.1) | 0 (0.0) | 8 (4.6) | 0 (0.0) | 8 (4.5) |
Recurrent wheezing (≥ 3 episodes/year)a | 2 (10.0) | 23 (13.5) | 2 (11.8) | 23 (13.3) | 3 (25.0) | 22 (12.4) |
Persistent pathologic auscultation (lasting > 4 weeks)a | 3 (15.0) | 13 (7.7) | 2 (11.8) | 14 (8.1) | 2 (16.7) | 14 (7.9) |
Persistent infiltrates/atelectasis (lasting > 1 month)a | 8 (40.0) | 57 (33.5) | 8 (47.1) | 57 (33.0) | 4 (33.3) | 61 (34.3) |
Recurrent infiltrates/atelectasis (≥ 3 occurrences/year)a | 1 (5.0) | 13 (7.7) | 1 (5.9) | 13 (7.5) | 1 (8.3) | 13 (7.3) |
Pre-existing respiratory conditions, n (%) | ||||||
Pneumonia | 13 (65.0) | 101 (59.4) | 10 (58.8) | 104 (60.1) | 8 (66.7) | 106 (59.6) |
Bronchiolitis | 8 (40.0) | 77 (45.2) | 11 (64.7) | 74 (42.8) | 4 (33.3) | 81 (45.5) |
Bronchiectasis | 2 (10.0) | 13 (7.7) | 1 (5.9) | 14 (8.1) | 0 (0.0) | 15 (8.4) |
Bronchitis | 16 (80.0) | 126 (74.1) | 12 (70.6) | 130 (75.1) | 9 (75.0) | 133 (74.7) |
Rhinitis | 1 (5.0) | 14 (8.2) | 0 (0.0) | 15 (8.7) | 1 (8.3) | 14 (7.9) |
Serotype distribution
Antimicrobial susceptibility
Antibiotic | Cultures with any bacterial load | Cultures meeting the cut-off for infectiona | |||||||
---|---|---|---|---|---|---|---|---|---|
BALF | NPS | BALF | |||||||
S
|
I
|
R
|
S
|
I
|
R
|
S
|
I
|
R
| |
S. pneumoniae
| N = 65 | N = 105 | N = 21 | ||||||
Penicillin, n (%) | 36 (55.4%) | 13 (20.0%) | 16 (24.6%) | 55 (52.4%) | 27 (25.7%) | 23 (21.9%) | 15 (71.4%) | 2 (9.5%) | 4 (19.0%) |
Amoxicillin/clavulanate, n (%) | 50 (76.9%) | 7 (10.8%) | 8 (12.3%) | 86 (81.9%) | 10 (9.5%) | 9 (8.6%) | 17 (81.0%) | 3 (14.3%) | 1 (4.8%) |
Erythromycin, n (%) | 43 (66.2%) | 1 (1.5%) | 21 (32.3%) | 55 (52.4%) | 1 (1.0%) | 49 (46.7%) | 17 (81.0%) | 0 (0.0%) | 4 (19.0%) |
Azithromycin, n (%) | 41 (63.1%) | 3 (4.6%) | 21 (32.3%) | 57 (54.3%) | 4 (3.8%) | 44 (41.9%) | 15 (71.4%) | 2 (9.5%) | 4 (19.0%) |
Tetracycline, n (%) | 51 (78.5%) | 14 (21.5%) | 0 (0.0%) | 71 (67.6%) | 3 (2.9%) | 31 (29.5%) | 18 (85.7%) | 0 (0.0%) | 3 (14.3%) |
Levofloxacin, n (%) | 65 (100%) | 0 (0.0%) | 0 (0.0%) | 103 (98.1%) | 0 (0.0%) | 2 (1.9%) | 21 (100%) | 0 (0.0%) | 0 (0.0%) |
TMP/SMX, n (%) | 24 (36.9%) | 13 (20.0%) | 28 (43.1%) | 52 (49.5%) | 13 (12.4%) | 40 (38.1%) | 3 (14.3%) | 5 (23.8%) | 13 (61.9%) |
MDR, n (%) | 33 (50.8%) | 59 (56.2%) | 7 (33.3%) | ||||||
H. influenzae
| N = 98 | N = 92 | N = 18 | ||||||
Penicillin, med (min, max) | 0.5 (0.13, 16.00) | 0.5 (0.13, 16.00) | 0.50 (0.25, 16.00) | ||||||
Amoxicillin/clavulanate, n (%) | 91 (92.9%) | 0 (0.0%) | 7 (7.1%) | 91 (98.9%) | 0 (0.0%) | 1 (1.1%) | 15 (83.3%) | 0 (0.0%) | 3 (16.7%) |
Erythromycin, med (min, max) | 4 (1.00, 16.00) | 4.00 (0.25, 16.00) | 4.00 (2.00, 16.00) | ||||||
Azithromycin, n (%) | 95 (96.9%) | 0 (0.0%) | 3 (3.1%) | 89 (96.7%) | 0 (0.0%) | 3 (3.3%) | 17 (94.4%) | 0 (0.0%) | 1 (5.6%) |
Tetracycline, n (%) | 98 (100%) | 0 (0.0%) | 0 (0.0%) | 92 (100%) | 0 (0.0%) | 0 (0.0%) | 18 (100%) | 0 (0.0%) | 0 (0.0%) |
Levofloxacin, n (%) | 98 (100%) | 0 (0.0%) | 0 (0.0%) | 92 (100%) | 0 (0.0%) | 0 (0.0%) | 18 (100%) | 0 (0.0%) | 0 (0.0%) |
TMP/SMX, n (%) | 51 (52.0%) | 16 (16.3%) | 31 (31.6%) | 49 (53.3%) | 18 (19.6%) | 25 (27.2%) | 5 (27.8%) | 7 (38.9%) | 6 (33.3%) |
Beta-lactamase positive, n % | 7 (7.1%) | 9 (9.8%) | 3 (16.7%) | ||||||
MDR, n (%) | 7 (7.1%) | 6 (6.5%) | 4 (22.2%) | ||||||
M. catarrhalis
| N = 98 | N = 110 | N = 13 | ||||||
Penicillin, med (min, max) | 8.00 (0.02, 16.00) | 16.00 (0.02, 16.00) | 16.00 (0.50, 16.00) | ||||||
Amoxicillin/clavulanate, n (%) | 95 (96.9%) | 0 (0.0%) | 3 (3.1%) | 105 (95.5%) | 0 (0.0%) | 5 (4.5%) | 12 (92.3%) | 0 (0.0%) | 1 (7.7%) |
Erythromycin, n (%) | 90 (91.8%) | 0 (0.0%) | 8 (8.2%) | 106 (96.4%) | 0 (0.0%) | 4 (3.6%) | 12 (92.3%) | 0 (0.0%) | 1 (7.7%) |
Azithromycin, n (%) | 84 (85.7%) | 0 (0.0%) | 14 (14.3%) | 106 (96.4%) | 0 (0.0%) | 4 (3.6%) | 11 (84.6%) | 0 (0.0%) | 2 (15.4%) |
Tetracycline, n (%) | 98 (100%) | – | 0 (0.0%) | 110 (100%) | 0 (0.0%) | 0 (0.0%) | 13 (100%) | 0 (0.0%) | 0 (0.0%) |
Levofloxacin, n (%) | 98 (100%) | – | 0 (0.0%) | 110 (100%) | 0 (0.0%) | 0 (0.0%) | 13 (100%) | 0 (0.0%) | 0 (0.0%) |
TMP/SMX, n (%) | 56 (57.1%) | 35 (35.7%) | 7 (7.1%) | 103 (93.6%) | 0 (0.0%) | 7 (6.4%) | 7 (53.8%) | 5 (38.5%) | 1 (7.7%) |
Beta-lactamase positive, n (%) | 93 (94.9%) | 108 (98.2%) | 13 (100%) | ||||||
MDR, n (%) | 10 (10.2%) | 5 (4.5%) | 2 (15.4%) |
Concordance between BAL and NP isolates
Isolates with any bacterial load, n (%) | Isolates with a bacterial load meeting the cut-off for infectiona, n (%) | |||||
---|---|---|---|---|---|---|
S. pneumoniae N = 49 |
H. influenzae
N = 71 |
M. catarrhalis
N = 82 |
S. pneumoniae
N = 30 |
H. influenzae
N = 15 |
M. catarrhalis
N = 18 | |
BALF | 49 (100%) | 71 (100%) | 82 (100%) | 20 (66.7%) | 12 (80.0%) | 11 (61.1%) |
NPS | 49 (100%) | 71 (100%) | 82 (100%) | 18 (60.0%) | 6 (40.0%) | 10 (55.6%) |
Both BALF and NPS | 49 (100%) | 71 (100%) | 82 (100%) | 8 (26.7%) | 3 (20.0%) | 3 (16.7%) |
Concordance | 25 (51.0%) | 37 (52.1%) | 18 (22%) | 2 (6.7%) | 2 (13.3%) | 1 (5.6%) |
Isolates with any bacterial load | Isolates with a bacterial load meeting the cut-off for infectiona | |||||
---|---|---|---|---|---|---|
S. pneumoniae
|
H. influenzae
|
M. catarrhalis
|
S. pneumoniae
|
H. influenzae
|
M. catarrhalis
| |
BALF, n | 58 | 97 | 94 | 20 | 17 | 12 |
NPS, n | 98 | 89 | 106 | 98 | 89 | 106 |
Both BALF and NPS, n | 49 | 71 | 83 | 20 | 12 | 11 |
Sensitivity, value (95% CI) | 0.84 (0.73–0.93) | 0.73 (0.63–0.82) | 0.88 (0.80–0.94) | 1.00 (0.83–1.00) | 0.71 (0.44–0.90) | 0.92 (0.62–1.00) |
Specificity, value (95% CI) | 0.63 (0.54–0.71) | 0.81 (0.71–0.88) | 0.76 (0.66–0.84) | 0.54 (0.46–0.62) | 0.55 (0.48–0.63) | 0.47 (0.39–0.54) |
PPV, value (95% CI) | 0.50 (0.40–0.60) | 0.80 (0.70–0.88) | 0.78 (0.69–0.86) | 0.20 (0.13–0.30) | 0.13 (0.07–0.22) | 0.10 (0.05–0.18) |
NPV, value (95% CI) | 0.90 (0.82–0.95) | 0.74 (0.65–0.82) | 0.87 (0.78–0.93) | 1.00 (0.96–1.00) | 0.95 (0.89–0.98) | 0.99 (0.94–1.00) |